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China Pharmaceutical University is a university in Nanjing, China that specializes in the pharmaceutical science. Wikipedia.


Huang H.-L.,Guangdong Medical College | Wang Y.-J.,China Pharmaceutical University | Zhang Q.-Y.,Guangdong Medical College | Liu B.,Guangdong Medical College | And 3 more authors.
World Journal of Gastroenterology | Year: 2012

AIM: To investigate the hepatoprotective effect of baicalein against carbon tetrachloride (CCl4)-induced liver damage in mice. METHODS: Mice were orally administered with baicalein after CCl4 injection, and therapeutic baicalein was given twice a day for 4 d. The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement. Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation. Serum interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6, TNF-α, transforming growth factor-α (TGF-α), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) genes expression were determined by quantitative real-time polymerase chain reaction. RESULTS: CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice. The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl4 treatment in baicalein administration groups, but at 24, 48 and 72 h, the expression of IL-6 and TNF-α was kept at lower levels compared with the control. The expression of TGF-α, HGF and EGF was enhanced dramatically in baicalein administration group at 12, 24, 48 and 72 h. Furthermore, we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase, which indicated that baicalein could facilitate the initiating events in liver regeneration. CONCLUSION: Baicalein may be a therapeutic candidate for acute liver injury. Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways. © 2012 Baishideng. All rights reserved. Source


Lu T.,Laboratory of Molecular Design and Drug Discovery | Lu T.,China Pharmaceutical University
Mini-Reviews in Organic Chemistry | Year: 2012

This review describes recent development in the aerobic oxidation of amines. A variety of ruthenium catalysts have shown excellent activity for the aerobic oxidation of amines. Several gold and copper catalysts are also effective for this reaction. Other metalcontaining complexes are revealed to be active catalysts and an enzyme is also investigated for this oxidation. Meanwhile, various supports have been explored for this reaction and the availability of various supports with differing physical properties allows chemists to design and create many catalytic systems. © 2012 Bentham Science Publishers. Source


Wang C.,Nanjing University | Wang C.,China Pharmaceutical University | Ouyang J.,Nanjing University | Wang Y.-Y.,Nanjing University | And 2 more authors.
Analytical Chemistry | Year: 2014

A fast and sensitive assay of protease activity on a micro/nanofluidics preconcentrator combining with fluorescence resonance energy transfer (FRET) detection technique has been developed in a homogeneous real-time format. First, the functionalized nanoprobes are formed by loading dye labeled protein onto gold nanoparticles (AuNPs), in which, the photoluminescence of donor dye was strongly quenched by AuNPs due to FRET mechanisms. For protease activity assay, the nanoprobes are enriched by a micro/nanofluidics preconcentrator. When the target protease is transported to the enriched nanoprobes, cleavage of protein occurs as a consequence of molecular recognition of enzyme to substrate. The release of cleavage fragments from AuNPs nanoprobes leads to the enhancement of fluorescence and enables the protease activity assay on the micro/nanofluidics chip. As a demonstration, digestion of fluorescein isothiocyanate labeled dog serum albumin (FITC-DSA) by trypsin was used as a model reaction. Because of the highly efficient preconcentration and space confinement effect, significantly increased protein cleavage rate and protease assay sensitivity can be achieved with enhanced enzyme activity. The present micro/nanofluidics platform fused with the FRET detection technique is promising for fast and sensitive bioanalysis such as immunoassay, DNA hybridization, drug discovery, and clinical diagnosis. © 2014 American Chemical Society. Source


Zhang D.,Nanjing Southeast University | Yang M.,China Pharmaceutical University | Dong S.,Nanjing Southeast University
Journal of Physical Chemistry C | Year: 2015

Hydroxylation of the rutile TiO2(110) surface has attracted much attention as the excess unpaired electrons introduced by hydroxyls play a critical role in surface chemistry and photocatalysis process of this material. In this work, based on density functional theory calculations with the Hubbard U correction, the electronic structures of the hydroxylated TiO2(110) surfaces have been studied. One interesting effect is found that the hydroxylation can elevate band edges of TiO2 and thus can enhance its reducing power for photocatalysis. The underlying physical mechanism for such shifts of the band edges are associated with the electric dipoles arising from the hydroxyl groups on the surface. © 2014 American Chemical Society. Source


Ji B.-S.,Henan University | Cen J.,Henan University | Liu L.,Henan University | He L.,China Pharmaceutical University
International Journal of Developmental Neuroscience | Year: 2013

It has been commonly recognized that accumulated amyloid-β (Aβ) in the brain plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Since the deficiency of the P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in AD may aggravate Aβ deposition and the P-gp reversal agents display lower selectivity of the action, to selectively restore activity of the efflux pump is eagerly required. This study was designed to investigate the influence of dolichyl-phosphate (dolichyl-P) on the P-gp at the BBB. The results revealed that treatment with dolichyl-P increased transendothelial transfer of Rhodamine123 (Rh123) and Aβ42 from the apical compartment to the basolateral compartment but reduced that from the basolateral compartment to the apical compartment in the co-culture of rat brain microvessel endothelial cells (rBMECs) and astrocytes, down regulated P-gp expression in rBMECs and significantly elevated content of Rh123 in rat cortex and hippocampus tissues. The present results implied that accumulated dolichyl-P in the brain may exert an important role in the depression of the P-gp at the BBB, which may suggest valuable clues to promote function of the pump at the BBB in AD. © 2013 ISDN. Source


Wang L.,Nanjing University of Technology | Chen H.,China Pharmaceutical University | Wang H.,Nanjing University of Technology | Wang F.,Nanjing University of Technology | And 4 more authors.
Sensors and Actuators, B: Chemical | Year: 2014

A new fluorescent probe based on fluorescein fluorophore displays an excellent selectivity and sensitivity for GSH in buffer solution containing CTAB. The fluorescence intensity of sensor is linearly proportional to GSH concentrations ranging from 0 to 10 μM, and as low as 22 nM concentration of GSH was evaluated with 3.3 σ/s. The optical changes are attributed to the release of free fluorescein after the electron withdrawing dinitrophenyl ether reacted efficiently with GSH in CTAB micelles. The enhanced selectivity toward GSH over Cys and Hcy considered to be related to the carboxyl groups in thiols. The confocal microscopy experiments implied that this probe is a promising candidate for imaging of GSH in living cells. © 2013 Published by Elsevier B.V. All rights reserved. Source


Wen X.,China Pharmaceutical University | Wen X.,University of Lille Nord de France | Bakali J.E.,University of Lille Nord de France | Deprez-Poulain R.,University of Lille Nord de France | Deprez B.,University of Lille Nord de France
Tetrahedron Letters | Year: 2012

Propylphosphonic anhydride (®T3P) promotes cyclization of o-aminobenzenethiol, o-aminophenol, and o-phenylenediamine with carboxylic acids under microwave irradiation. The one-pot procedure is efficient and allows short reaction times, easy workup, and good yields. Thus, we describe here a method for quick preparation of benzothiazoles, benzoxazoles and benzimidazoles. © 2012 Elsevier Ltd. All rights reserved. Source


Zhou L.,Nanjing Normal University | Wei S.,Nanjing Normal University | Ge X.,Nanjing Normal University | Zhou J.,Nanjing Normal University | And 2 more authors.
Journal of Physical Chemistry B | Year: 2012

Introduction of heavy atoms around photosensitizers (PSs) generally facilitates intersystem crossing (ISC) and improves their quantum yield of singlet oxygen (1O2) generation ability, which is a key species in photodynamic therapy (PDT). Here, we report Pt(IV)- and Au(III)-modified silica nanoparticles (SN) as the drug delivery system of a hypocrellin A (HA) to improve its photodynamic activity through external heavy atom effect. Comparative studies with Pt- and Au-modified and unmodified nanoparticles have demonstrated that the intraparticle external heavy atom effect on the encapsulated HA molecules significantly enhances their efficiency of 1O2 generation and, thereby, the in vitro photodynamic efficacy to cancer cells. The results well elucidated the potential of our PSs/heavy metal ions doped nanocarrier for improving the actual efficacy of PDT. © 2012 American Chemical Society. Source


Xiong Y.,University of Cincinnati | Xiong Y.,China Pharmaceutical University | Shen L.,University of Cincinnati | Liu K.J.,Yale University | And 5 more authors.
Diabetes | Year: 2010

OBJECTIVE - Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies. RESEARCH DESIGN AND METHODS - Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus. RESULTS - Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Four-week administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1's antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis. CONCLUSIONS - These results identify Rb1 as an antiobesity and antihyperglycemic agent. © 2010 by the American Diabetes Association. Source


Li X.L.,China Pharmaceutical University
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi | Year: 2011

To evaluate the association between polymorphism of 5,10-methylenetrahydrofolate reductase C677T and risk of acute lymphoblastic leukemia (ALL). Electronic search strategy was carried out among the databases from home and abroad to collect qualified research papers, according to the inclusion and exclusion criteria. Data on case-control studies on association between MTHFR C677T polymorphism and susceptibility to ALL were collected and analyzed by models of TT vs. CC + CT or TT vs. CC through Meta-analysis. Stratified analysis was carried out according to different age groups (children or adult). In systematical analysis, the pooled odds ratios of MTHFR C677T genetype TT vs. CC + CT or TT vs. CC were 0.87 (0.69 - 1.09) and 0.82 (0.63 - 1.06) respectively; in children's group, the pooled odds ratios of MTHFR C677T genetype TT vs. CC + CT or TT vs. CC were 0.92 (0.79 - 1.08), 0.88 (0.75 - 1.05) while in adult group, the pooled odds ratios of MTHFR C677T genetype TT vs. CC + CT or TT vs. CC were 0.45 (0.26 - 0.77), and 0.41 (0.22 - 0.72) respectively. The MTHFR gene 677T variant might not be associated with the risk of children's ALL but might be associated with a reduced risk on adult's ALL. Source


Chen G.,Flinders University | Liu G.G.,Peking University | Xu F.,China Pharmaceutical University
PharmacoEconomics | Year: 2014

Background: The Urban Resident Basic Medical Insurance (URBMI), launched in 2007 by the State Council, aims to cover around 420 million urban residents in China. Objective: This study aimed to assess the impact of URBMI on health services access (especially inpatient utilisation) in urban China. Methods: Data was drawn from the recent four-wave URBMI Survey (2008-2011). Probit and recursive bivariate probit models have been adopted to handle the possible endogeneity of medical insurance in the utilisation equations. Results: Based on the preferred results from the unbalanced four-wave panel data, we found that the URBMI had significantly increased the likelihood of receiving inpatient treatment in the past year. However, the insurance effect on reducing the refused hospitalisation was insignificant. Finally, the URBMI had also increased the probability of using outpatient services in the past 2 weeks, although the insurance reimburses mainly against critical outpatient care. Conclusions: Given that it is still early days for the URBMI scheme, the positive effect on health services utilisation is appreciable. © 2013 Springer International Publishing. Source


Chen C.,Northeast Agricultural University | Chi Y.-J.,Northeast Agricultural University | Zhao M.-Y.,China Pharmaceutical University | Xu W.,Northeast Agricultural University
Food Science and Biotechnology | Year: 2012

Functional properties, antioxidant, and angiotensin-I converting enzyme (ACE) inhibitory activities of egg white protein hydrolysate (EWPH) prepared with trypsin at different degree of hydrolysis (DH) were investigated. The DPPH radical scavenging activity, reducing power, lipid peroxidation inhibitory activity, and ACE inhibitory activity increased with DH at first and then decreased gradually. Hydrolysates with 12. 4% DH had the highest antioxidant and ACE inhibitory activities. As DH increased, the solubility of EWPH increased while the emulsifying and foaming properties decreased. The functional properties of EWPH were also controlled by pH. Ultrafiltration of the hydrolysate with 12. 4% DH revealed that the fractions of molecular weight lower than 3 kDa exhibited the highest antioxidant and ACE inhibitory activities. The results indicated that EWPH with different DH have different bioactive and functional properties and EWPH by controlled hydrolysis may be useful ingredients in food and nutraceutical applications with potential bioactive properties. © 2012 The Korean Society of Food Science and Technology and Springer Netherlands. Source


Ma L.,Stanford University | Wang X.,Stanford University | Wang X.,Sun Yat Sen University | Jia T.,China Pharmaceutical University | And 3 more authors.
Oncotarget | Year: 2015

Deregulated WNT/ß-catenin signaling contributes to the development of a subgroup of hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide. Within this pathway, the tankyrase enzymes (TNKS1 and TNKS2) degrade AXIN and thereby enhance ß-catenin activity. We evaluate TNKS enzymes as potential therapeutic targets in HCC, and the anti-tumor efficacy of tankyrase inhibitors (XAV939, and its novel nitro-substituted derivative WXL-8) in HCC cells. Using semi-quantitative RT-PCR, we found significantly elevated levels of TNKS1/2 mRNA in tumor liver tissues compared to adjacent non-tumor livers, at protein levels only TNKS1 is increased. In HepG2, Huh7cells, siRNA-mediated knockdown suppression of endogenous TNKS1 and TNKS2 reduced cell proliferation, together with decreased nuclear ß-catenin levels. XAV939 and WXL-8 inhibited cell proliferation and colony formation in HepG2, Huh7, and Hep40 cells (p < 0.05), with stabilization of AXIN1 and AXIN2, and decreased ß-catenin protein levels. XAV939 and WXL-8 also attenuated rhWNT3A-induced TOPflash luciferase reporter activity in HCC cells, indicating reduced ß-catenin transcriptional activity, consistent with decreased nuclear ß-catenin levels. In vivo, intra-tumor injections of XAV939 or WXL-8 significantly inhibited the growth of subcutaneous HepG2 xenografts (P < 0.05). We suggest that tankyrase inhibition is a potential therapeutic approach for treating a subgroup HCC with aberrant WNT/ß-catenin signaling pathway. © 2015. Source


Freeling J.P.,University of Washington | Koehn J.,University of Washington | Shu C.,University of Washington | Sun J.,University of Washington | And 2 more authors.
AIDS Research and Human Retroviruses | Year: 2015

HIV patients on combination oral drug therapy experience insufficient drug levels in lymph nodes, which is linked to viral persistence. Following success in enhancing lymph node drug levels and extending plasma residence time of indinavir formulated in lipid nanoparticles, we developed multidrug anti-HIV lipid nanoparticles (anti-HIV LNPs) containing lopinavir (LPV), ritonavir (RTV), and tenofovir (PMPA). These anti-HIV LNPs were prepared, characterized, scaled up, and evaluated in primates with a focus on plasma time course and intracellular drug exposure in blood and lymph nodes. Four macaques were subcutaneously administered anti-HIV LNPs and free drug suspension in a crossover study. The time course of the plasma drug concentration as well as intracellular drug concentrations in blood and inguinal lymph nodes were analyzed to compare the effects of LNP formulation. Anti-HIV LNPs incorporated LPV and RTV with high efficiency and entrapped a reproducible fraction of hydrophilic PMPA. In primates, anti-HIV LNPs produced over 50-fold higher intracellular concentrations of LPV and RTV in lymph nodes compared to free drug. Plasma and intracellular drug levels in blood were enhanced and sustained up to 7 days, beyond that achievable by their free drug counterpart. Thus, multiple antiretroviral agents can be simultaneously incorporated into anti-HIV lipid nanoparticles to enhance intracellular drug concentrations in blood and lymph nodes, where viral replication persists. As these anti-HIV lipid nanoparticles also prolonged plasma drug exposure, they hold promise as a long-acting dosage form for HIV patients in addressing residual virus in cells and tissue. © Mary Ann Liebert, Inc. 2015. Source


Wang P.,Harvard University | Yoo B.,Harvard University | Yang J.,Harvard University | Zhang X.,Harvard University | And 5 more authors.
Diabetes | Year: 2014

Noninvasive assessment of pancreatic β-cell mass would tremendously aid in managing type 1 diabetes (T1D). Toward this goal, we synthesized an exendin-4 conjugated magnetic iron oxide-based nanoparticle probe targeting glucagon-like peptide 1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic β-cells. In vitro studies in βTC-6, the β-cell line, showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a significant transverse relaxation time (T2) shortening in the pancreata of mice injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with the nontargeted probe at 7.5 and 24 h after injection. Furthermore, ΔT2 of the pancreata of prediabetic NOD mice was significantly higher than that of diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease of probe accumulation in these animals due to β-cell loss. Of note, ΔT2 of prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We believe our results point to the potential for using this agent for monitoring the disease development and response of T1D to therapy. © 2014 by the American Diabetes Association. Source


Wu X.J.,China Pharmaceutical University
BMC complementary and alternative medicine | Year: 2014

Radix Astragali is famous for its beneficial effect on inflammation associated diseases. This study was to assess the efficacy of astragalosides (AST) extracted from Radix Astragali, on the progression of experimental autoimmune encephalomyelitis (EAE), and explore its possible underlying molecular mechanisms. EAE was induced by subcutaneous immunization of MOG35-55. Infiltration of inflammatory cells was examined by HE staining. ROS level was detected by measuring infiltrated hydroethidine. Leakage of blood brain barrier (BBB) was assessed using Evan's blue dye extravasation method. Levels of inflammatory cytokines were measured using ELISA kits. Activities of total-SOD, GSH-Px, and iNOS and MDA concentration were measured using biochemical analytic kits. Gene expression was detected using real-time PCR method. Protein expression was assayed using western blotting approach. AST administration attenuated the progression of EAE in mice remarkably. Further studies manifested that AST treatment inhibited infiltration of inflammatory cells, lessened ROS production and decreased BBB leakage. In peripheral immune-systems, AST up-regulated mRNA expression of transcriptional factors T-bet and Foxp3 but decreased that of RORγt to modulate T cell differentiation. In CNS, AST stopped BBB leakage, reduced ROS production by up-regulation of T-SOD, and reduced neuroinflammation by inhibition of iNOS and other inflammatory cytokines. Moreover, AST inhibited production of p53 and phosphorylation of tau by modulation of the Bcl-2/Bax ratio. AST orchestrated multiple pathways, including immuno-regulation, anti-oxidative stress, anti-neuroinflammation and anti-neuroapoptosis involved in the MS pathogenesis, to prevent the deterioration of EAE, which paves the way for the application of it in clinical prevention/therapy of MS. Source


Hao W.,Nanjing University | Di B.,China Pharmaceutical University | Chen Q.,Nanjing University | Wang J.,CAS Dalian Institute of Chemical Physics | And 2 more authors.
Journal of Chromatography A | Year: 2013

The expressions accounting for the peak variance in isocratic and gradient liquid chromatography is derived from the transport model. In mathematical treatments, the dwelling time is taken into account, and the type of solvent strength, gradient profile and the variation of plate height (H) with mobile phase composition is not specified. By applying a coordinate transformation, the transport model is solved by using the Laplace transform approach. A plate height equation that is suited for both isocratic and gradient elution is obtained. Based on this equation, the plate height equations for any combination of stepwise and linear gradients are derived. These equations will be algebraic when the solvent strength is linear and the H- plot is parabolic. The plate height equations for single stepwise, single linear and the ladder-like gradients are also given. © 2013 Elsevier B.V. Source


Huang W.,China Pharmaceutical University
Medicinal chemistry (Shāriqah (United Arab Emirates)) | Year: 2014

BACKGROUND: Cholesterol, derived from two different sources of endogenous synthesis and diet, is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann- Pick C1-like 1 (NPC1L1).OBJECTIVE: The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening.CONCLUSION: Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose novel cholesterol absorption inhibitors. Source


Mo R.,University of North Carolina at Chapel Hill | Mo R.,China Pharmaceutical University | Jiang T.,University of North Carolina at Chapel Hill | Sun W.,University of North Carolina at Chapel Hill | Gu Z.,University of North Carolina at Chapel Hill
Biomaterials | Year: 2015

Stimuli-triggered drug delivery systems are primarily focused on the applications of the tumor microenvironmental or cellular physiological cues to enhance the release of drugs at the target site. In this study, we applied adenosine-5'-triphosphate (ATP), the primary "energy molecule", as a trigger for enhanced release of preloaded drugs responding to the intracellular ATP concentration that is significantly higher than the extracellular level. A new ATP-responsive anticancer drug delivery strategy utilizing DNA-graphene crosslinked hybrid nanoaggregates as carriers was developed for controlled release of doxorubicin (DOX), which consists of graphene oxide (GO), two single-stranded DNA (ssDNA, denoted as DNA1 and DNA2) and ATP aptamer. The single-stranded DNA1 and DNA2 together with the ATP aptamer serve as the linkers upon hybridization for controlled assembly of the DNA-GO nanoaggregates, which effectively inhibited the release of DOX from the GO nanosheets. In the presence of ATP, the responsive formation of the ATP/ATP aptamer complex causes the dissociation of the aggregates, which promoted the release of DOX in the environment with a high ATP concentration such as cytosol compared with that in the ATP-deficient extracellular fluid. This supports the development of a novel ATP-responsive platform for targeted on-demand delivery of anticancer drugs inside specific cells. © 2015 Elsevier Ltd. Source


Liu J.,CAS Shanghai Institute of Organic Chemistry | Chen M.,CAS Shanghai Institute of Organic Chemistry | Zhang L.,CAS Shanghai Institute of Organic Chemistry | Zhang L.,China Pharmaceutical University | Liu Y.,CAS Shanghai Institute of Organic Chemistry
Chemistry - A European Journal | Year: 2015

A gold-catalyzed cycloisomerization of 1,6-diynes containing an ynamide propargyl ester or carbonate moiety has been developed that provides an attractive route to a diverse-substituted 3-acyloxy-1,4-dihydrocyclopenta[b]indoles. Mechanistic studies indicate that the reaction likely proceeds through a competitive 1,2-OAc migration followed by [3+2] cycloaddition of the vinyl gold-carbenoid intermediate with the pendant triple bond. The synthetic utility of the obtained cyclopenta[b]indole products was demonstrated by their efficient transformations by deprotection or double-bond isomerization reactions. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA. Source


Ding L.,Yancheng Institute of Technology | Qiu J.,Yancheng Institute of Technology | Zhu Z.,China Pharmaceutical University
Macromolecular Rapid Communications | Year: 2013

The synthesis of thiol-functionalized long-chain highly branched polymers (LCHBPs) has been accomplished in combination of ring-opening metathesis polymerization (ROMP) and thiol-Michael addition click reaction. A monotelechelic polymer with a terminal acrylate and many pendent thiol groups is first prepared through adding an internal cis-olefin terminating agent to the reaction mixture immediately after the completion of the living ROMP, and then utilized as an ABn-type macromonomer in subsequent thiol-ene reaction between acrylate and thiol, yielding LCHBPs as the reaction time prolonged. Au nanoparticles are then covalently conjugated onto the surface of thiol-functionalized LCHBP to fabricate novel hybrid nanostructures, which is shown as one interesting application of such functionalized metathesis polymers. This facile approach can be extended toward the fabrication of novel nanomaterials with sophisticated structures and tunable multifunctionalities. Branched ring-opening metathesis polymerization (ROMP)-polymer architecture is successfully constructed employing ABn-type macromonomer that carries several thiol groups along the polymer chain and one acrylate group at the chain end. A thiol-Michael addition click reaction between these functional groups yields long-chain highly branched polymer. The coating of gold nanoparticles is shown as one interesting application of such functionalized metathesis polymers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Qi Y.,U.S. National Institutes of Health | Qi Y.,China Pharmaceutical University | Jiang C.,U.S. National Institutes of Health | Cheng J.,U.S. National Institutes of Health | And 6 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-β-muricholic acid (T-β-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-β-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-β-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. © 2014 Elsevier B.V. All rights reserved. Source


Feng Z.,Nanjing University | Feng Z.,China Pharmaceutical University | Cheng-Gang F.,Nanjing University | You-Ting W.,Nanjing University | And 3 more authors.
Chemical Engineering Journal | Year: 2010

Four ionic liquids (ILs)-tetramethylammonium glycinate (=[Gly]), tetraethylammonium glycinate ([N2222][Gly]), tetramethylammonium lysinate ([N1111][Lys]) and tetraethylammonium lysinate ([N2222][Lys]) were synthesized and mixed with water or N-methyldiethanolamine (MDEA) aqueous solutions to form a new type of solvents for the uptake of CO2. The solubility or absorption of CO2 in these IL+MDEA aqueous solutions was investigated over a wide range of IL concentrations (5-100%), temperature (298-318K) and partial pressure of CO2 (4-400kPa). The results indicated that ionic liquid could greatly enhance the absorption and increased the absorption rate of CO2 in MDEA aqueous solutions. It had been found that the aqueous solutions of 15% IL and 15% MDEA had higher absorption rate and larger uptake than other IL+MDEA solutions of 30% total amines. Temperature (298-318K) seemed to have some influence on the absorption of CO2 in IL+MDEA aqueous solutions. Noticeably, due to the two amino groups in a molecular, the mole absorption of the 30% lysine based ionic liquids aqueous solutions was 0.98 ([N1111][Lys]) and 1.21 ([N2222][Lys]) mole CO2, being about 2-3 times the absorption capacity of MDEA under the same condition. Regeneration under the condition of temperature 353K, 4kPa for 240min showed that aqueous solution of 15% [N1111][Gly]+15% MDEA had significant regeneration efficiency (over 98%). © 2010 Elsevier B.V. Source


Xiu A.,Nanjing University of Science and Technology | Kong Y.,China Pharmaceutical University | Zhou M.,Nanjing University of Science and Technology | Zhu B.,Nanjing University of Science and Technology | And 2 more authors.
Carbohydrate Polymers | Year: 2010

A salt-tolerant strain Agrobacterium sp. ZX09 produced a high molecular mass, water-soluble extracellular polysaccharide (EPS) composed of d-glucose. By examining periodate oxidation, 1H NMR and 13C NMR spectra, it was proven that the EPS consisted of the following repeating unit: →3)-β-d-Glcp-(1 → 3)-[β-d-Glcp-(1 → 3)-β-d-Glcp-(1 → 3)]3-α-d-Glcp-(1 → 3)-α-d-Glcp-(1→. In vitro the EPS was indigestible by α-amylase, and strongly inhibited pancreatic α-amylase activity. Fasting mice fed on the EPS failed to increase blood glucose levels. Experimental diets containing the EPS suppressed steep increase in blood glucose concentration. These results suggest that the novel water-soluble glucan could be potentially useful for decreasing absorption of dietary carbohydrate and postprandial blood glucose level. © 2010 Elsevier Ltd. All rights reserved. Source


Gao C.,Peking University | Gao C.,Novo Nordisk AS | Xu F.,Peking University | Xu F.,China Pharmaceutical University | Liu G.G.,Peking University
Social Science and Medicine | Year: 2014

This paper is intended to assess the primary effects on cost, utilization and quality of care from payment reform of capitation and open enrollment in Changde city, Hunan Province of China. Open enrollment policy was introduced to deal with possible cream skimming associated with capitation. Based on the longitudinal Urban Resident Basic Medical Insurance (URBMI) Household Survey, this study analyses the URBMI data through a set of regression models. The original data included over five thousand inpatient admissions during the study period between 2008 and 2010. The study finds the payment reform to reduce its inpatient out-of-pocket cost by 19.7%, out-of-pocket ratio by 9.5%, and length of stay by 17.7%. However, the total inpatient cost, drug cost ratio, treatment effect, and patient satisfaction showed little difference between Fee-For-Service and capitation models. We conclude that the payment reform in Changde did not reduce overall inpatient expenditure, but it decreased the financial risk and length of stay of inpatient patients without compromising quality of care. The findings would contribute to the health care payment literatures from developing countries and open further research tracks on the ability of open enrollment to compensate for capitation drawbacks. © 2014 Elsevier Ltd. Source


Li J.,China Pharmaceutical University | Liu L.,Changzhou University
RSC Advances | Year: 2012

A simple and effective amination of diaryliodonium salts with aqueous ammonia has been developed, giving anilines in high yields without metal-catalyst and ligand. This journal is © 2012 The Royal Society of Chemistry. Source


Li D.,China Pharmaceutical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2012

To investigate the effect of overexpressing rat aldo-keto reductases (AKR7A1) in V79-4 cells on crotonaldehyde-induced mutagenicity. The expression level and enzyme activity of AKR7A1 protein expressed in V79-4 cells were measured by Western blotting and AKR enzyme assay, respectively. HGPRT assay was applied to evaluate the effect of AKR7A1 overexpression on crotonaldehyde-induced mutagenicity in V79-4 cells. Western blotting confirmed a high expression level of AKR7A1 protein in V79-4 cells. AKR enzyme assay showed that the overexpressed AKR7A1 protein was functionally active. HGPRT assay demonstrated that cells overexpressing AKR7A1 exhibited a significant increase in resistance to crotonaldehyde-induced mutagenicity compared to control cells. Overexpression of AKR7A1 can protect V79-4 cells against crotonaldehyde-induced mutagenicity. Source


Song X.,Linyi Normal University | Xu S.,Linyi Normal University | Chen L.,CAS Yantai Institute of Coastal Zone Research | Wei Y.,China Pharmaceutical University | Xiong H.,Nanchang University
Journal of Applied Polymer Science | Year: 2014

Food security as a world issue has received increasing concern, and therefore, effective analytical methods and technologies have been continuously developed. However, the matrix complexity of food samples and the trace/ultratrace presence of targeted analytes require highly efficient cleanup and enrichment materials and procedures. Molecularly imprinted polymers (MIPs) with specific recognition abilities as versatile materials are being increasingly developed for diverse species in various fields, especially in food analysis. In this review, we mainly summarize the recent advances in MIPs used for food matrices over the last 5 years. We focus on toxic and harmful substances, such as pesticide/drug residues, heavy metals, microbial toxins, and additives. Some relatively new preparation methods involving surface imprinting, composites, and stimuli responsiveness are reviewed. Different MIPs as solid-phase adsorbents in solid-phase extraction, solid-phase microextraction, matrix solid-phase dispersion, stirring bar sorptive extraction, and magnetic material extraction and as stationary phases in chromatographic separation for foodstuff have been comprehensively summarized. MIP-based biomimetic sensing and enzymelike catalysis receive special attention. Moreover, some limitations and comparisons related to MIPs performances are also discussed. Finally, some significant attempts to further promote MIP properties and applications to ensure food safety are discussed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40766. © 2014 Wiley Periodicals, Inc. Source


Deng D.,China Pharmaceutical University | Deng D.,Nanjing University | Yu J.,Nanjing University
Crystal Growth and Design | Year: 2015

In this report, nonspherical Se crystals were synthesized from the transformation of CdSe nanoparticles (NPs) under ambient conditions, including nanowires (-), microscale or nanoscale rods (-), crossheads, crosses (+), and other unusual highly anisotropic structures. Here, CdSe NPs are used as the starting point of synthesis; the presence of EDTA triggers the decomposition of primary CdSe NPs, and resultant gradual release of Se2- anions into solution; finally, highly pure well-crystallized nonspherical hexagonal Se (h-Se) crystals are formed via the oxidation of the released Se2- anions in air (this redox reaction will stimulate further the release of Se2- anions) and the subsequent spontaneous crystallization of Se monomers. Some key variables such as the concentrations of EDTA and CdSe NPs, and the ligand of primary NPs, were explored systematically. The experimental results show that the ligand nature of the NP precursor influences the transformation rate of CdSe NPs to Se crystals and dominates the shape and aspect ratio of Se product, while the concentrations of EDTA and CdSe NPs only influence the size of the product. Meanwhile, we also investigated intensively the transformation process of CdSe NP precursors to multiarmed Se crystals, aside from the detailed characterizations on their sizes, shapes, and crystal structures. © 2014 American Chemical Society. Source


Niu X.,Yantai University | Chen H.,China Pharmaceutical University | Wang Y.,CAS Yantai Institute of Coastal Zone Research | Wang W.,CAS Yantai Institute of Coastal Zone Research | And 2 more authors.
ACS Applied Materials and Interfaces | Year: 2014

Fluorescent-surface enhanced Raman scattering (F-SERS) dual mode tags showed great potential for bioimaging due to the combined advantages of intuitive, fast imaging of fluorescence and multiplex capability of SERS technique. In previously reported F-SERS tags, organic fluorescent dyes or quantum dots were generally selected to generate fluorescence signal. Herein, we reported the first proof-of-concept upconversion fluorescence (UCF)-SERS dual mode tags based on near infrared (NIR) laser (980 nm) excited upconversion nanoparticles (UCNPs) for live-cell and in vivo imaging. Three components involved in this tag: NaYF4:Yb,Er UCNPs@SiO2 serving as the fluorescent core of the tag; silver nanoparticles in situ grown on the surface of UCNPs@SiO2 for generating characteristic Raman signal; and denatured BSA coating rendering the tag's stability and biocompatibility. The UCF-SERS tags integrated the NIR imaging capability of both fluorescent UCNPs and plasmonic SERS nanoprobe, which facilitated dual mode bioimaging investigation, especially for living animals. Ex vivo experiments revealed that with 980 nm and 785 nm NIR laser irradiations, the UCF and SERS signals of the tags could be detected from 3 and 7 mm deep pork tissues, respectively. Furthermore, the in vivo imaging capabilities of UCF-SERS tags were successfully demonstrated on living mice. The developed dual modality tags held great potential for medical diagnostics and therapy. © 2014 American Chemical Society. Source


Jin X.,China Pharmaceutical University | Hu B.,Nanjing University of Science and Technology
Zeitschrift fur Anorganische und Allgemeine Chemie | Year: 2016

The chemical and physical properties of the energetic intermediate 7-imino-3-nitroimino-2,4,6,8-tetraazabicyclo[3.3.0]octane hydrochloride (compound A) were investigated. The crystal structure and thermal behavior were measured by X-ray diffraction and TG-DTG-DSC coupling system, respectively. The electronic structure was also studied by electronic density, nature bond orbital charges, frontier molecular orbital, density of state, and electrostatic potentials. Compound A crystallizes orthorhombic in space group Pna21. Thermodynamic properties indicate that it has moderate thermal stability with a sharp exothermic peak (298.5 °C, 10 K·min-1) and high critical temperature of thermal explosion (558.5 K). The positive electrostatic potentials of compound A were stronger than that of the negative electrostatic potentials, which can stabilize the molecule. Compound A can also be considered as an energetic intermediate, which may shine light on the exploring of other 7-imino-3-nitroimino-2,4,6,8-tetraazabicyclo[3.3.0]octane hydrochloride based high density energetic materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Zhao L.,Nanjing Agricultural University | Dong Y.,Nanjing Agricultural University | Chen G.,China Pharmaceutical University | Hu Q.,Nanjing Agricultural University
Carbohydrate Polymers | Year: 2010

Ultrasonic-aid extraction (UAE) was applied to the extraction of polysaccharides from Ganoderma lucidum and then the crude polysaccharides were purified by filtration, DEAE cellulose-52 chromatography and Sephadex G-100 size-exclusion chromatography in that order. Two main fractions, GP-1 and GP-2, were obtained through the extraction and purification steps. The characterizations, such as molecular weight, monosaccharides composition, ultraviolet spectrum and infrared spectrum of the two fractions were analyzed in this study. Furthermore, the influence of G. lucidum polysaccharides fractions upon activation of macrophage cell (RAW 264.7) and antitumor activities to the human breast cancer cell (MDA-MB-231) in vitro were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The results indicated that GP-1 and GP-2 can increase the proliferation and pinocytic activity of macrophage significantly and play an inhibited effect on the cancer cell, moreover, the antitumor activity of the GP-1 and GP-2 increased with the participation of the antitumor factors induced from macrophage by polysaccharides fractions. © 2009 Elsevier Ltd. All rights reserved. Source


Hsieh M.-T.,China Medical University at Taichung | Shia K.-S.,National Health Research Institute | Liu H.-J.,National Tsing Hua University | Kuo S.-C.,China Pharmaceutical University
Organic and Biomolecular Chemistry | Year: 2012

A highly efficient annulative approach towards the construction of the structurally attractive methylenecyclohexane ring was developed through a convenient 1,4-addition of 4-pentenylmagnesium bromide to 2-cyano-2- cycloalkenones followed by a Pd(ii)-mediated oxidative cyclization of the resulting ω-unsaturated α-cyano ketones. Based on this newly developed protocol, polycyclic adducts bearing various ring sizes and substitutions can be prepared in moderate to high yields. © 2012 The Royal Society of Chemistry. Source


Senthilkumar R.,Nanjing Southeast University | Chen B.-A.,Nanjing Southeast University | Cai X.-H.,Nanjing Southeast University | Fu R.,China Pharmaceutical University
Chinese Journal of Natural Medicines | Year: 2014

Multidrug resistance remains a serious clinical problem in the successful therapy of malignant diseases. It occurs in cultured tumor cell lines, as well as in human cancers. Therefore, it is critical to develop novel anticancer drugs with multidrug-resistance modulating potential to increase the survival rate of leukemia patients. Plant-derived natural products have been used for the treatment of various diseases for thousands of years. This review summarizes the anticancer and multidrug-resistance reversing properties of the extracts and bioactive compounds from traditional medicinal plants in different leukemia cell lines. Further mechanistic studies will pave the road to establish the anticancer potential of plant-derived natural compounds. © 2014 China Pharmaceutical University. Source


Wang D.,Nanjing Normal University | Chen S.,Nanjing Normal University | Liu M.,Nanjing Normal University | Liu C.,Nanjing Normal University | Liu C.,China Pharmaceutical University
Chronobiology International | Year: 2015

Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood. © 2015 Informa Healthcare USA, Inc. Source


Xu H.-B.,Tongji University | Li L.,Tongji University | Liu G.-Q.,China Pharmaceutical University
Chemotherapy | Year: 2011

Background: Multidrug resistance (MDR) presents a serious problem in cancer chemotherapy. Our previous studies have shown that the MDR of K562/DOX cells could be reversed by guggulsterone through inhibiting the function and expression of P-glycoprotein. The purpose of this study was to investigate the reversal effect of guggulsterone on MDR in drug-resistant MCF-7 cells and the parental MCF-7 cells. Methods: MTT cytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with guggulsterone, to study the reversal of drug resistance and to examine the inhibitory effects on MRP1 expression. Results: The results showed that co-administration of guggulsterone (10 μM) resulted in a significant increase in chemosensitivity of MCF-7/DOX cells to doxorubicin, compared with doxorubicin treatment alone (p < 0.01). The fold reversal of 10 μM guggulsterone (11.48) was comparable to that of 10 μM verapamil (13.23). Rhodamine123 and doxorubicin accumulation in MCF-7/DOX cells was significantly enhanced after the incubation with guggulsterone (10 μM), compared with untreated MCF-7/DOX cells (p < 0.01). When doxorubicin (10 μM) was combined with guggulsterone (10 μM), the mean apoptotic population of MCF-7/DOX cells was 24.91%. It was increased by 6.15 times, compared with doxorubicin (10 μM) treatment alone. However, guggulsterone had little inhibitory effect on the expression of MRP1 proteins. Conclusion: Guggulsterone is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumor chemotherapy. Copyright © 2011 S. Karger AG. Source


Ding L.,Yancheng Institute of Technology | Qiu J.,Yancheng Institute of Technology | Wei J.,Yancheng Institute of Technology | Zhu Z.,China Pharmaceutical University | Zhu Z.,National University of Singapore
Macromolecular Rapid Communications | Year: 2014

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)-based brush poly(phosphoamidate)s are successfully synthesized by a combination of ring-opening metathesis polymerization (ROMP) and atom transfer radical polymerization (ATRP) following either a commutative two-step procedure or a straightforward one-pot process using Grubbs ruthenium-based catalysts for tandem catalysis. Compared with the traditional polymerization method, combining ROMP and ATRP in a one-pot process allows the preparation of brush copolymers characterized by a relatively moderate molecular weight distribution and quantitative conversion of monomer. Moreover, the surface morphologies and aggregation behaviors of these polymers are studied by AFM and TEM measurements. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Yang Y.,Nanjing Medical University | Yang Y.,China Pharmaceutical University | Cheng X.,Nanjing Medical University | Tian W.,Nanjing Medical University | And 7 more authors.
Nucleic Acids Research | Year: 2014

Endothelin (ET-1) was initially identified as a potent vasoconstrictor contributing to the maintenance of vascular rhythm. Later studies have implicated ET-1, when aberrantly up-regulated within the vasculature, in a range of human pathologies associated with disruption of vascular homeostasis. ET-1 has been shown to invoke strong pro-inflammatory response in vascular smooth muscle cells (VSMCs); the underlyingmechanism, however, remains elusive. Here, we report that the transcriptionalmodulatorMRTF-Amediates the activation of pro-inflammatory mediators by ET-1 in VSMCs. ET-1 increased nuclear enrichment and activity of MRTF-A in cultured VSMCs. MRTF-A silencing attenuated ET-1 induced synthesis and release of pro-inflammatory mediators including IL-6, MCP-1 and IL-1 likely as a result of diminished NF-κB activity. In addition,MRTF-Awas indispensible for the accumulation of active histone modifications on the gene promoters. Of intrigue, MRTF-A interacted with and recruited ASH2, a component of the mammalian histone methyltransferase complex, to transactivate pro-inflammatory genes in response to ET-1 treatment. The chromatin remodeling proteins BRG1 and BRM were also required for ET-1-dependent induction of pro-inflammatory mediators by communicating with ASH2, a process dependent on MRTF-A. In conclusion, our data have identified a novel epigenetic complex responsible for vascular inflammation inflicted by ET-1. © The Author(s) 2014. Source


Li N.-G.,Nanjing University | Shi Z.-H.,China Pharmaceutical University | Tang Y.-P.,Nanjing University | Wang Z.-J.,Nanjing University | And 4 more authors.
Current Medicinal Chemistry | Year: 2011

Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage that eventually leads to a complex process involving degradation of various components of the cartilage matrix, chief among them are the cartilage-specific type II collagen (CII) and aggrecan. While the loss of aggrecan is thought to be an early and reversible process, degradation of CII is considered to be irreversible and a key step in the loss of structural and functional integrity of cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. It is the major collagenase in OA cartilage and has the highest activity against CII. However, the clinical utility of broad-spectrum MMP inhibitors developed for treatment of OA has been restricted by dose- and duration- dependent musculoskeletal side effects in humans. Consequently, selectively inhibiting the MMP-13 would seem to be an attractive therapeutic objective. This review mainly focuses on selective MMP-13 inhibitors development in terms of OA since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, non-zinc-binding groups. In addition, dual inhibitors of MMP-13 and aggrecanase are also reviewed. Special emphasis is placed on logistic concerns for lead compound search as well as the structure-activity relationship (SAR) in this field. Through these methods, new hope is emerging for the treatment of OA through selective inhibition of MMP-13. © 2011 Bentham Science Publishers Ltd. Source


Xu J.,Sichuan University | Liu B.,Sichuan University | Liu B.,China Pharmaceutical University
Chinese Chemical Letters | Year: 2015

First total synthesis of norleucosceptroids F and G has been achieved through key steps of Michael-Aldol cascade, oxa-Michael cyclization-dehydration-deprotection cascade and cross metathesis (CM), this work developed a general and concise method to the synthesis of leucosceptroid and norleucosceptroid. © 2015 Bo Liu. Source


Cao J.,Hangzhou Normal University | Li P.,China Pharmaceutical University | Yi L.,Hong Kong Baptist University
Journal of Chromatography A | Year: 2011

A new CE system using ionic liquids coated multi-walled carbon nanotubes (ILs-MWNTs) as pseudostationary phase was developed for the simultaneous determination of four flavonoids, four phenolic acids and two saponins. Several parameters affecting the separation were studied, including the choice of ILs, ILs-MWNTs concentration, the respective use of ILs and MWNTs, buffer pH, SDS concentration and borate content. Results revealed that the addition of ILs-MWNTs in running electrolytes enhanced the separation of target compounds compared to conventional micelle because the surface of carbon nanotubes interacted favorably with the analytes. Under the optimum conditions, a baseline separation was achieved for these analytes within 11min in a 41.5cm of effective length fused-silica capillary. At a voltage of 28.0kV, the separation was carried out in a 10mM borate buffer (pH 9.0) containing 100mM SDS, 6% propanol and 4μgmL -1 ILs-MWNTs. All calibration curves showed good linearity (r 2>0.9990) within the test ranges. The intra- and inter-day precisions as determined from standard solutions were below 3.30% and 6.23%, respectively. The recoveries for ten compounds were found to range from 85.5 to 101.8%. The method was successfully applied for the determination of three types of compounds in Qishenyiqi dropping pills. Our experimental results indicated that the proposed method offered new opportunities for the analysis of complex samples. © 2011 Elsevier B.V. Source


Li X.,Nanjing Medical University | Lu X.,Nanjing Medical University | Xu H.,Nanjing Medical University | Zhu Z.,Nanjing University | And 6 more authors.
Molecular Pharmaceutics | Year: 2012

Paclitaxel (Ptx) has demonstrated encouraging activity in the treatment of gastric cancer. Development of drug-containing biodegradable polymeric nanoparticles (np) becomes one of the solutions to relieve side effects of Ptx. However, Ptx-loaded nanoparticles prepared by the nanoprecipitation method are unstable in the aqueous phase. Here we report that tetrandrine (Tet) effectively increases the stability of Ptx-loaded nanoparticles when Tet is coencapsulated with Ptx into mPEG-PCL nanoparticles. The current study demonstrates the synergistic antitumor effect of Tet and Ptx against gastric cancer cells, which provides the basis of coadministration of Tet and Ptx by nanoparticles. It is reported that the cellular chemoresistance to Ptx correlates with intracellular antioxidant capacity and the depletion of cellular antioxidant capacity could enhance the cytotoxicity of Ptx. Tet effectively induces intracellular ROS production. Therefore, the present study provides a promising novel therapeutic strategy basing on "oxidation therapy" that it could amplify the antitumor effect of paclitaxel by employing Tet as a pro-oxidant. More intracellular Tet accumulation by endocytosis of Ptx/Tet-np than equivalent doses of free drug leads to more intracellular ROS induction, which could efficiently enhance the cytotoxicity of Ptx by sequential inhibition of ROS-dependent Akt pathway and activation of apoptotic pathways, all of which would mediate the superior cytotoxicity of Ptx/Tet-np over free drug. The present results suggest that the codelivery of Ptx and Tet by nanoparticles provides a novel therapeutic strategy basing on "oxidation therapy" against gastric cancer. © 2011 American Chemical Society. Source


Ye B.,Nanjing Southeast University | Ye B.,China Pharmaceutical University | Rong F.,Nanjing Southeast University | Rong F.,Suzhou University | And 7 more authors.
Chemical Communications | Year: 2013

An angle-independent photonic crystal (PhC) colorimetric sensor was developed by using a stimuli-response hydrogel to replicate the template arrays of isotropic photonic crystal beads (PCBs) for the detection of Hg2+. This journal is © The Royal Society of Chemistry 2013. Source


Liu X.-H.,Anhui Medical University | Liu X.-H.,Guizhou University | Li J.,Anhui Medical University | Shi J.B.,Anhui Medical University | And 2 more authors.
European Journal of Medicinal Chemistry | Year: 2012

A series of novel 5-phenyl-N-piperidine ethanone-4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassays demonstrated that compounds 4d, 4f, 7a and 7b occupied high antiproliferative activities against SGC-7901, MGC-803 and Bcap-37 cell lines. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 7b showed the most potent inhibitory activity with IC 50 value at 2.00 ± 0.40 μM. The active compound 4d was also docked into the telomerase TERT active site to determine the probable binding model. The results indicated that conserved residues Lys189, Asp254 and Gln308 were important for ligand binding via hydrogen bond interactions. © 2012 Elsevier Masson SAS. All rights reserved. Source


Minobe E.,Kagoshima University | Maeda S.,Kagoshima University | Maeda S.,Sapporo Medical University | Xu J.,Kagoshima University | And 4 more authors.
American Journal of Physiology - Cell Physiology | Year: 2014

Cardiac L-type Ca2+channels are modulated by phosphorylation by protein kinase A (PKA). To explore the PKA-targeted phosphorylation site(s), five potential phosphorylation sites in the carboxyl (COOH) terminal region of the α1C-subunit of the guinea pig Cav1.2 Ca2+channel were mutated by replacing serine (S) or threonine (T) residues with alanine (A): S1574A (C1 site), S1626A (C2), S1699A (C3), T1908A, (C4), S1927A (C5), and their various combinations. The wild-type Ca2+channel activity was enhanced three-to fourfold by the adenylyl cyclase activator forskolin (Fsk, 5 μM), and that of mutants at C3, C4, C5, and combination of these sites was also significantly increased by Fsk. However, Fsk did not modulate the activity of the C1 and C2 mutants and mutants of combined sites involving the C1 site. Three peptides of the COOH-terminal tail of α1C, termed CT1 [corresponding to amino acids (aa) 1509-1789, containing sites C1-3], CT2 (aa 1778-2003, containing sites C4 and C5), and CT3 (aa 1942-2169), were constructed, and their phosphorylation by PKA was examined. CT1 and CT2, but not CT3, were phosphorylated in vitro by PKA. Three CT1 mutants at two sites of C1-C3 were also phosphorylated by PKA, but the mutant at all three sites was not. The CT2 mutant at the C4 site was phosphorylated by PKA, but the mutant at C5 sites was not. These results suggest that Ser1574(C1 site) may be a potential site for the channel modulation mediated by PKA. © 2014 the American Physiological Society. Source


Yu W.,Wuhan University | Chen L.,Wuhan University | Yang Y.-Q.,China Pharmaceutical University | Falck J.R.,University of Texas Southwestern Medical Center | And 3 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: Cytochrome P450 (CYP) ω-hydroxylase, mainly consisting of CYP4A and CYP4F, converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) that induces angiogenic responses in vivo and in vitro. The present study examined the role of CYP ω-hydroxylase in angiogenesis and metastasis of human non-small cell lung cancer (NSCLC). Methods: The effect of WIT003, a stable 20-HETE analog, on invasion was evaluated using a modified Boyden chamber in three NSCLC cell lines. A549 cells were transfected with CYP4A11 expression vector or exposed to CYP ω-hydroxylase inhibitor (HET0016) or 20-HETE antagonist (WIT002), and then ω-hydroxylation activity toward arachidonic acid and the levels of matrix metalloproteinases (MMPs) and VEGF were detected. The in vivo effects of CYP ω-hydroxylase were tested in established tumor xenografts and an experimental metastasis model in athymic mice. Results: Addition of WIT003 or overexpression of CYP4A11 with an associated increase in 20-HETE production significantly induced invasion and expression of VEGF and MMP-9. Treatment of A549 cells with HET0016 or WIT002 inhibited invasion with reduction in VEGF and MMP-9. The PI3 K or ERK inhibitors also attenuated expression of VEGF and MMP-9. Compared with control, CYP4A11 transfection significantly increased tumor weight, microvessel density (MVD), and lung metastasis by 2.5-fold, 2-fold, and 3-fold, respectively. In contrast, WIT002 or HET0016 decreased tumor volume, MVD, and spontaneous pulmonary metastasis occurrences. Conclusion: CYP ω-hydroxylase promotes tumor angiogenesis and metastasis by upregulation of VEGF and MMP-9 via PI3 K and ERK1/2 signaling in human NSCLC cells. © 2010 Springer-Verlag. Source


Ma S.,Qiqihar University | Liu X.,China Pharmaceutical University | Xu Q.,Heilongjiang Academy of Traditional Chinese Medicine | Zhang X.,Guangdong Research Institute of Traditional Chinese Medicine
Life Sciences | Year: 2014

In this report, the transport of ginkgolides with different lipophilicities was investigated using an hCMEC/D3 cell monolayer as a blood-brain barrier (BBB) cell model in vitro in an attempt to explain ginkgolide transport path mediated by lipophilicity.Main methods: The log P values of ginkgolides were determined by measuring the distribution of the molecule between oil and water. Additionally, the cytotoxicity of ginkgolides on hCMEC/D3 cells was assayed with the MTT method. Ginkgolide contents were determined with an ultra performance liquid chromatograph equipped with an evaporative light scattering detector (ULPC-ELSD) method. Apparent permeability coefficients (Papp) and efflux ratios (PappBL → AP/PappAP → BL) were then calculated to describe the transport characteristics of ginkgolide.Key findings: The transport of ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J across the hCMEC/D3 cell monolayer was non-directional. Additionally, ginkgolide C transport on the cell monolayer was time- and concentration-dependent in the paracellular pathway controlled by cytochalasin D (a tight junction modulator). The transport of ginkgolide N, ginkgolide L, and ginkgolide K across the cell monolayer displayed clear directionality at low ginkgolide concentrations. This behavior indicated that the transport of ginkgolide N, ginkgolide L, and ginkgolide K was influenced by the transcellular pathway containing an efflux protein accompanied by the paracellular pathway for passive diffusion. Additionally, the transport of ginkgolide K was increased significantly by co-culturing with a P-gp inhibitor.Significance: These findings provide important information for elucidating ginkgolide transport pathways and may be beneficial for the design of ginkgolide molecules with high neuroprotective effects. © 2014 Elsevier Ltd. All rights reserved. Source


Zhang X.,Harvard University | Zhang X.,China Pharmaceutical University | Kuo C.,Perkin Elmer Corporation | Moore A.,Harvard University | Ran C.,Harvard University
PLoS ONE | Year: 2013

Objective:Brown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BAT's presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with 18F-FDG showed significant uptake of 18F-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using 18F-FDG could be utilized for in vivo optical imaging of BAT in mice.Methods:Mice were injected with 18F-FDG and imaged 60 minutes later with open filter and 2 minute acquisition. In vivo activation of BAT was performed by norepinephrine and cold treatment under isoflurane or ketamine anesthesia. Spectral unmixing and 3D imaging reconstruction were conducted with multiple-filter CLI images.Results:1) It was feasible to use CLI with 18F-FDG to image interscapular BAT in mice, with the majority of the signal (>85%) at the interscapular site originating from BAT; 2) The method was reliable because excellent correlations between in vivo CLI, ex vivo CLI, and ex vivo radioactivity were observed; 3) CLI could be used for monitoring BAT activation under different conditions; 4) CLI signals from the group under short-term isoflurane anesthesia were significantly higher than that from the group under long-term anesthesia; 5) The CLI spectrum of 18F-FDG with a peak at 640 nm in BAT after spectral unmixing reflected the actual context of BAT; 6) Finally 3D reconstruction images showed excellent correlation between the source of the light signal and the location and physical shape of BAT.Conclusion:CLI with 18F-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT. © 2013 Zhang et al. Source


Qin Y.,Korea University | Guo X.W.,China Pharmaceutical University | Li L.,Chongqing Medical University | Wang H.W.,Shandong Agricultural University | Kim W.,Korea University
Journal of Medicinal Food | Year: 2013

The present study examined, for the first time, the in vitro wound healing potential of chitosan green tea polyphenols (CGP) complex based on the activation of transglutaminase (TGM) genes in epidermal morphogenesis. Response surface methodology was applied to determine the optimal processing condition that gave maximum extraction of green tea polyphenols. The antioxidant activity, scavenging ability, and chelating ability were studied and expressed as average EC50 values of CGP and other treatments. In silico analysis and gene coexpression network was subjected to the TGM sequences analysis. The temporal expressions of TGMs were profiled by semi-quantitative reverse transcription (RT)-PCR technology within 10 days after wounding and 2 days postwounding. CGP showed the effectiveness of antioxidant properties, and the observations of histopathological photography showed advanced tissue granulation and epithelialization formation by CGP treatment. In silico and coexpression analysis confirmed the regulation via TGM gene family in dermatological tissues. RT-PCR demonstrated increased levels of TGM1-3 expression induced by CGP treatment. The efficacy of CGP in wound healing based on these results may be ascribed to its antioxidant properties and activation of the expression of TGMs, and is, thus, essential for the facilitated repair of skin injury. © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition. Source


Li N.-G.,Nanjing University | Shi Z.-H.,China Pharmaceutical University | Tang Y.-P.,Nanjing University | Wei-Li,Nanjing University | And 2 more authors.
Current Medicinal Chemistry | Year: 2012

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that afflicts 1-2% of the world population, characterized by an immune mediated inflammatory synovitis that leads to joint destruction, functional impairment, and reduced quality of life. The treatment goals of RA should be longterm substantial relief of pain, arrested joint inflammation and damage, and improved function. Current treatment can be divided into four classes, namely general analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and biological agents (tumor-necrosis factor modifiers). However, gastrointestinal (GI) side effects of NSAIDs cannot be neglected, direct joint injections of glucocorticoids cannot be injected more than once every 3 months, synthetic DMARDs is far from optimal and only minority of patients achieved longterm remission, the biologics are very expensive to manufacture, need to be injected, and can cause allergic reactions. An alternative and good approach to the treatment of this disease is to lower the levels of tumour necrosis factor-α (TNF-α) in RA, which can be achieved by selectively inhibiting the tumour necrosis factor-α converting enzyme (TACE) that generate these cytokines using cheaper small molecules. This review focuses on the current status of selective small molecule inhibitors of TACE, with respect to lead compound search, inhibitors design approach, structure-activity relationship (SAR) and pharmacological studies in animals and humans. Through these methods, new hope is emerging for the treatment of RA through selective inhibition of TACE. © 2012 Bentham Science Publishers. Source


Yan L.,Nanjing Medical University | Zhao L.,Nanjing Medical University | Long Y.,China Pharmaceutical University | Zou P.,Nanjing Medical University | And 3 more authors.
PLoS ONE | Year: 2012

Background: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs. Methods: An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis. Results: A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis (TT versus CC: OR = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls. Conclusion: The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted. © 2012 Yan et al. Source


He J.,University of Washington | Yu Y.,University of Washington | Prasad B.,University of Washington | Chen X.,China Pharmaceutical University | Unadkat J.D.,University of Washington
Biopharmaceutics and Drug Disposition | Year: 2014

An unusual, but clinically significant, digoxin (DIG)-bupropion (BUP) drug interaction (DDI), in which BUP increased DIG renal clearance by 80% is reported. To investigate the mechanism(s) of this unusual DDI, first the effect of BUP, its circulating metabolites or their combination on [3H]-DIG transport by cells expressing human P-gp or human OATP4C1 was determined. Second, the study asked whether this DDI could be replicated in the rat so that it could be used to conduct mechanistic studies. Then, the effect of BUP and its rat metabolites on [3H]-DIG transport were tested by cells expressing rat Oatp4c1. Bupropion and its metabolites had no effect on human P-gp mediated transepithelial transport of [3H]-DIG. Bupropion and hydroxybupropion (HBUP) significantly stimulated H-OATP4C1 mediated transport of [3H]-DIG. In addition, BUP cocktail (BUP plus its metabolites) significantly increased the H-OATP4C1 mediated transport of [3H]-DIG, and partially reversed the inhibition by 100 μm DIG. However, erythro-hydrobupropion (EBUP) and threo-hydrobupropion (TBUP) did not affect the [3H]-DIG uptake by H-OATP4C1 cells. Bupropion administration significantly increased digoxin renal clearance in rats. Surprisingly, bupropion significantly inhibited r-Oatp4c1 mediated transport of [3H]-DIG at clinically relevant unbound plasma concentrations of BUP or those observed in the rat study, while HBUP or TBUP did not. These data support our hypothesis that at clinically relevant plasma concentrations, bupropion and its metabolites activate H-OATP4C1 mediated DIG tubular secretion, and could possibly explain the increase in digoxin renal clearance produced by bupropion. While bupropion increased digoxin renal clearance in the rat, it appeared to do so by inhibiting r-Oatp4c1-mediated digoxin renal reabsorption. Copyright © 2014 John Wiley & Sons, Ltd. Source


Jin W.,Yangzhou University | Yang G.,China Pharmaceutical University | Shao H.,Yangzhou University | Qin A.,Yangzhou University
Food Control | Year: 2014

A novel label-free impedimetric immunosensor for detection 1-aminohydantoin (AHD) was first constructed by the silica sol-gel immobilization of monoclonal antibody against 1-aminohydantoin antibody (AHD-McAb) on the surface of glassy carbon electrode (GCE). The electrochemical impedance spectroscopy of ferricyanide was used as a marker to probe the interface and as a redox probe to determinate AHD. The effect of operational parameters, such as amount of immobilized AHD-McAb, pH, incubation time, and incubation temperature, has been explored for the optimum analytical performance of the impedimetric immunosensor. Under the optimized conditions, the change in impedance was proportional to AHD concentrations in the range of 2.0-1.0×103ng/mL (r=0.9990) with the detection limit of 2.0ng/mL. The specificity, reproducibility, stability, and accuracy of the proposed impedimetric immunosensor were also evaluated. In addition, the proposed immunosensor was successfully applied for the determination of AHD in food samples using the standard adding method with recoveries of 93.7-104.9%. The results obtained by the proposed immunosensor corroborate very well with the method of HPLC-MS/MS for the determination of AHD in food samples. © 2013 Elsevier Ltd. Source


Sun S.,Macau University of Science and Technology | Liu H.,China Pharmaceutical University | Xu S.,Macau University of Science and Technology | Yan Y.,Macau University of Science and Technology | Xie P.,Macau University of Science and Technology
Journal of Pharmaceutical Analysis | Year: 2014

Due to the scarcity of resources of Ziziphi spinosae semen (ZSS), many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern established in this paper showed three main bioactive compounds in one chromatogram simultaneously. Principal component analysis based on DAD signals could discriminate adulterants and inferiorities. Principal component analysis indicated that all samples could be mainly regrouped into two main clusters according to the first principal component (PC1, redefined as Vicenin II) and the second principal component (PC2, redefined as zizyphusine). PC1 and PC2 could explain 91.42% of the variance. Content of zizyphusine fluctuated more greatly than that of spinosin, and this result was also confirmed by the HPTLC result. Samples with low content of jujubosides and two common adulterants could not be used equivalently with authenticated ones in clinic, while one reference standard extract could substitute the crude drug in pharmaceutical production. Giving special consideration to the well-known bioactive saponins but with low response by end absorption, a fast and cheap HPTLC method for quality control of ZSS was developed and the result obtained was commensurate well with that of HPLC analysis. Samples having similar fingerprints to HPTLC common pattern targeting at saponins could be regarded as authenticated ones. This work provided a faster and cheaper way for quality control of ZSS and laid foundation for establishing a more effective quality control method for ZSS. © 2014 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. All rights reserved. Source


Ye B.-F.,Nanjing Southeast University | Ye B.-F.,China Pharmaceutical University | Zhao Y.-J.,Nanjing Southeast University | Zhao Y.-J.,Suzhou University | And 6 more authors.
Nanoscale | Year: 2012

We have developed a robust method for the visual detection of heavy metal ions (such as Hg2+ and Pb2+) by using aptamer- functionalized colloidal photonic crystal hydrogel (CPCH) films. The CPCHs were derived from a colloidal crystal array of monodisperse silica nanoparticles, which were polymerized within the polyacrylamide hydrogel. The heavy metal ion-responsive aptamers were then cross-linked in the hydrogel network. During detection, the specific binding of heavy metal ions and cross-linked single-stranded aptamers in the hydrogel network caused the hydrogel to shrink, which was detected as a corresponding blue shift in the Bragg diffraction peak position of the CPCHs. The shift value could be used to estimate, quantitatively, the amount of the target ion. It was demonstrated that our CPCH aptasensor could screen a wide concentration range of heavy metal ions with high selectivity and reversibility. In addition, these aptasensors could be rehydrated from dried gels for storage and aptamer protection. It is anticipated that our technology may also be used in the screening of a broad range of metal ions in food, drugs and the environment. This journal is © 2012 The Royal Society of Chemistry. Source


Liu Y.,Northwestern Polytechnical University | Liu Y.,China Pharmaceutical University | Wu G.,Zhongkai University of Agriculture and Engineering | Cui Y.,Northwestern Polytechnical University | Cui Y.,Zhongkai University of Agriculture and Engineering
Applied Organometallic Chemistry | Year: 2013

As a nanoparticle support material, carbon nanotubes (CNTs) provide a certain potential activation of catalysis in heterogeneous catalytic organic reactions. Herein, an efficient Ag/CNT-catalyzed synthesis of enamines via hydroamination of activated alkynes with aromatic amines has been described. This catalyst still retains catalytic activity after being recycled and reused three times. In addition, it represents a green and environmentally friendly process for preparation of enamines. Copyright © 2013 John Wiley & Sons, Ltd. Ag/CNTs catalysis has been developed to synthesize enamines via hydroamination of asymmetry alkylnates with aromatic amines. The catalysis can be recycled and reused 3 times, which also remain catalytic activity. In addition, it represents a green and environmentally friendly process for preparation of enamines. Copyright © 2013 John Wiley & Sons, Ltd. Source


Zhang X.,Lanzhou University | Xu L.,Lanzhou University | Shen J.,Lanzhou University | Cao B.,China Pharmaceutical University | And 4 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

Focused metabolic profiling is a powerful tool for the determination of biomarkers. Here, a more global proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with a relative simple ultra high performance liquid chromatography (UHPLC)-based focused metabolomic approach was developed and compared to characterize the systemic metabolic disturbances underlying esophageal cancer (EC) and identify possible early biomarkers for clinical prognosis. Serum metabolic profiling of patients with EC (n=25) and healthy controls (n=25) was performed by using both 1H NMR and UHPLC, and metabolite identification was achieved by multivariate statistical analysis. Using orthogonal projection to least squares discriminant analysis (OPLS-DA), we could distinguish EC patients from healthy controls. The predictive power of the model derived from the UHPLC-based focused metabolomics performed better in both sensitivity and specificity than the results from the NMR-based metabolomics, suggesting that the focused metabolomic technique may be of advantage in the future for the determination of biomarkers. Moreover, focused metabolic profiling is highly simple, accurate and specific, and should prove equally valuable in metabolomic research applications. A total of nineteen significantly altered metabolites were identified as the potential disease associated biomarkers. Significant changes in lipid metabolism, amino acid metabolism, glycolysis, ketogenesis, tricarboxylic acid (TCA) cycle and energy metabolism were observed in EC patients compared with the healthy controls. These results demonstrated that metabolic profiling of serum could be useful as a screening tool for early EC diagnosis and prognosis, and might enhance our understanding of the mechanisms involved in the tumor progression. © 2013. Source


Ding L.,Yancheng Institute of Technology | Qiu J.,Yancheng Institute of Technology | Wei J.,Yancheng Institute of Technology | Zhu Z.,China Pharmaceutical University | Zhu Z.,National University of Singapore
Polymer Chemistry | Year: 2014

A novel divergent approach was developed for the first time for the synthesis of linear-dendritic polyphosphoester (PPE) structures using an acrylated poly(ethylene glycol) methyl ether as a linear macromolecular chain stopper by acyclic diene metathesis (ADMET) polymerization of phosphoester functional asymmetric α,ω-diene monomers. This synthesis is remarkable, because unlike all others, each low-generation linear-dendron copolymer could be readily converted, by thiol-Michael addition click reaction and esterification, to a new selective macromolecular chain stopper by subsequent ADMET polymerization to synthesize high-generation linear-dendron block PPEs, and it requires no means of purification other than a simple precipitation. The prepared linear-dendritic PPEs can self-assemble spontaneously in a selective solvent to form polymeric nanoparticles, which were characterized in detail by DLS, AFM, and TEM analyses. To the best of our knowledge, this is the first report that describes the synthesis of linear-dendron-like block PPEs via ADMET polymerization. Consequently, this provides a versatile strategy not only for the synthesis of biodegradable and amphiphilic block PPEs with linear-dendron-like architecture but also for the fabrication of biocompatible nanoparticles with a suitable size for biomedical applications. © 2014 the Partner Organisations. Source


Lu X.,Nanjing Medical University | Xu H.,Nanjing Medical University | Sun B.,Nanjing Medical University | Zhu Z.,China Pharmaceutical University | And 2 more authors.
Molecular Pharmaceutics | Year: 2013

Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b- poly(ε-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke. © 2013 American Chemical Society. Source


Wang P.,CAS Shanghai Institute of Materia Medica | Wang P.,China Pharmaceutical University | Liao W.,CAS Shanghai Institute of Materia Medica | Fang J.,CAS Shanghai Institute of Materia Medica | And 4 more authors.
Carbohydrate Polymers | Year: 2014

Inhibition of Aβ aggregation and attenuation of its cytotoxicity are considered to valuable therapeutics for Alzheimer's disease (AD). Here, a glucan named as LJW0F2 was purified from flowers of Lonicera japonica Thunb. Using monosaccharides composition analysis, methylation analysis, IR and NMR spectroscopy, this polysaccharide was elucidated to be an α-d-(1→4)- glucan with an α-(1→4) linked branch attached to the C-6 position. Its inhibitory effect on Aβ42 aggregation was measured by fluorescence spectroscopic analysis with thioflavine T (ThT) and atomic force microscopy (AFM). We showed that polysaccharide LJW0F2 could inhibit Aβ42 aggregation in a dose-dependent-manner. Besides, LJW0F2 could attenuate the cytotoxicity induced by Aβ42 aggregation in SH-SY5Y neuroblastoma cells. To the best of our knowledge, this was the first report that the exogenous plant-derived polysaccharide might block Aβ42 aggregation directly and reduce its toxicity in SH-SY5Y cells. © 2014 Elsevier Ltd. Source


Wang C.-Z.,Tang Center for Herbal Medicine Research | Qi L.-W.,Tang Center for Herbal Medicine Research | Qi L.-W.,China Pharmaceutical University | Yuan C.-S.,Tang Center for Herbal Medicine Research | Yuan C.-S.,University of Chicago
American Journal of Chinese Medicine | Year: 2015

Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger. © 2015 World Scientific Publishing Company. Source


Zhang H.,Shandong University | Wei K.,Shandong University | Zhang M.,Shandong University | Liu R.,Shandong University | Chen Y.,China Pharmaceutical University
Journal of Photochemistry and Photobiology B: Biology | Year: 2014

Lead still possesses great threats to human health owing to its widespread distribution in the environment caused by human activities, although various actions have been taken to cut down the use and distribution of lead. In this work, mechanisms of DNA damage caused by lead through indirect and direct interactions were investigated. Results from comet assay showed lead at 1-10 μM induced DNA strand breaks in mice liver cells according to olive tail moment analysis. Signals of DNA-protein crosslinks (DPC) were not significantly detected until exposed at 100 μM Pb2+. Further more, direct interactions between Pb2+ and DNA were explored to determine the binding mode between them using spectra analysis, isothermal titration calorimetry studies and molecular docking investigations, which indicated that Pb2+ could bind to DNA with four binding sites to form Pb 2+-DNA complex by minor groove binding effects and electrostatic forces, resulting in damage to the structure of DNA double helix. Combined studies of lead genotoxicity in indirect (comet assay and DPC assay) and direct (binding mode investigations) interactions can be applied to study the potential damages to DNA induced by heavy metal pollutants. © 2014 Elsevier B.V. All rights reserved. Source


Jiang Z.-X.,China Pharmaceutical University | Zhi S.,Huaiyin Normal University | Zhang W.,University of Massachusetts Boston
Molecular Diversity | Year: 2014

This article highlights research papers published in 2011 and 2012 on fluorous linker-assisted synthesis of biologically interesting small molecules and biomolecules. © 2014 Springer Science+Business Media Dordrecht. Source


Dai D.-Z.,China Pharmaceutical University
Biochemical Pharmacology | Year: 2015

Over the period 1995-2012, David Triggle was a frequent visitor to the China Pharmaceutical University in Nanjing, China making many important contributions that enhanced the activities of the Research Division of Pharmacology at the University. In addition to providing collegial advice and facilitating interactions with the international pharmacological community, Professor Triggle's international reputation as a thought leader in the field of ion channel research and drug discovery provided important insights into the potential pathophysiological and therapeutic effects of targeting ion channels. This included the L-type calcium channel and the outward delayed rectified potassium currents of rapid (IKr) and slow (IKs) components in the myocardium. The Nanjing research team had been particularly interested in ion channel dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery. With Professor Triggle's assistance, the relationship between an increase in ICa.L and other biological events including an enhancement of IKr and IKr currents, NADPH oxidase and endothelin receptor activation, down regulation of calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca2+ATPse (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic reticulum stress, were evaluated and are discussed. Additionally, the organization of several international symposia was greatly enhanced by input from Professor Triggle as were the published research manuscripts in international pharmacology journals. During his association with the China Pharmaceutical University, Professor Triggle aided in enhancing the scientific standing of the Pharmacology department and was a highly effective ambassador for international research cooperation. © 2015 Published by Elsevier Inc. Source


Chen Y.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2012

To study the water-soluble chemical constituents of the flower buds of Lonicera macranthoides. The chemical constituents were isolated and purified by means of chromatographic techniques and their structures were elucidated by spectroscopic methods. Six compounds were isolated and identified as trans-linalool-3,7-oxide-6-O-beta-D-glucopyranoside(1), secol oganoside(2), secoxyloganin(3),chlorogenic acid(4), caffeic acid(5), sucrose(6). Compound 1 is isolated from nature as a single compound for the first time, compounds 2-3 are isolated from this plant for the first time. Source


Xing X.D.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2012

To study the chemical constituents from the stems of Ilex pubescens Hook. et Am. The chemical constituents were isolated and purified by various column chromatographic methods with diatomite, silica gel, ODS and Sephadex LH-20. Their structures were identified on physical properties and spectroscopic methods. Nine compounds were isolated and determined as luteolin(1), quercetin(2), hyperoside(3), rutin(4), 1, 5-dihydroxy-3-methyl-anthraquinone(5),3,5-dimethoxy-4-hydroxy-benzoic acid-1-O-beta-D-glucoside(6), hexadecanoic acid(7), stearic acid(8), n-tetratriacontanol(9), respectively. All the compounds are isolated from this plant for the first time, and compounds 5 and 6 are isolated from this genus for the first time. Source


Wang X.,China Pharmaceutical University
Pharmacogenomics Journal | Year: 2015

The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs.The Pharmacogenomics Journal advance online publication, 16 June 2015; doi:10.1038/tpj.2015.42. © 2015 Macmillan Publishers Limited Source


Ye B.,Nanjing Southeast University | Ye B.,China Pharmaceutical University | Ding H.,Nanjing Southeast University | Cheng Y.,Nanjing Southeast University | And 7 more authors.
Advanced Materials | Year: 2014

A novel suspension array, which possesses the joint advantages of photonic crystal encoded technology, bioresponsive hydrogels, and photonic crystal sensors with capability of full multiplexing label-free detection is developed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Wang D.-W.,Chinese Academy of Agricultural Sciences | Ouyang C.-B.,Chinese Academy of Agricultural Sciences | Liu Q.,Chinese Academy of Agricultural Sciences | Yuan H.-L.,China Pharmaceutical University | Liu X.-H.,Chinese Academy of Agricultural Sciences
Carbohydrate Polymers | Year: 2013

An inclusion complex between chemosterilant quinestrol and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) was prepared using the solution-ultrasonic method. A 1:1 stoichiometry was confirmed by elemental analysis. Analytical techniques such as UV-vis spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize the complex. Proton NMR and nuclear Overhauser effect spectroscopy results indicate that the hydroxyl end and alkynyl end of quinestrol was included in the DM-β-CD cavity, which agrees with the most predominant configuration optimized by molecular modeling. The water solubility of quinestrol was significantly increased through complexation with DM-β-CD. The DM-β-CD complexes can be used in the design of a novel formulation of quinestrol for rat control products in agriculture. © 2013 Published by Elsevier Ltd. Source


Jin W.-J.,Yangzhou University | Yang G.-J.,China Pharmaceutical University | Shao H.-X.,Yangzhou University | Qin A.-J.,Yangzhou University
Sensors and Actuators, B: Chemical | Year: 2013

l-Cysteine (Cys) and chitosan (Chi) were cross-linked to form the functional polymer composite with active groups of thiol and amino groups (denoted as Chi-Cys) under the coupling reagents of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide and N-hydrosuccinimide (EDC/NHS). Then it was modified on the surface of glassy carbon electrode (GCE). The active groups in Chi-Cys composite can adsorb gold nanoparticles by self-assembly technique. The electrochemical immunosensor can be fabricated by using gold nanoparticles-functional chitosan biological composite film as matrix to immobilize the monoclonal antibody against semicarbazide (SEM) (SEM-McAb). The detection of SEM residue was performed with the technique of electrochemical impedance spectroscopy. Under the optimized conditions, the relative change in impedance was proportional to the logarithmic value of SEM concentrations in the range of 1.0-1.0 × 104 ng mL-1 (r = 0.9998) with the detection limit of 1.0 ng mL-1. The specificity, reproducibility, stability, and accuracy of the proposed impedimetric immunosensor were also evaluated. The proposed immunosensor showed economical, efficient, and potential application for the detection of SEM in food samples. © 2013 Elsevier B.V. Source


Zhu H.-J.,University of Florida | Wang X.,China Pharmaceutical University | Markowitz J.S.,University of Florida
Journal of Pharmacology and Experimental Therapeutics | Year: 2013

Clopidogrel pharmacotherapy is associated with substantial interindividual variability in clinical response, which can translate into an increased risk of adverse outcomes. Clopidogrel, a recognized substrate of hepatic carboxylesterase 1 (CES1), undergoes extensive hydrolytic metabolism in the liver. Significant interindividual variability in the expression and activity of CES1 exists, which is attributed to both genetic and environmental factors. We determined whether CES1 inhibition and CES1 genetic polymorphisms would significantly influence the biotransformation of clopidogrel and alter the formation of the active metabolite. Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. As anticipated, clopidogrel and 2-oxoclopidogrel were efficiently hydrolyzed by the cell s9 fractions prepared from wild-type CES1 transfected cells. The enzymatic activity of the CES1 variants G143E and D260fs were completely impaired in terms of catalyzing the hydrolysis of clopidogrel and 2-oxo-clopidogrel. However, the natural variants G18V, S82L, and A269S failed to produce any significant effect on CES1- mediated hydrolysis of clopidogrel or 2-oxo-clopidogrel. In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Additionally, CES1 genetic variants have the potential to serve as a biomarker to predict clopidogrel response and individualize clopidogrel dosing regimens in clinical practice. © 2013 by The American Society for Pharmacology and Experimental Therapeutics. Source


Shi J.-M.,Jinan University | Bai L.-L.,Jinan University | Zhang D.-M.,Jinan University | Yiu A.,Chinese University of Hong Kong | And 6 more authors.
Biochemical Pharmacology | Year: 2013

Breast cancer is the leading cause of cancer death among females, and novel chemotherapeutic drugs for treating breast cancer are needed urgently. Saxifragifolin D (SD) was isolated by our group from Androsace umbellata which is commonly used to treat solid tumor. In this study, we evaluated its growth inhibitory effect on breast cancer cells and explored the underlying molecular mechanisms. Our results showed that SD inhibited the growth of both MCF-7 and MDA-MB-231 cells significantly. Mechanistic studies demonstrated that SD induced apoptosis through mitochondrial apoptotic pathway. Evidence of SD-induced autophagy included the occurrence of autophagic vacuoles, up-regulation of LC3-II, Beclin1 and Vps34. Inhibition of autophagy by bafilomycin A1 or Beclin1 siRNA pretreatment decreased the ratio of apoptosis, indicating that autophagy induction contributes to apoptosis and is required for the latter. SD was also found to induce endoplasmic reticulum stress, accompanied by ROS production, increase of intracellular calcium and up-regulation of Bip, IRE1α and XBP-1s. Inhibition of endoplasmic reticulum stress by N-acetyl-l-cysteine, tauroursodeoxycholic acid or IRE1α siRNA pretreatment could suppress both apoptosis and autophagy. Besides, increases in CHOP, calnexin, calpain, p-JNK and p-Bcl-2 were followed by subsequent dissociation of Beclin1 from Bcl-2, further suggesting endoplasmic reticulum stress to be the common signaling pathway shared by SD-induced apoptosis and autophagy. In conclusion, SD inhibits breast cancer cell growth and induces interplay between apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress. It will provide molecular bases for developing SD into a drug candidate for the treatment of breast cancer. © 2013 Elsevier Inc. Source


Liu Y.,Nanjing University | Huang J.,Nanjing University | Sun M.-J.,China Pharmaceutical University | Yu J.-C.,Nanjing University | And 4 more authors.
Nanoscale | Year: 2014

The present study describes a flexible nanoplatform based on electrostatic assembly of conjugated polyelectrolytes (CPEs) and carboxylated multi-walled carbon nanotubes (cMWNTs). It is demonstrated that the obtained nanocomposites inherit intrinsic optical properties of CPEs and characteristic Raman vibration modes of MWNTs, providing a fluorescence-Raman dual-imaging method for intracellular tracking and locating of MWNTs. We suggest that the cellular internalization of the CPE-cMWNT nanocomposites is a surface charge-dependent process. The strengths of this nanoplatform include satisfying biocompatibility, enhanced protein-repellent property, and ease of implementation, making it available for both in vitro and in vivo applications. © 2013 The Royal Society of Chemistry. Source


Pan X.,Nanjing Medical University | Zhu Y.,Nanjing Medical University | Zheng D.,University of Sydney | Liu Y.,Nanjing Medical University | And 2 more authors.
International Journal of Stroke | Year: 2015

Background: There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke. Aim: We performed a systematic review with a final meta-analysis to evaluate the efficacy and safety of prior antiplatelet use before intravenous recombinant tissue plasminogen activator for acute ischemic stroke. Summary of review: We searched PubMed and Embase databases from 1997 to 2014. Primary outcome was functional outcome at the end of follow-up; secondary outcomes were symptomatic intracranial hemorrhage and recanalization rate. The meta-analysis was performed with Review Manager 5·2 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). Eleven studies with a total of 19453 patients were included. A total of 6517 (33·5%) patients who had received intravenous recombinant tissue plasminogen activator were taking antiplatelet agent before stroke onset. Pooled analysis demonstrated a clear trend that previous antiplatelet users had a reduced probability of good outcome, although it was not conventionally statistically significant (OR 0·86; 95% CI 0·73-1·01; P=0·06). There was no difference in recanalization rate between two groups (OR 1·23; 95% CI 0·30-4·99; P=0·77). The risk of symptomatic intracranial hemorrhage was significantly increased in the antiplatelet group (OR 1·65; 95% CI 1·44-1·90; P<0·01). Conclusions: In acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator therapy, prior antiplatelet agent use did not lead to a significant difference in functional outcome, although it significantly increased the risk of symptomatic intracranial hemorrhage. Recanalization rate was not different between two groups. In the subgroup analysis, prior clopidogrel mono therapy may not increase the risk of symptomatic intracranial hemorrhage, which will need further studies to confirm. © 2014 World Stroke Organization. Source


Chang L.,Fudan University | Ding M.,China Pharmaceutical University | Bao L.,Fudan University | Chen Y.,Fudan University | And 2 more authors.
Applied Microbiology and Biotechnology | Year: 2011

A new gene, RuCelA, encoding a bifunctional xylanase/endoglucanase, was cloned from a metagenomic library of yak rumen microorganisms. RuCelA showed activity against xylan and carboxymethylcellulose (CMC), suggesting bifunctional xylanase/endoglucanase activity. The optimal conditions for xylanase and endoglucanase activities were 65°C, pH 7.0 and 50°C, pH 5.0, respectively. In addition, the presence of Co + and Co 2+ can greatly improve RuCelA's endoglucanase activity, while inhibits its xylanase activity. Further examination of substrate preference showed a higher activity against barley glucan and lichenin than against xylan and CMC. Using xylan and barley glucan as substrates, RuCelA displayed obvious synergistic effects with β-1,4-xylosidase and β-1,4-glucosidase. Generation of soluble oligosaccharides from lignocellulose is the key step in bioethanol production, and it is greatly notable that RuCelA can produce xylo-oligosaccharides and cello-oligosaccharides in the continuous saccharification of pretreated rice straw, which can be further degraded into fermentable sugars. Therefore, the bifunctional RuCelA distinguishes itself as an ideal candidate for industrial applications. © 2011 Springer-Verlag. Source


Wang J.-T.,Sun Yat Sen University | Li Y.,Sun Yat Sen University | Tan J.-H.,Sun Yat Sen University | Ji L.-N.,Sun Yat Sen University | And 2 more authors.
Dalton Transactions | Year: 2011

Herein we reported three new platinum(ii)-triarylpyridines complexes with peralkylated ammonium pendants that strongly stabilize G-quadruplex DNA. © 2011 The Royal Society of Chemistry. Source


Zhang D.,Nanjing Southeast University | Yang M.,China Pharmaceutical University
Physical Chemistry Chemical Physics | Year: 2013

The advantages of one-dimensional nanostructures, such as excellent charge separation and charge transport, low charge carrier recombination losses and so on, render them the photocatalysts of choice for many applications that exploit solar energy. In this work, based on very recently synthesized ultrathin anatase TiO2 nanowires, we explore the possibility of these wires as photocatalysts for photoelectrochemical water-splitting via the mono-doping (C, N, V, and Cr) and n-p codoping (C&V, C&Cr, N&V, and N&Cr) schemes. Our first-principles calculations predict that the C&Cr and C&V codoped ANWs may be strong candidates for photoelectrochemical water-splitting, because they have a substantially reduced band gap of 2.49 eV, appropriate band edge positions, no carrier recombination centers, and enhanced optical absorption in the visible light region. © 2013 the Owner Societies. Source


Du B.,Sichuan University | Yuan C.,Sichuan University | Yu T.,Sichuan University | Yang L.,Sichuan University | And 4 more authors.
Chemistry - A European Journal | Year: 2014

In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations. From terpenes to terpenes: Two strategies toward the synthesis of bolivianine are described. Based on the modified biogenetic hypothesis, biomimetic total synthesis was evolved and accomplished, involving onoseriolide, bolivianine, and isobolivianine (see figure). Experimental results and DFT calculations support a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade leading to bolivianine. In addition, the synthesis features a new Pd-catalyzed intramolecular cyclopropanation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Li S.,Nanjing Southeast University | Wang Z.,Nanjing University | Wei Y.,China Pharmaceutical University | Wu C.,Nanjing Southeast University | And 5 more authors.
Biomaterials | Year: 2013

Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to threaten the health of human beings. Developing new antibacterial agents, therefore, are urgently needed. Herein, we have explored the possibility to design and synthesize some novel antibacterial agents including ferrocene-substituted carborane derivative (Fc2SBCp1) and have evaluated the relevant antibacterial action against two clinical common MDR pathogens (i.e., Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro and in vivo. The results demonstrate that in vitro antimicrobial activity of Fc2SBCp1 could be gradually transformed into a bactericidal effect from a bacteriostatic effect with the increasing concentration of the active carborane derivative, which can also prevent biofilm formation at concentrations below MIC (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that there exists no/or little toxic effect of Fc2SBCp1 on normal cells/tissues and leads to little hemolysis. In vivo studies illustrate that the new carborane derivative Fc2SBCp1 is highly effective in treating bacteremia caused by S. aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus. This raises the possibility for the potential utilization of the new ferrocene-substituted carborane derivatives as promising antibacterial therapeutic agents against MDR bacterial infections in future clinical applications. © 2012 Elsevier Ltd. Source


Previously we constructed a fusion protein based on GLP-1 and globular adiponectin but unfortunately its yield was low because it was mainly expressed as inclusion bodies. Herein to optimize the soluble expression of this fusion protein we tried several fusion tag systems. Fusion tags, including GST-, Trx- and MBP-tag, greatly improved the soluble expression of the fusion protein. However, these tag-fusion proteins were aggregation-prone as judged by Native PAGE and gel filtration chromatography, and this aggregation reduced the specificity of enterokinase-mediated enzyme cleavage which was essential to remove the fusion tags. To improve the specificity of protein cleavage, we employed on-column cleavage for downstream purification. Finally using optimized expression followed by on-column cleavage, we obtained the product fusion protein with a yield of 1.2 mg per g wet bacterial cells which was 8-fold higher than before. This method improved the yield and simplified the process, and as a convenient method it can also be used for the preparation of other aggregation-prone proteins. Source


Hu R.,China Pharmaceutical University | Saw C.L.-L.,Rutgers University | Yu R.,University of Texas Health Science Center at Houston | Kong A.-N.T.,Rutgers University
Antioxidants and Redox Signaling | Year: 2010

Cancer chemoprevention is a process of using either natural or synthetic compounds to reduce the risk of developing cancer. Observations that NF-E2-related factor 2 (Nrf2)-deficient mice lack response to some chemopreventive agents point to the important role of Nrf2 in chemoprevention. Nrf2 is a member of basic-leucine zipper transcription factor family and has been shown to regulate gene expression by binding to a response element, antioxidant responsive element. It is generally believed that activation of Nrf2 signaling is an adaptive response to the environmental and endogenous stresses. Under homeostatic conditions, Nrf2 is suppressed by association with Kelch-like ECH-associated protein 1 (Keap1), but is stimulated upon exposure to oxidative or electrophilic stress. Once activated, Nrf2 translocates into nuclei and upregulates a group of genes that act in concert to combat oxidative stress. Nrf2 is also shown to have protective function against inflammation, a pathological process that could contribute to carcinogenesis. In this review, we will discuss the current progress in the study of Nrf2 signaling, in particular, the mechanisms of Nrf2 activation by chemopreventive agents. We will also discuss some of the potential caveats of Nrf2 in cancer treatment and future opportunity and challenges on regulation of Nrf2-mediated antioxidant and antiinflammatory signaling in the context of cancer prevention. © 2010 Mary Ann Liebert, Inc. Source


Li N.-G.,Nanjing University | Tang Y.-P.,Nanjing University | Duan J.-A.,Nanjing University | Shi Z.-H.,Nanjing University | Shi Z.-H.,China Pharmaceutical University
Expert Opinion on Therapeutic Patents | Year: 2014

Introduction: The MMPs are involved in tissue remodeling. An imbalance between the inhibition and activation of MMPs results in excessive degradation of the extracellular matrix, which leads to some diseases including cancer, rheumatoid arthritis, osteoarthritis, heart disease and neurodegenerative diseases such as stroke. In this review, recent advances in the research of MMP inhibitors are reviewed. Areas covered: This updated review summarized new patents on MMP inhibitors within January 2011-December 2013. Expert opinion: This review gives the latest development in the area of MMP inhibitors, which aim to treat disease processes associated with the MMPs. Structure-based design techniques have been used successfully in the search of selective MMP inhibitors, and these inhibitors can also be derived from natural products. Furthermore, imaging 'in vivo' technologies have been developed in order to follow the drug distribution to the targeted tissues, and to quantify the drug efficiency. © 2014 Informa UK, Ltd. Source


Chen C.,Northeast Agricultural University | Chi Y.-J.,Northeast Agricultural University | Zhao M.-Y.,China Pharmaceutical University | Lv L.,Northeast Agricultural University
Amino Acids | Year: 2012

Egg white proteins were hydrolysed separately using five different proteases to obtain antioxidant peptides. The antioxidant activity of egg white protein hydrolysates was influenced by the time of hydrolysis and the type of enzyme. Of the various hydrolysates produced, papain hydrolysate obtained by 3-h hydrolysis (PEWPH) displayed the highest DPPH radical scavenging activity. PEWPH could also quench the superoxide anion and hydroxyl radicals, effectively inhibit lipid peroxidation and exhibit reducing power. Then, PEWPH was purified sequentially by ultrafiltration, gel filtration, RP-HPLC and two fractions with relatively strong antioxidant activity were subsequently subjected to LC-MS/MS for peptide sequence identification. The sequences of the two antioxidant peptides were identified to be Tyr-Leu-Gly-Ala-Lys (551.54 Da) and Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe-Gln (974.55 Da), and they were identified for the first time from food-derived protein hydrolysates. Last, the two purified peptides were synthesized and they showed 7.48- and 6.02-fold higher DPPH radical scavenging activity compared with the crude PEWPH, respectively. These results indicate that PEWPH and/or its isolated peptides may be useful ingredients in food and nutraceutical applications. © 2011 Springer-Verlag. Source


Li J.,Nanjing Medical University | Fang H.,China Pharmaceutical University
Current Bioinformatics | Year: 2012

This paper presents a transformation method of original score matrix by correspondently normalizing its elements in row and column. The sequence alignment of 4830 superfamilies and 9570 fold related protein pairs showed that the quality of the alignment based on the transformed matrices is significantly improved compared to that based on the original matrices, especially for the fold related protein pairs, which is possibly due to that the elements in the transformed matrix contain more similarity information between two residues than those in the original matrix. These results indicate that for the sequence alignment of distantly related proteins, the original score matrix should probably be replaced by its correspondently transformed matrix to enhance the quality of sequence alignment. © 2012 Bentham Science Publishers. Source


Geng J.,National University of Singapore | Zhu Z.,China Pharmaceutical University | Qin W.,Hong Kong University of Science and Technology | Ma L.,Nanyang Technological University | And 6 more authors.
Nanoscale | Year: 2014

Near-infrared (NIR) fluorescence signals are highly desirable to achieve high resolution in biological imaging. To obtain NIR emission with high brightness, fluorescent nanoparticles (NPs) are synthesized by co-encapsulation of 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenylamino)phenyl)fumaronitrile (TPETPAFN), a luminogen with aggregation-induced emission (AIE) characteristics, and a NIR fluorogen of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (NIR775) using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] as the encapsulation matrix. The good spectral overlap between the emission of TPETPAFN and the absorption of NIR775 leads to efficient energy transfer, resulting in a 47-fold enhancement of the NIR775 emission intensity upon excitation of TPETPAFN at 510 nm as compared to that upon direct excitation of NIR775 at 760 nm. The obtained fluorescent NPs show sharp NIR emission with a band width of 20 nm, a large Stokes shift of 275 nm, good photostability and low cytotoxicity. In vivo imaging study reveals that the synthesized NPs are able to provide high fluorescence contrast in live animals. The Förster resonance energy transfer strategy overcomes the intrinsic limitation of broad emission spectra for AIE NPs, which opens new opportunities to synthesize organic NPs with high brightness and narrow emission for potential applications in multiplex sensing and imaging. © 2013 The Royal Society of Chemistry. Source


Zhang S.,Nanjing University of Science and Technology | Wang H.,Nanjing University of Science and Technology | Tang J.,Nanjing University of Science and Technology | Wang W.,China Pharmaceutical University | Tang W.,Nanjing University of Science and Technology
Analytical Methods | Year: 2014

The baseline enantioseparation of 19 racemic drugs including ondansetron, citalopram, galanthamine base, pregabalin, timolol, atenolol, tropicamide, ephedrine hydrochloride, flavanoids and aryl alcohols has been successfully achieved with a cyclodextrin clicked chiral stationary phase in high performance liquid chromatography. The best separation results were presented under optimized conditions. The effect of organic modifiers including methanol and acetonitrile on the enantioseparation of racemates was also studied. Chiral resolutions of 4.19 and 4.42 were achieved for citalopram and tropicamide, respectively. This journal is © the Partner Organisations 2014. Source


Liu C.,Yangzhou University | Zhang W.,Yangzhou University | Wang Q.,China Pharmaceutical University | Sun Y.,Yangzhou University | Diao G.-W.,Yangzhou University
Organic and Biomolecular Chemistry | Year: 2013

A new water-soluble inclusion complex of ilexgenin A (IGA) with β-cyclodextrin polymer (CDP) was prepared by a facile strategy and characterized by 1H NMR, FT-IR, and UV-vis spectroscopy. Compared with IGA and the inclusion complex of IGA with β-cyclodextrin (IGA-CD), the solubility of IGA-β-cyclodextrin polymer (IGA-CDP) was greatly enhanced due to the water-soluble CDP host. The ratio of β-cyclodextrin (β-CD) units in CDP to IGA was determined as 2:1. KD of the inclusion complex was evaluated as 2.6 × 10-3 mol L-1. The effects of IGA-CDP on a hyperlipidemia mouse model were studied by intragastric administration. After 4 weeks, the IGA-CDP treatment resulted in decreased serum levels of total cholesterol and low-density lipoprotein-cholesterol. The effects of IGA-CDP on serum apolipoprotein levels were similar to its effects on lipid levels. By comparing liver area, the effects of IGA-CDP on pre-existing lesions were assessed. Furthermore, the efficacy and potency of water-soluble inclusion complex of IGA-CDP was 2-3 times higher than that of IGA. Taken together, it was possible to develop it to a novel drug candidate to regulate lipid abnormality. © 2013 The Royal Society of Chemistry. Source


Wu Q.,Nanjing Southeast University | Wang W.,Nanjing Southeast University | Li Y.,Nanjing Southeast University | Ye B.,China Pharmaceutical University | And 2 more authors.
Journal of Hazardous Materials | Year: 2012

In Caenorhabditis elegans, although acute toxicity of TiO2 nanoparticles (TiO2-NPs) at high concentrations has been investigated, we still know little about chronic toxicity of TiO2-NPs. Our data here showed that acute TiO2-NPs exposure in the range of μg/L had no obviously adverse effects on nematodes, but the chronic toxicities of large sizes (60nm and 90nm) of TiO2-NPs in the range of μg/L were detected in nematodes in a modified chronic toxicity assay system. Moreover, chronic toxicities of small sizes (4nm and 10nm) of TiO2-NPs in the range of ng/L were observed in nematodes with locomotion behavior and ROS production as endpoints. In nematodes chronically exposed to small sizes of TiO2-NPs at predicted environmental relevant concentrations, locomotion behavior was significantly (P<0.01) correlated with ROS production. Furthermore, treatment with antioxidants (ascorbate and N-acetyl-l-cysteine) inhibited both the induction of ROS production and the decrease of locomotion behaviors observed in nematodes chronically exposed to small sizes of TiO2-NPs at predicted environmental relevant concentrations. Therefore, chronic exposure to small sizes of TiO2-NPs at predicted environmental relevant concentrations can cause adverse effects on nematodes, and formation of such adverse effects may be largely due to the induction of oxidative stress. © 2012 Elsevier B.V. Source


Qiao H.,China Pharmaceutical University
International journal of pharmaceutics | Year: 2013

A novel amphiphilic linear-dendritic block copolymer, semi-polyamidoamine-b-poly(D,L-lactic acid) (PALA) was synthesized and evaluated for its potential as a drug delivery system in this study. PALA was self-assembled in aqueous solution to form nanomicelles with low critical micelle concentration; antitumor drug docetaxel (DTX) was successfully encapsulated into micelles. The prepared micelles demonstrated pH-induced charge conversion and dimension changes. In vitro drug release suggested susceptibility of DTX-loaded micelles to acidic microenvironment. Hemolysis and cytotoxicity testing also indicated in vitro biocompatibility of PALA. Pharmacokinetic study in rats proved that DTX-loaded PALA micelles enhanced the AUC of DTX and prolonged drug clearance in comparison to conventional DTX injection (Taxotere(®)). It was concluded that self-assembled micelles from linear-dendritic block copolymer PALA demonstrated potential for intracellular delivery of anticancer molecules, and that its safety and efficacy in chemotherapy should be further studied. Copyright © 2013 Elsevier B.V. All rights reserved. Source


Yang L.,Nanjing Medical University | Ge W.,Nanjing Medical University | Yu F.,China Pharmaceutical University | Zhu H.,Nanjing Medical University
Thrombosis Research | Year: 2010

Introduction: Warfarin is the most widely used oral anticoagulant. It has been suggested that anticoagulation effect of warfarin is significantly associated with the polymorphism of certain genes, including Cytochrome P450 complex subunit 2C9 (CYP2C9), Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), Gamma-Glutamyl Carboxylase (GGCX) and Apolipoprotein E (APOE) etc. The purpose of the present study was to conduct a systemic review and meta-analysis to investigate the relationship between mean daily warfarin dose (MDWD) and VKORC1 single nucleotide polymorphisms (SNPs). Materials and Methods: Inclusion and exclusion criteria were made, and the studies between 2004 and present were searched. References were examined, and experts were consulted for additional information. Data were extracted. Revman 4.2.10 software was applied to analyze the relationship between MDWD and VKORC1 SNPs. Results: Total 19 studies were included in the meta-analysis. The frequencies of 1173TT and - 1639 AA in Asian patients were higher than those in Caucasian and African populations. Patients with VKORC1 1173 CT and 1173 CC required 44% [95% Confidence Interval (CI); 32%, 56%] and 97% [73%, 122%] higher MDWD than 1173 TT carriers, - 1639GA and - 1639GG carriers required 52% [41%, 64%] and 102% [85%, 118%] higher MDWD than - 1639AA carriers, 3730GA and 3730AA carriers required 27% [3%, 58%] and 52% [3%, 109%] higher MDWD than 3730GG carriers. In addition, 1173C, - 1639 G and 3730 A carriers required 63% [44%, 82%], 61% [49%, 73%] and 32% [4%, 59%] higher MDWD than 1173TT, - 1639 AA and 3730GG, respectively. Sensitive analyses demonstrated that the impacts of gene polymorphism on warfarin dosage requirement were significantly different between Caucasian and Asian population, and the results of meta-analyses were stable and reliable. Conclusion: This is the first meta-analysis about the impact of VKORC1 gene polymorphism on warfarin dose requirement. Our studies showed that gene polymorphisms of VKORC1 significantly associated with the variation of interindividual warfarin dose requirement variation, and the effects are different in ethnicities. © 2009 Elsevier Ltd. All rights reserved. Source


Zhang F.,Zhejiang University | Zhang J.,Zhejiang University | Tong C.,Zhejiang University | Chen Y.,China Pharmaceutical University | And 2 more authors.
Journal of Hazardous Materials | Year: 2013

Benzophenone (BP)-type UV filters have been widely used in many personal care products to protect human from UV exposure. Their dermal applications can cause direct human health risk following accumulation in bloodstream. Few studies have addressed whether BP-type UV filters could bind and alter the structure and function of human serum albumin (HSA), the major carrier protein in plasma. Four benzophenones, BP-1, BP-2, BP-3 and BP-8 were selected to investigate their potentially toxic interactions with HSA and the intrinsic binding mechanism using combined spectroscopies and molecular docking techniques. Four benzophenones significantly quench the intrinsic fluorescence of HSA via static mode. The competitive binding fluorescence assay and molecular docking both revealed that the benzophenones bind at site II of HSA. Their binding constants range from 1.91×104M-1 to 12.96×104M-1 at 296K. BP-8 interacts with HSA mainly through hydrogen bonding interactions and van der Waals interactions, while hydrophobic interactions and electrostatic interactions are dominant for interactions between BP-1, BP-2, BP-3 and HSA. Molecular docking revealed that the changes in structural moiety and hydrophobicity of four benzophenones account for their different binding affinities. As further revealed by circular dichroism and time-resolved fluorescence decay, these benzophenones cause global and local structural changes of HSA, which illustrates their potential toxicity to cause structural damage of HSA. Two degradation products of BP-3 have higher binding affinities to HSA, suggesting higher potencies in causing adverse effects on human health. © 2013 Elsevier B.V. Source


Ye B.-F.,China Pharmaceutical University
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

In the crystal structure of the title hydrate, C8H 4Br2O4·H2O, O - H⋯O hydrogen bonds link the molecules into a two-dimensional network parallel to (102̄). The acid groups of the main molecule and the water molecule are all involved in the supra-molecular structure. The dihedral angles between the benzene ring and the acid groups are 37.8 (4) and 36.4 (5)°, while the dihedral angle between the acid groups is 10.9 (4)°. Source


Mao L.,Nanjing University | Wang H.,Nanjing University | Wang X.,Nanjing University | Liao H.,China Pharmaceutical University | Zhao X.,Nantong University
Journal of Surgical Research | Year: 2011

Background: Inflammation plays an important role in the pathogenesis of secondary damage after spinal cord injury (SCI). Previous studies have suggested that nuclear factor-erythroid 2-related factor 2 (Nrf2), a pleiotropic transcription factor, may play a key role in modulating inflammation in a variety of experimental models. This study evaluated the neuroprotective role of Nrf2 in the inflammatory response after SCI in mice. Materials and Methods: Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) mice spinal cord compression injury was induced by the application of vascular clips (force of 10 g) to the dura. Sulforaphane (SFN) was used to activate Nrf2 after SCI. Inflammatory cytokines, NF-κB activity, histologic injury score, dying neurons count in grey matter, water content of impaired spinal cord, and Basso open-field motor score (BMS) were assessed to determine the extent of SCI-mediated damage. Results: The results showed that SFN activated Nrf2 in impaired spinal cord tissue, improved hindlimb locomotor function assessed by BMS, reduced inflammatory damage, histologic injury, dying neurons count, and spinal cord edema caused by SCI. Nrf2-/- mice demonstrated more severe neurologic deficit and spinal cord edema after SCI and did not benefit from the protective effect of SFN. Conclusions: Taken together, our results suggest that Nrf2 may represent a strategic target for SCI therapies. © 2011 Elsevier Inc. All rights reserved. Source


Wang J.,National Health Research Institute | Pang T.,National Health Research Institute | Pang T.,China Pharmaceutical University | Hafko R.,National Health Research Institute | And 4 more authors.
Neuropharmacology | Year: 2014

Sartans (Angiotensin II AT1 Receptor Blockers, ARBs) are powerful neuroprotective agents in vivo and protect against IL-1β neurotoxicity in vitro. The purpose of this research was to determine the extent of sartan neuroprotection against glutamate excitotoxicity, a common cause of neuronal injury and apoptosis. The results show that sartans are neuroprotective, significantly reducing glutamate-induced neuronal injury and apoptosis in cultured rat primary cerebellar granule cells (CGCs). Telmisartan was the most potent sartan studied, with an order of potency telmisartan > candesartan > losartan > valsartan. Mechanisms involved reduction of pro-apoptotic caspase-3 activation, protection of the survival PI3K/Akt/GSK-3β pathway and prevention of glutamate-induced ERK1/2 activation. NMDA receptor stimulation was essential for glutamate-induced cell injury and apoptosis. Participation of AT1A receptor was supported by glutamate-induced upregulation of AT1A gene expression and AT 1 receptor binding. Conversely, AT1B or AT2 receptors played no role. Glutamate-induced neuronal injury and the neuroprotective effect of telmisartan were decreased, but not abolished, in CGCs obtained from AT1A knock-out mice. This indicates that although AT1 receptors are necessary for glutamate to exert its full neurotoxic potential, part of the neuroprotective effect of telmisartan is independent of AT1 receptor blockade. PPARγ activation was also involved in the neuroprotective effects of telmisartan, as telmisartan enhanced PPARγ nuclear translocation and the PPARγ antagonist GW9662 partially reversed the neuroprotective effects of telmisartan. The present results substantiate the therapeutic use of sartans, in particular telmisartan, in neurodegenerative diseases and traumatic brain disorders where glutamate neurotoxicity plays a significant role. Source


Liu J.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

OBJECTIVE : To study the chemical constituents of roots of Rumex patientia. The compounds were separated and purified by silica column chromatopraphy, Sephadex LH-20 and identified by several spectroscopic methods. Seven constituents were identified as nepodin (1), nepodin-8-O-beta-D-glucopyranoside (2), chrysophanol-8-O-beta-D-glucopyranoside (3), emodin-6-O-beta-D-glucopyranoside (4), emodin-8-O-beta-D-glucopyranoside (5), 1, 3, 5-trihydroxy-7-methylanthraquinone (6), physcion-8-O-beta-D-glucopyranoside (7), respectively. Compound 1 is isolated from this plant for the first time and compound 6 is isolated from Rumex L. for the first time. Source


Zhang J.Y.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To study the chemical constituents in the fruits of Acanthopanax gracilistylus. The chemical components were isolated and purified by silica gel, ODS C-18, and Sephadex LH-20 column chromatogram. The chemical structures were elucidated on the basis of physicochemical properties and spectral data. Ten compounds were isolated and identified as acankoreoside D(1), 3alpha, 11alpha-dihydroxylup-20(29)-en-28-oic acid(2), 3/3-([O-beta-D-glucopyranuronosyl] oxy) -olean-12-ene-28-olc acid (3),3beta-([O-beta-D-glucopyranuronosyl]oxy)-28-O-P3-D-glucopyranosyl-olean-12-ene-28-olc acid(4),oleanolic acid-3-O-6'-O-methyl-beta-D-glucuronopyranoside(5), acantrifoside A(6), acankoreoside A(7), (-)-kaur-16-en-19-oic acid(8), protocatechuic acid (9),beta-sitosterol(10). Compounds 2-5 are obtained from the fruits of the plant for the first time. Source


Li Y.Z.,China Pharmaceutical University
Zhonghua nan ke xue = National journal of andrology | Year: 2012

To establish a high-sensitivity, high-specificity and low-cost hydrogel chip platform for the clinical screening of Y chromosome microdeletions. Site-specific extended primers with a common sequence at the 5' end were used for hybridizing with the target. The Cy5-dUTP was incorporated into the products by primer extension, and the products were labeled with fluorescence. Then the extended products were added to the chip for hybridizing with acrylamide-modified common probes immobilized on the chip. After removal of the free Cy5-dUTP by electrophoresis, the signals were obtained by fluorescence scanning. And the detecting conditions of this method were optimized. SY254 of 9 samples was successfully detected with the hydrogel chip. The results showed that 3 were normal and the other 6 with microdeletions (1 female sample as a negative control), which coincided with the results of conventional multiplex PCR-electrophoresis. The hydrogel chip platform we established has provided a new technique for the detection of Y chromosome microdeletions, and is beneficial to the diagnosis and treatment of male infertility. Source


Miao X.N.,University of California at Los Angeles | Miao X.N.,China Pharmaceutical University | Siu K.L.,University of California at Los Angeles | Cai H.,University of California at Los Angeles
Journal of Molecular and Cellular Cardiology | Year: 2015

Rupture of abdominal aortic aneurysm (AAA) is a lethal event. No oral medicine has been available to prevent or treat AAA. We have recently identified a novel mechanism of eNOS uncoupling by which AAA develops, in angiotensin II (Ang II) infused hyper. phenylalaninemia 1 (hph-1) mice. Using this unique model we investigated effects on AAA formation of the L-type calcium channel blocker nifedipine, in view of the unclear relationship between hypertension and AAA, and unclear mechanisms of aneurysm protective effects of some blood pressure lowering drugs. Six-month old hph-1 mice were infused with Ang II (0.7 mg/kg/day) for 2 weeks, and fed nifedipine chow at two different doses (5 and 20 mg/kg/day). While the high dose of nifedipine reduced blood pressure, the lower dose had no effect. Interestingly, the incidence rate of AAA dropped from 71% to 7 and 12.5% for low and high dose nifedipine, respectively. Expansion of abdominal aorta, determined by ultrasound imaging, was abolished by both doses of nifedipine, which recoupled eNOS completely to improve NO bioavailability. Both also abrogated aortic superoxide production. Of note, Ang II activation of NADPH oxidase in vascular smooth muscle cells and endothelial cells, known to uncouple eNOS, was also attenuated by nifedipine. Although low dose was a sub-pressor while the high dose reduced blood pressure via inhibition of calcium channels, both doses were highly effective in preventing AAA by preserving eNOS coupling activity to eliminate sustained oxidative stress from uncoupled eNOS. These data demonstrate that oral treatment of nifedipine is highly effective in preserving eNOS function to attenuate AAA formation. Nifedipine may be used for AAA prevention either at low dose in AAA risk group, or at high dose in patients with co-existing hypertension. © 2015 Elsevier Ltd. Source


Wu Y.-M.,Academia Sinica, Taiwan | Chang J.-W.,Academia Sinica, Taiwan | Wang C.-H.,Academia Sinica, Taiwan | Lin Y.-C.,Academia Sinica, Taiwan | And 7 more authors.
EMBO Journal | Year: 2012

In mammals, a distinct RNA polymerase II form, RNAPII(G) contains a novel subunit Gdown1 (encoded by POLR2M), which represses gene activation, only to be reversed by the multisubunit Mediator co-activator. Here, we employed single-particle cryo-electron microscopy (cryo-EM) to disclose the architectures of RNAPII(G), RNAPII and RNAPII in complex with the transcription initiation factor TFIIF, all to.. Difference analysis mapped Gdown1 mostly to the RNAPII Rpb5 shelf-Rpb1 jaw, supported by antibody labelling experiments. These structural features correlate with the moderate increase in the efficiency of RNA chain elongation by RNAP II(G). In addition, our updated RNAPII-TFIIF map showed that TFIIF tethers multiple regions surrounding the DNA-binding cleft, in agreement with cross-linking and biochemical mapping. Gdown1's binding sites overlap extensively with those of TFIIF, with Gdown1 sterically excluding TFIIF from RNAPII, herein demonstrated by competition assays using size exclusion chromatography. In summary, our work establishes a structural basis for Gdown1 impeding initiation at promoters, by obstruction of TFIIF, accounting for an additional dependent role of Mediator in activated transcription. © 2012 European Molecular Biology Organization | All Rights Reserved. Source


Chen M.,China Pharmaceutical University
International journal of nanomedicine | Year: 2011

The purpose of the present study was to elucidate the antimicrobial activity and mechanism of silver nanoparticles incorporated into thermosensitive gel (S-T-Gel) on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study investigated the growth, permeability, and morphology of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa cells in order to observe the action of S-T-Gel on the membrane structure of these three bacteria. The cell morphology of normal and treated bacteria cells was assessed by transmission electron microscopy (TEM), and the effects of S-T-Gel on genome DNA of bacterial cells were evaluated by agarose gel electrophoresis. S-T-Gel showed promising activity against Staphylococcus aureus and moderate activity against Escherichia coli and Pseudomonas aeruginosa. The observation with TEM suggested that S-T-Gel may destroy the structure of bacterial cell membranes in order to enter the bacterial cell. S-T-Gel then condensed DNA and combined and coagulated with the cytoplasm of the damaged bacteria, resulting in the leakage of the cytoplasmic component and the eventual death of these three bacteria. In addition, the analysis of agarose gel electrophoresis demonstrated that S-T-Gel could increase the decomposability of genome DNA. These results about promising antimicrobial activity and mechanism of S-T-Gel may be useful for further research and development in in-vivo studies. Source


Chen X.,Nanjing University of Technology | Ma Y.,Nanjing University of Technology | Chen H.,China Pharmaceutical University | Wang F.,Nanjing University of Technology | And 3 more authors.
Dyes and Pigments | Year: 2014

A ratiometric sensor (QA) for detecting Zn2+ with high sensitivity and selectivity was reported. The fluorescence changes of sensor upon the addition of Zn2+ were attributed to the conjugation of internal charge transfer and fluorescence resonance energy transfer mechanisms. There is a good linear relationship between the fluorescence ratio I 497nm/I420nm and the concentrations of Zn2+ ranging from 0 μM to 40 μM, which makes an effective ratiometric detection of Zn2+ ion. The limit of detection (LOD) was evaluated to be 33.6 nM. The imaging experiments indicated that QA is cell-permeable and can be used to detect Zn2+ within living cells with good selectivity over Cd2+. © 2013 Elsevier B.V. All rights reserved. Source


Li Q.,Shanghai University | Chen J.,Shanghai University | Xiao Y.,Shanghai University | Xiao Y.,Shanghai University of Traditional Chinese Medicine | And 3 more authors.
BMC Genomics | Year: 2014

Background: Isatis indigotica Fort. is one of the most commonly used traditional Chinese medicines. Its antiviral compound is a kind of lignan, which is formed with the action of dirigent proteins (DIR). DIR proteins are members of a large family of proteins which impart stereoselectivity on the phenoxy radical-coupling reaction, yielding optically active lignans from two molecules of E-coniferyl alcohol. They exist in almost every vascular plant. However, the DIR and DIR-like protein gene family in I. indigotica has not been analyzed in detail yet. This study focuses on discovery and analysis of this protein gene family in I. indigotica for the first time.Results: Analysis of transcription profiling database from I. indigotica revealed a family of 19 full-length unique DIR and DIR-like proteins. Sequence analysis found that I. indigotica DIR and DIR-like proteins (IiDIR) were all-beta strand proteins, with a signal peptide at the N-terminus. Phylogenetic analysis of the 19 proteins indicated that the IiDIR genes cluster into three distinct subfamilies, DIR-a, DIR-b/d, and DIR-e, of a larger plant DIR and DIR-like gene family. Gene-specific primers were designed for 19 unique IiDIRs and were used to evaluate patterns of constitutive expression in different organs. It showed that most IiDIR genes were expressed comparatively higher in roots and flowers than stems and leaves.Conclusions: New DIR and DIR-like proteins were discovered from the transcription profiling database of I. indigotica through bioinformatics methods for the first time. Sequence characteristics and transcript abundance of these new genes were analyzed. This study will provide basic data necessary for further studies. © 2014 Li et al.; licensee BioMed Central Ltd. Source


Hou Y.T.,China Pharmaceutical University
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2010

Fibroblast growth factor (FGF)-21 is a recently discovered glucose regulator and has potential to become therapeutics for treatment of type 2 diabetes. The aim of this study was to clone and express human FGF-21 gene and characterize its bioactivity for glucose regulation. The hFGF-21 cDNA was cloned from human liver by RT-PCR and subcloned into the pSUMO vector after sequencing confirmation. The recombinant plasmid was transformed into Escherichia coli Rosetta strain. The FGF-21 protein expression was induced by IPTG and purified by Ni-NTA agarose. The FGF-21 product was verified by Western blotting analysis with specific antibody. The bioactivity of the purified protein was examined by glucose uptake assay in 3T3-L1 adipocytes. The cloned hFGF-21 gene consisted of 546 bp, which was in agreement with the published data in GenBank. SDS-PAGE analysis showed that hFGF-21 expressed in the E. coli system was 19.4 kDa in size. The glucose uptake assay in 3T3-L1 adipocytes indicated that the purified hFGF-21 could stimulate glucose uptake in a dose-dependent manner, and glucose transporters (GLUT1) is the functional unit. Source


Li H.,China Pharmaceutical University
Chinese Journal of Ophthalmology | Year: 2014

Objective: To evaluate the cost-effectiveness of bevacizumab versus ranibizumab for patients with neovascular age-related macular degeneration (AMD) in China. Methods: A Markov model was constructed to compare cost per quality-adjusted life year of bevacizumab with ranibizumab in patients with neovascular AMD. In the Markov model, with cycle length of 3 months and time horizon of 10 years, three health states were defined by visual acuity. One way deterministic and probabilistic sensitivity analyses were conducted to explore the uncertainties from a number of variables. Results: In the base case analysis, patients in ranibizumab group obtained 0.007 QALY more than patients in bevacizumab group, while the average total cost was ¥794400 higher. The ICUR reached ¥ 109.23 million per QALY. In all sensitivity analyses, the ICURs were over ¥ 2.48 million per QALY between ranibizumab and bevacizumab groups. Conclusions: Ranibizumab for neovascular AMD patients gained similar QALY at significantly higher costs in comparison with bevacizumab. The ICURs generated in this study were much higher than the possible QALY threshold in the society of China. Compared with ranibizumab, bevacizumab was cost-effective for neovascular AMD patients. Copyright © 2014 by the Chinese Medical Association. Source


Mo R.,China Pharmaceutical University | Gu Z.,University of North Carolina at Chapel Hill
Materials Today | Year: 2015

Cancer-associated stimuli-responsive nanosystems have been increasingly considered for the delivery of anticancer drugs, which primarily target the tumor microenvironment and/or intracellular elements to enhance intratumoral accumulation and promote drug release at the target site. The signals facilitating drug delivery include tumor and endocytic acidities, hypoxia, enzyme overexpression, as well as high levels of intracellular glutathione, reactive oxygen species, and adenosine-5'-triphosphate. This article reviews the current techniques and ongoing developments in anticancer drug delivery using these signals. In particular, the focus is placed on design strategies and methods of formulating novel nanoscaled materials. The merits and drawbacks of recent strategies, as well as potential future developments, are discussed. © 2015. Source


Li J.,China Pharmaceutical University | Liu L.,Changzhou University
Synthetic Communications | Year: 2013

A novel recyclable functionalized chiral ionic liquid has been developed to promote asymmetric Michael additions of cyclohexanone to both aryl and alkyl nitroolefins in the presence of 20mol% of organocatalyst 4 in MeOH. The process affords synthetically valuable chiral products in good yields (up to 93%) and high enantioselectivities (up to 92%). The chiral ionic liquid could be easily reused six times without remarkable decrease in yields and enantioselectivities. © 2013 Copyright Taylor and Francis Group, LLC. Source


Yang J.,China Pharmaceutical University | Lu Y.,China Pharmaceutical University | Yang J.,Center for Drug Evaluation | Zhang H.,Jiangsu University
Clinical Pharmacokinetics | Year: 2013

Background and Objectives: Many attempts have been made to predict the warfarin maintenance dose in patients beginning warfarin therapy using a descriptive model based on multiple linear regression. Here we report the first attempt to develop a comprehensive mechanistic model integrating in vitro-in vivo extrapolation (IVIVE) with a pharmacokinetic-pharmacodynamic model to predict the warfarin maintenance dose in Han Chinese patients. The model incorporates demographic factors [sex, age, body weight (BW)] and the genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1). Methods: Information on the various factors, mean warfarin daily dose and International Normalized Ratio (INR) was available for a cohort of 197 Han Chinese patients. Based on in vitro enzyme kinetic parameters for S-warfarin metabolism, demographic data for Han Chinese and some scaling factors, the S-warfarin clearance (CL) was predicted for patients in the cohort with different CYP2C9 genotypes using IVIVE. The plasma concentration of S-warfarin after a single oral dose was simulated using a one-compartment pharmacokinetic model with first-order absorption and a lag time and was combined with a mechanistic coagulation model to simulate the INR response. The warfarin maintenance dose was then predicted based on the demographic data and genotypes of CYP2C9 and VKORC1 for each patient and using the observed steady-state INR (INRss) as a target value. Finally, sensitivity analysis was carried out to determine which factor(s) affect the warfarin maintenance dose most strongly. Results: The predictive performance of this mechanistic model is not inferior to that of our previous descriptive model. There were significant differences in the mean warfarin daily dose in patients with different CYP2C9 and VKORC1 genotypes. Using IVIVE, the predicted mean CL of S-warfarin for patients with CYP2C9*1/*3 (0.092 l/h, n = 11) was 57 % less than for those with wild-type*1/*1 (0.215 l/h, n = 186). In addition,*1/*1 patients needed about 1 week to reach steady state, whereas*1/*3 patients needed about 2 weeks. In terms of the predicted INRss values, only ten patients had INRss values outside the expected therapeutic range (1.5-2.8). To evaluate our mechanistic model, we predicted the warfarin maintenance dose for 183 patients and explained 42 % of its variation, which is comparable to our previous prediction using a descriptive model based on multiple linear regression. The mean predicted/observed warfarin doses (mg/day) for different combinations of CYP2C9 and VKORC1 genotypes were 1.54/3.75 (n = 1) for*1/*1 and GG, 3.33/3.66 (n = 36) for*1/*1 and AG, 2.31/2.41 (n = 136) for*1/*1 and AA, and 1.56/1.69 (n = 10) for*1/*3 and AA, respectively. Sensitivity analysis indicated BW and genetic polymorphisms of CYP2C9 and VKORC1 were important factors affecting the warfarin maintenance dose in the study population. Conclusion: The mechanistic model reported is the first to integrate IVIVE with a pharmacokinetic-pharmacodynamic model to describe the association of the warfarin maintenance dose with sex, age, BW and the genotypes of CYP2C9 and VKORC1. The model was effective in predicting S-warfarin clearance and in simulating its plasma concentration-time curve in a cohort of Han Chinese patients. In addition, the model accurately predicted the INR response and warfarin maintenance dose in a cohort of Han Chinese patients. © 2013 Springer International Publishing Switzerland. Source


Zhang T.-T.,Jinan University | Zhou J.-S.,Xiangxue Pharmaceutical Factory Co. | Wang Q.,China Pharmaceutical University
Chinese Journal of Natural Medicines | Year: 2010

Aim: To establish a quantitative analysis method with HPLC-UV for simultaneous determination of flavonoids in the aerial parts of Bupleurum, to investigate the content and distribution of flavonoids in different species of Bupleurum with the established method for quality control. Method: A rapid and accurate HPLC-UV method was developed and validated for the quantitative determination of twelve flavonoids, (+)-catechin (1), apigenin-6, 8-di-C-glucopyranoside (2), quercetin-3-O-rutinoside (3), kaempferol-3, 7-di-O-rhamnoside (4), quercetin-3-O-arabinoside (5), quercetin-3-O-rhamnoside (6), 7-hydroxyl-2, 5-dimethyl-4H-chromone (7), acacetin-7-O-rutinoside (8), kaempferol-7-O-rhamnoside (9), quercetin (10), kaempferol (11) and isoramnetin (12). The subsequent HPLC separation and quantification was achieved in 60 minutes using a Shimpack ODS C18 column and at 254 nm. The mobile phase comprised solvent A (0.1% formic acid aqueous, V/V, pH 2.6) and solvent B (acetonitrile) and gradient elution mode was applied. This established method was therefore applied to determine the amounts of flavonoids in twenty-eight samples collected from different regions in China. Result: The linear regression analytical data for the calibration plots showed a good linear relationship with r2 > 0.9995 within the test ranges. The average recovery was from 97.10 to 102.86% indicating good accuracy. It was successfully applied to quantify twelve flavonoids in different samples. Conclusion: It is the first time to establish a quantitative method to investigate the content and distribution of flavonoids in different species of Bupleurum. © 2010 China Pharmaceutical University. Source


Fang X.,Nanjing Southeast University | Fang L.,Nanjing Southeast University | Fang L.,China Pharmaceutical University | Gou S.,Nanjing Southeast University | Cheng L.,Nanjing Southeast University
Bioorganic and Medicinal Chemistry Letters | Year: 2013

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. © 2012 Elsevier Ltd. All rights reserved. Source


Shi D.,CAS Qingdao Institute of Oceanology | Li J.,CAS Qingdao Institute of Oceanology | Jiang B.,CAS Qingdao Institute of Oceanology | Guo S.,CAS Qingdao Institute of Oceanology | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

A series of bromophenol derivatives were synthesized and evaluated as protein tyrosine phosphatase 1B (PTP1B) inhibitors in vitro and in vivo based on bromophenol 4e (IC 50 = 2.42 μmol/L), which was isolated from red algae Rhodomela confervoides. The results showed that all of the synthesized compounds displayed weak to good PTP1B inhibition at tested concentration. Among them, highly brominated compound 4g exhibited promising inhibitory activity against PTP1B with IC 50 0.68 μmol/L, which was approximately fourfold more potent than lead compound 4e. Further, compound 4g demonstrated high selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). More importantly, in vivo antidiabetic activities investigations of compound 4g also demonstrated inspiring results. © 2012 Elsevier Ltd. All rights reserved. Source


Xiong Y.,Zhejiang Chinese Medical University | Chen J.,China Pharmaceutical University | Guo D.,Shanghai Institute for Food and Drug Control
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

Nobiliside A (Nob) is a new triterpenoid saponin separated from Holothuria noblilis. In this article, a liquid chromatography-electrospray ionization-tandem mass spectrometry method was established to quantify Nob, a hemolytic saponin, in rat blood and tissue homogenates. Standard curves were linear (r= 0.9988-0.9995) over the range 50-5000. ng/mL in blood and 100-10000. ng/g in tissues. The lower limit of quantification (LLOQ) was 50. ng/mL for Nob. The novel method was rapid, accurate, highly sensitive and highly selective. Using this method, the pharmacokinetics and biodistribution of Nob liposome and Nob solution in Sprague-Dawley rats after a single intravenous dose of 1. mg/kg were then investigated. Nob was cleared slowly from circulation. There was no significant difference of the pharmacokinetic parameters in blood between Nob solution and Nob liposome. The highest AUC of Nob was observed in liver for the two groups, followed by spleen, lungs, kidney and heart. Compared with Nob solution, Nob liposome showed much higher AUC in liver and spleen and much lower AUC in kidney, heart and lung, which might be one important reason for the decreased toxicity of Nob. © 2014 Elsevier B.V. Source


Xu Y.-Y.,Soochow University of China | Li S.-N.,Soochow University of China | Yu G.-J.,Soochow University of China | Hu Q.-H.,China Pharmaceutical University | Li H.-Q.,Soochow University of China
Bioorganic and Medicinal Chemistry | Year: 2013

Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N6-((5-bromothiophen-2-yl)methyl)-N4-(3- chlorophenyl)quinazoline-4,6-diamine (5e), showed the most potent inhibitory activity (IC50 = 3.11 μM for Hep G2, IC50 = 0.82 μM for A549). The EGFR molecular docking model suggested that the new compound is nicely bound to the region of EGFR, and cell morphology by Hoechst stain experiment suggested that these compounds efficiently induced apoptosis of A549 cells. © 2013 Elsevier Ltd. All rights reserved. Source


Song L.,Sichuan University | Zhu G.,Sichuan University | Liu Y.,Sichuan University | Liu B.,Sichuan University | And 2 more authors.
Journal of the American Chemical Society | Year: 2015

Few examples of [4 + 2] cycloaddition with unmasked ortho-benzoquinones (UMOBs) as carbodiene have been reported in complex molecule synthesis. Herein we report that this cycloaddition with podocarpane-type UMOB was developed and applied to construct fully functionalized bicyclo[2.2.2]octanes. Based on this methodology, divergent total syntheses of atisane-type diterpenoids, including (±)-crotobarin, crotogoudin, atisane-3β,16α-diol, and 16S,17-dihydroxy-atisan-3-one, were accomplished in 14, 14, 12, and 16 steps, respectively. Key elements in these total syntheses include: (1) FeCl3-catalyzed cationic cascade cyclization to construct podocarpane-type skeleton; (2) Mn(III)/Co(II)-catalyzed radical hydroxylation of alkene with high regio-, diastereo-, and chemoselectivities; (3) and a ketal-deprotection/lactone-opening/deprotonation/lactonization cascade. Additionally, the synthetic utility of the fully functionalized bicyclo[2.2.2]octane framework was further elucidated by applying ring distortion strategy to afford different skeleton-rearranged natural product-like compounds. © 2015 American Chemical Society. Source


Ding Y.,University of Massachusetts Amherst | Ding Y.,China Pharmaceutical University | Jiang Z.,University of Massachusetts Amherst | Saha K.,University of Massachusetts Amherst | And 4 more authors.
Molecular Therapy | Year: 2014

Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.© The American Society of Gene & Cell Therapy. Source


Qi J.,China Pharmaceutical University
International journal of nanomedicine | Year: 2011

A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor(®) RH40, and water (30/46/24 w/w). The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs. Source


Zhang Z.-F.,Peking University | Guo Y.,China Pharmaceutical University | Zhang J.-B.,Inner Mongolia University of Technology | Wei X.-H.,Peking University
Archives of Pharmacal Research | Year: 2011

The objective of this study was to evaluate the antitumor activity of chelerythrine chloride (CHE) and investigate its potential apoptotic induction mechanism in SMMC-7721 cells. Our results suggested that the proliferation of SMMC-7721 cells was inhibited by CHE in a time and dose dependent manner, with a significant accumulation in S phase, and the cells exhibited typical apoptotic features. Moreover, CHE remarkably induced apoptosis by disruption of the mitochondrial membrane potential, release of Cyt-c, activation of caspase-3, and cleavage of poly-ADP-ribose polymerase in a dose dependent manner. Furthermore, the expression of Bcl-xl was downregulated while Bax and Bid expression was upregulated, and no variation was found for Bcl-2. These results indicated that CHE may play an important role in suppression of tumor growth by inducing apoptosis in human hepatoma cells via the activation of a mitochondrial pathway and regulating the expression of Bcl-2 family proteins. © 2011 The Pharmaceutical Society of Korea and Springer Netherlands. Source


Hao L.,University of Wisconsin - Madison | Zhong X.,University of Wisconsin - Madison | Greer T.,University of Wisconsin - Madison | Ye H.,China Pharmaceutical University | Li L.,University of Wisconsin - Madison
Analyst | Year: 2015

Tandem mass spectrometry (MS/MS)-based relative quantification by isobaric labeling is a useful technique to compare different metabolic expression levels in biological systems. For the first time, we have labeled primary and secondary amine-containing small molecules using 4-plex isobaric N,N-dimethyl leucine (DiLeu) to perform relative quantification. Good labeling efficiency and quantification accuracy were demonstrated with a mixture of 12 metabolite standards including amino acids and small molecule neurotransmitters. Labeling amine-containing metabolites with DiLeu reagents also enabled the separation of polar metabolites by nanoRPLC and improved the detection sensitivity by CE-ESI-MS. The 4-plex DiLeu labeling technique combined with LC-MS/MS and CE-MS/MS platforms were applied to profile and quantify amine-containing metabolites in mouse urine. The variability of concentrations of identified metabolites in urine samples from different mouse individuals was illustrated by the ratios of reporter ion intensities acquired from online data-dependent analysis. © 2014 The Royal Society of Chemistry. Source


Wang X.-Y.,PLA Fourth Military Medical University | Chen X.-L.,PLA Fourth Military Medical University | Tang H.-F.,PLA Fourth Military Medical University | Gao H.,No.309 Hospital of Chinese PLA | And 2 more authors.
Planta Medica | Year: 2011

Two new oleanane-type triterpenoid saponins, 1 and 2, and a new natural product, 3, together with five known saponins, 48, were isolated from the rhizomes of Anemone taipaiensis. Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Six saponins, 1, 2, 47, which possessed a free carboxylic group at C-28, exhibited significant cytotoxicity against human leukemia HL-60 cells and human hepatocellular carcinoma Hep-G2 cells with ICvalues in the range of 1.3110.12M. © Georg Thieme Verlag KG Stuttgart - New York. Source


Huang P.,China Pharmaceutical University | Lian F.,CAS Shanghai Institute of Materia Medica | Wen Y.,CAS Shanghai Institute of Materia Medica | Guo C.,Xiamen University | Lin D.,Xiamen University
Acta Biochimica et Biophysica Sinica | Year: 2013

The prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. According to the 'protein only' hypothesis, the key molecular event in the pathogenesis of prion disease is the conformational conversion of the host-derived cellular prion protein (PrPC) into a misfolded form (scrapie PrP, PrPsc). Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrPsc are rich in β-sheet structure and resistant to the proteolysis of proteinase K. The prion oligomer is soluble in physiologic environments whereas PrPsc is insoluble. Various prion oligomers are formed in different conditions. Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPsc, implying that prion oligomers could be potential drug targets for attacking prion diseases. In this article, we describe recent experimental evidence regarding prion oligomers, with a special focus on prion oligomer formation and its neurotoxicity. © The Author 2013. Source


Jin L.,China Pharmaceutical University | Sun Q.,University of Science and Technology of China | Xu Q.,University of Science and Technology of China | Xu Y.,Shaanxi University of Science and Technology
Bioresource Technology | Year: 2015

A novel nanocomposite microgel based on nanocellulose and amphoteric polyvinylamine (PVAm) was fabricated via a two-step method. Firstly, cellulose nanocrystal was oxidized by sodium periodate to yield dialdehyde nanocellulose (DANC). DANC was then used as a crosslinker to react with PVAm to obtain a pH responsive microgel with high density of free amine groups. The microgel was characterized using FTIR, XRD, AFM and elemental analysis. AFM images revealed that the nanocomposite was microspherical particles with a diameter ranging from 200 to 300nm. The microgel was found to be effective in anionic dye removal at acidic conditions. The adsorption isotherms for congo red 4BS, acid red GR and reactive light yellow K-4G fit well with the Sips model, and the maximum adsorption capacities were 869.1mgg-1, 1469.7mgg-1 and 1250.9mgg-1, respectively. The adsorption for these three anionic dyes all followed pseudo second order kinetics, indicating a chemisorption nature. © 2015 Elsevier Ltd. Source


Zhang B.,China Pharmaceutical University | Studer A.,University of Munster
Chemical Society Reviews | Year: 2015

Nitrogen heterocycles belong to a highly important class of compounds which are found in various natural products, biologically active structures, and medicinally relevant compounds. Therefore, there is continuing interest in the development of novel synthetic methods for the construction of nitrogen containing heterocycles. Recently, radical insertion reactions into isonitriles have emerged as an efficient and powerful strategy for the construction of nitrogen heterocycles, such as phenanthridines, indoles, quinolines, quinoxalines, and isoquinolines. This review highlights recent advances in this fast growing research area and also includes important pioneering studies in this area. © The Royal Society of Chemistry 2015. Source


Han Q.,Nanjing University of Science and Technology | Xu K.,China Pharmaceutical University
Materials Letters | Year: 2012

The Cu 2S dendrites were formed on TEM grids from elemental sulfur (S) in CS 2 solution by one day's ageing under ambient conditions and became denser with ageing. The shape and structures were stable in air for at least a month. If S/ethanol solution was dropped on Cu grid, uniform Cu 2S nanowires were produced one day later, which could only be obtained by one week's ageing when using S/ethanol suspension as source in our previous work. The influence of the sulfur dispersion and concentration in several kinds of solvent on the growth and structures of Cu 2S was discussed based on electron microscopic observation. This simple synthesis method from elemental reactants without any additives was useful for studying formation mechanism of hierarchical nanostructures, and more importantly, it was environmentally friendly. © 2012 Elsevier B.V. All rights reserved. Source


Chang J.S.,Pennington Biomedical Research Center | Huypens P.,Pennington Biomedical Research Center | Zhang Y.,Pennington Biomedical Research Center | Zhang Y.,China Pharmaceutical University | And 3 more authors.
Journal of Biological Chemistry | Year: 2010

Peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) plays a central role in the regulation of cellular energy metabolism and metabolic adaptation to environmental and nutritional stimuli. We recently described a novel, biologically active splice variant of PGC-1α (NT-PGC-1α, amino acids 1-270) that retains the ability to interact with and transactivate nuclear hormone receptors through its N-terminal transactivation domain. Whereas PGC-1α is an unstable nuclear protein sensitive to ubiquitin-mediated targeting to the proteasome, NT-PGC-1α is relatively stable and predominantly cytoplasmic, suggesting that its ability to interact with and activate nuclear receptors and transcription factors is dependent upon regulated access to the nucleus. We provide evidence that NT-PGC-1α interacts with the nuclear exportin, CRM1, through a specific leucine-rich domain (nuclear export sequence) that regulates its export to the cytoplasm. The nuclear export of NT-PGC-1α is inhibited by protein kinase A-dependent phosphorylation of Ser-194, Ser-241, and Thr-256 on NT-PGC-1α, which effectively increases its nuclear concentration. Using site-directed mutagenesis to prevent or mimic phosphorylation at these sites, we show that the transcriptional activity of NT-PGC-1α is regulated in part through regulation of its subcellular localization. These findings suggest that the function of NT-PGC-1α as a transcriptional co-activator is regulated by protein kinase A-dependent inhibition of CRM1-mediated export from the nucleus. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Yuan X.,Nanjing University | Sun S.,China Pharmaceutical University | Wang S.,Nanjing University | Sun Y.,Jiangsu Province Hospital of Traditional Chinese Medicine
Planta Medica | Year: 2011

Astragaloside IV (AST) is the main active constituent of Radix Astragali, a Chinese herb traditionally used to prevent asthma attack from chronic asthma patients. Its efficacy and action mechanisms in asthma attack prevention remain nonetheless to be further explored. In this study, chronic asthma was induced exposing ovalbumin (OVA) sensitized mice to repeated OVA challenges twice every two weeks for 12 weeks. Mice were treated with AST for 4 weeks just after the final challenge. In this murine model of chronic asthma, the airway dysfunction and remodeling remained severe and was accompanied with suppression of the IFN-gamma level in the bronchoalveolar lavage fluid (BALF) even four weeks after the final challenge, indicating that the airway structural changes continued to develop even after interruption of OVA challenges. However, after AST treatment, the airway hyperresponsiveness was sharply relieved, accompanied by the reduction of collagen deposition and mucus production, meanwhile the inflammatory cells were decreased but the IFN-gamma level increased in BALF. In conclusion, AST could prevent the development of chronic asthma, thus reducing asthma attacks. Our results indicated that it should be used as a supplementary therapy on preventing asthma attacks from chronic asthma patients. © Georg Thieme Verlag KG Stuttgart New York. Source


Ding Z.-Q.,China Pharmaceutical University
Chinese Journal of New Drugs | Year: 2015

Based on the analysis of pharmaceutical patents and international patents of 11 countries during 2007-2011, and the investigation on technical field distribution of China, the USA, and India by using of patent map, this paper found that the field of natural products and polymers was the research focus of the 11 countries in the last several years. Moreover, the biology research level of China lags behind the USA, which suggests that more attention should be paid by China to the original innovative capacity in drug development. Although the number of total pharmaceutical patents of China ranked the 2nd, its international patents just ranked the 7th. Besides, Chinese pharmaceutical industries didn't pay much attention to patent application. It is suggested that our country attach more importance to the application of biological patent and international patent, and the pharmaceutical industries reinforce their patent application. ©, 2014, Chinese Journal of New Drugs Co. Ltd. All right reserved. Source


Zhang J.,Beijing Normal University | Zhang J.,China Pharmaceutical University | He M.,Beijing Normal University
Journal of Hazardous Materials | Year: 2010

Sorption and desorption isotherms of phenanthrene (PHE) on sediment organic matter (SOM) prepared at different combustion temperature were studied to examine the impact of SOM structure on sorption and desorption. With the increase of combustion temperature from 0 to 400°C, the aromatic groups (-CC) in SOM samples increased, while the aliphatic groups (-CH, -CH 2) and polar structures (-C-O, -OH) decreased. When the combustion temperature increased to 500°C, aliphatic structures, polar structures and most aromatic structures were burnt out, and the mineral materials were dominant in the sample. The increase of combustion temperature decrease the sorption isotherm nonlinearity index n value, and enhanced the adsorption capacity and desorption hysteresis for PHE on SOM. However, higher n value, lower sorption capacity and sorption irreversibility were presented in the sample treated at 500°C (T500). Positive correlations between single-point organic carbon-normalized distribution coefficient logK oc values and aromatic carbon (p<0.01) and negative correlations between logK oc values and aliphaticity or H/C ratios (p<0.05) were observed. There was a negative relation between hysteresis index (HI) value and aromatic carbon (p<0.01) and a negative trend of the sorption isotherm nonlinearity index n values and aromatic carbon (p<0.01). The above results indicated the dominance of aromatic structures in the sorption nonlinearity, sorption capacity and desorption hysteresis of PHE on SOM. © 2010 Elsevier B.V. Source


Jia L.-H.,China Pharmaceutical University | Liu Y.,Peking University | Li Y.-Z.,Peking University
Journal of Pharmaceutical Analysis | Year: 2011

An inductively coupled plasma mass spectrometry (ICP-MS) or inductively coupled plasma atomic emission spectrometry (ICP-AES) was developed to determine 19 elements in safflower, a traditional Chinese medicinal herb from Xinjiang Autonomous Region and Henan Province of China. Totally 19 elements in safflower included heavy metals, i.e. As, Cd, Cu, Hg and Pb, and wholesome elements, i.e. Al, Ca, Co, Cr, Fe, Mg, Mn, Mo, Ni, P, Se, Sr, V and Zn. The results showed that the concentrations of heavy metals in safflower samples were both low, all of which met the national hygiene standards except for Pb in Xinjiang sample. Meanwhile, the distribution tendency of elements in the two samples was similar, which indicated that the plant might absorb given elements in a proportional way. The method can be used for the quality control of elements in safflower, and it provides a way for the determination of the contents of safflower from Xinjiang and Henan. Source


Weng W.,Tongji University | Wu Q.,Tongji University | Yu Y.,Tongji University | Mei W.,China Pharmaceutical University | Wang X.,Capital Medical University
Anticancer Research | Year: 2013

Aim: Organometallic arene Ru(II) complexes have long been considered as most promising substitutes for cisplatinum as an anti-tumor drug, with low toxicity towards human normal cells and high selectivity to tumor cells. In this study, we synthesized a novel arene Ru(II) drug named Rawq01. We evaluated its activity in an in vitro model of esophageal cancer (ESCC) and further explored the cellular signaling pathways altered by Rawq01. Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphe nyltetrazolium bromide (MTT) assay, colony forming assay and apoptosis assays were used to evaluate the antitumor activity of Rawq01. We treated ESCC cells with Rawq01 alone or combined with microRNA-21(miR-21) and LY294002 to explore whether Rawq01 altered the effect of miR-21 on PTEN/AKT signaling pathway in ESCC cell. Results: ESCC cells were sensitive to RAWQ01. We also found that Rawq01 up-regulated the expression of PTEN through mir-21 inhibition and therefore inhibited the PI3K-AKT pathway. Furthermore, when we combined Rawq01 treatment with miR-21 inhibitor or LY294002, the inhibitory effect of Rawq01 was significantly enhanced. Conclusion: The effect of miR-21 on PTEN/AKT signaling pathway is abrogated by the novel arene Ru(II) drug Rawq01. Our data may be useful for the future development of a chemosensitizing strategies through manipulating microRNA expression for tumor treatment. Source


Ye B.-F.,Nanjing Southeast University | Ye B.-F.,China Pharmaceutical University | Zhao Y.-J.,Nanjing Southeast University | Li T.-T.,Nanjing Southeast University | And 3 more authors.
Journal of Materials Chemistry | Year: 2011

A suspension array with microcarriers encoded by both structural color and shape was developed. The microcarriers with high stability, large capacity, low background noise and simplicity for practical application were the hydrogel colloidal crystals fabricated by photolithography. The aptamer based multiplex array, as an example, was constructed using the encoded microcarriers as the carrier of suspension array. The ssDNA functionalized hydrogel microcarriers are achieved by co-polymerization. Based on the high selectivity recognition of aptamer to its target, a novel hydrogel microcarrier suspension array platform, as a potential tool for the efficient quantification of biomolecules, is established. © 2011 The Royal Society of Chemistry. Source


Qi L.-W.,University of Chicago | Qi L.-W.,China Pharmaceutical University | Wang C.-Z.,University of Chicago | Yuan C.-S.,University of Chicago
Natural Product Reports | Year: 2011

Ginseng occupies a prominent position in the list of best-selling natural products in the world. Because of its complex constituents, multidisciplinary techniques are needed to validate the analytical methods that support ginseng's use worldwide. In the past decade, rapid development of technology has advanced many aspects of ginseng research. The aim of this review is to illustrate the recent advances in the isolation and analysis of ginseng, and to highlight new applications and challenges. Emphasis is placed on recent trends and emerging techniques. © The Royal Society of Chemistry 2011. Source


Zhang X.,CAS Dalian Institute of Chemical Physics | Zhang X.,China Pharmaceutical University | Qi Z.,CAS Dalian Institute of Chemical Physics | Li X.,CAS Dalian Institute of Chemical Physics
Angewandte Chemie - International Edition | Year: 2014

[Cp∗RhIII]-catalyzed C-H activation of arenes assisted by an oxidizing N-O or N-N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N-O bond is well-known to undergo O-atom transfer (OAT) to alkynes. Despite the liability of N-O bonds in both C-H activation and OAT, these two important areas evolved separately. In this report, [Cp∗RhIII] catalysts integrate both areas in an efficient redox-neutral coupling of quinoline N-oxides with alkynes to afford α-(8-quinolyl)acetophenones. In this process the N-O bond acts as both a directing group for C-H activation and as an O-atom donor. A chance meeting: A rhodium(III)-catalyzed redox-neutral coupling of quinoline N-oxides with alkynes has been realized, thus leading to the synthesis of α-substituted acetophenones. This system integrates C-H activation with O-atom transfer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Jiang T.,Seoul National University | Singh B.,Seoul National University | Li H.-S.,Seoul National University | Kim Y.-K.,China Pharmaceutical University | And 4 more authors.
Biomaterials | Year: 2014

M cells, the key players of the mucosal immunity induction, are one of the intestinal barriers for the efficient delivery of vaccines to mucosal immune tissues. To overcome the barrier, we have developed an efficient oral vaccine carrier that constitutes poly (lactic-co-glycolic acid) (PLGA) microparticle coated with M cell targeting peptide. In this study, a membrane protein B of Brachyspira hyodysenteriae (BmpB) as a model vaccine against swine dysentery was loaded into porous PLGA microparticles (MPs). The PLGA MPs were further coated with the water-soluble chitosan (WSC) conjugated with M cell homing peptide (CKS9) to prepare BmpB-CKS9-WSC-PLGA MPs. Oral immunization of BmpB vaccine with CKS9-WSC-PLGA MPs in mice showed elevated secretory IgA responses in the mucosal tissues and systemic IgG antibody responses, providing a complete immune response. Specifically, the immunization with these MPs demonstrated to induce both Th1- and Th2-type responses based on elevated IgG1 and IgG2a titers. The elevated immune responses were attributed to the enhanced M cell targeting and transcytosis ability of CKS9-WSC-PLGA MPs to Peyer's patch regions. The high binding affinity of CKS9-WSC-PLGA MPs with the M cells to enter into the Peyer's patch regions of mouse small intestine was investigated by closed ileal loop assay and it was further confirmed by confocal laser scanning microscopy. These results suggest that the M cell targeting approach used in this study is a promising tool for targeted oral vaccine delivery. © 2013 Elsevier Ltd. Source


Pan C.,Nanjing Southeast University | Wang J.,Jintan Hospital | Liu W.,China Pharmaceutical University | Liu L.,Nanjing Southeast University | And 3 more authors.
Respiratory Research | Year: 2012

Background: Sepsis could induce indirect acute lung injury(ALI), and pulmonary vasomotor dysfunction. While low tidal volume is advocated for treatment of ALI patients. However, there is no evidence for low tidal volume that it could mitigate pulmonary vasomotor dysfunction in indirect ALI. Our study is to evaluate whether low tidal volume ventilation could protect the pulmonary vascular function in indirect lipopolysaccharide (LPS) induced acute lung injury rats.Methods: An indirect ALI rat model was induced by intravenous infusion of LPS. Thirty rats (n = 6 in each group) were randomly divided into (1)Control group; (2) ALI group; (3) LV group (tidal volume of 6mL/kg); (4) MV group (tidal volume of 12mL/kg); (5)VLV group (tidal volume of 3mL/kg). Mean arterial pressure and blood gas analysis were monitored every 2 hours throughout the experiment. Lung tissues and pulmonary artery rings were immediately harvested after the rats were bled to be killed to detect the contents of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and TNF-α. Acetylcholine (Ache)-induced endothelium-dependent and sodium nitroprusside (SNP)-induced endothelium-independent relaxation of isolated pulmonary artery rings were measured by tensiometry.Results: There was no difference within groups concerning blood pressure, PaCO2 and SNP-induced endothelium-independent relaxation of pulmonary artery rings. Compared with MV group, LV group significantly reduced LPS-induced expression of ET-1 level (113.79 ± 7.33pg/mL vs. 152.52 ± 12.75pg/mL, P < 0.05) and TNF-α (3305.09 ± 334.29pg/mL vs.4144.07 ± 608.21pg/mL, P < 0.05), increased the expression of eNOS (IOD: 15032.05 ± 5925.07 vs. 11454.32 ± 6035.47, P < 0.05). While Ache (10-7mol/L-10-4mol/L)-induced vasodilatation was ameliorated 30% more in LV group than in MV group.Conclusions: Low tidal volume could protect the pulmonary vasodilative function during indirect ALI by decreasing vasoconstrictor factors, increasing expressions of vasodilator factors in pulmonary endothelial cells, and inhibiting inflammation injuries. © 2012 Pan et al.; licensee BioMed Central Ltd. Source


Zhao Z.,Jilin University | Gong S.,China Pharmaceutical University | Wang S.,Jilin University | Wang S.,Changchun University of Chinese Medicine | And 2 more authors.
International Immunopharmacology | Year: 2015

Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40 mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway. © 2015 Elsevier B.V. All rights reserved. Source


Chen L.,South-Central University for Nationalities | Zhao L.,Gansu College of Traditional Chinese Medicine | Zhang C.,China Pharmaceutical University | Lan Z.,Hubei University of Chinese Medicine
Inflammation | Year: 2014

In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor alpha (TNF-α), IL-1β, and IL-6 were assayed by enzyme-linked immunosorbent assay method. The pathological changes of the lung tissues were observed by hematoxylin and eosin staining. The inflammatory signal pathway-related protein levels of NF-κB were measured using Western blotting. The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice. © 2013 Springer Science+Business Media New York. Source


Huang S.-M.,National University of Singapore | Xu F.,National University of Singapore | Xu F.,China Pharmaceutical University | Lam S.H.,National University of Singapore | And 2 more authors.
Molecular BioSystems | Year: 2013

Zebrafish embryogenesis is a rapid process driven by a myriad of gene products and small molecules. As previous studies have detailed the relevant transcriptional and proteomics changes, here we assess the metabolomic changes that occur at different stages of embryogenesis (4, 8, 12, 24 and 48 hours post fertilization). Metabolite levels were detected using GC-MS and LC-MS, following which multivariate analysis (OPLS-DA) was applied to identify metabolites that were differentially regulated throughout embryogenesis. From the two robust OPLS-DA models that were generated (Q2(cum) = 0.940 and Q 2(cum) = 0.894), a total of 60 detected metabolites (20 from GC-MS, 40 from LC-MS) were identified and found to be important in discriminating between developmental stages. Hierarchical clustering analysis was applied to the dataset and metabolite classes such as amino acids and lipids were shown to be differentially regulated. Biologically relevant transcriptomic and proteomic data were associated with metabolites to provide a more holistic systems perspective of embryogenesis. In summary, the metabolic profiles of different developmental stages highlight the dynamic changes occurring during embryogenesis. These data could serve as a basis for future toxicological or developmental studies. © 2013 The Royal Society of Chemistry. Source


Yin R.,Nantong University | Wang R.,Shanghai JiaoTong University | Guo L.,Ningxia Medical University | Zhang W.,Nantong University | Lu Y.,China Pharmaceutical University
Journal of Vascular Research | Year: 2013

MicroRNAs (miRs) are endogenously expressed small noncoding RNAs that regulate gene expression at the posttranscriptional level. Previous works indicated that the miR-17-92 cluster could regulate endothelial cell (EC) functions involved in angiogenesis. miR-17-3p, a component of the miR-17-92 cluster, could control the angiogenic activity of human umbilical vein ECs in a cell-autonomous manner in vitro. A 21-bp fragment from the Flk-1 3′-untranslated region containing miR-17-3p targeting sites was required for the rapid downregulation of Flk-1 expression by in silico and experimental analysis. Subsequently, the downstream cell growth pathway was inhibited by forced upregulation of miR-17-3p. Based on these data, we conclude that miR-17-3p is a negative regulator of the angiogenic phenotype of ECs through its ability to modulate the expression of Flk-1, which is implicated in the pleiotropic effects of miR-17-92 in angiogenesis. © 2012 S. Karger AG, Basel. Source


Jin L.,China Pharmaceutical University | Li W.,University of Science and Technology of China | Xu Q.,University of Science and Technology of China | Sun Q.,University of Science and Technology of China
Cellulose | Year: 2015

In this present work, amino-functionalized nanocrystalline cellulose (ANCC) was prepared by a process involving, (1) extraction of nanocrystalline cellulose (NCC) from fully bleached hardwood kraft pulp by sulfuric acid hydrolysis, (2) sodium periodate oxidation of NCC to yield the corresponding C-2/C-3 dialdehyde nanocellulose (DANC) and (3) grafting with ethylenediamine to obtain ANCC through a reductive amination treatment. Properties of DANC and ANCC were characterized by conductometric titration, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction and atomic force microscopy. It was found that the primary amine groups of ANCC (0.77–1.28 mmol g−1) increased with the increase of ethylenediamine dosage. The successful grafting was further evidenced by Kaiser test and FT-IR analysis. Zeta potential measurements showed that ANCCs were amphoteric, and their isoelectric points were between pH of 7–8. Chemical modifications of the cellulose nanowhiskers reduced the crystallinity but the initial cellulose I polymorph was retained. The cross-sectional dimension of nanowhiskers was slightly decreased from about 5–10 to 3–8 nm after the oxidation, and a better dispersibility was observed. ANCC sample was then applied as an adsorbent to remove anionic dyes in aqueous solutions. It demonstrated the maximum removal efficiency at acidic conditions. The acid red GR adsorption on ANCC fitted well with the Langmuir model, with a maximum theoretical adsorption capacity of 555.6 mg g−1. The adsorption of congo red 4BS, acid red GR and reactive light yellow K-4G followed pseudo second order kinetics, indicating a chemisorption nature. © 2015, Springer Science+Business Media Dordrecht. Source


Yuan H.D.,Kyung Hee University | Yuan H.D.,China Pharmaceutical University | Chung S.H.,Kyung Hee University
Phytotherapy Research | Year: 2010

In this study, we investigated the protective effects of fermented ginseng (FG) on hyperglycemia induced by streptozotocin (STZ) in Sprague Dawley rats. FG was administered orally at dose of 250 (FGL) or 500 mg/kg (FGH) for 20 days starting one week before STZ injection. FG restored the plasma insulin levels by 266% and 334% in FGL and FGH, respectively, and resulting in reduction of plasma glucose concentration. Histological observation indicated that STZ-induced destruction of pancreatic islets was protected by FG. Consistent with this observation, FG reduced protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as determined by Western blotting and RT-PCR, respectively. The molecular mechanism of FG's inhibition of iNOS and COX-2 gene expressions appeared to involve the inhibition of nuclear factor-κB (NF-κB) activation via prevention of inhibitor κB (IκB) phosphorylation and degradation. The cytoprotective effects of FG were also mediated through suppression of extracelluar signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK) pathways. Collectively, these results suggest that FG might be used to preserve functional β-cell mass. Copyright © 2009 John Wiley & Sons, Ltd. Source


Cao Z.,University of California at Davis | Cao Z.,China Pharmaceutical University | Cui Y.,University of California at Davis | Nguyen H.M.,University of California at Davis | And 3 more authors.
Molecular Pharmacology | Year: 2014

Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used. We investigated whether nanomolar bifenthrin alters synchronous Ca2+ oscillations (SCOs) necessary for activity-dependent dendritic development. Primary mouse cortical neurons were cultured 8 or 9 days in vitro (DIV), loaded with the Ca2+ indicator Fluo-4, and imaged using a Fluorescence Imaging Plate Reader Tetra. Acute exposure to bifenthrin rapidly increased the frequency of SCOs by 2.7-fold (EC50 = 58 nM) and decreased SCO amplitude by 36%. Changes in SCO properties were independent of modifications in voltage-gated sodium channels since 100 nM bifenthrin had no effect on the whole-cell Na+ current, nor did it influence neuronal resting membrane potential. The L-type Ca 2+ channel blocker nifedipine failed to ameliorate bifenthrin-triggered SCO activity. By contrast, the metabotropic glutamate receptor (mGluR)5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine] normalized bifenthrin-triggered increase in SCO frequency without altering baseline SCO activity, indicating that bifenthrin amplifies mGluR5 signaling independent of Na+ channel modification. Competitive [AP-5; (-)-2-amino-5-phosphonopentanoic acid] and noncompetitive (dizocilpine, or MK-801 [(5S, 10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate]) N-methyl-D-aspartate antagonists partially decreased both basal and bifenthrin-triggered SCO frequency increase. Bifenthrin-modified SCO rapidly enhanced the phosphorylation of cAMP response element-binding protein (CREB). Subacute (48 hours) exposure to bifenthrin commencing 2 DIV-enhanced neurite outgrowth and persistently increased SCO frequency and reduced SCO amplitude. Bifenthrin-stimulated neurite outgrowth and CREB phosphorylation were dependent on mGluR5 activity since MPEP normalized both responses. Collectively these data identify a new mechanism by which bifenthrin potently alters Ca2+ dynamics and Ca2+-dependent signaling in cortical neurons that have long term impacts on activity driven neuronal plasticity. Source


Liu Z.,Chinese PLA General Hospital | Luo Y.,Shenyang Yaoda Pharmaceutical Co. | Zhou T.-T.,China Pharmaceutical University | Zhang W.-Z.,Chinese PLA General Hospital
Cell Proliferation | Year: 2013

Plant lectins, a group of highly diverse carbohydrate-binding proteins of non-immune origin, are ubiquitously distributed through a variety of plant species, and have recently drawn rising attention due to their remarkable ability to kill tumour cells using mechanisms implicated in autophagy. In this review, we provide a brief outline of structures of some representative plant lectins such as concanavalin A, Polygonatum cyrtonema lectin and mistletoe lectins. These can target autophagy by modulating BNIP-3, ROS-p38-p53, Ras-Raf and PI3KCI-Akt pathways, as well as Beclin-1, in many types of cancer cells. In addition, we further discuss how plant lectins are able to kill cancer cells by modulating autophagic death, for therapeutic purposes. Together, these findings provide a comprehensive perspective concerning plant lectins as promising new anti-tumour drugs, with respect to autophagic cell death in future cancer therapeutics. © 2013 John Wiley & Sons Ltd. Source


Li J.,Tianjin Medical University | Zhou L.,Tianjin Medical University | Chen X.,China Pharmaceutical University | Ba Y.,Tianjin Medical University
Clinical and Translational Oncology | Year: 2015

Background: This systematic review and meta-analysis analyzed randomized controlled trials (RCTs) assessing the efficacy and tolerance of incorporating bevacizumab into chemotherapy in patients with advanced ovarian cancer. Methods: MEDLINE, Web of Science, EMBASE and the Cochrane Central Register of Controlled Trials were reviewed for RCTs evaluating add-on bevacizumab in advanced ovarian cancer. Progression-free survival (PFS), overall survival (OS), objective response rate and adverse events were obtained from RCTs comparing first- and second-line bevacizumab plus chemotherapy with chemotherapy alone for advanced ovarian cancer. Meta-analyses were performed to determine hazard ratios for time-to-event variables and odds ratios for dichotomous outcomes using random-effects or fixed-effects model based on the heterogeneity of included studies. Results: Four RCTs, including 4246 patients, were identified and analyzed. Two trials, GOG218 and ICON7, assessing bevacizumab in first-line chemotherapy, found that bevacizumab significantly extended PFS (HR 0.82; 95 % CI 0.75–0.89) and OS (HR 0.86; 95 % CI 0.75–0.99). The other two trials, OCEANS and AURELIA, analyzing second-line bevacizumab, found that this agent extended PFS (HR 0.48; 95 % CI 0.41–0.57), but did not enhance OS (HR 0.93; 95 % CI 0.78–1.12). The most common adverse events associated with bevacizumab included hypertension, proteinuria and gastrointestinal perforation. Conclusion: The addition of bevacizumab to chemotherapy followed by bevacizumab significantly improved PFS and OS in frontline setting and PFS in recurrent settings compared with that of chemotherapy alone in patients with advanced ovarian cancer. © 2015, Federación de Sociedades Españolas de Oncología (FESEO). Source


Ouyang L.,University of Sichuan | Shi Z.,Sichuan University | Shi Z.,Guizhou Normal University | Zhao S.,Sichuan University | And 5 more authors.
Cell Proliferation | Year: 2012

Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment. © 2012 Blackwell Publishing Ltd. Source


Su X.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2012

To establish TLC fingerprint of Glehniae Radix for the identification and quality control of the drug. 10 batches of Glehniae Radix commercial drugs collected from different gathering areas and 3 batches from Laiyang, Shandong were used as qualitative identification samples. Falcarindiol, scopoletin umbelliferone and isoimperatorin were used as the chemical reference substances. Double wavelength TLCS was performed with petroleum and ethyl acetate (4:1) as developer,detection wavelength at 300 nm and reference wavelength at 260 nm. TLC chromatogram of 13 samples had 8 well-resolved characteristic peaks, in which 4 peaks were falcarindiol, umbelliferone, scopoletin and isoimperatorin, respectively. The method is accurate and simple, and can be used for the quality control of Glehniae Radix. Source


Zheng Y.-F.,Nanjing University | Wei J.-H.,Nanjing University | Qi L.-W.,China Pharmaceutical University | Cheng J.-M.,Nanjing University | Peng G.-P.,Nanjing University
Journal of Separation Science | Year: 2013

A green and efficient method for large-scale preparation of glycyrrhizic acid from licorice roots was developed by combination of polyamide and macroporous resin. The entire preparation procedure consisted of two simple separation steps. The first step is to use polyamide resin to remove licorice flavoniods from the licorice crude extract. Subsequently, various macroporous resins were tried to purify glycyrrhizic acid, and HPD-400 showed the most suitable adsorption and desorption properties. Under the optimized conditions, a large-scale preparation of glycyrrhizic acid from licorice roots was carried out. A 20 kg raw material produced 0.43 kg of glycyrrhizic acid using green aqueous ethanol as the solvent. The purity of glycyrrhizic acid was increased from 11.40 to 88.95% with a recovery of 76.53%. The proposed method may be also extended to produce large-scale other triterpenoid saponins from herbal materials. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Li J.,China Pharmaceutical University | Liu L.,Changzhou University | Zhou Y.-Y.,Changzhou University | Xu S.-N.,Changzhou University
RSC Advances | Year: 2012

Highly effective palladium-catalyzed Heck-type arylation of acrylate with diaryliodonium salts has been developed, giving cinnamate in high yields without ligand and base. © 2012 The Royal Society of Chemistry. Source


Wang J.-J.,Nanjing Medical University | Xia X.,General Hospital of Beijing Military Region | Tang S.-D.,Nanjing Medical University | Wang J.,Nanjing Medical University | And 4 more authors.
PLoS ONE | Year: 2013

Background:Publications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.Methods:A systematic search was performed for published studies on the relationship between TLR2 polymorphisms and PTB susceptibility. Information was gathered from each eligible study, and statistically analyzed.Results:6 eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and 8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be associated with decreased PTB susceptibility (A vs. G: OR = 3.02, 95% CI: 2.22-4.12, P<0.001, GA+AA vs. GG: OR = 2.69, 95% CI = 1.49-4.87, P = 0.001). In the subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a protective effect of PTB risk in Asians (A vs. G: OR = 2.95, 95% CI: 1.91-4.55, P<0.001; GA+AA vs. GG: OR = 3.59, 95% CI: 2.23-5.78, P<0.001), while no associations were observed in Caucasians. No significant associations between T597C polymorphism and PTB were found in the allele model (C vs. T: OR = 0.95, 95% CI: 0.86-1.04, P = 0.28), co-dominant model (CC vs. TT: OR = 0.88, 95% CI = 0.92-1.40, P = 0.25; CT vs. TT: OR = 0.92, 95% CI = 0.80-1.06, P = 0.28), recessive model (CC vs. TT+TC: OR = 0.96, 95% CI: 0.80-1.16, P = 0.69), or dominant model (TC+CC vs. TT: OR = 0.93, 95% CI = 0.76-1.15, P = 0.51). The associations of T597C polymorphism with PTB susceptibility, in the ethnic-specific analyses, were still not significant.Conclusion:TLR2 2258G allele may provide protective effects against PTB susceptibility, particularly among Asians, whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility. © 2013 Wang et al. Source


Wang C.Q.,China Pharmaceutical University
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica | Year: 2012

To establish a quantitative method of multi-components by single marker (QAMS) for determining ginsenoside Rg1, Rb1, Rd, Re and notoginsenoside R1 for the purpose of the quality control of Panax notoginseng. The relative correction factors (RCFs) between the five active saponins were determined by HPLC-DAD. With any of the five consituents as reference, a QAMS method was established for detect the quantitation of the other four consituents. The durability of the method was evaluated with five different HPLC instruments, five different Cis18 chromatographic columns and four detective wavelengths. Subsequently, the new QAMS method was used to determine the contents of five saponins contained in 43 batches of notoginseng samples, and compare with external standard methods, in order to evaluate the accuracy of the QAMS method. When the five saponins were taken for reference, there was no significant difference between the contents of Rg1, Rb1, Rd, Re and R1 contained in the 43 batches of medicines calculated by the QAMS method (Wf) and the content determination result of the external standard method (Ws). The ratio of their results was (Ws/Wr) (94.02 +/- 2.11)%-(99.75 +/- 0.79)%, suggesting that the method was highly accurate. Their relative correction factors showed good durability, ranging between 0.42%-3.7%, 0.52%-3.5% and 0.79%-4.9%, respectively, with different chromatographic columns, different instruments and different detective wavelengths. The relative retention value method could be adopted for accurately position the chromatographic peak of the five consituents, with their values ranging between 0.18%-13%. An accurate, rapid and highly durable QAMS method is established for simultaneous determination and location of five saponins, so as to provide reliable basis for the application of the QAMS method in quality control of traditional Chinese medicines. Source


Xu K.,China Pharmaceutical University | Han Q.,Nanjing University of Science and Technology
Journal of Nanoparticle Research | Year: 2016

Abstract: Monodisperse CdS nanospheres assembled by small nanoparticles were prepared using dimethyl sulfoxide (DMSO) as a solvent through several routes including thermolysis of xanthate, the reaction of cadmium acetate (Cd(CH3CO2)2) with thiourea, and interfacial reaction of CS2 and Cd(CH3CO2)2/DMSO. The corresponding products possessed the particle sizes ranging from around 35 to 45 nm, 63 to 73 nm, and 240 to 280 nm, respectively. These products presented uniform spherical morphology, which provide insights into the effect of DMSO on CdS morphology. DMSO, as an aprotic and polar solvent, possesses unique properties. The oxygen and sulfur atoms in DMSO can coordinate to metal ions on nanoparticles surface, and the high polarity of DMSO is favorable to fast reaction, nucleation, growth, and Ostwald ripening, forming monodisperse nanospheres with narrow size distribution. The influence of CdS size on its photocatalytic activity was evaluated using Rhodamine B (RhB) as a model compound under visible light irradiation. Graphical Abstract: [Figure not available: see fulltext.] © 2016, Springer Science+Business Media Dordrecht. Source


Liu D.,Hubei University of Chinese Medicine | Liu Y.-W.,Hubei University of Chinese Medicine | Guan F.-Q.,CAS Institute of Botany | Liang J.-Y.,China Pharmaceutical University
Fitoterapia | Year: 2014

Two new dimeric diarylheptanoids, named Alpinin C (1) and D (2), a new natural product of diarylheptanoid (3) along with three known diarylheptanoids (4-6) were isolated from the rhizomes of Alpinia officinarum Hance. Their structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR, HRTOFMS, IR). The isolated compounds were evaluated for their cytotoxicity against human tumor cell lines HepG2, MCF-7, T98G and B16-F10. Compound 1 showed selective cytotoxicity against cell lines of MCF-7 and T98G, while compound 6 showed significant cytotoxicity to the all tested tumor cell lines with IC 50 in the range from 8.46 to 22.68 μmol/L. © 2014 Elsevier B.V. Source


Lin S.Y.,China Pharmaceutical University
Expert reviews in molecular medicine | Year: 2014

Calcinosis cutis (CC) is a type of calcinosis wherein insoluble compounds or salts deposited on the skin. Clinical diagnosis of CC is usually achieved through time consuming histopathological or immunohistochemical procedures, but it can only be empirically identified by experienced practitioners. The use of advanced vibrational spectroscopy has been recently shown to have great potential as a diagnostic technique for various diseased tissues because it analyses the chemical composition of diseased tissue rather than its anatomy and predicts disease progression. This review article includes a summary of the application of Fourier transform infrared (FT-IR) and Raman spectroscopic or microspectroscopic analysis for the rapid diagnosis and identification of the chemical composition of skin calcified deposits in patients with various CC symptoms. Both advanced techniques not only can detect the types of insoluble salts such as calcium phosphate, calcium carbonate, and monosodium urate, and β-carotene in the calcified deposits of human skin tissue but also can directly differentiate the carbonate substitution in the apatite structure of the skin calcified deposits. In particular, the combination of both vibrational techniques may provide complementary information to simultaneously assess the intact components of the calcified deposits. In the future, both FT-IR and Raman vibrational microspectroscopic techniques will become available tools to support the standard test techniques currently used in some clinical diagnoses. Molecular spectroscopy technique is rapidly changing disease diagnosis and management. Source


Chen Z.,Nanjing University | Chen Z.,Johns Hopkins University | Chen Z.,China Pharmaceutical University | Zhang P.,Johns Hopkins University | And 5 more authors.
Journal of Controlled Release | Year: 2014

Covalent modification of a drug with a peptide moiety has been extensively used as an effective strategy to improve the drug's therapeutic outcome. One important consideration in the design of such a prodrug is the release of the free drug from the covalently bound form in a desired fashion. In most cases, the free drug release rate is controlled by the use of various chemical linkers that bridge the drug to the auxiliary segment. We report here that the degree of drug conjugation per peptide could also regulate the drug release in addition to its apparent effect on drug loading of the resulting conjugates. In this work, we synthesized three peptide-drug conjugates (NTD, d-NTD and q-NTD) in which the cell penetrating peptide Tat is covalently connected to one, two, or four doxorubicin, respectively, through a cathepsin B degradable tetrapeptide linker (-Gly-Phe-Leu-Gly-).We found that the number of doxorubicin within the conjugate impacts the release of doxorubicin in a significant way, with q-NTD showing the slowest release rate while NTD showing the fastest release rate. Our cellular uptake experiments reveal that q-NTD accumulated most effectively within cancer cells while NTD shows the lowest intracellular accumulation concentration. Interestingly, our cell viability assessment using a SRB assay reveals that d-NTD is the most potent conjugate against HepG2 human liver cancer cells. These results suggest that intracellular accumulation efficiency and the free drug release rate are two important factors that determine the in vitro efficacy of drug conjugates. To further validate this conclusion, we conjugated a short hydrocarbon onto the NTD to improve its cellular uptake, and found that the resulting conjugate, C16NTD, exhibited comparable intracellular accumulation as the q-NTD conjugate but superior anticancer activity due to its more effective release of free doxorubicin. © 2014 Elsevier B.V. All rights reserved. Source


Ding L.,Yancheng Institute of Technology | An J.,Yancheng Institute of Technology | Zhu Z.,China Pharmaceutical University | Zhu Z.,National University of Singapore
Polymer Chemistry | Year: 2014

The click chemistry strategy was successfully applied for the preparation of long-chain highly branched ring-opening metathesis polymers (LCHBPs). The hydroxyl-functionalized monotelechelic polymers with various molecular weights were synthesized first via ring-opening metathesis polymerization of N-azidopentyl oxanorbornene imide in the presence of a symmetrical functional terminating agent, and then transformed into alkynyl-monotelechelic polymers, which acted as ABn-type macromonomers for subsequent click reaction to finally produce LCHBPs as the reaction time prolonged. All intermediates, macromonomer, and the resultant LCHBPs were characterized in detail by mass spectroscopy, elemental analysis, FTIR, GPC, and NMR measurements. The experimental results showed that polymerization has a two-step feature, that is, a fast and a slow increase of the average degree of polymerization at the initial and the subsequent stages, respectively. The final LCHBPs have high molecular weight up to Mn,NMR = 210600, and relatively moderate molecular weight distributions (Mw/Mn = 2.12-1.67). This journal is © 2014 The Royal Society of Chemistry. Source


Li L.-F.,Nanjing Medical University | Yang J.,Nanjing University of Traditional Chinese Medicine | Ma S.-P.,China Pharmaceutical University | Qu R.,Nanjing University of Traditional Chinese Medicine
European Journal of Pharmacology | Year: 2013

Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20 mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. © 2013 Elsevier B.V. Source


Wu P.,China Pharmaceutical University | Liu N.,Nanjing Southeast University
Patient Preference and Adherence | Year: 2016

Purpose: The objective of this study was to identify, using the theory of planned behavior (TPB), patients’ beliefs about taking oral antidiabetic drugs (OADs) as prescribed, and to measure the correlations between beliefs and medication adherence. Patients and methods: We performed a cross-sectional study of type 2 diabetic patients using structured questionnaires in a Chinese tertiary hospital. A total of 130 patients were enrolled to be interviewed about TPB variables (behavioral, normative, and control beliefs) relevant to medication adherence. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8). Spearman’s rank correlation was used to assess the association between TPB and MMAS-8. Logistic regression analysis was performed to examine the relationship between different variables and MMAS-8, with statistical significance determined at P<0.05. Results: From 130 eligible Chinese patients with an average age of 60.6 years and a male proportion of 50.8%, a nonsignificant relationship between behavioral, normative, and the most facilitating control beliefs and OAD adherence was found in our study. Having the OADs on hand (P=0.037) was the only facilitating control belief associated with adherence behavior. Being away from home or eating out (P=0.000), not accepting the disease (P=0.000), ignorance of life-long drug adherence (P=0.038), being busy (P=0.001), or poor memory (P=0.008) were control belief barriers found to be correlated with poor adherence. TPB is the only important determinant influencing OAD adherence among all the factors (P=0.011). Conclusion: The results indicate that the TPB model could be used to examine adherence to OADs. One facilitating control belief, and most of the barrier control beliefs of TPB were related to medication adherence among Chinese type 2 diabetes inpatients. It will be helpful to understand patients’ self-medication and provide methods to develop instruments for identifying factors that influence OAD adherence. © 2016 Wu and Liu. Source


Shi B.J.,China Pharmaceutical University
Natural product research | Year: 2010

Two new compounds, including petasinoside A and chloridate-[N-chloromethyl-hectorine], were isolated from Senecio nemorensis. The structures of these compounds were elucidated by spectroscopic methods including 1D and 2D NMR experiments. Source


Xi F.,Shanghai Pudong New area Peoples Hospital | Ye J.,China Pharmaceutical University
Oncology Research | Year: 2016

Hexokinase 2 (HK2) has been identified as an oncogene in some malignant diseases such as breast cancer and ovarian cancer. However, the role of HK2 in lung cancer remains unclear. In this study, we explored the functional role of HK2 in lung cancer cell proliferation and tumorigenesis and determine its expression profile in lung cancer. HK2 expression was increased in primary lung cancer tissues of patients. Knocking down HK2 expression by small interfering RNA (siRNA) inhibited cell proliferation in lung cancer cells and nude mice. Thus, HK2 is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our study provided evidence that HK2 functions as a novel oncogene in lung cancer and may be a potential therapeutic target for lung cancer. Copyright © 2016 Cognizant, LLC. Source


Wang Q.Z.,CAS Institute of Botany | Liang J.Y.,China Pharmaceutical University | Feng X.,CAS Institute of Botany
Chinese Chemical Letters | Year: 2010

Two new indole alkaloids, evodiagenine 1 and dievodiamine 2 were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth. The structure of compounds 1 and 2 were elucidated by comprehensive spectroscopic analysis and compound 1 was confirmed by X-ray crystallographic analysis. © 2009 Xu Feng. Source


Shi Y.,Taiyuan Normal University | Li Z.,Taiyuan Normal University | Qiao Y.,China Pharmaceutical University | Lin J.,Analytical science
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

This work aimed to develop a rapid capillary zone electrophoresis (CZE) method to provide abundant purity and identity information of monoclonal antibodies. The CZE running buffer system was optimized to be 20. mM acetate-acetic acid (pH 6.0) together with the co-addition of 0.3% polyethylene oxide (PEO) and 2. mM triethylenetetramine (TETA), which was further tested with advantages on the peak resolution improvements. The conditioning period was scheduled to 1. min for both 0.1. M HCl and CZE running buffer to reduce total separation time. Additionally, the applied voltage and effective separation length were optimized at 30. kV and 20. cm separately. Compared with the method reported by Yan [1], this newly developed method showed a higher resolution in separating the two unknown basic peaks by testing monoclonal antibody sample (mAb1). The further validation results showed that for all five of charge isoform peaks of test mAb1, repeatability, intraday and interday precision had a RSD less than 0.58% for migration time and less than 3.18% for corrected area percent. The correlation coefficients of more than 0.98 for all peaks also demonstrated the good linearity for the method. In addition to the application of distinguishing intact antibody from C-terminal Lys variants, the method also has advantage in separating the Fab, Fc and intact antibody-relevant substances quickly, which facilitated the rough evaluation of papain induced digestion. © 2012 Elsevier B.V. Source


Zhou X.,Jiangsu Institute for Drug Control | Xiang B.,China Pharmaceutical University | Zhang M.,Jiangsu Institute for Drug Control
Analytical Letters | Year: 2012

Synchronous 2D correlation spectroscopy was first proposed to select informational spectral intervals in PLS calibration. The proposed method could extract the spectral intervals related to analyte. The results of its application to NIR/PLS determination of quercetin in extract of Ginkgo biloba leaves showed that the proposed method could find out an optimized region with which one could improve the performance of the corresponding PLS model, in terms of low prediction error, root mean square error of prediction (RMSEP), and comparing with the result obtained using whole spectra and interval PLS. © 2013 Copyright Taylor and Francis Group, LLC. Source


Chang M.,China Pharmaceutical University
Wei sheng wu xue bao = Acta microbiologica Sinica | Year: 2010

To identify Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff and to characterize antibacterial compounds from the ethyl acetate extracts of its fermentation broth. Strain F12 was identified based on its morphological characters and internal transcribed spacer (ITS) sequence. Its secondary metabolites were purified by chromatography, and elucidated by mass spectroscopy, H-NMR, 13C-NMR and physicochemical characters. The antibacterial activities of these compounds were tested against Staphyloccocus aureus and Bacillus subtilis. Strain F12 was identified as Aspergillus awamori. Three compounds, including 1,4-dimethoxybenzene (1), emodin (2) and 3, 6-dibenzylpiperazine-2, 5-dione (3), were purified and elucidated from the ethyl acetate extracts of fermentation broth, among which compound 1 was first reported for the genus of Aspergillus. Compound 2 suppressed the growth of Staphyloccocus aureus and Bacillus subtilis with MIC values of 16 microg/mL and 32 microg/mL respectively, while the other two compounds have no effects on these bacteria. Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff can produce 1, 4-dimethoxybenzene and emodin, among which the latter can suppress the growth of bacteria apparently. Source


Yu Y.,China Pharmaceutical University
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

In the title compound, C 8H 3ClN 4O 5·C 2H 4O 2, both the nitro groups are close to perpendicular [dihedral angles = 67.62 (15) and 86.73 (12)°] to the almost planar quinazoline unit [r.m.s. deviation = 0.014Å]. In the crystal, both the quinazoline and acetic acid molecules form inversion dimers linked by pairs of N - H⋯O and O - H⋯O hydrogen bonds, respectively. R 2 2(8) loops arise in each case. Source


Fu L.,University of Sichuan | Zhang S.,University of Sichuan | Zhang L.,University of Sichuan | Zhang L.,Shenyang Pharmaceutical University | And 8 more authors.
Oncotarget | Year: 2015

The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy. Source


BACKGROUND: Piperaquine, 1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]-propane, is an anti-malarial compound belonging to the 4-aminoquinolines, which has received renewed interest in treatment of drug resistant falciparum malaria in artemisinin-based combination therapy with dihydroartemisinin. The impurity profile of this drug product is paid an ever-increasing attention. However, there were few published studies of the complete characterization of related products or impurities in piperaquine phosphate bulk and forced degradation samples.METHODS: The impurities in piperaquine phosphate bulk drug substance were detected by a newly developed gradient phase HPLC method and identified by TOF-MS and ESI-MS. The structures of impurities were confirmed by NMR. Forced degradation studies were also performed for the stability of piperaquine phosphate bulk drug samples and the specificity of the newly developed HPLC method. In silico toxicological predictions for these piperaquine phosphate related impurities were made by Toxtree® and Derek®.RESULTS: Twelve impurities (imp-1-12) were detected and identified, of which eight impurities (imp-1, 2, 4, 6-10) were first proposed as new related substances. Based on TOF-MS/ESI-MS and NMR analysis, the structures of imp-2, 6 and 12 were characterized by their synthesis and preparation. The possible mechanisms for the formation of impurities were also discussed. These piperaquine phosphate related impurities were predicted to have a toxicity risk by Toxtree® and Derek®.CONCLUSIONS: From forced degradation and bulk samples of piperaquine phosphate, twelve compounds were detected and identified to be piperaquine phosphate related impurities. Two of the new piperaquine phosphate related substances, imp-2 and imp-6, were identified and characterized as 4-hydroxy-7-chloro-quinoline and a piperaquine oxygenate with a piperazine ring of nitrogen oxide in bulk drug and oxidation sample, respectively. The MS data of imp-1, 2, 4, 6-10 were first reported. The in-silico toxicological prediction showed a toxicity risk for piperaquine related impurities by Toxtree® and Derek®. Source


Ye B.,China Pharmaceutical University | Ye B.,Nanjing Southeast University | Rui Q.,Nanjing Southeast University | Rui Q.,Nanjing Agricultural University | And 2 more authors.
PLoS ONE | Year: 2010

Metallothioneins (MTs) are small, cysteine-rich polypeptides, but the role of MTs in inducing the formation of adaptive response is still largely unknown. We investigated the roles of metallothionein genes (mtl-1 and mtl-2) in the formation of cross-adaptation response to neurobehavioral toxicity from metal exposure in Caenorhabditis elegans. Pre-treatment with mild heat-shock at L2-larva stage effectively prevented the formation of the neurobehavioral defects and the activation of severe stress response in metal exposed nematodes at concentrations of 50 and 100 μM, but pre-treatment with mild heatshock did not prevent the formation of neurobehavioral defects in 200 μ M of metal exposed nematodes. During the formation of cross-adaptation response, the induction of mtl-1 and mtl-2 promoter activity and subsequent GFP gene expression were sharply increased in 50 μM or 100 μM of metal exposed Pmtl-1::GFP and Pmtl-2::GFP transgenic adult animals after mild heat-shock treatment compared with those treated with mild heat-shock or metal exposure alone. Moreover, after pre-treatment with mild heat-shock, no noticeable increase of locomotion behaviors could be observed in metal exposed mtl-1 or mtl-2 mutant nematodes compared to those without mild heat-shock pre-treatment. The defects of adaptive response to neurobehavioral toxicity induced by metal exposure formed in mtl-1 and mtl-2 mutants could be completely rescued by the expression of mtl-1 and mtl-2 with the aid of their native promoters. Furthermore, overexpression of MTL-1 and MTL-2 at the L2-larval stage significantly suppressed the toxicity on locomotion behaviors from metal exposure at all examined concentrations. Therefore, the normal formation of cross-adaptation response to neurobehavioral toxicity induced by metal exposure may need the enough accumulation of MTs protein in animal tissues. © 2010 Ye et al. Source


Li H.,Nanjing University | Sun Z.,Nanjing University | Zhong W.,China Pharmaceutical University | Hao N.,Nanjing University | And 2 more authors.
Analytical Chemistry | Year: 2010

Multiplexed DNA target detection is of great significance in many fields including clinical diagnostics, environmental monitoring, biothreat detection and forensics. Although the emergence of DNA chip technology has accelerated this process, it is still a challenge to perform ultrasensitive DNA assay at low attomol concentrations so that DNA detection can be directly achieved without a PCR protocol. In this work, an oligonucleotide-functionalized silver nanoparticle tag has been successfully developed for multiplexed DNA electrochemical detection with ultrahigh sensitivity. The multiprobes containing oligo(d)A and the reporting probes were anchored onto the silver nanoparticles, followed by hybridizing with the silver nanoparticle conjugate modified with oligo(d)T. The hybridization-induced tag was found to show an aggregated nanostructure 10 times larger than the individual nanoparticle, as revealed by TEM. For sandwich-based assays, the tag was specifically coupled to a gold electrode surface via target DNA. Compared to a single nanoparticle label, this novel tag has shown excellent electroactive property and produces 10 3-fold amplification in the differential pulse voltammetric (DPV) method. Hepatitis B virus (HBV) sequence was employed as a sample model, and we have achieved a detection limit of 5 aM (∼120 molecules in 40 μL volume), demonstrating ultrasensitive measurement for DNA. The property of the electrochemical process involving silver aggregates was further investigated and the integrative oxidation of the silver tag was observed. We further demonstrated the multiplexed DNA target detection using array chips functionalized with Herpes simplex virus (HSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) sequences, which shows effective recognition of the relative sequences individually or simultaneously. The method offers a uniquely new approach for DNA detection with ultrahigh sensitivity as well as advantages of rapidity, throughput, and miniaturization. © 2010 American Chemical Society. Source


Ji G.,Nanjing Medical University | Ji G.,Nanjing Institute of Environmental Sciences | Long Y.,China Pharmaceutical University | Zhou Y.,CAS Shanghai Institutes for Biological Sciences | And 3 more authors.
BMC Medicine | Year: 2012

Background: The mismatch repair (MMR) pathway plays an important role in the maintenance of the genome integrity, meiotic recombination and gametogenesis. This study investigated whether genetic variations in MMR genes are associated with an increased risk of sperm DNA damage and male infertility.Methods: We selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five MMR genes (MLH1, MLH3, PMS2, MSH4 and MSH5) using the SNPstream 12-plex platform in a case-control study of 1,292 idiopathic infertility patients and 480 fertile controls in a Chinese population. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation techniques were employed to determine the effects of functional variants.Results: One intronic SNP in MLH1 (rs4647269) and two non-synonymous SNPs in PMS2 (rs1059060, Ser775Asn) and MSH5 (rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia. Meanwhile, we also identified a possible contribution of PMS2 rs1059060 to the risk of male infertility with normal sperm count. Among patients with normal sperm count, MLH1 rs4647269 and PMS2 rs1059060 were associated with increased sperm DNA damage. Functional analysis revealed that the PMS2 rs1059060 can affect the interactions between MLH1 and PMS2.Conclusions: Our results provide evidence supporting the involvement of genetic polymorphisms in MMR genes in the aetiology of male infertility. © 2012 Ji et al; licensee BioMed Central Ltd. Source


Chen Q.L.,China Pharmaceutical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2013

To study the chemical constituents of the aerial part of Echinacea purpurea. The compounds were separated and purified by repeatedly silica gel, ODS, D101 macroporous resin, MCI, Sephadex LH-20 column chromatography and recrystallization. Their structures were elucidated on the basis of physiochemical properties and spectral analysis. Sixteen compounds were isolated and identified as (2S)-1-O-octacosanoyl glycerol (1), (5R,6S)-6-hydroxy-6-((E)-3-hydroxybut-1-enyl)-1,1, 5-trimethylcyclohexanone (2), (3S, 6E, 10R)-3, 10, 11-trihydroxy-3, 7, 11-trimethyl-dodeca-1, 6-diene (3), negunfurol (4), schensianol A (5), ent-4 (15) -eudesmene-1beta, 6alpha-diol (6), (E) -5-hydroxy-N-isobutylpentadec-2-enamide (7), syringaresinol (8), quercetin (9), ethyl laurate (10), ethyl caffeate (11), ferulic acid (12), alpha-spinasterol (13), stigmasterol (14), beta-daucosterol (15), octacosanoic acid (16). Compound 1 - 5 are isolated from the Asteraceae for the first time, compound 6 ,7, 9, 10, 12 are isolated from genus of Echinacea for the first time, compound 15, 16 are isolated from this plant for the first time. Source


Gu J.-F.,China Pharmaceutical University
Chinese Journal of New Drugs | Year: 2013

Neuraminidase(NA) Inhibitor, a recent developed Anti-Influenza Virus agent, possessed the advantages of broad-spectrum, highly efficiency, lower resistance, good patient tolerability against each sub-type influenza virus. It becomes the most important class of drug against the highly pathogenic avian influenza and the new HxNy influenza virus. As an novel NA inhibitor, Peramivir could inhibited the neuraminidase activity of many kind of A, B group influenza viruses, entered into the phase III clinical trial. Peramivir sodium chlorideinjection has been developed against the low oral bioavailability. Chinese self-developed new agent of peramivirinjection has been approved on the market by SFDA and centre of observation comment of medicine at the first time, in order to repartee H7N9 CPK virus epidemic situation occurred new up at Shanghai, Jiangsu, Zhejiang. The development course, physical-chemistry properties, mechanism, anti-Influenza virus effect in vitro and in vivo, pharmacokinetics, clinical trial of Peramivir were presented at home and abroad, and R&D dynamic of domestic production enterprises were summarized. Source


In this work, a rapid and simple method based on matrix solid-phase dispersion (MSPD) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. Guge Fengtong preparation (GGFT), a traditional Chinese herbal medicine, was investigated for validation, and eight major constituents were determined including four saponins (protodioscin, protogracillin, pseudoprotodioscin and dioscin) and four gingerols (6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol). Response surface methodology and desirability function were employed to optimize the extraction conditions, such as dispersant, dispersant/sample ratio, solvent concentration, and elution volume, of MSPD. Results showed that MSPD using C18 (1.75 g) as the dispersant material and methanol (89%, v/v) as the eluting solvent (12.00 mL) resulted in a high extraction efficiency. MSPD extraction had the advantages of combining extraction and clean-up in a single step, was less time consuming and required lower solvent volumes compared with conventional methods. Quantification of chemical compounds from GGFT preparations were performed using UPLC-MS/MS in multiple-reaction monitoring mode. The proposed method afforded a low limit of detection ranging from 0.02 to 0.40 ng for saponins and gingerols. For all the analytes, recoveries ranged from 80.9% to 103% and repeatabilities were acceptable with relative standard deviations of less than 6.81%. The proposed MSPD-UPLC-MS/MS method was successfully utilized to analyze five batches of GGFTs, and the results demonstrated that this method is simple, efficient and has potential to be applied for the quality control of herbal preparations. Source


Zhu C.,Zhejiang University | Hu W.,China Pharmaceutical University | Wu H.,Zhejiang University | Hu X.,Zhejiang University
Scientific Reports | Year: 2014

Targeting cancer via ROS-based mechanism has been proposed as a radical therapeutic approach. Cancer cells exhibit higher endogenous oxidative stress than normal cells and pharmacological ROS insults via either enhancing ROS production or inhibiting ROS-scavenging activity can selectively kill cancer cells. In this study, we randomly chose 4 cancer cell lines and primary colon or rectal cancer cells from 4 patients to test the hypothesis and obtained following paradoxical results: while piperlongumin (PL) and Ǐ 2-phenylethyl isothiocyanate (PEITC), 2 well-defined ROS-based anticancer agents, induced an increase of cellular ROS and killed effectively the tested cells, lactic acidosis (LA), a common tumor environmental factor that plays multifaceted roles in promoting cancer progression, induced a much higher ROS level in the tested cancer cells than PL and PEITC, but spared them; L-buthionine sulfoximine (L-BSO, 20â €...Ǐ 1/4M) depleted cellular GSH more effectively and increased higher ROS level than PL or PEITC but permitted progressive growth of the tested cancer cells. No evident dose-response relationship between cellular ROS level and cytotoxicity was observed. If ROS is the effecter, it should obey the fundamental therapeutic principle - the dose-response relationship. This is a major concern. Source


Wang X.-Z.,Nanjing University | Liang J.-Y.,China Pharmaceutical University | Wen H.-M.,Nanjing University | Shan C.-X.,Nanjing University | Liu R.,Nanjing University
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

A rapid and sensitive ultra fast performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of five bioactive secolignans in Peperomia dindygulensis extract, including peperomin A, peperomin B, peperomin C, 4"-hydroxypeperomin B and 4"-hydroxypeperomin C in rat plasma. Arctigenin was used as the internal standard. The separation was performed on an Innovation™ Polar-RP C18 column by a gradient elution within a runtime of 7min. The mobile phase consisted of A (methanol) and B (0.1% formic acid in water) at a flow rate of 0.4mL/min. The detection was accomplished by using positive ion TurboIonSpray ionization in multiple reaction monitoring mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.9972. The lower limits of quantification were 1.1ng/mL for peperomin A, 1.24ng/mL for peperomin B, 1.02ng/mL for peperomin C, 1.91ng/mL for 4"-hydroxypeperomin B and 1.27ng/mL for 4"-hydroxypeperomin C. The intra- and inter-day precision (RSD%) was within 15% and the accuracy (RE%) ranged from -11.7% to 10.3%. This simple and sensitive method was fully validated and successfully applied to the pharmacokinetic study of peperomin A, peperomin B, peperomin C, 4"-hydroxypeperomin B and 4"-hydroxypeperomin C in rat plasma after oral administration of P. dindygulensis extract. © 2013. Source


Liu J.,Medical College of Wisconsin | Liu J.,China Pharmaceutical University | Yuan Y.,Medical College of Wisconsin | Yuan Y.,Shanghai University of Traditional Chinese Medicine | And 9 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a negative immune-checkpoint protein that suppresses T-cell responses. To determine whether VISTA synergizes with another immune-checkpoint, programmed death 1 (PD-1), this study characterizes the immune responses in VISTA-deficient, PD-1-deficient (KO) mice and VISTA/PD-1 double KO mice. Chronic inflammation and spontaneous activation of T cells were observed in both single KO mice, demonstrating their nonredundancy. However, the VISTA/PD-1 double KO mice exhibited significantly higher levels of these phenotypes than the single KO mice. When bred onto the 2D2 T-cell receptor transgenic mice, which are predisposed to development of inflammatory autoimmune disease in the CNS, the level of disease penetrance was significantly enhanced in the double KO mice compared with in the single KO mice. Consistently, the magnitude of T-cell response toward foreign antigens was synergistically higher in the VISTA/PD-1 double KO mice. A combinatorial blockade using monoclonal antibodies specific for VISTA and PD-L1 achieved optimal tumor-clearing therapeutic efficacy. In conclusion, our study demonstrates the nonredundant role of VISTA that is distinct from the PD-1/PD-L1 pathway in controlling T-cell activation. These findings provide the rationale to concurrently target VISTA and PD-1 pathways for treating T-cell-regulated diseases such as cancer. © 2015, National Academy of Sciences. All rights reserved. Source


Xia J.,Drexel University | Pan R.,Drexel University | Gao X.,Drexel University | Gao X.,China Pharmaceutical University | And 2 more authors.
Journal of Physiology | Year: 2014

A previous study indicates that store-operated calcium channels (SOCs) play a role in pain hypersensitivity. Here we report for the first time that SOCs are expressed and functional in spinal cord dorsal horn neurons. Using the small inhibitory RNA knockdown approach, we have demonstrated that Orai1 is necessary, and both STIM1 and STIM2 are important for SOC entry and SOC current in dorsal horn neurons. Our findings demonstrate that STIM1, STIM2 and Orai1 play an important role in resting Ca2+ homeostasis. Our results also indicate that SOCs are involved in the function of neurokinin 1 receptors and activation of SOCs produces an excitatory action in dorsal horn neurons. The present study reveals that a novel calcium signal mediated by SOCs is present in dorsal horn neurons and provides a potential mechanism for SOC inhibition-induced central analgesia. Store-operated calcium channels (SOCs) are calcium-selective cation channels that mediate calcium entry in many different cell types. Store-operated calcium entry (SOCE) is involved in various cellular functions. Increasing evidence suggests that impairment of SOCE is responsible for numerous disorders. A previous study demonstrated that YM-58483, a potent SOC inhibitor, strongly attenuates chronic pain by systemic or intrathecal injection and completely blocks the second phase of formalin-induced spontaneous nocifensive behaviour, suggesting a potential role of SOCs in central sensitization. However, the expression of SOCs, their molecular identity and function in spinal cord dorsal horn neurons remain elusive. Here, we demonstrate that SOCs are expressed in dorsal horn neurons. Depletion of calcium stores from the endoplasmic reticulum (ER) induced large sustained calcium entry, which was blocked by SOC inhibitors, but not by voltage-gated calcium channel blockers. Depletion of ER calcium stores activated inward calcium-selective currents, which was reduced by replacing Ca2+ with Ba2+ and reversed by SOC inhibitors. Using the small inhibitory RNA knockdown approach, we identified both STIM1 and STIM2 as important mediators of SOCE and SOC current, and Orai1 as a key component of the Ca2+ release-activated Ca2+ channels in dorsal horn neurons. Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca2+ levels. We also found that activation of neurokinin 1 receptors led to SOCE and activation of SOCs pro