Yu H.,Daping Hospital |
Yu H.,Second Affiliated Hospital |
Jin H.,Peking University |
Gong W.,First Affiliated Hospital |
And 2 more authors.
Molecules | Year: 2013
Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and themoregulative effects. Evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design. © 2013 by the authors.
Li X.,Peking University |
Xu G.,Fudan University |
Wang Y.,Xijing University |
Xu X.,Shanghai First Peoples Hospital |
And 8 more authors.
Ophthalmology | Year: 2014
Purpose To assess the safety and efficacy of multiple injections of 0.5 and 2.0 mg conbercept using variable dosing regimens in patients with neovascular age-related macular degeneration (AMD). Design Randomized, double-masked, multicenter, controlled-dose, and interval-ranging phase 2 clinical trial divided into a 3-month loading phase followed by a maintenance phase. Participants Patients with choroidal neovascularization secondary to AMD with lesion sizes of 12 disc areas or less and a best-corrected visual acuity (BCVA) letter score of between 73 and 24 were enrolled. Methods Patients were randomized 1:1 to receive either 0.5 or 2.0 mg intravitreal conbercept for 3 consecutive monthly does. After the third dose, each group was reassigned randomly again to monthly (Q1M group) or as-needed (pro re nata [PRN] group) treatment without changing the drug assignment. Main Outcome Measures The primary end point was the mean change in BCVA from baseline to month 3, with secondary end points being the mean change in BCVA, mean change in central retinal thickness (CRT), and safety at month 12. Results We enrolled 122 patients. At the primary end point at month 3, mean improvements in BCVA from baseline in the 0.5- and 2.0-mg groups were 8.97 and 10.43 letters, respectively. At month 12, mean improvements in BCVA from baseline were 14.31, 9.31, 12.42, and 15.43 letters for the 0.5-mg PRN, 0.5-mg Q1M, 2.0-mg PRN, and 2.0-mg Q1M regimens, respectively. At month 12, mean reductions in CRT in the 4 regimens were 119.8, 129.7, 152.1, and 170.8 μm, respectively. There were no significant differences for the pairwise comparisons between all study groups. The difference in the number of injections between the 2 PRN groups was not statistically significant. Treatment with conbercept generally was safe and well tolerated. Conclusions The significant gains in BCVA at 3 months were the same or better at 12 months in all conbercept dosing groups of neovascular AMD patients. During the 12 months, repeated intravitreal injections of conbercept were well tolerated in these patients. Future clinical trials are required to confirm its long-term efficacy and safety. © 2014 by the American Academy of Ophthalmology.
Hu R.-F.,Fujian Medical University |
Jiang X.-Y.,Fujian Medical University |
Zeng Y.-M.,Second Affiliated Hospital |
Chen X.-Y.,Second Affiliated Hospital |
Zhang Y.-H.,Fujian Province Hospital
Critical Care | Year: 2010
Introduction: Environmental stimulus, especially noise and light, is thought to disrupt sleep in patients in the intensive care unit (ICU). This study aimed to determine the physiological and psychological effects of ICU noise and light, and of earplugs and eye masks, used in these conditions in healthy subjects.Methods: Fourteen subjects underwent polysomnography under four conditions: adaptation, baseline, exposure to recorded ICU noise and light (NL), and NL plus use of earplugs and eye masks (NLEE). Urine was analyzed for melatonin and cortisol levels. Subjects rated their perceived sleep quality, anxiety levels and perception of environmental stimuli.Results: Subjects had poorer perceived sleep quality, more light sleep, longer rapid eye movement (REM) latency, less REM sleep when exposed to simulated ICU noise and light (P < 0.05). Nocturnal melatonin (P = 0.007) and cortisol secretion levels (P = 0.004) differed significantly by condition but anxiety levels did not (P = 0.06). Use of earplugs and eye masks resulted in more REM time, shorter REM latency, less arousal (P < 0.05) and elevated melatonin levels (P = 0.002).Conclusions: Earplugs and eye masks promote sleep and hormone balance in healthy subjects exposed to simulated ICU noise and light, making their promotion in ICU patients reasonable. © 2010 Hu et al.; licensee BioMed Central Ltd.
Chen S.,Second Affiliated Hospital |
Chen S.,Loma Linda University |
Ma Q.,Loma Linda University |
Krafft P.R.,Loma Linda University |
And 4 more authors.
Critical Care Medicine | Year: 2013
OBJECTIVES:: Brilliant blue G, a selective P2X7 receptor antagonist, exhibits neuroprotective properties. This study examined whether brilliant blue G treatment ameliorates early brain injury after experimental subarachnoid hemorrhage, specifically via inhibiting p38 mitogen-activated protein kinase-related proapoptotic pathways. DESIGN:: Controlled in vivo laboratory study. SETTING:: Animal research laboratory. SUBJECTS:: One hundred fifty-four adult male Sprague-Dawley rats weighing 280-320 g. INTERVENTIONS:: Subarachnoid hemorrhage was induced in rats by endovascular perforation. Experiment 1 implemented sham-operated rats (sham) and subarachnoid hemorrhage animals, which received vehicle (subarachnoid hemorrhage + vehicle), brilliant blue G (subarachnoid hemorrhage + brilliant blue G), or brilliant blue G plus 2'(3')-O-(4-Benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) (subarachnoid hemorrhage + brilliant blue G + BzATP). The animals were intraperitoneally treated with brilliant blue G (30 mg/kg) at 30 minutes after subarachnoid hemorrhage. BzATP (50 μg/rat), a P2X7 receptor agonist, was intracerebroventricularly administered. Experiment 2 implemented sham-operated rats (sham) and subarachnoid hemorrhage animals, which received vehicle (subarachnoid hemorrhage + vehicle), scramble small interfering RNA (subarachnoid hemorrhage + scramble small interfering RNA), or P2X7 receptor small interfering RNA (subarachnoid hemorrhage + P2X7 receptor small interfering RNA). Subarachnoid hemorrhage grading, neurobehavioral score, and brain edema were evaluated at 24 and 72 hours after surgery. The expression of phosphorylated p38 mitogen-activated protein kinase, phosphorylated extracellular signal-regulated kinases, phosphorylated c-Jun N-terminal kinases, P2X7 receptor, Bcl-2, and cleaved caspase-3 in the left cerebral hemisphere were determined by Western blot. Neuronal apoptosis was examined by double immunofluorescence staining using P2X7 receptor, terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling, and neuronal nuclei. MEASUREMENTS AND MAIN RESULTS:: Brilliant blue G significantly improved neurobehavioral function and ameliorated brain water content at 24 and 72 hours after subarachnoid hemorrhage. BzATP reversed these treatment effects. Brilliant blue G attenuated neuronal apoptosis in the subcortex, which was associated with decreased expression of phosphorylated p38 mitogen-activated protein kinase and cleaved caspase-3 and an increased expression of Bcl-2 in the left cerebral hemisphere. The beneficial effects of P2X7 receptor small interfering RNA were also mediated by a p38 mitogen-activated protein kinase pathway. CONCLUSIONS:: Inhibition of P2X7 receptor by brilliant blue G or P2X7 receptor small interfering RNA can prevent early brain injury via p38 mitogen-activated protein kinase after subarachnoid hemorrhage. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
Wu C.-X.,Chongqing Medical University |
Sun H.,Second Affiliated Hospital |
Liu Q.,Second Affiliated Hospital |
Guo H.,Second Affiliated Hospital |
Gong J.-P.,Chongqing Medical University
Journal of Surgical Research | Year: 2012
Background: High mobility group protein B1 (HMGB1) is an important late inflammatory mediator in sepsis. Understanding the mechanisms that regulate HMGB1 release from cells and their downstream signal transduction pathways may lead to the ability to develop anti-HMGB1 therapies to treat inflammation. Materials and Methods: We stimulated murine macrophage-like RAW 264.7 cells with lipopolysaccharide (LPS) and LPS+ ethylpyruvate (EP) and examined the resulting HMGB1 expression and release. We also studied the expression of related signal transduction factors (NF-κB, p38 MAPK, and CBP). Results and Conclusion: Gene expression of HMGB1 mRNA in RAW264.7 cell showed no significant change at 0-18 h after stimulation with LPS, but increased significantly at 24, 36, and 48 h. HMGB1 mRNA expression in the LPS+EP group was significantly lower than in LPS alone. HMGB1 was distributed mainly in the nucleus; the cytoplasmic level was low before LPS stimulation. After stimulation with LPS, cytoplasmic HMGB1 increased gradually and plateaued at a high level at 12-48 h. Nuclear HMGB1 decreased gradually at 12-24 h, then increased, maintaining a comparatively high level at 36-48 h. EP prevented this pattern significantly. LPS induced p38 MAPK activation and NF-κB signal pathways first, followed by CBP activation. Activated CBP acetylated HMGB1 was stored in a crino-lysosome and secreted activated NF-κB resulted in increased transcription and synthesis of HMGB1, but the expression of up-regulated HMGB1 mRNA was delayed. Extracellular HMGB1 originated from early synthetic reserves present in the nucleus. New HMGB1 protein was synthesized in the nucleus and transferred into the cytoplasm, causing an increase in HMGB1 in the nucleus and cytoplasm. EP inhibits HMGB1 mRNA up-regulation and release from LPS- stimulated macrophages. The molecular function of EP is to attenuate the activation p38 MAPK, NF-κB, and CBP signaling pathways. © 2012 Elsevier Inc. All rights reserved.
News Article | February 15, 2017
Research and Markets has announced the addition of the "T-Cell Immunotherapy Market (2nd Edition), 2017-2030" report to their offering. The "T-Cell Immunotherapy Market, 2017-2030 (2nd edition)" report features an extensive study of the current market landscape and the future potential of T-cell immunotherapies. Immuno-oncology has been gradually nurtured by researchers over the last several years and is now considered as the fourth major pillar of cancer therapy, after surgery, chemotherapy and radiotherapy. As indicated earlier, the T-cell therapy market has evolved significantly over the last few years, offering promising opportunities for a variety of stakeholders. The overall market is expected to witness a significant growth in opportunities for a variety of stakeholders in the coming decade. It is important to highlight that various technology providers, aiming to develop and/or support the development of T-cell immunotherapy products with improved efficacy and safety, have designed and introduced advanced platforms for engineering of T-cells. Innovation in this domain, backed by lucrative rounds of venture capital (VC) funding, has led to the discovery of several novel molecular targets and strengthened the research pipelines of companies focused in this space. The capability to target diverse therapeutic areas is amongst the most prominent growth drivers of this market. The domain is characterized by a robust and opportunistic pipeline of product candidates focused on targeting hematological cancers and solid tumors. However, with no marketed products, this emerging field is still in its infancy. The report provides a comprehensive overview of the market, focusing particularly on CAR-T therapies, TCR therapies and TIL therapies. - Second Affiliated Hospital of Henan University of Traditional Chinese Medicine For more information about this report visit http://www.researchandmarkets.com/research/sxjg8d/tcell
Xie J.,Second Affiliated Hospital
National Medical Journal of China | Year: 2015
Objective To explore the serum level of sclerostin in ankylosing spondylitis (AS) patients and evaluate its diagnostic value and the relationship of sclerostin with inflammation and ossification process in AS. Methods A total of 75 AS patients and 45 healthy controls were enrolled into this randomized controlled study. The clinical indices (age, gender, course of disease and disease activity), changes in radiographic studies and indices of bone metabolism or inflammation, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated or measured. The disease activity was assessed by Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI) and Bath arthritis spondylitis radiology index (BASRI). And radiographic changes were evaluated according to the modified Stoke AS spine score (mSASSS) and serum level of sclerostin was measured by enzyme-linked immunosorbent assay (ELISA). The relationship between sclerostin and clinical indices, radiographic scores and inflammatory indices was estimated by SPSS software and the diagnostic value of sclerostin analyzed by-receiver operator characteristic (ROC) curve. Results The levels of ESR and CRP were higher in AS patients than those in healthy controls. However, serum sclerostin was lower (55.6 ± 19.5 pmol/L) compared with healthy controls (78 ±27. 6 pmol/L, P <0.01). ROC analysis revealed that the diagnostic specificity and sensitivity of sclerostin were 91.5% and 82. 02% respectively with a cut-off of 62. 75 pmol/L (Youden index 0.735, AUC 0.905, 95% CI 0.812 - 0.947). And the diagnostic validity was high. No significant correlation existed between sclerostin and ESR, CRP, BASDAI, BASMI and BASFI scores. ESR, CRP. BASDAI, BASMI and BASFI score were improved significantly in AS patients after anti-TNF treatment compared with baseline (P <0.01). There was little difference between BASRI and mSASSS score after anti-TNF treatment compared with baseline (P = 0.19, 0.67). A significant negative correlation existed between the radiographic progression in spine of patients with AS and sclerostin serum levels (r = 0.768, P < 0.01). This correlation became stronger when radiographic scores rose (mSASSS > 10, r =0.768, P < 0.01) and it diminished when radiographic scores dropped (0 < mSASSS < 10, r = - 0.097, P = 0.43). Conclusion Serum sclerostin may serve as a diagnostic biomarker of AS and progression index of ossification, especially in late stage of AS. A low serum level of sclerostin in the setting of AS is linked to greater structural damage.
Guo C.,Second Affiliated Hospital |
Jiang K.,Hangzhou Normal University |
Zheng S.,Second Affiliated Hospital
Rapid Communications in Mass Spectrometry | Year: 2014
RATIONALE: Electrospray ionization mass spectrometry (ESI-MS) combined with the collision-induced dissociation (CID) technique has assumed increasing importance as an invaluable tool for the structural analysis of organic and biological molecules. However, general rules for elucidating the fragmentation behaviors of charged molecules in the gas phase are still lacking. Therefore, explorations on the mechanistic information are desirable at all times. METHODS: CID experiments of protonated N-benzyltetrahydroquinolines were carried out on ESI ion trap mass spectrometer and accurate mass measurements were performed on a high-resolution ESI quadrupole time-of-flight (Q-TOF) mass spectrometer in positive ion mode. RESULTS: An ion/neutral complex, [RC6H 4CH2 +/tetrahydroquinoline], resulting from cleavage of the C-N bond induced by the positive charge brought in by protonation, was proposed to be the intermediate to elucidate the fragmentation reactions. For all the compounds investigated, benzyl cation transfer, electron transfer and hydride transfer reactions mediated by the complex were observed. Moreover, for the compound substituted by a methyl group at the para-position of the benzylic phenyl ring, proton transfer reaction via the complex also occurs. CONCLUSIONS: This study is a case for better understanding the intriguing roles of ion/neutral complexes in gas-phase fragmentation reactions and enriching the knowledge about the gas-phase chemistry of the benzyl cation. In addition, it provides useful information for researchers working on analysis or structural elucidation of complicated compounds which contain the N- benzyltetrahydroquinoline substructure. Copyright © 2014 John Wiley & Sons, Ltd.
Wang X.F.,Second Affiliated Hospital |
Lei Y.,Second Affiliated Hospital |
Chen M.,Second Affiliated Hospital |
Chen C.B.,Second Affiliated Hospital |
And 2 more authors.
Journal of Viral Hepatitis | Year: 2013
α-Galactosylceramide (α-GalCer)-activated natural killer T (NKT) cells have antiviral properties against hepatitis B virus (HBV). However, α-GalCer activation of NKT cells can induce anergy. We hypothesized that this effect may be overcome by a treatment strategy that includes manipulation of CD28/CD80 costimulatory and PD-1/PDL1 coinhibitory signals of NKT cells, thereby enhancing the anti-HBV effect of α-GalCer. We established a transgenic mouse model of chronic HBV infection and investigated hepatic NKT cell frequencies, functions and expression of immunomodulatory factors. Our results showed that compared with uninfected control mice, hepatic NKT cells from HBV transgenic mice displayed lower frequencies (7.91% vs 16.74%, P < 0.05), impaired capabilities to produce interferon (IFN)-γ (5.6% vs 1.4%, P < 0.05) and interleukin (IL)-4 (6.8% vs 0.3%, P < 0.05), higher expression of PD-1 (9.64% vs 6.36%, P < 0.05) and lower expression of CD28 (5.05% vs 28.88%, P < 0.05). However, when hepatic mononuclear cells (MNCs) were isolated from HBV transgenic mice, α-GalCer exposure in culture remarkably upregulated both PD-1+ NKT cells (P < 0.05) and CD28+ NKT cells (P < 0.05). Furthermore, when HBV transgenic mice were treated with combination therapies consisting of α-GalCer and anti-PDL1 monoclonal antibody (mAb) and/or anti-CD80/anti-CD28 mAbs, IFN-γ+ NKT cell frequency was selectively increased (P < 0.05) and HBV replication was suppressed; these effects were accompanied by varying degrees and types of liver damage. Surprisingly, activating CD28/CD80 signal in HBV transgenic mice was more effective but caused less liver injury than blocking PD-1/PDL1 signal in modulating αGalCer-activated NKT cell function to inhibit HBV infection. Our findings also show that combined therapy with blocking PD-1/PDL1 and activating CD28/CD80 signal in the presence of aGalCer cannot superimpose the effect of antivirus. α-GalCer combination therapy that modulates the CD28/CD80 pathways of NKT cells may represent a promising approach to inhibit HBV replication in chronically infected patients. © 2012 Blackwell Publishing Ltd.
Zhou Q.-H.,Second Affiliated Hospital |
Xiao W.-P.,Second Affiliated Hospital |
Zhou H.-M.,Second Affiliated Hospital
Paediatric Anaesthesia | Year: 2015
Summary Background It is challenging for anesthetists to determine the optimal tracheal intubation depth in children. We hypothesize that a measure three times the length of the middle finger can be used for predicting tracheal tube depth in children. Methods Eighty-six children (4-14 years of age) were included in this study. After the children were anesthetized, a fiberoptic bronchoscope (FOB) was inserted into the trachea, the lengths from the upper incisor teeth to carina and vocal cords were measured, and a suitably sized cuffed tracheal tube was inserted into the trachea. Age-based and middle finger length-based formulas were used to determine the tracheal intubation depth. Results All 86 children enrolled were included in this study. Compared with the age-based intubation, the rate of appropriate tube placement was higher for middle finger length-based intubation (88.37% vs 66.28%, P = 0.001). The proximal intubation rate was lower in middle finger length-based intubation (4.65% vs 32.56%, P < 0.001). There was only weak evidence for a difference in the distal intubation rate between the two methods (6.97% vs 1.16%, P = 0.054). The correlation coefficient between middle finger length and optimal tracheal tube depth was larger than that between age and optimal tracheal tube depth (0.883 vs 0.845). Conclusions Our data indicate that the appropriate tube placement rate can be improved by using three times the middle finger length as the tracheal intubation depth in children. © 2015 John Wiley and Sons Ltd.