摘要：
OBJECTIVE: Postpartum depression (PPD) is an episode of major depressive disorder that affecting women of childbearing age. 5-HTTLPR is 1 of the most extensively investigated polymorphisms in PPD. However, the previous results were inconsistent and inclusive. Hence, we performed a meta-analysis to precisely evaluate the association between 5-HTTLPR polymorphism and PPD susceptibility. METHODS: The studies were retrieved through databases including PubMed, web of science, EMASE, and CNKI. The odd ratios (ORs) and 95% confidence interval (CIs) were applied for evaluating the genetic association between 5-HTTLPR (L/S) polymorphism and PPD risk. RESULTS: Six studies with 519 cases and 737 controls were enrolled in the present study. The frequencies of allelic (OR = 0.72, 95%CI = 0.60-0.85, P = .0001) and dominant (OR = 0.57, 95%CI = 0.44-0.73, P = .004) models of 5-HTTLPR polymorphism significantly decreased in patients with PPD than those in the healthy controls. Subgroup analysis based on ethnicity revealed that the allelic (OR = 0.71, 95%CI = 0.60-0.85, P = .0001) and dominant (OR = 0.51, 95%CI = 0.32-0.79, P = .003) models of 5-HTTLPR polymorphism were significantly associated with PPD risk in Asian population (P > .05). No evidence was observed between the recessive model of 5-HTTLPR polymorphism and PPD risk (P > .05). CONCLUSIONS: The allelic and dominant models of 5-HTTLPR polymorphism might be protective factors for PPD. To confirm these results, larger number of association studies or multicenter case-control studies are necessary in the future.
摘要：
Minimally modified low-density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study was designed to investigate the effect of a Toll-like receptor 4 monoclonal antibody (TLR4 mAb) on mmLDL-induced endothelium-dependent vasodilation (EDV) impairment in mouse mesenteric arteries and to explore the underlying mechanism. Animals were divided into a normal control group, an mmLDL treatment group, and a TLR4 mAb intervention group. The serum concentrations of IL-1beta and TNF-alpha were detected using enzyme-linked immunosorbent assays (ELISAs). EDV function was measured using a microvascular tension tracing method. The protein levels and mRNA expression of IL-1beta and TNF-alpha in vascular tissue were detected using western blot analysis and reverse transcription polymerase chain reaction, respectively. TLR4 mAb improved mmLDL-induced EDV functional impairment in a dose-dependent manner. TLR4 mAb significantly upregulated KCa3.1 and KCa2.3 channel protein levels and downregulated TNF-alpha and IL-1beta expression. These effects were possibly associated with the competitive antagonism of TLR4 mAb on the TLR4 signaling pathway and the downstream NF-kappaB p65 and p38 MAPK pathways, which are activated by mmLDL. In conclusion, pretreatment with TLR4 mAb lessens mmLDL-induced EDV dysfunction and inhibits overexpression of inflammatory factors. Regulation of the TLR4 pathway, as well as its downstream NF-kappaB p65 and p38 MAPK pathways, may be an effective strategy for the prevention and treatment of cardiovascular diseases.
作者机构：
[Li, Jie; Tang, Hong-Xia; Qin, Xu-Ping] Univ South China, Peoples Hosp Chenzhou 1, Inst Pharm & Pharmacol, Chenzhou, Hunan, Peoples R China.;[Li, Jie] Southern Med Univ, Sch Pharm, Guangzhou, Guangdong, Peoples R China.;[Li, Jie] Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
通讯机构：
[Li, Jie] U;Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
关键词：
STAT3;VSMCs;CVDs;proliferation;pathway
摘要：
OBJECTIVES: Cardiovascular disease (CVD) remains the primary cause of morbidity and mortality worldwide. The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of CVD. The functional and phenotypic changes in vascular cells are mediated by complex signaling cascades that initiate and control genetic reprogramming. Many studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) regulates a diverse array of functions relevant to atherosclerosis. METHODS: In this review, we summarize the studies on the STAT3-mediated proliferation of VSMCs and subsequent CVDs such as hypertension, atherosclerosis, stroke, coronary artery disease, and myocardial infarction. Furthermore, we describe the general background of STAT3, its structure, function and regulation as well as the STAT3 signaling pathway. Finally, we highlight some potential issues and propose some solutions to these issues. Results and conclusions: STAT3 activation promotes the proliferation of VSMCs by regulating the transcription of genes. Studying the mechanism of VSMC proliferation induced by the STAT3 pathway is valuable for finding therapeutic targets for CVD.
作者机构：
[Li, Jiexin; Peng, Yanxi; Wang, Hongsheng; Chen, Feng; Li, Zihan] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China.;[Tu, Jian; Li, Zihan] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Peng, Yanxi] Xiangnan Univ, Dept Basic Med, Chenzhou 423000, Hunan, Peoples R China.;[Chen, Zhuojia] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China.;[Lin, Shuibin] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, Guangzhou, Peoples R China.
通讯机构：
[Wang, Hongsheng] S;Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China.
摘要：
Studies on biological functions of N-6-methyladenosine (m(6)A) modification in mRNA have sprung up in recent years. We find m(6)A can positively regulate the glycolysis of cancer cells. Specifically, m(6)A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m(6)A regulated glycolysis and ATP generation. The m(6)A modified 5UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of PDK4 m(6)A by dm(6)ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m(6)A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m(6)A regulates glycolysis of cancer cells through PDK4. p id=Par ysregulation of N6-Methyladenosine (m(6)A) is associated with cancer progression. Here, authors show that m(6)A methylation of pyruvate dehydrogenase kinase 4 (PDK4) positively regulates its mRNA stability and translation, and consequently affects glycolysis in cancer cells
作者机构：
[李洁] The First People's Hospital of Chenzhou, Chenzhou, 423000, China;[秦旭平] Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China;[周楠] Medical College, Xi'an Jiaotong University, Xi'an, 710061, China;[林杰; 陈根] The First People's Hospital of Chenzhou, Chenzhou, 423000, China, Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China
通讯机构：
[Li, J.] T;The First People's Hospital of ChenzhouChina
关键词：
TLR4单克隆抗体;轻度氧化修饰低密度脂蛋白;炎症;肠系膜动脉;内皮依赖性舒张
摘要：
目的探讨预先使用TLR4单克隆抗体(TLR4mAb)对轻度氧化修饰低密度脂蛋白(mmLDL)诱发小鼠肠系膜动脉内皮依赖性舒张功能损伤的影响及作用机制。方法实验分为:空白对照组、mmLDL处理组、TLR4mAb干预组。采用ELISA方法测定血浆中白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的浓度水平,微血管张力描记技术测定血管内皮依赖性舒张功能, Western blot技术和RT-PCR技术分别考察血管组织蛋白表达量和mRNA表达水平,透射电镜观察肠系膜动脉内皮细胞超显微结构。结果TLR4mAb剂量依赖性改善mmLDL损伤血管内皮依赖性舒张功能的损伤作用,显著上调KCa3.1-通道、KCa 2.3-通道蛋白表达和下调炎症因子TNF-α和IL-1β表达。TLR4mAb改善mmLDL损伤血管内皮细胞及内皮依赖性舒张功能,可能与其竞争性拮抗mmLDL激活TLR4信号转导通路及其下游的NF-κBp65和p-38MAPK通路有关。结论预先使用TLR4mAb可以减轻mmLDL所诱发的内皮细胞损伤和内皮依赖性舒张功能降低,以及抑制炎症因子的过度表达,调控TLR4通路及其下游的NF-κBp65和p-38MAPK通路可能是预防治疗心血管疾病的有效靶点。 <&wdkj&>OBJECTIVE To investigate the effect and mechanism of TLR4 monoclonal antibody (TLR4mAb) on mmLDL induced impairment of endothelium-dependent vasodilatation in mouse mesenteric artery. METHODS The experiment established three groups of normal saline group,mmLDL treatment group and TLR4mAb intervention group. The concentration of IL-1β and TNF-α in plasma was determined by enzyme-linked immunosorbent assay (ELISA) . Measurement of endothelium-dependent vasodilatation was achieved by microvascular tension mapping. Western blot and RT-PCR were used to investigate the expression level of protein and mRNA expressions in vascular tissues. In addition,ultra-structure of mesenteric artery endothelial cells was observed by transmission electron microscope. RESULTS TLR4mAb could improve the damage of mmLDL induced impairment of endothelium-dependent vasodilatation in a dose-dependent manner. Besides,TLR4mAb obviously up-regulated protein expressions in KCa 3.1-channel and KCa 2.3-channel,and down-regulated the expression of inflammatory factors TNF-α and IL-1β. Furthermore,the improvement of mmLDL impaired vascular endothelial cells and endothelium-dependent vasodilatation might be correlated with its competitive antagonism of mmLDL-activated TLR4 signal transduction pathway and its downstream NF-κBp65 and p-38 MAPK pathway. CONCLUSION Administration of TLR4mAb in advance can alleviate the impairment of endothelial cells and the decrease of endothelium-dependent vasodilatation induced by mmLDL,and inhibit the overexpression of inflammatory factors. Regulation of TLR4 pathway as well as its downstream NF-κBp65 and P-38 MAPK pathways may be effective targets for the prevention and treatment of cardiovascular diseases.
期刊：
Cancer Cell International,2019年19(1):1-13 ISSN：1475-2867
通讯作者：
Luo, Dixian
作者机构：
[Li, Jia; Hu, Zheng; Luo, Wenna; He, Rongzhang; Luo, Weihao; Duan, Lili; Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.;[Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Ctr Clin Pathol, Chenzhou 423000, Peoples R China.;[He, Rongzhang] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Luo, Dixian] U;Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.
作者机构：
[Li, Junyu] Canc Hosp Jiangxi Prov, Dept Radiotherapy, Nanchang 330029, Jiangxi, Peoples R China.;[Li, Yuehua; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Li, Ying] Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Li, Ying] H;Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
biomarker;head and neck squamous cell carcinoma;long non-coding RNA;signature;survival
摘要：
Long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10-lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10-lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression-based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.
作者机构：
[Li, Jie; Tian, Shao-Wen; Chen, Fang-Ling] Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Wang, Bo] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Hunan, Peoples R China.;[Tian, Shao-Wen] Guilin Med Univ, Guangxi Key Lab Brain & Cognit Neurosci, Guilin 541000, Guangxi, Peoples R China.;[Long, Chen] Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
通讯机构：
[Tian, Shao-Wen] U;[Long, Chen] C;Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
关键词：
Apelin-13;Fear extinction;Memory;PTSD;Rats
摘要：
Fear extinction is considered as a new learning process that is valid to model features of post-traumatic stress disorder (PTSD). The neuropeptide apelin, such as apelin-13, apelin-17 and apelin-36, are endogenous ligands of the G-protein coupled receptor APJ. Apelin and its receptor APJ are widely distributed in the central nervous system. Accumulating evidence suggests the critical role of apelin-13 in modulation of learning and memory, however, its specific role in fear extinction remains unclear. In the present study, we investigated the effect of apelin-13 administration on contextual fear extinction in rats. The behavioral procedure included four sessions: habitation, conditioning, extinction training and extinction recall. Rats received intracerebroventricular infusion of apelin-13 (3 or 6 mu g) 0.5 h prior to the extinction training. Percentage of freezing was utilized to assess the conditioned fear response. Results showed that apelin-13, with the dose of 6 but not 3 mu g, significantly decreased freezing response during both extinction training and extinction recall test sessions. Furthermore, apelin-13 did not affect the levels of baseline freezing, locomotor activity and anxiety. The results suggest that apelin-13 dose-dependently enhances contextual fear extinction, and may function as a novel target for treatment of PTSD.
通讯机构：
[Tang, Guotao] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
摘要：
According to the pharmacophore combination principle, a set of new 3,4,5-trimethoxy flavonoid salicylate derivatives were designed, synthesized, and evaluated for biological activity. The cytotoxicity evaluation revealed that compound 10v exhibited higher potency than 5-Fu against HCT-116 cells. Preliminary biological activity studies showed that compound 10v could inhibit the colony formation and migration of HCT-116 cells. Besides, the Hoechst 33258 staining assay and flow cytometry revealed that treatment with compound 10v induced the apoptosis of HCT-116 cells in a concentration-dependent manner, while it had no effect on their cell cycle. The WB analysis suggested that HIF-1, tubulin, HK-2, and PFK might be the potential pharmacophore targets of compound 10v. Tubulin was a potential drug target for compound 10v, which was explained by analyzing the crystal structure of compound 10v complexed with tubulin. These results indicated that compound 10v might be a promising anti-tumor agent candidate, deserving further optimization and evaluation.
摘要：
Here, we report a new approach of on-resin peptide ligation using C-terminal benzyl ester as the stabilized precursor of thioester, which enables both N-terminal elongation and C-terminal peptide ligation on a Rink Amide resin. On-resin native chemical ligation and auxiliary-assisted peptide ligation were successfully achieved. This method is compatible to both protected and unprotected peptide fragments and has potential application in poor water-soluble peptide ligation.
摘要：
The chemical compound LY2874455 has the potential to overcome drug resistance driven by FGFR gatekeeper mutations. X-ray crystallographic studies provide the structural explanation for why this compound is effective against the FGFR gatekeeper mutations.
作者机构：
[Jia, Zeming; Chen, Jie; Ding, Chengming; Zhang, Yaoting; Peng, Jian] Cent S Univ, Xiangya Hosp, Dept Gen Surg, Changsha, Hunan, Peoples R China.;[He, Jun; Li, Chong; Ding, Chengming; Zhu, Zhu; Han, Dong] Univ South China, Dept Hepatopancreatobiliary Surg, Affiliated Hosp 1, Hengyang, Peoples R China.;[Li, Junhua; Ding, Chengming; Zhao, Jun] Univ Southern Calif, Dept Mol Microbiol & Immunol, Norris Comprehens Canc Ctr, Los Angeles, CA USA.;[Liao, Wenyan] Univ South China, Dept Obstet & Gynecol, Affiliated Hosp 1, Hengyang, Peoples R China.;[Zeng, Yi] Youjiang Med Univ Nationalities, Dept Pathol & Immunol, Baise, Peoples R China.
通讯机构：
[Peng, Jian; Xia, Zanxian] C;Cent S Univ, Xiangya Hosp, Dept Gen Surg, Changsha, Hunan, Peoples R China.;Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China.;Cent S Univ, Sch Life Sci, Changsha, Hunan, Peoples R China.
