作者机构：
[Li, Ao; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Qun] Cent South Univ, Xiangya Hosp 3, Hlth Management Ctr, Changsha, Hunan, Peoples R China.;[Li, Zhiyue] Cent South Univ, Dept Orthoped, Xiangya Hosp 3, Changsha, Hunan, Peoples R China.
通讯机构：
[Linxi Chen] I;[Zhiyue Li] D;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Orthopedics, Third Xiangya Hospital of Central South University, Changsha, China
摘要：
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.
期刊：
European Journal of Pharmacology,2022年931:175195 ISSN：0014-2999
通讯作者：
Liao, D.;Liu, Z.
作者机构：
[Wang, Chuyao; Yuan, Yulin; Zhao, Qian; Jiang, Susu; Yang, Huixian; Long, Shiyin; Zhang, Caiping] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;[Wen, Hongyan; Liao, Duanfang; Xiang, Debiao; Huang, Ying; Tuo, Qinhui; Zeng, Yaling] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Changsha, Peoples R China.;[Huang, Zhixin; Liu, Xuanyou; Liu, Zhenguo; Hao, Hong; Zhang, Caiping] Univ Missouri, Ctr Precis Med, Dept Med,Sch Med, Div Cardiovasc Med, Columbia, MO USA.;[Xiang, Debiao] Third Hosp Changsha, Dept Pharm, Changsha, Peoples R China.;[Liu, Zhenguo] Univ Missouri, Sch Med, Dept Med, Div Cardiovasc Med, 1 Hosp Dr, CE344, Columbia, MO 65211 USA.
通讯机构：
[Liu, Z.] D;[Liao, D.] K;Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine 1 Hospital DriveUnited States;Key Lab for Quality Evaluation of Bulk Herbs of Hunan Province, 300# Xueshi Rd, Hanpu Science & Education District, Hunan, China
摘要：
Curcumin nicotinate (Curtn) is a synthesized ester derivative of curcumin and niacin. Our previous study has shown that Curtn lowers serum low-density lipoprotein cholesterol (LDL-C) levels in apoE(-/-) mice and promotes LDL-C uptake into HepG2 cells in vitro. The present study was to test the hypothesis that Curtn decreases serum LDL-C levels through decreased expression of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and subsequent increase in LDL receptor expression. Male Wistar rats on high-fat diet (HFD) were treated with Curtn or rosuvastatin. Curtn or rosuvastatin treatment significantly decreased serum levels of total cholesterol (TC) and LDL-C in rats on HFD with increased liver LDL receptor expression. LDL-C-lowering effect of Curtn was not observed in LDL receptor deficient (LDLR(-/-)) mice on HFD, while rosuvastatin still decreased serum lipid levels in LDLR(-/-) mice, indicating that the reduction of serum LDL-C levels by Curtn treatment was LDL receptor-dependent. Curtn treatment also significantly decreased the protein expression of PCSK9 in Wistar rats and LDLR(-/-) mice. In HepG2 cells with overexpression of human PCSK9, Curtn treatment significantly increased LDL-C uptakes into hepatocytes, and increased LDL receptor distribution on cell surface in association with decreased PCSK9 protein expression. RNAi-LDLR significantly attenuated the effect of Curtn on LDLR distribution on cell surface. These data indicates that Curtn would decrease serum LDL-C level at least partially through inhibition of PCSK9 expression, and subsequent increase in LDL receptor expression and distribution in hepatocytes, serving as a potential novel compound to treat hyperlipidemia.
作者机构：
[Wang, Weiguo; Wu, Jingjun; Yang, Lin; He, Jian; Cao, Qianqian; He, Dongxiu; Li, Sang] Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.;[Wang, Weiguo; Wu, Jingjun; Yang, Lin; He, Jian; Cao, Qianqian; He, Dongxiu; Li, Sang] Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang, Hunan, Peoples R China.;[Wang, Weiguo; Wu, Jingjun; Yang, Lin; He, Jian; Cao, Qianqian; He, Dongxiu; Li, Sang] Hunan Xinhexin Biol Med Co Ltd, Pharm Grad Educ Innovat Base, Hengyang, Hunan, Peoples R China.;[Li, Ranhui] Univ South China, Hengyang Med Sch, Inst Pathogen Biol, Hengyang 421000, Hunan, Peoples R China.;[Wu, Xian; Duan, Yunfeng] Hunan Prov Directly Affiliated TCM Hosp, Affiliated Hosp 1, Hunan Coll Tradit Chinese Med, Zhuzhou, Peoples R China.
通讯机构：
[Dongxiu He; Weiguo Wang] I;Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421000, Hunan, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, Hunan, China<&wdkj&>Hunan Xinhexin Biological Medicine Co., Ltd., Pharmacy Graduate Education Innovation Base, Hengyang, Hunan, China
作者机构：
[Salami, Oluwabukunmi Modupe; Habimana, Olive] Univ South China, Int Coll, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Yi, Guang-Hui; Peng, Jinfu] Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Yi, Guang-Hui; Peng, Jinfu] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Yi, Guang-Hui] Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Guang-Hui Yi] I;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, 28, W Changsheng Road, Hengyang, Hunan 421001, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, 28, W Changsheng Road, Hengyang, Hunan 421001, China
摘要：
Heart failure remains a considerable clinical and public health problem, it is the dominant cause of death from cardiovascular diseases, besides, cardiovascular diseases are one of the leading causes of death worldwide. The survival of patients with heart failure continues to be low with 45-60% reported deaths within five years. Apoptosis, necrosis, autophagy, and pyroptosis mediate cardiac cell death. Acute cell death is the hallmark pathogenesis of heart failure and other cardiac pathologies. Inhibition of pyroptosis, autophagy, apoptosis, or necrosis reduces cardiac damage and improves cardiac function in cardiovascular diseases. Pyroptosis is a form of inflammatory deliberate cell death that is characterized by the activation of inflammasomes such as NOD-like receptors (NLR), absent in melanoma 2 (AIM2), interferon-inducible protein 16 (IFI-16), and their downstream effector cytokines: Interleukin IL-1β and IL-18 leading to cell death. Recent studies have shown that pyroptosis is also the dominant cell death process in cardiomyocytes, cardiac fibroblasts, endothelial cells, and immune cells. It plays a crucial role in the pathogenesis of cardiac diseases that contribute to heart failure. This review intends to summarize the therapeutic implications targeting pyroptosis in the main cardiac pathologies preceding heart failure.
期刊：
Journal of Drug Targeting,2022年30(3):244-258 ISSN：1061-186X
通讯作者：
Nian Fu<&wdkj&>Linxi Chen
作者机构：
[Jiang, Jinyong; Chen, Zhe; Chen, Linxi] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Coll Basic Med Sci, Hengyang 421001, Peoples R China.;[Fu, Nian] Univ South China, Affiliated Nanhua Hosp, Dept Gastroenterol, Hengyang, Peoples R China.
通讯机构：
[Nian Fu] D;[Linxi Chen] I;Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, University of South China, Hengyang, China
作者机构：
[Liu, Yuxin; Wu, DuanSheng; Wang, Yude; Yang, JingPing] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Liao, Xiao-Li] Hunan Inst Traff Engn, Sch Med Technol & Nursing, Hengyang 421001, Peoples R China.;[Zhang, Zhaohui; Chen, KeJie; Wu, DuanSheng; Liao, Xiao-Li] Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Zhang, Zhaohui; Chen, KeJie; Wu, DuanSheng; Liao, Xiao-Li] Univ South China, Dept Lab Anim Sci, Hengyang 421001, Peoples R China.
通讯机构：
[DuanSheng Wu] S;State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China<&wdkj&>University of South China, Hengyang Medical College, Hengyang, China<&wdkj&>University of South China, Department of Laboratory Animal Science, Hengyang, China
关键词：
Laboratory red crucian carp;Irradiation;MicroRNA
作者机构：
[Gao, Jiayin; Gao, Anbo; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.;[Zhou, Hong] Univ South China, Affiliated Hosp 1, Dept Radiol, Hengyang 421001, Peoples R China.
通讯机构：
[Hong Zhou] D;[Linxi Chen] I;Department of Radiology of the First Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
作者机构：
[Cao, Zhaohui; Hu, Xiaobo; Tang, Cifei; Zeng, Min; Huang, Di] Univ South China, Hengyang Med Sch, Sch Basic Med, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Cao, Zhaohui; Hu, Xiaobo; Tang, Cifei; Zeng, Min; Huang, Di] Univ South China, Hengyang Med Sch, Key Lab Ecol Environm & Crit Human Dis Prevent Hu, Dept Educ, Hengyang 421001, Peoples R China.
通讯机构：
[Xiaobo Hu] D;Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education, Hengyang Medical School, University of South China, Hengyang, China
关键词：
OXIDATIVE;predominant;NOX2
摘要：
Neutrophils are predominant leukocytes in the circulation, which are essential for killing invading pathogens via the activation of effector responses and the production of reactive oxygen species (ROS), also named as "oxidative burst." When infected, activated neutrophils fight bacteria, fungi, and viruses through oxidative burst, phagocytosis, degranulation, and the production of neutrophil extracellular traps (NETs) in a neutrophil death process named as "NETosis" (Mutua and Gershwin, 2021). NETs, consisting of DNA fibers decorated with modified histones and numerous antimicrobial proteins from cytoplasmic granules and the nucleus, can either be beneficial or detrimental (Mutua and Gershwin, 2021). Several pathways can lead to this death process. In response to various stimuli, NETosis traps and clears pathogens, facilitating phagocytosis by other neutrophils and phagocytes. However, excessive NETosis often results in disease due to increasing the pro-inflammatory response and perpetuating the inflammatory condition (Hellebrekers et al., 2018; Hidalgo et al., 2019; Klopf et al., 2021). Accordingly, inhibiting aberrant NETosis may alleviate the severity of various autoimmune and inflammatory diseases.
摘要：
Inositol 1, 4, 5-trisphosphate (IP3) signaling-mediated calcium release drives the contraction of vascular smooth muscles and hence regulates blood vessel volume and blood pressure. Melatonin supplementation has been suggested to be beneficial for hypertension. To determine whether the blood pressure-lowering effect of melatonin was accounted for by IP3 signaling, we evaluated the vasoconstriction response and IP3 signaling in isolated mouse thoracic aortic rings during melatonin incubation. C57BL/6 mice were given intraperitoneal injections daily with melatonin, and the systolic blood pressure and contractility of aortic rings from melatonin-treated mice were decreased, and the contraction suppression effect of melatonin was attributed to the impaired expression of contractile proteins in vascular smooth muscle cells rather than IP3 signaling. Our results further showed that melatonin increased the expression of γ-secretase, which could cleave and release the notch intracellular domain, and the notch intracellular domain prevented the transcription of contractile genes by interfering with the interaction between serum response factor and myocardin, the master regulator of contractile protein. In this article, we report a novel mechanism by which melatonin regulates smooth muscle contractility that does not depend on IP3 signaling.
期刊：
Journal of Translational Medicine,2022年20(1):1-11 ISSN：1479-5876
通讯作者：
Jie Li<&wdkj&>Weiqiang Tang
作者机构：
[Li, Jie; Liao, Yajie] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.;[Wu, Xudong] Third Hosp Changsha, Dept Thorac Surg, Changsha 410035, Peoples R China.;[Wu, Mengyu] Jianghan Univ, Sch Med, Wuhan 430056, Peoples R China.;[Fang, Yuan] Kunming Med Univ, Affiliated Hosp 1, Organ Transplantat Ctr, Kunming 650032, Yunnan, Peoples R China.;[Tang, Weiqiang] Univ South China, Hengyang Med Sch, Inst Clin Med, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Jie Li; Weiqiang Tang] I;Institute of Pharmacy and Pharmacology, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, People’s Republic of China<&wdkj&>Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China
摘要：
Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.
作者机构：
[Duan, Dan-Qing; Peng, Jun; Zhou, Yuan-Jing; Lu, Li-Qun; Zhang, Xiao-Jie] Cent South Univ, Xiangya Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410078, Peoples R China.;[Zhou, Yuan-Jing] Guangdong Med Univ, Zhanjiang Cent Hosp, Dept Pharm, Zhanjiang 524045, Peoples R China.;[Tang, Li-Jing] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Luo, Xiu-Ju] Cent South Univ, Xiangya Hosp 3, Dept Lab Med, Changsha 410013, Peoples R China.;[Peng, Jun] Cent South Univ, Sch Pharmaceut Sci, Hunan Prov Key Lab Cardiovasc Res, Changsha 410078, Peoples R China.
通讯机构：
[Jun Peng] D;Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China<&wdkj&>Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China
摘要：
Ferroptosis is an iron-dependent cell death and contributes to doxorubicin-induced cardiotoxicity, but the mechanisms behind intracellular iron overload in cardiomyocyte after administration of doxorubicin remain largely unknown. Ferritinophagy is a selective type of autophagy and could be a novel source for intracellular free iron. Spermatogenesis-associated protein 2 (SPATA2), a member of the TNF signaling pathway, can recruit cylindromatosis (CYLD, a deubiquitinating enzyme) to regulate cell death. This study aims to explore whether ferritinophagy is the source for intracellular iron overload in cardiomyocyte upon doxorubicin treatment and whether the SPATA2/CYLD pathway is involved in regulation of nuclear receptor coactivator 4 (NCOA4) level, the selective cargo receptor for ferritinophagy. The C57BL/6J mice were subjected to a single injection of doxorubicin, which showed the compromised cardiac functions, accompanied by the upregulation of SPATA2 and CYLD and the enhanced interaction between them, the increases in ferritinophagy (reflecting by increases in NCOA4 and ratio of LC3Ⅱ/LC3Ⅰ while decreases in NCOA4 ubiquitination and ferritin) and ferroptosis (reflecting by intracellular iron overload and increase of acyl-CoA synthetase long chain family member 4). Consistently, similar results were achieved in the cultured cardiomyocytes after incubation with doxorubicin. Knocked down of SPATA2 notably reduced doxorubicin-induced cardiomyocyte injury concomitant with the attenuated ferritinophagy and the decreased ferroptosis. Based on these observations, we conclude that a novel pathway of SPATA2/CYLD has been identified, which contributes to doxorubicin-induced cardiomyocyte ferroptosis via enhancing ferritinophagy through a mechanism involving the deubiquitination of NCOA4.
通讯机构：
[Li-Chen Gao] S;School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, Changsha Central Hospital Affiliated to University of South China, University of South China, Hengyang, China
摘要：
BACKGROUND: Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine. OBJECTIVE: The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers. METHODS: A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC(0-72h)), under the plasma concentration-time curve from zero to infinity (AUC(0-∞)) and the maximal plasma concentration (C(max)). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs). RESULTS: A total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the C(max), AUC(0-72h) and AUC(0-∞) were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the C(max), AUC(0-72h) and AUC(0-∞) were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The C(max) and AUC(0-72h) values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial. CONCLUSIONS: The T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.
作者机构：
[Wu, Yueyue; Chen, Liesong; Zhu, Cuiming; You, Xiaoxing; Zeng, Yanhua; Xi, Yixuan; Qin, Lianmei; Chen, Yiwen; Xiu, Feichen; Liu, Lu] Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang Med Sch,Inst Pathogen Biol, Hengyang, Peoples R China.;[Wu, Yueping; Qin, Lianmei] Shenzhen Childrens Hosp, Dept Blood Transfus, Shenzhen, Peoples R China.;[Luo, Haodang; He, Jun] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Dept Clin Lab, Hengyang, Peoples R China.;[Hu, Jun] Univ South China, Hengyang Med Sch, Affiliated Hosp 2, Dept Cardiothorac Surg, Hengyang, Peoples R China.;[Wu, Ning] Hengyang 1 Peoples Hosp, Dept Clin Lab, Hengyang, Peoples R China.
通讯机构：
[Xiaoxing You] I;Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
关键词：
Mycoplasma pneumoniae;matrix metalloproteinase-9;reversion-inducing cysteine-rich protein with Kazal motifs (RECK);bronchial epithelial cell
作者机构：
[You Xiaoxing] Univ South China, Hengyang Med Sch, Inst Pathogen Biol, Hengyang, Peoples R China.;Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
通讯机构：
[You Xiaoxing] I;Institute of Pathogenic Biology, Hengyang Medical School<&wdkj&>Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
摘要：
Mycoplasma genitalium, a pathogen from class Mollicutes, has been linked to sexually transmitted diseases and sparked widespread concern. To adapt to its environment, M. genitalium has evolved specific adhesins and motility mechanisms that allow it to adhere to and invade various eukaryotic cells, thereby causing severe damage to the cells. Even though traditional exotoxins have not been identified, secreted nucleases or membrane lipoproteins have been shown to cause cell death and inflammatory injury in M. genitalium infection. However, as both innate and adaptive immune responses are important for controlling infection, the immune responses that develop upon infection do not necessarily eliminate the organism completely. Antigenic variation, detoxifying enzymes, immunoglobulins, neutrophil extracellular trap-degrading enzymes, cell invasion, and biofilm formation are important factors that help the pathogen overcome the host defence and cause chronic infections in susceptible individuals. Furthermore, M. genitalium can increase the susceptibility to several sexually transmitted pathogens, which significantly complicates the persistence and chronicity of M. genitalium infection. This review aimed to discuss the virulence factors of M. genitalium to shed light on its complex pathogenicity and pathogenesis of the infection.
通讯机构：
[Linxi Chen; Lanfang Li] I;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China
关键词：
ER-phagy;FAM134B;Cancer;HSAN II B;Viral diseases;Vascular dementia
通讯机构：
[Guo, ZF; Yu, CY ; Wei, H] U;Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词：
Cancer therapy;Chitosan;Co-delivery;Gene therapy;Polysaccharide
摘要：
Nanoparticles (NPs)-based on various ionic polysaccharides, including chitosan, hyaluronic acid, and alginate have been frequently summarized for controlled release applications, however, most of the published reviews, to our knowledge, focused on the delivery of a single therapeutic agent. A comprehensive summarization of the co-delivery of multiple therapeutic agents by the ionic polysaccharides-based NPs, especially on the optimization of the polysaccharide structure for overcoming various extracellular and intracellular barriers toward maximized synergistic effects, to our knowledge, has been rarely explored so far. For this purpose, the strategies used for overcoming various extracellular and intracellular barriers in vivo were introduced first to provide guidance for the rational design of ionic polysaccharides-based NPs with desired features, including long-term circulation, enhanced cellular internalization, controllable drug/gene release, endosomal escape and improved nucleus localization. Next, four preparation strategies were summarized including three physical methods of polyelectrolyte complexation, ionic crosslinking, and self-assembly and a chemical conjugation approach. The challenges and future trends of this rapidly developing field were finally discussed in the concluding remarks. The important guidelines on the rational design of ionic polysaccharides-based NPs for maximized synergistic efficiency drawn in this review will promote the future generation and clinical translation of polysaccharides-based NPs for cancer therapy.
作者机构：
[Lv, Deguan; Luo, Xuling; Zhou, Qionglin; Tang, Mingzhu; Jiang, Jinyong; Li, Lanfang; Liu, Jiaqi; Lu, Liqun; Chen, Zhe; Chen, Linxi] Univ South China, Coll Basic Med Sci, Hengyang Med Coll, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Lv, Deguan] Univ Calif San Diego, Dept Med, Div Regenerat Med, San Diego, CA 92103 USA.;[Zhong, Cuiqing] Shanghai Jiao Tong Univ, Ren Ji Hosp, Ctr Reprod Med, Sch Med, Shanghai, Peoples R China.;[Liu, Meiqing] Kunming Med Univ, Dept Pharm, YanAn Hosp, Kunming, Yunnan, Peoples R China.;[Li, Yao] Yueyang Maternal & Child Hlth Care Hosp, Dept Pharm, Yueyang, Peoples R China.
通讯机构：
[Cuiqing Zhong] C;[Lanfang Li; Linxi Chen] I;Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical College, University of South China, Hengyang, China<&wdkj&>Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China<&wdkj&>Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
摘要：
Nature Reviews' clinical content is written by internationally renowned clinical academics and researchers and targeted towards readers in the medical sciences, from postgraduate level upwards. While intended to be read by practicing doctors, researchers and academics within a specialty, we aim to make all our articles accessible to readers working in any medical discipline. In-depth Reviews present authoritative, up-to-date information on a topic, placing it in the context of a field's history and development. Topical discussion and opinions are proffered in Perspectives and News & Views articles, and in the Research Highlights section we filter primary research from a range of specialty and general medical journals. Finally, Case Studies enable authors to present novel and interesting cases and discuss the most useful features to bear in mind for treating future cases.Subjects coveredRheumatoid arthritisOsteoarthritisMetabolic bone disease (including osteoporosis, osteonecrosis, Paget disease of bone)Connective tissue diseases (including systemic lupus erythematosus, scleroderma (systemic sclerosis), antiphospholipid antibody disease, S�gren disease, Raynaud phenomenon, Cogan keratitis syndrome, relapsing polychondritis) Spondyloarthropathies (including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis of inflammatory bowel disease)Acute inflammatory arthritis (including monoarthritis, oligoarthritis, polyarthritis, infectious/septic arthritis, crystal deposition diseases, Lyme disease)The idiopathic inflammatory myopathies (including polymyositis, dermatomyositis, juvenile dermatomyositis, inclusion body myositis)FibromyalgiaPolymyalgia RheumaticaVasculitis syndromes (including systemic vasculitides, large, medium and small vessel vasculitides, vasculitis of small vessels)Periarticular rheumatic disease (including bursitis, tendonitis)Pediatric rheumatic diseaseMiscellaneous rheumatic diseasesTherapy (including pharmacotherapy, physical therapy [exercise and rest], surgery, splinting, complementary and alternative treatments)Pain managementRehabilitationEpidemiologyGeneticsImmunologyInflammationHealth services, economics and outcomes research
