期刊：
European Journal of Pharmacology,2024年:176481 ISSN：0014-2999
通讯作者：
Zhao, Xiao-Mei;Jiang, Miao
作者机构：
[He, Xueke; Zhou, Yangyang; Peng, Weiqiang; Liao, Minjun] Institute of Cardiovascular Disease, Department of Pathophysiology, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, 421001, PR China;[Zhou, Yangyang; Peng, Weiqiang; Liao, Minjun] Department of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, PR China;[Zhao, Xiao-Mei] College of Public Health, University of South China, Hengyang, 421001, Hunan, PR China. Electronic address: mavis1015@163.com;[Jiang, Miao] Institute of Cardiovascular Disease, Department of Pathophysiology, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, 421001, PR China. Electronic address: miao_jiang@usc.edu.cn
通讯机构：
[Jiang, Miao] I;[Zhao, Xiao-Mei] C;College of Public Health, University of South China, Hengyang, 421001, Hunan, PR China. Electronic address:;Institute of Cardiovascular Disease, Department of Pathophysiology, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, 421001, PR China. Electronic address:
摘要：
Atherosclerotic disease is a chronic disease that predominantly affects the elderly and is the most common cause of cardiovascular death worldwide. Atherosclerosis is closely related to processes such as abnormal lipid transport and metabolism, impaired endothelial function, inflammation, and oxidative stress. Coenzyme Q10 (CoQ10) is a key component of complex Ⅰ in the electron transport chain and an important endogenous antioxidant that may play a role in decelerating the progression of atherosclerosis. Here, the different forms of CoQ10 presence in the electron transport chain are reviewed, as well as its physiological role in regulating processes such as oxidative stress, inflammatory response, lipid metabolism and cellular autophagy. It was also found that CoQ10 plays beneficial effects in atherosclerosis by mitigating lipid transportation, endothelial inflammation, metabolic abnormalities, and thrombotic processes from the perspectives of molecular mechanisms, animal experiments, and clinical evidence. Besides, the combined use of CoQ10 with other drugs has better synergistic therapeutic effects. It seems reasonable to suggest that CoQ10 could be used in the treatment of atherosclerotic cardiovascular diseases while more basic and clinical studies are needed.
期刊：
FRONTIERS IN NEUROLOGY,2024年15:1291950 ISSN：1664-2295
作者机构：
Department of Neurology, Brain Hospital of Hunan Province, The Second People's Hospital of Hunan Province, Changsha, China;Department of Neurology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
摘要：
Background: Inflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear.
期刊：
CRITICAL REVIEWS IN IMMUNOLOGY,2024年44(4):1-12 ISSN：1040-8401
作者机构：
[Jing Guo; Jinglou Chen] School of Medicine, Jianghan University, Wuhan 430056, China;[Yi-Zhi Yan; Yang Duan; Peng Zeng] Department of Histology and Embryology, School of Basic Medicine, Hengyang Medical College, University of South China, Hengyang 421001, China
关键词：
stroke;aging;MCAO;gene expression omnibus database;differentially expressed genes;pathway
摘要：
Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signaling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signaling pathway, the IL-17 and other signaling pathways were significantly correlated with the aged MCAO rats. Our study indicates that multiple genes and pathological processes involved in the aged people of stroke. The immune response might be the key pathway in the intervention of cerebral infarction in aged people.
作者机构：
[Xie, Xiaoping; Chen, Cong; He, Yuqi] The First Affiliated Hospital, Department of Laboratory Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Yuan, Qing; Zhao, Zhibo; Gao, Yan; Liu, Jianghua; Cao, Jingsong] The First Affiliated Hospital, Institute of Endocrinology and Metabolism;[Yuan, Qing; Zhao, Zhibo; Gao, Yan; Liu, Jianghua; Cao, Jingsong] Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Zu, Xuyu] The First Affiliated Hospital, Institute of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
通讯机构：
[Xuyu Zu; Jianghua Liu] T;The First Affiliated Hospital, Institute of Endocrinology and Metabolism;Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Institute of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
期刊：
Cell Death Discovery,2024年10(1):143 ISSN：2058-7716
通讯作者：
Hao, Yue;Chu, Bizhu;Jiang, Yuyang
作者机构：
[Zheng, Wenwen; Huang, Wenjun; Zhu, Qingyun; Tu, Yao] School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China;[Zhu, Qingyun; Zu, Xuyu] The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Shi, Zhichao] Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China;[Li, Qinyuan; Li, Lulu; Yuan, Zigao] State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China;[Hao, Yue] School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China. yuehao@szu.edu.cn
通讯机构：
[Hao, Yue; Jiang, Yuyang; Chu, Bizhu] S;School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.;Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.;State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.;School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
摘要：
The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo. Mechanistically, 15a induces a viral mimicry response by promoting the expression of endogenous retroviral elements in breast cancer cells, thus increasing the intracellular level of double-stranded RNA to activate the RIG-I-MAVS pathway. This in turn promotes the production of interferons and chemokines and augments the expression of interferon-stimulated genes and PD-L1. The combination of 15a and an anti-PD-L1 antibody had an additive effect in vivo. These findings indicate that this DNMT/HDACi has immunomodulatory functions and enhances the effectiveness of immune checkpoint blockade therapy. A novel dual DNMT and HDAC inhibitor induces viral mimicry, which induces the accumulation of dsRNA to activate tumoral IFN signalling and cytokine production to enhance the immune response in breast cancer.
摘要：
Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.
作者：
Zhou, Zhou;Liu, Yuanjun;Yang, Chunfu;Saka, Hector Alex
期刊：
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,2024年14:1372714 ISSN：2235-2988
作者机构：
Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical College, University of South China, China;Department of Dermatovenereology, Tianjin Medical University General Hospital, China;School of Public Health and Emergency Management, Southern University of Science and Technology, China;Laboratory of Cellular and Molecular Microbiology, Centre for Research in Clinical Biochemistry and Immunology (CIBICI), National Council on Scientific and Technical Research (CONICET), Argentina;Department of Clinical Biochemistry, School of Chemical Sciences, National University of Cordoba, Argentina
摘要：
replicative, labile, and non-infectious reticulate bodies (RBs). Once EBs infect their host cells, 24 they are internalized into a parasitophorous vacuole named an "inclusion" and then differentiate into 25 RBs, which rely on nutrients acquisition from the host to replicate. At mid to late times post-26 infection, RBs redifferentiate into infectious EBs and exit to the extracellular environment where 27 neighboring cells can be infected (2)(3)(4). Among the Chlamydiaceae family, the genus Chlamydia 28 contains 13 species (5), 3 of which are the most relevant as human pathogens. Chlamydia 29 trachomatis is the main bacterial cause of sexually transmitted infections and the leading agent of 30 infectious blindness worldwide (6, 7), C. pneumoniae is a common etiology of atypical pneumoniae 31 TmeA and they both are secreted within minutes after Chlamydia attachment. These authors 46 generated and manipulated ΔtmeA, ΔtmeB, ΔtmeAB mutants as well as strains null for multiple genes 47 to uncover that, as opposed to TmeA, lack of TmeB does not significantly impair the invasion 48 efficiency of C. trachomatis. Intriguingly, they found that loss of TmeB turned TmeA dispensable for 49 invasion and that overabundance of TmeB hinders host-cell invasion and Arp2/3-mediated actin 50 polymerization. Altogether, these results point out a complex and dynamic interplay between TmeA 51 and TmeB and host actin polymerization during chlamydial entry. 52 in an in-vitro mimicking a co-infection ...
期刊：
Journal of Nanobiotechnology,2024年22(1):1-1 ISSN：1477-3155
通讯作者：
Jikai Wang
作者机构：
[Yanli Zhu] School of Resources and Environment, Hunan University of Technology and Business, Changsha, P. R. China;[Jikai Wang; Pengfei Zeng; Yiyang Sun; Ziyi Mo] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, P. R. China;[Chengxiao Fu; Shuangquan Liu; Danjun Chen] The First Affiliated Hospital, Department of Clinical Laboratory, Department of Pharmacy, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, P. R. China;[Pragati Awasthi] State Key Laboratory of Silicon Materials & School of Materials Science and Engineering, Zhejiang University, Hangzhou, P. R. China;[Hailing Liu] Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, P. R. China
通讯机构：
[Jikai Wang] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, P. R. China
期刊：
Ecotoxicology and Environmental Safety,2024年273:116128 ISSN：0147-6513
通讯作者：
Lan Yi
作者机构：
[Lin, Xiang; Wei, Yuanyun; Wei, Shuang; Gong, Yaqi; Cui, Jian; Yan, Hongxia; Qin, Hui; Yu, Yueqiu; Li, Linwei; Li, Guoqing] Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, The First Affiliated Hospital, Institute of Cardiovascular Disease, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Yi, Lan] Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, The First Affiliated Hospital, Institute of Cardiovascular Disease, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: yilanoky@126.com
通讯机构：
[Lan Yi] I;Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, The First Affiliated Hospital, Institute of Cardiovascular Disease, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
摘要：
BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 μGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.
摘要：
Gram-negative Bartonella species are facultative intracellular bacteria that can survive in the harsh intracellular milieu of host cells. They have evolved strategies to evade detection and degradation by the host immune system, which ensures their proliferation in the host. Following infection, Bartonella alters the initial immunogenic surface-exposed proteins to evade immune recognition via antigen or phase variation. The diverse lipopolysaccharide structures of certain Bartonella species allow them to escape recognition by the host pattern recognition receptors. Additionally, the survival of mature erythrocytes and their resistance to lysosomal fusion further complicate the immune clearance of this species. Certain Bartonella species also evade immune attacks by producing biofilms and anti-inflammatory cytokines and decreasing endothelial cell apoptosis. Overall, these factors create a challenging landscape for the host immune system to rapidly and effectively eradicate the Bartonella species, thereby facilitating the persistence of Bartonella infections and creating a substantial obstacle for therapeutic interventions. This review focuses on the effects of three human-specific Bartonella species, particularly their mechanisms of host invasion and immune escape, to gain new perspectives in the development of effective diagnostic tools, prophylactic measures, and treatment options for Bartonella infections.
作者机构：
[Jing Yang; Shishan Teng; Rongzhang He; Bo Liu; Xingyu Zheng; Rui Lu; Dong Pan; Liting Peng; Wenpei Liu] College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang, 421001, China;Translational Medicine Institute, The First People's Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, 423000, China;[Zhanpeng Liu; Xiaoyue Zhang; Lulu Liu; Hongying chen] College of Life Sciences, Northwest A&F University, Yangling, 712100, China;[Yi-Ping Li] Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China;[You Wang] School of Public Health, University of South China, Hengyang, 421001, China
通讯机构：
[Hongying chen; Wenpei Liu; Xiaowang Qu] C;[Yi-Ping Li] I;College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang, 421001, China<&wdkj&>Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China<&wdkj&>College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang, 421001, China<&wdkj&>School of Public Health, University of South China, Hengyang, 421001, China<&wdkj&>College of Life Sciences, Northwest A&F University, Yangling, 712100, China
期刊：
Annals of Clinical and Translational Neurology,2024年11(1):57-66 ISSN：2328-9503
通讯作者：
Zhou, HC
作者机构：
[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha 410013, Peoples R China.;[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Inst Pain Med, Changsha 410013, Peoples R China.;[Chen, Li] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Anesthesiol, Changsha 410028, Peoples R China.;[Zhou, Haocheng; Huang, Dong] Cent South Univ, Hunan Key Lab Brain Homeostasis, Changsha 410013, Peoples R China.;[Huang, Yuzhao] Cent South Univ, Xiangya Hosp 3, Dept Orthopaed, Changsha 410013, Hunan, Peoples R China.
通讯机构：
[Zhou, HC ] C;Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha, Peoples R China.;Cent South Univ, Inst Pain Med, Changsha, Peoples R China.
摘要：
AIM: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain. It is necessary to identify the responders of SCS analgesia before implantation. The aim of this study is to investigate the relationship between the cortical dynamics and SCS analgesia responders in pain management. METHODS: Resting-state EEG recording was performed in patients who underwent short-term implantation of spinal cord stimulation for pain therapy. We then did spectral analysis to capture the pattern of cortical oscillation between neuromodulation therapy analgesia responders and nonresponders. RESULTS: About 58.3% (14 out of 24) of participants were considered as analgesia responders, with average visual analogue scores reduction of 4.8 ± 1.0 after surgery, and 2.1 ± 0.7 for the nonresponder subgroup, respectively. The alpha oscillation was significantly enhanced in responder cohort compared with nonresponders. We also observed an increasing spectral power of gamma band in responders. Furthermore, the attenuation of pain severity was significantly correlated with the global alpha oscillation activity (r = 0.60, P = 0.002). Likely, positive and significant correlation was found between the pain relief and gamma activity (r = 0.58, P = 0.003). CONCLUSIONS: Distinct pattern of neural oscillation is associated with the analgesic effect of spinal cord stimulation in pain management, enhancement of cortical alpha and gamma oscillation may be a predictor of analgesia responders.
期刊：
CURRENT MOLECULAR MEDICINE,2024年 ISSN：1566-5240
作者机构：
[Ouyang, Siyu; Liu, Zhiyang; Xie, Zhongcheng; Hou, Qin] Department of Anatomy, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China;[Yang, Jimin; Liu, Jifeng] Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, 37 Guo Xue Lane, Chengdu 610064, Sichuan Province, China;[Jiao, Chunmeng] Department of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China;[Chen, Hui] Institute of Acupuncture Research, Institutes of Integrative Medicine, Fudan University, Shanghai 200032, China
摘要：
INTRODUCTION: Skeletal muscle degeneration is a common effect of chronic muscle injuries, including fibrosis and fatty infiltration, which is the replacement of preexisting parenchymal tissue by extracellular matrix proteins and abnormal invasive growth of fibroblasts and adipocytes. METHOD: This remodeling limits muscle function and strength, eventually leading to reduced quality of life for those affected. Chemokines play a major role in the regulation of immunocyte migration, inflammation, and tissue remodeling and are implicated in various fibrotic and degenerative diseases. In this study, we aimed to investigate the role of the B-cell chemokine CXCL13 in the gastrocnemius muscle of the Achilles tendon rupture model mouse. We hypothesize that CXCL13 may promote fibrosis and aggravate skeletal muscle degeneration. We performed RNA sequencing and bioinformatics analysis of gastrocnemius muscle from normal and model mice to identify differentially expressed genes and signal pathways related to skeletal muscle degeneration and fibrosis. RESULTS: Our results show that CXCL13 is highly expressed in chronically degenerating skeletal muscle. Furthermore, CXCL13-neutralising antibodies with therapeutic potential were observed to inhibit fibrosis and adipogenesis in vivo and in vitro. CONCLUSION: Our study reveals the underlying therapeutic implications of CXCL13 inhibition for clinical intervention in skeletal muscle degeneration, thereby improving patient prognosis.
摘要：
In heat shock, various enzyme activities are clearly altered due to high body temperature. Evidence accumulated in the last few years indicates that endogenous carboxylesterase (CE) can be regarded as a biomarker of heat shock due to its close relationship to heat shock. To monitor CE activity, this study aims to develop excellent fluorescent probe for CE detection. Fluorescent probe DCM-Br-CE with a NIR turn-on signal at 660 nm and a large Stokes shift of 160 nm, as well as high sensitivity (0.117 x 10-4 U/mL) and good detection capability (30 min) for CE. DCM-Br-CE also has excellent subcellular localization for endoplasmic reticulum (ER). Furthermore, DCM-Br-CE has been shown to effectively visualize endogenous CE in PC12 or HT22 cells, can also monitor changes in CE activity during heat shock in cells and in living mice. This suggests that the probe has potential to be used for CE studies across a variety of pathological conditions, making it a promising tool for heat shock research.
摘要：
Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.
期刊：
FRONTIERS IN IMMUNOLOGY,2024年15:1355949 ISSN：1664-3224
通讯作者：
Liu, Wenpei;Qu, XW
作者机构：
[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Xie, Tianyi] Univ South China, Hengyang Med Sch, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Li, Yi-Ping; Xie, Tianyi] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Hengyang, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Li, Yi-Ping; Xie, Tianyi] Univ South China, Minist Educ Key Lab Rare Pediat Dis, Hengyang, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Xie, Tianyi] Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou, Peoples R China.;[Wu, Qian; Li, Yi-Ping] Sun Yat sen Univ, Inst Human Virol, Zhongshan Sch Med, Guangzhou, Peoples R China.
通讯机构：
[Qu, XW ; Liu, WP] U;Univ South China, Hengyang Med Sch, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Hengyang, Peoples R China.;Univ South China, Minist Educ Key Lab Rare Pediat Dis, Hengyang, Peoples R China.
关键词：
SARS-CoV-2;monoclonal antibody;naïve B cell;preexisting memory B cell;vaccination
摘要：
INTRODUCTION: Since December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown. METHODS: To elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells. RESULTS: The frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination. DISCUSSION: Our findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development.
摘要：
BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
摘要：
The Pgp3 subunit vaccine elicits immune protection against Chlamydia trachomatis infection, but additional adjuvants are still required to enhance its immunoprotective efficacy. Flagellin can selectively stimulate immunity and act as an adjuvant. In this research, the FliC-Pgp3 recombinant was successfully expressed and purified. Tri-immunization with the FliC-Pgp3 vaccine in Balb/C mice induced rapid and persistent germinal center B-cell response and Tfh differentiation, promoting a significantly higher IgG antibody titer compared to the Pgp3 group. FliC-Pgp3 immunization primarily induced Th1-type cellular immunity, leading to higher levels of IFN-γ, TNF-α, and IL-2 secreted by CD4(+) T cells than in Pgp3-vaccinated mice. Chlamydia muridarum challenge results showed that FliC-Pgp3-vaccinated mice exhibited more rapid clearance of Chlamydia muridarum colonization in the lower genital tract, ensuring a lower hydrosalpinx rate and cumulative score. Histological analysis showed reduced dilation and inflammatory infiltration in the oviduct and uterine horn of FliC-Pgp3-vaccinated mice compared to the PBS and Pgp3 control. Importantly, tri-immunization with FliC-Pgp3 effectively activated CD4(+) T cells and dendritic cells, as confirmed by the adoptive transfer, resulting in better immune protection in recipient mice. In summary, the novel FliC-Pgp3 chimeric is hoped to be a novel vaccine with improved immunoprotection against Chlamydia muridarum.
