State Key Laboratory of Medicinal Chemical Biology

State Key Laboratory of Medicinal Chemical Biology

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Wang C.,Nankai University | Wang S.,Nankai University | Cai W.,Nankai University | Shao X.,Nankai University | And 2 more authors.
Talanta | Year: 2017

Near-infrared diffuse reflectance spectroscopy (NIRDRS) has been proved to be a convenient and fast quantitative method for complex samples. The sensitivity or the detection limit, however, has been the obstacle in practical uses, although great efforts have been made through experimental and chemometric approaches. Due to the strong reflectivity of silver in near–infrared region, a novel method that utilizes silver layer as the adsorption substrate was developed to enhance the detection ability of NIRDRS in this study. For investigating the enhancement effect of the method, lysozyme samples with different concentrations were spotted on the silver layer and NIR spectra were measured. Then quantitative determination was performed using multivariate calibration. For comparison, the comparative experiment was performed using the copper sheet as the substrate. The results show that the intensity of diffuse reflection can be enhanced, and the background variation was reduced by taking the mirror layer as the substrate. A linear variation was obtained between the concentrations and the intensities of the spectral response at a wavenumber. Using multivariate calibration for quantitative analysis, the optimal PLS model was obtained. The maximum deviation of the prediction results can be as low as 12.8 µg. Therefore, this study made a progress for NIRDRS technique in microanalysis. © 2016 Elsevier B.V.

Zhang S.,Nankai University | Han P.,State Key Laboratory of Medicinal Chemical Biology | Xia Y.,Nankai University | Xia Y.,State Key Laboratory of Medicinal Chemical Biology
Journal of Chromatography A | Year: 2017

Quaternary amine functionalized metal-organic framework MIL-101(Cr) (MIL-101(Cr)-NMe3) was prepared as the sorbent for the magnetic solid-phase extraction (MSPE) of azide from sartan drugs before ion chromatography determination. Magnetization of MIL-101-NMe3 were achieved concurrently by adding MIL-101-NMe3 and Fe3O4@SiO2 to the sample solution under ultrasonication. The prepared Fe3O4@SiO2/MIL-101-NMe3 gave the adsorption capacity of 37.5mgg-1. The developed method had a detection limit of 0.24μgL-1 and quantitation limit of 0.79μgL-1 for azide. The relative standard deviations for the intra-day retention time and peak area were 0.52% and 0.36% (n=5), respectively. The developed method was successfully applied for the determination of azide in sartan drugs with the recoveries from 96.5% to 100.5%. © 2017.

Wei C.,Nankai University | Feng D.,Nankai University | Xia Y.,Nankai University | Xia Y.,Key Laboratory of Biosensing and Molecular Recognition | Xia Y.,State Key Laboratory of Medicinal Chemical Biology
RSC Advances | Year: 2016

An amino functionalized zirconium-based MOF named UiO-66-NH2 was synthesized and explored as a novel adsorbent for the fast removal of 2-methyl-4-chlorophenoxy acetic acid (MCPA) in aqueous solution. The adsorption process of kinetics, adsorption isotherms, thermodynamics, and adsorbent regeneration were investigated and the effects of key parameters such as adsorbent dosage, pH value and ionic strength on the adsorption of MCPA were also studied. The results showed that the adsorption of MCPA on UiO-66-NH2 was very fast, and most of MCPA were adsorbed in the first 3 min. A pseudo-second-order rate equation effectively described the adsorption kinetics. The adsorption process fits the Langmuir adsorption model well, and the maximum adsorption capacity is 300.3 mg g-1 at 25 °C. The analysis of the adsorption mechanism showed that the hydrogen bond interaction, electrostatic interaction and π-π stacking interaction between the MCPA and UiO-66-NH2 were responsible for the efficient adsorption. Regeneration experiments indicated that the used UiO-66-NH2 was recycled at least six times without significant loss of adsorption capacity. The fast adsorption kinetics, high adsorption capacity, excellent reusability and good chemical stability make UiO-66-NH2 attractive for removal MCPA from aqueous solution. © 2016 The Royal Society of Chemistry.

Yang X.,Nankai University | Xia Y.,Nankai University | Xia Y.,Key Laboratory of Biosensing and Molecular Recognition | Xia Y.,State Key Laboratory of Medicinal Chemical Biology
Microchimica Acta | Year: 2016

Mass spectrometry (MS) is the most powerful tool in phosphoproteomics research. However, phosphopeptides usually are present in low concentrations and their preconcentration therefore is highly desired. We describe a two-step method for the synthesis of a metal organic framework of the type MIL-101(Cr) that is modified with urea (then designated as MIL-101(Cr)-UR2). It possesses large surface area, good solvent stability and high affinity for some phosphates. Due to the presence of modified urea functions, this material allows for selective and effective enrichment of phosphorylated peptides. It was successfully applied to the enrichment of phosphopeptides from non-fat-milk. The method was applied to the detection of phosphopeptides in a tryptic digest of β-casein where is showed a detection sensitivity as low as 10−10 M. [Figure not available: see fulltext.] © 2016 Springer-Verlag Wien

PubMed | Nankai University, PLA Fourth Military Medical University and State Key Laboratory of Medicinal Chemical Biology
Type: | Journal: Scientific reports | Year: 2015

We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-B signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells.

Zhang D.,State Key Laboratory of Medicinal Chemical Biology | Zhang X.,State Key Laboratory of Medicinal Chemical Biology | Zeng M.,State Key Laboratory of Medicinal Chemical Biology | Yuan J.,State Key Laboratory of Medicinal Chemical Biology | And 5 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2015

Purpose: Ovarian aging is closely tied to the decline in ovarian follicular reserve and oocyte quality. During the prolonged reproductive lifespan of the female, granulosa cells connected with oocytes play critical roles in maintaining follicle reservoir, oocyte growth and follicular development. We tested whether double-strand breaks (DSBs) and repair in granulosa cells within the follicular reservoir are associated with ovarian aging. Methods: Ovaries were sectioned and processed for epi-fluorescence microscopy, confocal microscopy, and immunohistochemistry. DNA damage was revealed by immunstaining of γH2AX foci and telomere damage by γH2AX foci co-localized with telomere associated protein TRF2. DNA repair was indicated by BRCA1 immunofluorescence. Results: DSBs in granulosa cells increase and DSB repair ability, characterized by BRCA1 foci, decreases with advancing age. γH2AX foci increase in primordial, primary and secondary follicles with advancing age. Likewise, telomere damage increases with advancing age. In contrast, BRCA1 foci in granulosa cells of primordial, primary and secondary follicles decrease with monkey age. BRCA1 positive foci in the oocyte nuclei also decline with maternal age. Conclusions: Increased DSBs and reduced DNA repair in granulosa cells may contribute to ovarian aging. Discovery of therapeutics that targets these pathways might help maintain follicle reserve and postpone ovarian dysfunction with age. © 2015, Springer Science+Business Media New York.

Zhang Z.,Nankai University | Zhang Z.,State Key Laboratory of Medicinal Chemical Biology | Li L.-Y.,Nankai University | Li L.-Y.,State Key Laboratory of Medicinal Chemical Biology
Cancer Microenvironment | Year: 2012

Tumor necrosis factor superfamily-15 (TNFSF15; also known as VEGI or TL1A) is a unique cytokine that functions in the modulation of vascular homeostasis and inflammation. TNFSF15 is expressed abundantly in established vasculature but is down-regulated at sites of neovascularization such as in cancers and wounds. TNFSF15 inhibits endothelial cell proliferation and endothelial progenitor cell differentiation. Additionally, TNFSF15 stimulates T cell activation, Th1 cytokine production, and dendritic cell maturation. Some of the functions of TNFSF15 are mediated by death receptor-3. We review the experimental evidences on TNFSF15 activities in angiogenesis, vasculogenesis, inflammation, and immune system mobilization. © 2012 Springer Science+Business Media B.V.

Jiang D.,State Key Laboratory of Medicinal Chemical Biology | Jiang D.,Nankai University | Zhang Q.,State Key Laboratory of Medicinal Chemical Biology | Zhang Q.,Nankai University | And 12 more authors.
FEBS Journal | Year: 2014

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most devastating human diseases, and is responsible for ∼ 2 million deaths worldwide each year. The nutritional requirements for the growth of mycobacteria have been extensively studied since the discovery of M. tuberculosis, but the essential nutrients for M. tuberculosis inside the human host and the identity of the corresponding transporters remain unknown. The UgpABCE transporter of M. tuberculosis is one of five putative permeases for carbohydrate uptake, and is genetically predicted to be an sn-glycerol 3-phosphate importer. We have determined the 1.5-Å crystal structure of M. tuberculosis UgpB, which has been reported to be a promising vaccine candidate against TB. M. tuberculosis UgpB showed no detectable binding activity for sn-glycerol 3-phosphate by isothermal titration calorimetry, but instead showed a preference for glycerophosphocholine (GPC). M. tuberculosis UgpB largely resembles its Escherichia coli homolog, but with the critical Trp169 in the substrate-binding site of E. Coli UgpB replaced by Leu205. Mutation of Leu205 abolishes GPC binding, suggesting that Leu205 is a determinant of GPC binding. The work reported here not only contributes to our understanding of the carbon and phosphate sources utilized by M. tuberculosis inside the human host, but will also promote improvements in TB chemotherapy. © 2013 FEBS.

Wu F.,Nankai University | Wu F.,Tianjin Key Laboratory of Protein science | Hu X.,Nankai University | Hu X.,Tianjin Key Laboratory of Protein science | And 7 more authors.
Protein and Cell | Year: 2014

Formation of the endoplasmic reticulum (ER) network requires homotypic membrane fusion, which involves a class of atlastin (ATL) GTPases. Purified Drosophila ATL is capable of mediating vesicle fusion in vitro, but such activity has not been reported for any other ATLs. Here, we determined the preliminary crystal structure of the cytosolic segment of Drosophila ATL in a GDP-bound state. The structure reveals a GTPase domain dimer with the subsequent three-helix bundles associating with their own GTPase domains and pointing in opposite directions. This conformation is similar to that of human ATL1, to which GDP and high concentrations of inorganic phosphate, but not GDP only, were included. Drosophila ATL restored ER morphology defects in mammalian cells lacking ATLs, and measurements of nucleotide-dependent dimerization and GTPase activity were comparable for Drosophila ATL and human ATL1. However, purified and reconstituted human ATL1 exhibited no in vitro fusion activity. When the cytosolic segment of human ATL1 was connected to the transmembrane (TM) region and C-terminal tail (CT) of Drosophila ATL, the chimera still exhibited no fusion activity, though its GTPase activity was normal. These results suggest that GDP-bound ATLs may adopt multiple conformations and the in vitro fusion activity of ATL cannot be achieved by a simple collection of functional domains. © 2014, The Author(s).

PubMed | State Key Laboratory of Medicinal Chemical Biology
Type: Journal Article | Journal: Angiogenesis | Year: 2012

Persistent inflammation and neovascularization are critical to cancer development. In addition to upregulation of positive control mechanisms such as overexpression of angiogenic and inflammatory factors in the cancer microenvironment, loss of otherwise normally functioning negative control mechanisms is likely to be an important attribute. Insights into the down-modulation of such negative control mechanisms remain largely unclear, however. We show here that tumor necrosis factor superfamily-15 (TNFSF15), an endogenous inhibitor of neovascularization, is a critical component of the negative control mechanism that operates in normal ovary but is missing in ovarian cancer. We show in clinical settings that TNFSF15 is present prominently in the vasculature of normal ovary but diminishes in ovarian cancer as the disease progresses. Vascular endothelial growth factor (VEGF) produced by cancer cells and monocyte chemotactic protein-1 (MCP-1) produced mainly by tumor-infiltrating macrophages and regulatory T cells effectively inhibits TNFSF15 production by endothelial cells in vitro. Using a mouse syngeneic tumor model, we demonstrate that silencing TNFSF15 by topical shRNA treatments prior to and following mouse ovarian cancer ID8 cell inoculation greatly facilitates angiogenesis and tumor growth, whereas systemic application of recombinant TNFSF15 inhibits angiogenesis and tumor growth. Our findings indicate that downregulation of TNFSF15 by cancer cells and tumor infiltrating macrophages and lymphocytes is a pre-requisite for tumor neovascularization.

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