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61.
Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening
JianMin Jia XiaoLi Xu Fang Liu XiaoKe Guo MingYe Zhang MengChen Lu LiLi Xu JinLian Wei Jia Zhu ShengLie Zhang ShengMiao Zhang HaoPeng Sun QiDong You 《PloS one》2013,8(4)
Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC50 value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization. 相似文献
62.
Yuan Lu Yan Dong Yan Zhang Di Shen Xiyao Wang Ruxiu Ge Meihua Zhang Yu Xia Xietong Wang 《Journal of cellular and molecular medicine》2020,24(12):6690-6703
Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell‐free DNA and NET marker levels. Live‐cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell‐free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS‐IgG) induced neutrophils from HCs to release NETs. Additionally, APS‐IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS‐IgG‐induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS. 相似文献
63.
Miaoda Shen Zhuoyang Li Duo Lv Ge Yang Ronghuan Wu Jun Pan Shuo Wang Yifan Li Sanzhong Xu 《Journal of cellular and molecular medicine》2020,24(13):7370-7377
This study aimed to describe the 25‐hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four‐season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals. 相似文献
64.
65.
Yun Ge Man Huang Yao Wu Ning Dong Yong‐Ming Yao 《Journal of cellular and molecular medicine》2020,24(2):2027-2039
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated immune response of CD4+CD25+ Tregs in sepsis. Here, we provide evidence that expressions of IL‐38 and its receptor were detected in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up‐regulated the expression of IL‐38. Treatment with rmIL‐38 dramatically enhanced the immunosuppressive activity of CD4+CD25+ Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti–IL‐38 antibody was administered. Administration of rmIL‐38 improved the survival rate of CLP mice. In addition, CD4+CD25+ Tregs depletion before the onset of sepsis obviously abolished IL‐38–mediated protective response. These findings suggest that IL‐38 enhances the immunosuppressive activity of CD4+CD25+ Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis. 相似文献
66.
Tong tong Ge Xiao Xiao Yao Feng Lian Zhao Xiao han Zou Wei Yang Ran Ji Cui Bing jin Li 《Journal of cellular and molecular medicine》2020,24(8):4524-4532
Leptin is well acknowledged as an anorexigenic hormone that plays an important role in feeding control. Hypothalamic GABA system plays a significant role in leptin regulation on feeding and metabolism control. However, the pharmacological relationship of leptin and GABA receptor is still obscure. Therefore, we investigated the effect of leptin or combined with baclofen on the food intake in fasted mice. We detected the changes in hypothalamic c‐Fos expression, hypothalamic TH, POMC and GAD67 expression, plasma insulin, POMC and GABA levels to demonstrate the mechanisms. We found that leptin inhibit fasting‐induced increased food intake and activated hypothalamic neurons. The inhibitory effect on food intake induced by leptin in fasted mice can be reversed by pretreatment with baclofen. Baclofen reversed leptin's inhibition on c‐Fos expression of PAMM in fasted mice. Therefore, these results indicate that leptin might inhibit fasting‐triggered activation of PVN neurons via presynaptic GABA synaptic functions which might be partially blocked by pharmacological activating GABA‐B. Our findings identify the role of leptin in the regulation of food intake. 相似文献
67.
Potassium ion hybrid capacitors have great potential for large‐scale energy devices, because of the high power density and low cost. However, their practical applications are hindered by their low energy density, as well as electrolyte decomposition and collector corrosion at high potential in potassium bis(fluoro‐sulfonyl)imide‐based electrolyte. Therefore, anode materials with high capacity, a suitable voltage platform, and stability become a key factor. Here, N‐doping carbon‐coated FeSe2 clusters are demonstrated as the anode material for a hybrid capacitor, delivering a reversible capacity of 295 mAh g?1 at 100 mA g?1 over 100 cycles and a high rate capability of 158 mAh g?1 at 2000 mA g?1 over 2000 cycles. Meanwhile, through density functional theory calculations, in situ X‐ray diffraction, and ex situ transmission electron microscopy, the evolution of FeSe2 to Fe3Se4 for the electrochemical reaction mechanism is successfully revealed. The battery‐supercapacitor hybrid using commercial activated carbon as the cathode and FeSe2/N‐C as the anode is obtained. It delivers a high energy density of 230 Wh kg?1 and a power density of 920 W kg?1 (the energy density and power density are calculated based on the total mass of active materials in the anode and cathode). 相似文献
68.
Lu Wan Cuili Zhang Kunpeng Ge Xueliang Yang Feng Li Wensheng Yan Zhuo Xu Lin Yang Ying Xu Dengyuan Song Jianhui Chen 《Liver Transplantation》2020,10(16)
Defect state passivation and conductivity of materials are always in opposition; thus, it is unlikely for one material to possess both excellent carrier transport and defect state passivation simultaneously. As a result, the use of partial passivation and local contact strategies are required for silicon solar cells, which leads to fabrication processes with technical complexities. Thus, one material that possesses both a good passivation and conductivity is highly desirable in silicon photovoltaic (PV) cells. In this work, a passivation‐conductivity phase‐like diagram is presented and a conductive‐passivating‐carrier‐selective contact is achieved using PEDOT:Nafion composite thin films. A power conversion efficiency of 18.8% is reported for an industrial multicrystalline silicon solar cell with a back PEDOT:Nafion contact, demonstrating a solution‐processed organic passivating contact concept. This concept has the potential advantages of omitting the use of conventional dielectric passivation materials deposited by costly high‐vacuum equipment, energy‐intensive high‐temperature processes, and complex laser opening steps. This work also contributes an effective back‐surface field scheme and a new hole‐selective contact for p‐type and n‐type silicon solar cells, respectively, both for research purposes and as a low‐cost surface engineering strategy for future Si‐based PV technologies. 相似文献
69.
70.
Zaiyu Zheng Jinxian Yang Junqing Ge Hongshu Chi Bin Chen Qinmei Fang Hui Gong 《Cell biology international》2020,44(3):808-820
In the present study, a new hepatic tissue‐origin cell line from European eel Anguilla anguilla has been developed and characterized. This cell line designated EL has been maintained in Leibovitz L‐15 supplemented with 10% fetal bovine serum over 72 months, and subcultured more than 90 times. The EL cell line consisted predominantly of fibroblast‐like cells, which could survive over 100 days in vitro, and could grow at 15–32°C. The optimum temperature for growth was 27°C. The chromosome analysis revealed a modal diploid karyotype of 2n = 38. The origin of this cell line was confirmed by the 18S recombinant (r)RNA sequencing. The susceptibility test indicated significant cytopathic effects in the EL cells with regard to the Rana grylio virus and the Herpesvirus anguillae. The viral replication was confirmed by transmission electron microscopy and polymerase chain reaction analysis. Following poly (I:C) exposure, the expression levels of the immune‐related molecules interferon regulatory factor‐7 (irf7) and transforming growth factor‐β (TGF‐β) were downregulated in EL cells, whereas the expression levels of the rf3 and the cytochrome P450 (CYP450) were upregulated. All four genes were significantly upregulated following inflammation by lipopolysaccharide (LPS). These data suggested the application of EL cell line for viral identification, as well as for immunodiagnosis and pharmacological targeting. 相似文献