FGFR-TKI resistance in cancer: current status and perspectives
作者：
Yue, Sitong;Li, Yukun;Chen, Xiaojuan;Wang, Juan;Li, Meixiang;...
期刊：
Journal of Hematology & Oncology ,2021年14(1):1-14 ISSN：1756-8722
通讯作者：
Chen, Yongheng;Wu, Daichao
作者机构：
[Chen, Xiaojuan; Chen, Yongheng; Wu, Daichao; Yue, Sitong] Cent South Univ, Xiangya Hosp, Dept Oncol, Lab Struct Biol,NHC Key Lab Canc Prote,State Loca, Changsha 410008, Hunan, Peoples R China.;[Li, Yukun; Li, Meixiang; Wu, Daichao; Wang, Juan] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hunan Prov Key Lab Canc Cellular & Mol Pathol, Hengyang 421001, Peoples R China.;[Chen, Yongheng; Wu, Daichao] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Wu, Daichao] Univ Maryland, WM Keck Lab Struct Biol, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
通讯机构：
[Chen, YH; Wu, DC] C;[Wu, Daichao] U;Cent South Univ, Xiangya Hosp, Dept Oncol, Lab Struct Biol,NHC Key Lab Canc Prote,State Loca, Changsha 410008, Hunan, Peoples R China.;Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hunan Prov Key Lab Canc Cellular & Mol Pathol, Hengyang 421001, Peoples R China.;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.
关键词：
FGFR;Tyrosine kinase inhibitor;Drug resistance;Gatekeeper mutation;Lysosome sequestration
摘要：
Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.
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英文
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Nucleolin regulates the proliferation of vascular smooth muscle cells in atherosclerotic via Aurora B
作者：
Sun, Hui;Huang, Lingjin;Liang, Pengfei;Tang, Yuting;Chen, Cheng;...
期刊：
Journal of Cellular and Molecular Medicine ,2021年25(2):751-762 ISSN：1582-1838
通讯作者：
Jiang, Bimei
作者机构：
[Xiao, Xianzhong; Luo, Zhengyang; Lin, Xiaofang; Sun, Hui; Chen, Cheng; Jiang, Bimei; Chen, Huan; Tang, Yuting] Cent South Univ, Xiangya Sch Med, Dept Pathophysiol, Sepsis Translat Med Key Lab Hunan Prov, Changsha, Hunan, Peoples R China.;[Sun, Hui] Univ South China, Inst Cardiovasc Dis, Dept Pathophysiol, Hengyang, Hunan, Peoples R China.;[Sun, Hui] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.;[Huang, Lingjin] Cent South Univ, Dept Cardiothorac Surg, Xiangya Hosp, Changsha, Hunan, Peoples R China.;[Liang, Pengfei] Cent South Univ, Xiangya Hosp, Dept Burns & Plast Surg, Changsha, Hunan, Peoples R China.
通讯机构：
[Jiang, Bimei] C;Cent South Univ, Xiangya Sch Med, Dept Pathophysiol, Sepsis Translat Med Key Lab Hunan Prov, Changsha, Hunan, Peoples R China.
关键词：
atherosclerosis;Aurora B;cell cycle;nucleolin;vascular smooth muscle cells
摘要：
Vascular smooth muscle cells (VSMCs) play a significant role in atherosclerosis. As a multifunctional protein, nucleolin (NCL) is involved in many important physiological and pathological processes. In this study, we aimed to investigate the role of nucleolin in VSMCs proliferation and cell cycle. The expression of nucleolin increased in VSMCs of mice with aortas advanced plaques. With the left common carotid-artery ligation-injury model, immunofluorescence staining revealed that nucleolin and Ki67 expression increased in VSMCs in mice left carotid artery compared with right carotid artery after surgery. POVPC or ox-LDL up-regulated nucleolin mRNA and protein expression in a dose- and time-dependent manner in HAVSMCs. POVPC (5μg/ml) or ox-LDL (50μg/ml) promoted the proliferation of HAVSMCs. Nucleolin ablation relieved the pro-proliferation role of VSMCs. The cell cycle assay and cell ability results showing that POVPC or ox-LDL increased the proliferation, but nucleolin ablation inhibited the proliferation of HAVSMCs. And nucleolin ablation can prevent DNA replication at S phase and induce cell cycle arrest in S phase. The bioinformatics database predicts protein-protein interactions with nucleolin and aurora B. Nucleolin overexpression and ablation affected the expression of aurora B. These findings indicate for the first time that nucleolin actively involved the proliferation of VSMCs via aurora B. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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英文
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Identification of HeLa cell proteins that interact with Chlamydia trachomatis glycogen synthase using yeast two-hybrid assays
作者：
Sun, Zhenjie;Sun, Yuhui;Li, Yumeng;Luan, Xiuli;Chen, Hui;...
期刊：
MOLECULAR MEDICINE REPORTS ,2020年21(3):1572-1580 ISSN：1791-2997
通讯作者：
Lu, Chunxue
作者机构：
[Sun, Yuhui; Lu, Chunxue; Li, Yumeng; Chen, Hui; Luan, Xiuli; Sun, Zhenjie; Wu, Haiying] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Peng, Bo] Univ South China, Hengyang Med Coll, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Lu, Chunxue] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Chlamydia trachomatis;glycogen synthase;yeast two-hybrid assay
摘要：
Chlamydia trachomatis (C. trachomatis) is the leading cause of bacterial sexually transmitted diseases and infectious diseases that cause blindness. The pathophysiology of chlamydial infections is poorly understood, but secreted proteins have emerged as key virulence factors. C. trachomatis glycogen synthase (GlgA) is a chlamydial secretory protein, which localizes in the lumen of chlamydial inclusion bodies and the cytosol of host cells. In order to improve understanding of the roles of GlgA in chlamydial pathogenesis, four proteins that interact with GlgA, Homo sapiens CXXC finger protein 1, prohibitin (PHB), gelsolin-like actin-capping protein and apolipoprotein A-I binding protein were identified using yeast two–hybrid assays. The functions of these proteins are complex, and preliminary results suggested that PHB interacts with GlgA. However, further studies are required to determine the specific interactions of these proteins with GlgA. The findings of the present study may provide a direction and foundation for future studies focusing on the mechanism of GlgA in C. trachomatis infection. © 2020 Spandidos Publications. All rights reserved.
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英文
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CircIQCH sponges miR-145 to promote breast cancer progression by upregulating DNMT3A expression
作者：
Li, Yuehua;Jiang, Baohong;He, Zhengxi;Zhu, Hongbo;He, Rongfang;...
期刊：
AGING-US ,2020年12(15):15532-15545 ISSN：1945-4589
通讯作者：
Xie, Liming;He, Xiusheng
作者机构：
[Zhu, Hongbo; Li, Yuehua; Xie, Liming; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Li, Yuehua; He, Xiusheng] Univ South China, Hengyang Med Coll, Canc Res Inst, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[He, Zhengxi] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Hunan, Peoples R China.;[He, Rongfang] Univ South China, Affiliated Hosp 1, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xie, Liming; He, Xiusheng] U;Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Canc Res Inst, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词：
DNMT3A;breast cancer;circIQCH;circular RNAs;competitive endogenous RNAs
摘要：
As a unique type of RNA, circular RNAs (circRNAs) are important regulators of multiple biological processes in the progression of cancer. However, the potential role of most circRNAs in breast cancer lung metastasis is still unknown. In this study, we characterized and further investigated circIQCH (hsa_circ_0104345) by analyzing the circRNA microarray profiling in our previous study. circIQCH was upregulated in breast cancer tissues, especially in the metastatic sites. CCK-8, transwell, wound-healing and mouse xenograft assays were carried out to investigate the functions of circIQCH. Knockdown of circIQCH inhibited breast cancer cell proliferation and migration to lung. Moreover, luciferase reporter assays and RNA immunoprecipitation assays were performed to elucidate the underlying molecular mechanism of circIQCH. The results showed that circIQCH sponges miR-145 and promotes breast cancer progression by upregulating DNMT3A. In summary, our study demonstrated the pivotal role of circIQCH-miR-145-DNMT3A axis in breast cancer growth and metastasis via the mechanism of competing endogenous RNAs. Thus, circIQCH could be a potential therapeutic target for breast cancer. © Li et al.
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英文
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TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation
作者：
Li, Yong;Huang, Xuan;Guo, Fang;Lei, Tianhua;Li, Shitao;...
期刊：
分子细胞生物学报：英文版 ,2020年12(3):190-201 ISSN：1674-2788
通讯作者：
Fu, Mingui;Xin, Hong-Bo
作者机构：
[Monaghan-Nichols, Paula; Guo, Fang; Li, Yong; Fu, Mingui; Lei, Tianhua; Huang, Xuan] Univ Missouri, Sch Med, Dept Biomed Sci, Kansas City, MO 64108 USA.;[Xin, Hong-Bo; Huang, Xuan] Nanchang Univ, Inst Translat Med, Nanchang 330031, Jiangxi, Peoples R China.;[Guo, Fang; Jiang, Zhisheng] Univ South China, Inst Cardiovasc Dis, Dept Pathophysiol, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Li, Shitao] Oklahoma State Univ, Dept Physiol Sci, Ctr Vet & Hlth Sci, Stillwater, OK 74078 USA.
通讯机构：
[Fu, Mingui] U;[Xin, Hong-Bo] N;Univ Missouri, Sch Med, Dept Biomed Sci, Kansas City, MO 64108 USA.;Nanchang Univ, Inst Translat Med, Nanchang 330031, Jiangxi, Peoples R China.
关键词：
TRIM65;VCAM-1;endothelial activation;lung inflammation;ubiquitination
摘要：
Although the adhesion molecules-mediated leukocyte adherence and infiltration into tissues is an important step of inflammation, the post-translational regulation of these proteins on the endothelial cells is poorly understood. Here, we report that TRIM65, an ubiquitin E3 ligase of tripartite protein family, selectively targets vascular cell adhesion molecule 1 (VCAM-1) and promotes its ubiquitination and degradation, by which it critically controls the duration and magnitude of sepsis-induced pulmonary inflammation. TRIM65 is constitutively expressed in human vascular endothelial cells. During TNFα-induced endothelial activation, the protein levels of TRIM65 and VCAM-1 are inversely correlated. Expression of wild-type TRIM65, but not expression of a TRIM65 mutant that lacks E3 ubiquitin ligase function in endothelial cells, promotes VCAM-1 ubiquitination and degradation, whereas small interference RNA-mediated knockdown of TRIM65 attenuates VCAM-1 protein degradation. Further experiments show that TRIM65 directly interacts with VCAM-1 protein and directs its polyubiquitination, by which TRIM65 controls monocyte adherence and infiltration into tissues during inflammation. Importantly, TRIM65-deficient mice are more sensitive to lipopolysaccharide-induced death, due to sustained and severe pulmonary inflammation. Taken together, our studies suggest that TRIM65-mediated degradation of VCAM-1 represents a potential mechanism that controls the duration and magnitude of inflammation. © The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.
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英文
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Reciprocal Regulation Between Forkhead Box M1/NF‐κB and Methionine Adenosyltransferase 1A Drives Liver Cancer
作者：
Li, Yuan;Lu, Liqing;Tu, Jian;Zhang, Jing;Xiong, Ting;...
期刊：
Hepatology ,2020年72(5):1682-1700 ISSN：0270-9139
通讯作者：
Liu, Ting;Lu, Shelly C.;Yang, Heping
作者机构：
[Li, Tony W. H.; Lu, Shelly C.; Wang, Jiaohong; Fan, Wei; Li, Yuan; Seki, Ekihiro; Zhang, Jing; Xiong, Ting; Tu, Jian; Lu, Liqing; Yang, Heping; Peng, Hui] Cedars Sinai Med Ctr, Div Digest & Liver Dis, Los Angeles, CA 90048 USA.;[Li, Yuan; Liu, Ting] Cent South Univ, Xiangya Hosp, Dept Gastroenterol, 78 Xiangya Rd, Changsha 410083, Hunan, Peoples R China.;[Xiong, Ting; Lu, Liqing; Chen, Yongheng; Liu, Ting] Cent South Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha, Peoples R China.;[Tu, Jian] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Zhang, Jing] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, Wuhan, Peoples R China.
通讯机构：
[Liu, Ting; Lu, Shelly C.; Yang, Heping] C;Cent South Univ, Xiangya Hosp, Dept Gastroenterol, 78 Xiangya Rd, Changsha 410083, Hunan, Peoples R China.;Cedars Sinai Med Ctr, Dept Med, Div Digest & Liver Dis, Davis Bldg,Room 2097,8700 Beverly Blvd, Los Angeles, CA 90048 USA.;Cedars Sinai Med Ctr, Dept Med, Div Digest & Liver Dis, Davis Bldg,Room 2094B,8700 Beverly Blvd, Los Angeles, CA 90048 USA.
关键词：
FDI-6;FOX-binding site;Hepatocellular carcinoma;TO901317;cholangiocarcinoma
摘要：
Background and Aims: Forkhead box M1 (FOXM1) and nuclear factor kappa B (NF-ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF-ĸB activity. Here, we examined the interplay between FOXM1/NF-κB and MAT1A in liver cancer. Approach and Results: We examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory-6 (FDI-6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF-κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF-κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF-κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF-κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI-6 inhibited liver cancer cell growth in vitro and in vivo. However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A. Conclusions: We have found a crosstalk between FOXM1/NF-κB and MAT1A. Up-regulation in FOXM1 lowers MAT1A, but raises NF-κB, expression, and this is a feed-forward loop that enhances tumorigenesis. © 2020 by the American Association for the Study of Liver Diseases.
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英文
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Dendrobium candidum aqueous extract attenuates isoproterenol-induced cardiac hypertrophy through the ERK signalling pathway
作者：
Cao, Yuan-Yuan;Li, Ke;Li, Ying;Tian, Xiao-Ting;Ba, Hui-Xue;...
期刊：
Pharmaceutical Biology ,2020年58(1):176-183 ISSN：1388-0209
通讯作者：
Ke Li<&wdkj&>Xiao-Hui Li
作者机构：
[Tian, Xiao-Ting; Ba, Hui-Xue; Cao, Yuan-Yuan; Li, Xiao-Hui] Cent South Univ, Xiangya Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410013, Peoples R China.;[Li, Ke] Hunan Acad Tradit Chinese Med, Changsha 410013, Hunan, Peoples R China.;[Li, Ying] Cent South Univ, Xiangya Hosp 3, Dept Hlth Management, Changsha, Peoples R China.;[Li, Xiao-Hui] Hunan Key Lab Bioanal Complex Matrix Samples, Changsha, Peoples R China.;[Wang, Aiping] Univ South China, Nanhua Affiliated Hosp, Inst Clin Res, Hengyang, Peoples R China.
通讯机构：
[Ke Li] H;[Xiao-Hui Li] D;Hunan Academy of Traditional Chinese Medicine, Hunan, China<&wdkj&>Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, Changsha, China<&wdkj&>Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China
关键词：
cardiac fibrosis;extracellular regulated protein kinases;H9c2;heart-to-body weight ratio;Left ventricular systolic pressure;left ventricular/tibia length;phalloidin staining
摘要：
Context: The pharmacological functions of Dendrobium candidum Wall. ex Lindl. (Orchidaceae) in cardiac hypertrophy remains unclear. Objective: To evaluate whether D. candidum aqueous extract (DCAE) can attenuate experimental cardiac hypertrophy. Materials and methods: Cardiac hypertrophy in SD rats was induced by subcutaneously injection of isoproterenol (2 mg/kg), once a day for ten days. Rats were gavaged with DCAE (0.13 and 0.78 g/kg) daily for one month. At the end of treatment, measurement of left ventricular systolic pressure (LVSP), heart-to-body weight ratio (HW/BW), left ventricular/tibia length (LV/TL), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) levels, haematoxylin-eosin staining, and Masson’s trichrome staining were conducted. In cultured H9c2 cells, DCAE (2 mg/mL) and U0126 (10 μM) were added 2 h before the isoproterenol (10 μM) stimulus. Phalloidin staining was used to evaluate cellular hypertrophy. The mRNA expression of ANP and BNP was measured by qRT-PCR. The expression of p-ERK was determined by immunoblotting. Results: DCAE treatment significantly reduced the following indicators in vivo: (1) the LVSP (16%); (2) HW/BW (13%); (3) LV/TL (6%); (4) ANP (39%); (5) BNP (32%). In cultured H9c2 cells, phalloidin staining showed that DCAE relieved cellular hypertrophy (53% reduction). Furthermore, immunoblotting showed that DCAE can significantly inhibit p-ERK protein expression in vivo and in vitro (39% and 27% reduction, respectively). Discussion and conclusions: DCAE prevents cardiac hypertrophy via ERK signalling pathway and has the potential for treatment of cardiac hypertrophy. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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英文
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TP53 somatic mutations are associated with poor survival in non-small cell lung cancer patients who undergo immunotherapy
作者：
Zhao, Liqin;Qu, Xiaofei;Wu, Zhenhua;Li, Yuehua;Zhang, Xiaowei* ;...
期刊：
AGING-US ,2020年12(14):14556-14568 ISSN：1945-4589
通讯作者：
Zhang, Xiaowei;Guo, WeiJian
作者机构：
[Zhao, Liqin; Zhang, Xiaowei; Guo, WeiJian; Wu, Zhenhua] Fudan Univ, Dept Med Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China.;[Qu, Xiaofei; Zhao, Liqin; Zhang, Xiaowei; Guo, WeiJian; Wu, Zhenhua] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.;[Qu, Xiaofei] Fudan Univ, Canc Inst, Shanghai Canc Ctr, Shanghai, Peoples R China.;[Li, Yuehua] Univ South China, Dept Med Oncol, Affiliated Hosp 1, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhang, XW; Guo, WJ] F;Fudan Univ, Dept Med Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China.;Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.
关键词：
TP53;immunotherapy;non-small cell lung cancer;somatic mutation;tumor mutation burden
摘要：
In this study, we investigated the association between TP53 somatic mutations and immunotherapeutic outcomes in non-small cell lung cancer (NSCLC) patients. Kaplan-Meier survival curve analysis of the MSK-IMPACT cohort of 350 NSCLC patients shows that overall survival (OS) is significantly lower for patients with truncating TP53 mutations than those with wild-type TP53 (OS: 9 months vs. 14 months; P=0.019). Multivariate analysis shows that truncating TP53 mutations are an independent predictor of immunotherapeutic outcomes. Moreover, among NSCLC patients with lower tumor mutation burden (TMB), those with TP53 truncating mutations showed significantly lower OS than those with wild-type TP53 [hazard ratio (HR) = 1.40, confidence interval (CI) = 1.13-1.73; P = 0.002]. TP53 mutations correlate with higher infiltration of CD8+ T cells, neutrophils and dendritic cells in lung adenocarcinoma tissues. A prognostic model with TP53 mutational status shows better survival prediction than the model without TP53 mutational status 1-year [area under curve (AUC): 64.9% vs. 60.2%; P = 0.052] and 2-years (AUC: 70.9% vs. 66.1%; P = 0.098) post-immunotherapy. These findings demonstrate that truncating TP53 mutations correlate with poor immunotherapy outcomes in NSCLC patients with low TMB. TP53 mutation status also improves the prognostic prediction in NSCLC patients that underwent immunotherapy. © Zhao et al.
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英文
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Stress-induced NLRP3 inflammasome activation negatively regulates fear memory in mice
作者：
Dong, Yuan;Li, Shuoshuo;Lu, Yiming;Li, Xiaoheng;Liao, Yajin;...
期刊：
Journal of Neuroinflammation ,2020年17(1):1-16 ISSN：1742-2094
通讯作者：
Hou, Lin;Yuan, Zengqiang;Cheng, Jinbo
作者机构：
[Dong, Yuan; Hou, Lin] Qingdao Univ, Med Coll, Dept Biochem, Qingdao 266071, Shandong, Peoples R China.;[Li, Shuoshuo] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China.;[Li, Shuoshuo] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China.;[Lu, Yiming] Beijing Inst Radiat Med, Beijing 100850, Peoples R China.;[Dong, Yuan; Li, Xiaoheng; Yuan, Zengqiang; Cheng, Jinbo; Yuan, ZQ] Beijing Inst Basic Med Sci, Brain Sci Ctr, 27 Taiping Rd, Beijing 100850, Peoples R China.
通讯机构：
[Hou, Lin] Q;[Yuan, ZQ; Cheng, JB] B;[Cheng, Jinbo] M;Qingdao Univ, Med Coll, Dept Biochem, Qingdao 266071, Shandong, Peoples R China.;Beijing Inst Basic Med Sci, Brain Sci Ctr, 27 Taiping Rd, Beijing 100850, Peoples R China.
关键词：
Fear memory;PTSD;NLRP3 inflammasome;Neuroinflammation;Postsynaptic density
摘要：
Background: Persistent inflammation dysregulation and cognitive decline have been associated with several trauma- and stress-related disorders such as posttraumatic stress disorder (PTSD) and anxiety disorder. Despite the abundant discoveries of neuroinflammation in such disorders, the underlying mechanisms still remain unclear. Method: Wild-type and Nlrp3 -/- mice were exposed to the electric foot shocks in the contextual fear memory paradigm. Three hours after the electric foot shocks, activation of the NLRP3 inflammasome was investigated through immunoblotting and ELISA. Microglia were isolated and analyzed by quantitative real-time PCR. Hippocampal tissues were collected 3 h and 72 h after the electric foot shocks and subjected to RNA sequencing. MCC950 was administrated to mice via intraperitoneal (i.p.) injection. Interleukin-1 receptor antagonist (IL-ra) and interleukin-1β (IL-1β) were delivered via intracerebroventricular (i.c.v.) infusion. Contextual fear responses of mice were tested on 4 consecutive days (test days 1-4) starting at 48 h after the electric foot shocks. Anxiety-like behaviors were examined by elevated plus maze and open-field test. Results: We demonstrated that, in the contextual fear memory paradigm, the NLRP3 inflammasome was activated 3 h after electric foot shocks. We also found an upregulation in toll-like receptor and RIG-I-like receptor signaling, and a decrease in postsynaptic density (PSD) related proteins, such as PSD95 and Shank proteins, in the hippocampus 72 h after the electric foot shocks, indicating an association between neuroinflammation and PSD protein loss after stress encounter. Meanwhile, Nlrp3 knockout could significantly prevent both neuroinflammation and loss of PSD-related proteins, suggesting a possible protective role of NLRP3 deletion during this process. For further studies, we demonstrated that both genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome remarkably enhanced the extinction of contextual fear memory and attenuated anxiety-like behavior caused by electric foot shocks. Moreover, cytokine IL-1β administration inhibited the extinction of contextual fear memory. Meanwhile, IL-1ra significantly enhanced the extinction of contextual fear memory and attenuated anxiety-like behavior. Conclusion: Taken together, our data revealed the pivotal role of NLRP3 inflammasome activation in the regulation of fear memory and the development of PTSD and anxiety disorder, providing a novel target for the clinical treatment of such disorders. © 2020 The Author(s).
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英文
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Tizoxanide mitigates inflammatory response in LPS-induced neuroinflammation in microglia via restraining p38/MAPK pathway
作者：
Li, X-W;He, R-Z;Li, Y.;Ruan, Z-F*
期刊：
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES ,2020年24(11):6446-6454 ISSN：1128-3602
通讯作者：
Ruan, Z-F
作者机构：
[Li, X-W; Ruan, Z-F] Univ South China, Dept Neurol, Affiliated Hosp 1, Hengyang, Peoples R China.;[He, R-Z] Univ South China, Natl & Local Joint Engn Lab High Mol Diag Technol, Translat Med Inst,Peoples Hosp 1, Collaborat Res Ctr Postdoctoral Mobile Stn,Cent S, Chenzhou, Peoples R China.;[Li, Y.] Univ South China, Affiliated Nanhua Hosp, Dept Anesthesiol, Hengyang, Peoples R China.
通讯机构：
[Ruan, Z-F] U;Univ South China, Dept Neurol, Affiliated Hosp 1, Hengyang, Peoples R China.
关键词：
Microglia;Neuroinflammation;P38/MAPK pathway;Tizoxanide;Traumatic brain injury
摘要：
OBJECTIVE: Traumatic brain injury (TBI) induced neuroinflammation is featured as excessive glial inflammatory activation and violent neurologic destruction and dysfunction. Massive microglia activation in situ and disrupt of blood-brain barrier contribute to severely collapsed nervous system. Tizoxanide (TIZ), a synthetic thiazolide derivative agent possessing a broad-spectrum anti-infective effect, currently shows a potential resistance against pathogens like bacteria, virus and parasites, while its underlying role in neuroinflammation is elusive. The study aimed to explore the effect of TIZ on neuroinflammation in vitro microglia. MATERIALS AND METHODS: Primary microglia were accepted to neuroinflammatory activation via lipopolysaccharide (LPS) administration. TIZ was conducted to pretreatment of microglia. Cell viability, inflammatory cytokines, chemotaxis, nitric oxide release, inflammation- related enzymes, and mitogen-activated protein kinase (MAPK) pathway activation in microglia were investigated respectively. RESULTS: We demonstrated that TIZ administration attenuates inflammatory cytokines and chemokines through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme- linked immunosorbent assay (ELISA) of medium supernatant. In addition, TIZ reduces pro-inflammatory mediators and nitric oxide release in microglia. Furtherly, TIZ inhibits the level of p38/MAPK pathway in LPS stimuli, indicating that TIZ negatively regulates neuroinflammation via inhibiting p38/MAPK pathway. CONCLUSIONS: TIZ is verified to be an anti- inflammation effect on neuroinflammation in microglia via downregulation of p38/MAPK pathway, which restrains inflammation by reduced inflammatory cytokines, chemokines and mediators and decreased nitric oxide release. To summarize, TIZ is considered to be a promising reagent to alleviate neuroinflammation targeting microglia in nervous system injury. © 2020 Verduci Editore s.r.l. All rights reserved.
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英文
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Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS).
作者：
Li, Yan;Chen, Changye;Ma, Yan;Xiao, Jiao;Luo, Guifang;...
期刊：
Life Sciences ,2019年228(4):167-175 ISSN：0024-3205
通讯作者：
Li, Yukun;Wu, Daichao
作者机构：
[Li, Yan] Cent S Univ, Sch Basic Med Sci, Inst Reprod & Stem Cell Engn, Changsha 410013, Hunan, Peoples R China.;[Li, Yan] Reprod & Genet Hosp Citic Xiangya, Changsha 410078, Hunan, Peoples R China.;[Chen, Changye; Luo, Guifang; Ma, Yan] Univ South China, Affiliated Hosp 1, Dept Gynecol, Hengyang 421001, Peoples R China.;[Xiao, Jiao] Univ South China, Affiliated Nanhua Hosp, Dept Endocrinol, Hengyang 421002, Peoples R China.;[Li, Yukun] Univ South China, Canc Res Inst, Coll Hunan Prov, Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, Yukun; Wu, Daichao] U;Univ South China, Canc Res Inst, Coll Hunan Prov, Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Dept Histol & Embryol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Hunan, Peoples R China.
关键词：
AGEs;IR;IVF;PCOS;UPR;therapy
摘要：
Polycystic ovary syndrome (PCOS), a multisystem disease, is a major reason for female infertility around the world. It is no longer considered simply as a disease of ovary. Now researchers growing awareness of the multisystem features of this disease. PCOS has a higher relationship with metabolic disturbance and hypothalamic-pituitary-ovarian axis (HPOA) function disorders. This syndrome results in hyperandrogenemia (HA), hyperinsulinemia/insulin resistance (IR), increased estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) ratio imbalance, infertility, cardiovascular diseases, endometrial dysfunction, obesity, and including a litany of other health issues. Furthermore, PCOS has been garnered in recent times. Interventions like metformin, orlistat, hormonal contraceptives, GLP1 agonists, and VitD have been applied to ameliorate or reverse the pathological characterization of PCOS. Moreover, drug-combined therapy of PCOS is superior to single drug administration. This review will focus on the recent progress in pathogenesis and therapy of PCOS.
语种：
英文
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Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders
作者：
Tian, Yun;Wang, Jun-Ling;Huang, Wen;Zeng, Sheng;Jiao, Bin;...
期刊：
American Journal of Human Genetics ,2019年105(1):166-176 ISSN：0002-9297
通讯作者：
Shen, Lu;Jin, Peng
作者机构：
[Tian, Yun; Sun, Qi-Ying; Yi, Fang; Tang, Bei-Sha; Zhou, Ya-Fang; Xu, Hong-Wei] Cent S Univ, Xiangya Hosp, Dept Geriatr, Changsha 410008, Hunan, Peoples R China.;[Zeng, Sheng; Jiao, Bin; Liu, Zhen; Chen, Zhao; Jiang, Hong; Zhou, Chao-Jun; Yan, Xin-Xiang; Hou, Xuan; Guo, Ji-Feng; Tang, Bei-Sha; Long, Hong-Yu; Wang, Jun-Ling; Shen, Lu] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Tian, Yun; Tang, Bei-Sha; Shen, Lu] Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Xia, Kun; Hu, Zheng-Mao; Huang, Wen; Duan, Ran-Hui] Cent S Univ, Sch Life Sci, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;[Kong, Ha Eun; Li, Yujing; Shafik, Andrew Mark; Allen, Emily G.; Jin, Peng] Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
通讯机构：
[Shen, Lu] C;[Jin, Peng] E;Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
关键词：
GGC repeat expansions;NOTCH2NLC;linkage analysis;long-read genome sequencing;neuronal intranuclear inclusion disease;whole-exome sequencing
摘要：
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
语种：
英文
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ApoM-S1P Modulates Ox-LDL-Induced Inflammation Through the PI3K/Akt Signaling Pathway in HUVECs
作者：
Zheng, Zhi;Zeng, Yongzhi;Zhu, Xiao;Tan, Ying;Li, Yi;...
期刊：
Inflammation ,2019年42(2):606-617 ISSN：0360-3997
通讯作者：
Yi, Guanghui
作者机构：
[Li, Qian; Zheng, Zhi; Zeng, Yongzhi; Tan, Ying; Yi, Guanghui; Li, Yi; Zhu, Xiao] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yi, Guanghui] U;Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
apoM-S1P;ox-LDL;inflammatory factors;adhesion molecules;atherosclerosis
摘要：
Studies have shown that apolipoprotein M (apoM), the main carrier of sphingosine-1-phosphate (S1P), is closely related to lipid metabolism and inflammation. While there are many studies on apoM and lipid metabolism, little is known about the role of apoM in inflammation. Atherosclerosis is a chronic inflammatory process. To clarify what role apoM plays in atherosclerosis, we used oxidized low-density lipoprotein (ox-LDL) to induce an inflammatory model of atherosclerosis. Our preliminary results indicate that ox-LDL upregulates the expression of S1P receptor 2 (S1PR2) in human umbilical vein endothelial cells (HUVECs). Ox-LDL-induced HUVECs were treated with apoM-bound S1P (apoM-S1P), free S1P or apoM, and apoM-S1P was found to significantly inhibit the expression of inflammatory factors and adhesion molecules. In addition, apoM-S1P inhibits ox-LDL-induced cellular inflammation via S1PR2. Moreover, apoM-S1P induces phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt, preventing nuclear translocation of nuclear factor-κB (NF-κB). PI3K-specific inhibitors and Akt inhibitors suppress apoM-S1P/S1PR2-induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) release and affect nuclear translocation of NF-κB. In conclusion, the results demonstrate for the first time that apoM-S1P inhibits ox-LDL-induced inflammation in HUVECs via the S1PR2-mediated PI3K/Akt signaling pathway. This finding may aid in the development of new treatments for atherosclerosis. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
语种：
英文
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Ghrelin attenuates myocardial fibrosis after acute myocardial infarction via inhibiting endothelial-to mesenchymal transition in rat model
作者：
Chen, Hainan;Liu, Yijian;Gui, Qingjun;Zhu, Xiao;Zeng, Lin;...
期刊：
Peptides ,2019年111(1):118-126 ISSN：0196-9781
通讯作者：
He, Jin;Yin, Kai
作者机构：
[Gao, Ling; Chen, Hainan; Yin, Kai; Feng, Juling; Jackson, Ampadu O.; Li, Yi; Gui, Qingjun; Qing, Jina; Zhu, Xiao] Univ South China, Med Sch, Res Lab Clin & Translat Med, Hengyang 421001, Peoples R China.;[Chen, Hainan; Yin, Kai; Zhu, Xiao] Univ South China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Liu, Yijian] Third Hosp Changsha, Changsha 410000, Hunan, Peoples R China.;[Zeng, Lin] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang 421001, Peoples R China.;[Meng, Jun; He, Jin] Univ South China, Affiliated Hosp 1, Funct Dept, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[He, Jin; Yin, Kai] U;Univ South China, Affiliated Hosp 1, Funct Dept, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Res Lab Clin & Translat Med, Hengyang 421001, Peoples R China.
关键词：
*Acute myocardial infarction;*EndMT;*Ghrelin;*Myocardial fibrosis;*Smad7;*TGF-beta1
摘要：
Ghrelin, a peptide hormone produced in the gastrointestinal tract, has recently been found to be associated with the onset of myocardial fibrosis (MF). The exact mechanism, however, remains elusive. This study sought to identify the function and mechanism of ghrelin on MF after acute myocardial infarction (AMI). AMI was established in Spraque-Dawley rats by ligation of the left anterior descending (LAD). Ghrelin or saline was intraperitoneally injected two times per day for 8 weeks after ligation. The weight of heart (mg) and the weight ratio of heart to body (mg/g) as well as the fibrotic area were increased, while serum level of ghrelin was decreased after AMI. Ghrelin significantly ameliorated MF and decreased deposition of collagens in perivascular fibrosis area. In addition, ghrelin inhibited Endothelial-to-mesenchymal transition (EndMT), a crucial process for MF, in perivascular fibrosis area and TGF-β1-induced human coronary artery endothelial cells (HCAECs). Mechanistically, ghrelin persistently decreased the phosphorylation of Smad2/3 and enhanced the expression of Smad7 and p-AMPK in vivo and in vitro. After the abolition of Smad7, GHSR-1a and AMPK pathway, the effect of ghrelin on EndMT was significantly inhibited. In conclusion, these results presented a novel finding that ghrelin attenuated MF after AMI via regulation EndMT in a GHSR-1a/AMPK/Smad7- dependent manner. © 2018 Elsevier Inc.
语种：
英文
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Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome
作者：
Li, Tao;Liu, Youtan;Xu, Wei;Dai, Xingui;Liu, Ruimeng;...
期刊：
Laboratory Investigation ,2019年99(6):819-829 ISSN：0023-6837
通讯作者：
Chen, Zhongqing;Li, Yunfeng
作者机构：
[Li, Tao; Chen, Zhongqing; Xu, Wei] Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China.;[Li, Tao; Li, Yunfeng; Dai, Xingui] Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China.;[Liu, Youtan; Liu, Ruimeng] Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518110, Peoples R China.;[Gao, Youguang] Fujian Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Sch Clin Med 1, Fuzhou 350005, Fujian, Peoples R China.
通讯机构：
[Chen, Zhongqing] S;[Li, Yunfeng] U;Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China.;Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China.
摘要：
Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin-/- mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.
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英文
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表现为腰痛、驼背及帕金森综合征的伴皮质下梗死和白质脑病的常染色体显性脑动脉病
作者：
曹蕾;张奇山;袁毓蔓;刘琳;何伶俐;...
期刊：
中华医学遗传学杂志 ,2019年36(9):922-925 ISSN：1003-9406
作者机构：
南华大学附属郴州医院神经内科,郴州,423000;郴州市第一人民医院神经内科 423000;南华大学第一附属医院神经内科,衡阳,421001;[刘琳; 袁毓蔓; 曹蕾] 南华大学附属郴州医院;[张翀; 刘玲英; 罗莎林; 李一峰; 张奇山; 何伶俐] 湖南省郴州市第一人民医院
关键词：
伴皮质下梗死和白质脑病的常染色体显性脑动脉病;驼背;帕金森综合征
摘要：
目的探讨1例伴皮质下梗死和白质脑病的常染色体显性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)患者的临床特征和基因检测结果。方法收集患者及其家系成员的临床表型、神经影像学及基因检测资料,结合文献总结其临床特点。结果患者无头痛、反复卒中、痴呆、情感障碍等CADASIL的典型临床表现,仅表现为进行性加重的帕金森症状以及后期出现的腰痛、驼背、吞咽困难、视物重影等。头颅MRI扫描显示左侧基底节和外囊腔隙性脑梗死。基因检测发现NOTCH3第11外显子c. 1630C>T(p. R544C)变异。其母亲、姐姐和弟弟均携带c. 1630C>T(p. R544C)变异,但具有不同的表型。结论 CADASIL的临床表型有较大的异质性,腰痛、驼背以及帕金森综合征可能是一种少见的临床表型。
语种：
中文
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A recombinant multi-epitope peptide vaccine based on MOMP and CPSIT_p6 protein protects against Chlamydia psittaci lung infection
作者：
Li, Yumeng;Zheng, Kang;Tan, Yuan;Wen, Yating;Wang, Chuan;...
期刊：
Applied Microbiology and Biotechnology ,2019年103(2):941-952 ISSN：0175-7598
通讯作者：
Wu, Yimou
作者机构：
[Wu, Yimou; Li, Yumeng; Tan, Manyi; Zheng, Kang; Wen, Yating; Wang, Chuan; Xu, Man; Chen, Qian] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol,Med Coll, Hengyang 421001, Peoples R China.;[Tan, Yuan] First Hosp Changsha, Dept Dermatol, Changsha 410000, Hunan, Peoples R China.;[Yu, Jian] Univ South China, Med Coll, Dept Expt Zool, Hengyang 421001, Peoples R China.
通讯机构：
[Wu, Yimou] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Inst Pathogen Biol,Med Coll, Hengyang 421001, Peoples R China.
关键词：
Chlamydia psittaci;Epitope;Vaccine;Major outer membrane protein;Chlamydial infection
摘要：
Chlamydia psittaci is an obligate intracellular pathogen with a broad host range that can lead to severe infectious disease by transferring from birds to humans. Vaccination has been considered the best way to prevent chlamydial infection; nevertheless, there is currently still no commercially available vaccine that can inhibit the spread of C. psittaci. In previous study, major outer membrane protein (MOMP) of C. psittaci was confirmed to be an appropriate candidate antigen for limiting C. psittaci respiratory infections in a murine model, and plasmid-encoded CPSIT_p6 also has functions similar to those of MOMP in our study. Therefore, according to bioinformatics analysis, we developed a recombinant peptide containing multiple antigenic epitopes from MOMP (24–32, 262–272) and CPSIT_p6 protein (109–119, 173–181) and evaluated the efficacy of peptide immunization. BALB/c mice were inoculated intraperitoneally with the recombinant multi-epitope antigens three times at 2-week intervals and subsequently intranasally infected with C. psittaci. We found that the recombinant multi-epitope antigens induced strong humoral and Th1 cellular immune responses by producing meaningfully high levels of antigen-specific antibodies, interferon-gamma (IFN-γ), or interleukin-2 (IL-2). Vaccination significantly reduced the bacterial burden and the degree of inflammation in the infected lungs and led to lower levels of IFN-γ and IL-6. Furthermore, adoptive transfer of CD4+ splenocytes harvested from the vaccinated mice produced a significantly lower chlamydial load, indicating the importance of the cellular immune response. Therefore, the recombinant multi-epitope antigens may provide the basis for a new peptide-based vaccine against C. psittaci infection. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
语种：
英文
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FOXD3 may be a new cellular target biomarker as a hypermethylation gene in human ovarian cancer.
作者：
Luo, Gui-fang;Chen, Chang-ye;Wang, Juan;Yue, Hai-yan;Tian, Yong;...
期刊：
Cancer Cell International ,2019年19(1):1-13 ISSN：1475-2867
通讯作者：
Li, Yu-kun;Li, Yan
作者机构：
[Luo, Gui-fang; Chen, Chang-ye] Univ South China, Affiliated Hosp 1, Dept Gynecol, Hengyang 421001, Peoples R China.;[Wang, Juan] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Yang, Ping; Yue, Hai-yan; Li, Yu-kun] Univ South China, Coll Hunan Prov, Canc Res Inst, Key Lab Tumor Cellular & Mol Pathol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Tian, Yong] Wuhan Univ, Cent Hosp Enshi Tujia & Miao Autonomous Prefectur, Enshi Clin Coll, Dept Obstet & Gynecol, Enshi 445000, Hubei, Peoples R China.;[Li, Yan] Cent S Univ, Sch Basic Med Sci, Inst Reprod & Stem Cell Engn, 932 South Lushan Rd, Changsha 410013, Hunan, Peoples R China.
通讯机构：
[Li, Yu-kun] U;[Li, Yan] C;Univ South China, Coll Hunan Prov, Canc Res Inst, Key Lab Tumor Cellular & Mol Pathol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Cent S Univ, Sch Basic Med Sci, Inst Reprod & Stem Cell Engn, 932 South Lushan Rd, Changsha 410013, Hunan, Peoples R China.
关键词：
Ovarian carcinoma;DNA methylation;5-Aza-dC;FOXD3
摘要：
Background: FOXD3 is aberrantly regulated in several tumors, but its underlying mechanisms in ovarian cancer (OC) remains largely unknown. The present study aimed to explore the role and associated mechanisms of FOXD3 in OC. Methods: Microarray data from GEO was used to analyze differential CpG sites and differentially methylated regions (DMR) in tumor tissues and Illumina 450 genome-wide methylation data was employed. The FOXD3 expression level was determined through qRT-PCR and western blot analysis. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, proliferation abilities, cell cycle and cell apoptosis, respectively. Finally, the effect of FOXD3 on tumor growth was investigated through in vivo xenograft experiments. Results: GEO data analysis showed that FOXD3 was hypermethylated in OC tissues. Also, qRT-PCR revealed that FOXD3 was low expressed and methylation-specific PCR (MSP) confirmed that the methylation level of FOXD3 was hypermethylated. Combined treatment of 5-aza-2′-deoxycytidine (5-Aza-dC) could synergistically restored FOXD3 expression. Finally, in vitro and in vivo experiments showed that demethylated FOXD3 decreased cell proliferation and migration abilities, and increased the cell apoptosis. In vivo experiment detected that demethylated FOXD3 restrained tumor growth. Conclusions: FOXD3 could act as a tumor suppressor to inhibit cell proliferation, migration and promote cell apoptosis in OC cells. © 2019 The Author(s).
语种：
英文
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Role of heterogeneous nuclear ribonucleoprotein K in tumor development
作者：
Chen, Yuting;Zeng, Ying;Xiao, Zheng;Chen, Shi;Li, Yukun;...
期刊：
JOURNAL OF CELLULAR BIOCHEMISTRY ,2019年120(9):14296-14305 ISSN：0730-2312
通讯作者：
Zeng, Xi
作者机构：
[Li, Yukun; Xiao, Zheng; Chen, Yuting; Zou, Juan; Chen, Shi; Zeng, Xi] Univ South China, Hengyang Sch Med, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.;[Zeng, Ying] Univ South China, Sch Nursing, Hengyang, Peoples R China.;[Zeng, Xi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Zeng, Xi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Peoples R China.
通讯机构：
[Zeng, Xi] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Peoples R China.
关键词：
AS;hnRNP K;ncRNAs;posttranslational modification;tumor;virus
摘要：
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA/DNA special binding protein that participates in regulating the expression of related genes, transcription, RNA alternative splicing, translation, posttranslational modification, cell signal transduction, cell movement, interacts with ncRNAs, and induces angiogenesis. Moreover, several cellular functions forcefully indicated that hnRNP K participates in tumorigenesis. Numerous studies indicated hnRNP K is aberrantly elevated in multiple tumors. In addition, hnRNP K abnormal accumulation in cytoplasmic is also associated with poor prognosis. This suggests that hnRNP K may play a role in the development and progression of tumors. However, related studies demonstrated that hnRNP K acts as a tumor suppressor to suppress tumor formation. Therefore, this paper aims to explore the role of hnRNPK in tumors.
语种：
英文
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Localization and characterization of a putative cysteine desulfurase in Chlamydia psittaci.
作者：
Wen, Yating;Chen, Yanbo;Li, Li;Xu, Man;Tan, Yuan;...
期刊：
JOURNAL OF CELLULAR BIOCHEMISTRY ,2019年120(3):4409-4422 ISSN：0730-2312
通讯作者：
Wu, Yimou
作者机构：
[Wu, Yimou; Li, Yumeng; Kuang, Xingxing; Tan, Yuan; Wen, Yating; Wang, Chuan; Xu, Man; Chen, Qian] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pathogen Biol,Med Coll, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang, Peoples R China.;[Chen, Yanbo] Jiangmen Wuyi Tradit Chinese Med Hosp, Dept Clin Lab, Jiangmen, Peoples R China.;[Li, Li] Hunan Prov Ctr Dis Control & Prevent, Toxicol Lab, Changsha, Hunan, Peoples R China.;[Wu, Yimou] Univ South China, Med Coll, Inst Pathogen Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, Yimou] U;Univ South China, Med Coll, Inst Pathogen Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Chlamydia psittaci;T3SS;cellular localization;cysteine desulfurase;mitochondria-mediated pathway
摘要：
Chlamydia psittaci is an obligate intracellular pathogen with a biphasic developmental life cycle. It is auxotrophic for a variety of essential metabolites and obtains amino acids from eukaryotic host cells. Chlamydia can develop inside host cells within chlamydial inclusions. A pathway secreting proteins from inclusions into the host cellular cytoplasm is the type III secretion system (T3SS). The T3SS is universal among several Gram-negative bacteria. Here, we show that CPSIT_0959 of C. psittaci is expressed midcycle and secreted into the infected cellular cytoplasm via the T3SS. Recombinant CPSIT_0959 possesses cysteine desulfurase and PLP-binding activity, which removes sulfur from cysteine to produce alanine, and helps chlamydial replication. Our study shows that CPSIT_0959 improve the infectivity of offspring elementary bodies and seems to promote the replication by its product. This phenomenon has inhibited by the PLP-dependent enzymes inhibitor. Moreover, CPSIT_0959 increased expression of Bim and tBid, and decreased the mitochondrial membrane potential of host mitochondria to induce apoptosis in the latecycle for release of offspring. These results demonstrate that CPSIT_0959 has cysteine desulfurase and PLP-binding activity and is likely to contribute to apoptosis of the infected cells via a mitochondria-mediated pathway to improve the infectivity of progeny.
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英文
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