期刊：
International braz j urol,2019年45(2):220-228 ISSN：1677-5538
通讯作者：
Cao, Zhaohui
作者机构：
[Cao, Zhaohui; Hu, Xiaobo] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Hu, Cong; Cao, Zhaohui; Hu, Xiaobo; Long, Shiyin; Zhang, Caiping; Zhang, Min] Univ South China, Sch Pharm & Biosci, Dept Biotechnol, Hengyang, Peoples R China.
通讯机构：
[Cao, Zhaohui] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
关键词：
ABSTRACT Obesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy. Keywords: Prostatic Neoplasms;Obesity;Stress, Physiological
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cholesterol transport system;Atherosclerosis;High-density lipoprotein
摘要：
Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.
作者机构：
[Yao P.; Cao J.] Affiliated Nanhua Hospital of University of South China, Hengyang, 421002, China;[Zhao H.; Chen L.] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, 421001, China
通讯机构：
[Cao, J.] A;Affiliated Nanhua Hospital of University of South China, Hengyang, China
摘要：
Pancreatitis, the pancreas digestion itself as well as its surroundings, is a potentially fatal disease involved in severe public health care burdens [1]. It is broadly classified into acute and chronic pancreatitis. The incidence of acute pancreatitis is 13–45 cases per 100,000 persons each year worldwide. Compared with acute pancreatitis, chronic pancreatitis, although lower in prevalence than acute pancreatitis, has profound effects on the patient’s quality of life. It has long been recognized that the pancreas is prominently sensitive to mechanical injury, which in turn triggers the occurrence of pancreatitis. For instance, gallstones are the most common cause for acute pancreatitis and the increased pressure within the gland could be responsible for gallstone pancreatitis [2]. In addition, endoscopic retrograde cholangiopancreatography (ERCP) carries a risk of post- ERCP pancreatitis. And it is believed that the acute pancreatitis induced by ERCP is due to the increased intraductal pressure [3]. Furthermore, in the process of surgery, manipulation of the pancreas can trigger acute pancreatitis, which is complicating postoperative recovery [4]. Therefore, it is widely believed that the pancreas itself is sensitive to mechanical forces.
作者机构：
[Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.
通讯机构：
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.
关键词：
macrophage colony-stimulating factor;breast cancer;apoptosis;HIF-1 and BINP3
摘要：
Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.
通讯机构：
[Yin, WD; Tang, CK] U;Univ South China, Med Res Expt Ctr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang 421001, Hunan, Peoples R China.
关键词：
AS;CCDC80;DNA methylation;LPL;TET2
摘要：
Recent studies showed that coiled-coil domain-containing 80 (CCDC80) has a positive link with atherosclerosis and that plasma CCDC80 levels are positively correlated with the levels of fasting plasma triglycerides (TG) in obese individuals. The underlying mechanisms, however, are unclear. Using Hematoxylin-eosin (H&E) and Oil Red O staining, we found that CCDC80 overexpression in vivo significantly increased plasma lipid contents, decreased the expression and activity of lipoprotein lipase (LPL), and accelerated the development of atherosclerosis. Conversely, knockdown of CCDC80 decreased plaque lesions area. In vitro, qRT-PCR and western blot results showed that CCDC80 overexpression significantly decreased, while CCDC80 knockdown increased, LPL expression in cultured vascular smooth muscle cells (VSMCs). Further, we found that CCDC80 reduced LPL expression via inhibiting the phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) and also increased the methylation of LPL promoter via down-regulating Tet methylcytosine dioxygenase 2 (TET2). Our results also revealed that CCDC80 significantly down-regulated TET2 expression through decreasing the phosphorylation of ERK1/2. In addition, we found that CCDC80 decreased binding of TET2 to forkhead box O3 (FOXO3a) but had no effect on FOXO3a expression. On the other hand, and that FOXO3a was partially involved in TET2-regulated LPL expression. CCDC80 down-regulated ERK1/2 phosphorylation and decreased expression of TET2 and its interaction with FOXO3a, leading to a reduction of LPL expression and acceleration of atherosclerosis.
摘要：
Exposure to Mycoplasma pneumoniae leads to lung inflammation through a host defense pathway. Increasing evidence has indicated that the mycoplasma-derived membrane lipoprotein, or its analogue macrophage-activating lipopeptide-2 (MALP-2), excretes LPS as an immune system-stimulating substance and plays a crucial role in pathological injury during M. pneumoniae infection. It has been established that Sulforaphane confers anti-inflammatory properties. However, the underlying mechanism responsible for the inhibitory actions of Sulforaphane in the context of mycoplasmal pneumoniae are poorly understood. Here, we report that Sulforaphane is an inducer of heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme through signaling pathways in human monocytes. Sulforaphane stimulated NF-E2-related factor 2 (Nrf2) translocation from the cytosol to the nucleus, and small interfering RNA-mediated knock-down of Nrf2 significantly inhibited Sulforaphane-induced HO-1 expression. Additionally, PI3K/Akt and ROS were also involved in Sulforaphane-induced Nrf2 activation and HO-1 expression, as revealed by the pharmacological inhibitors LY294002 and NAC. Moreover, Sulforaphane treatment inhibited MALP-2-induced pro-inflammatory cytokine secretion and pulmonary inflammation in mice, as well as MALP-2-triggered NF-kappaB activation. Furthermore, SnPP, a selective inhibitor of HO-1, reversed the inhibitory actions of Sulforaphane, while a carbon monoxide-releasing molecule, CORM-2, caused a significant decrease in MALP-2-induced cytokine secretion. Collectively, these results suggest that Sulforaphane functions as a suppressor of the MALP-2-induced inflammatory response, not only by inhibiting the expression of cytokines and the induction of HO-1 but also by diminishing NF-kappaB activation in cultured monocytes and the lungs of mice.
作者机构：
[Xie, Wan-Ying; Liu, Jie; Mcleod, Howard L.; He, Ruo-Hui; Li, Zhi; Tang, Yong-Jun; Wan, Zan; He, Yi-Jing; Zhou, Cheng-Fang] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, 110 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.;[Xie, Wan-Ying; Liu, Jie; He, Ruo-Hui; Li, Zhi; Wan, Zan; He, Yi-Jing; Zhou, Cheng-Fang] Cent S Univ, Inst Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha 410078, Hunan, Peoples R China.;[Liu, Jie; He, Ruo-Hui; Li, Zhi; He, Yi-Jing] Univ South China, Cooperat Innovat Ctr Mol Target New Drug Study, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Jun] Cent S Univ, Xiangya Hosp, Dept Nephrol, Changsha 410008, Hunan, Peoples R China.;[Tang, Yong-Jun] Cent S Univ, Xiangya Hosp, Dept Pediat, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Liu, Jie] C;Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, 110 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
关键词：
triple-negative breast cancer;-blocker;-adrenergic receptor;mitogen-activated protein kinase signaling pathway;(2)-adrenergic receptor single-nucleotide polymorphisms
摘要：
The (2)-adrenergic receptor ((2)-AR, encoded by the ADRB2 gene) is a member of the G-protein-coupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that -blockers (-AR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 single-nucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of (2)-AR, which may alter the -blocker drug response. The aim of the present study was to investigate the effect of -blockers on triple-negative breast cancer cells and determine whether ADRB2 SNPs affect the response to -blocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDA-MB-231 cells, arrested cell cycle progression at G(0)/G(1) and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellular-signal-regulated kinase (ERK)1/2 and the expression levels of cyclo-oxygenase 2 (COX-2) were significantly decreased following -blocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wild-type group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX-2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDA-MB-231 cells by downregulating the ERK/COX-2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.
摘要：
Flavan-3-ols are a series of natural products widely present in plants and show versatile biological activities. The structures of such compounds are characterized by owing two adjacent chiral centers and three rings. Their interesting structures and promising biological activities have driven increasing research developments toward the preparation of enantioenriched flavan-3-ols. This review summarizes the recent approaches for the asymmetric synthesis of chiral flavan-3-ols from two strategies in the construction of chiral centers. The key steps in the synthetic protocol involve Sharpless asymmetric dihydroxylation, Shi asymmetric epoxidation and Sharpless asymmetric epoxidation.
作者机构：
[Zeng, Si-yu; Lu, Hui-qin] Guangdong Second Prov Gen Hosp, Inst Drug Clin Trial, Guangzhou, Guangdong, Peoples R China.;[Yang, Li] Univ South China, Inst Pharm & Pharmacol, Lab Vasc Biol, Hengyang, Peoples R China.;[Yan, Qiu-jiang] Guangzhou Med Univ, Affiliated Hosp 3, Dept Cardiac & Thorac Surg, Guangzhou, Guangdong, Peoples R China.;[Gao, Ling] Guangdong Second Prov Gen Hosp, Dept Pharm, Guangzhou, Guangdong, Peoples R China.;[Yan, Peng-ke] Guangzhou Med Univ, Affiliated Hosp 3, Dept Pharm, Guangzhou, Guangdong, Peoples R China.
通讯机构：
[Zeng, SY; Lu, HQ; Yan, Peng-ke] G;Guangdong Second Prov Gen Hosp, Inst Drug Clin Trial, Guangzhou, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 3, Dept Pharm, Guangzhou, Guangdong, Peoples R China.
关键词：
GKT137831;Hypertensive cardiac remodelling;Proinflammatory cytokines;A disintegrin and metalloprotease 17
摘要：
NADPH oxidases (Noxs) 1/4 dual inhibitor GKT137831 prevents hypertensive cardiac remodelling in angiotensin II-infused transgenic mice with cardiomyocyte-specific human Nox4 (c-hNo x 4 Tg); however, further research is still required to determine the beneficial role of GKT137831 in hypertensive cardiac remodelling in other types of hypertensive models because this hypertensive model is insufficient to mimic the complicated pathological mechanisms of hypertension. A disintegrin and metalloprotease 17 (ADAM17) promotes the shedding of tumour necrosis factor alpha (TNF-alpha), TNF-alpha receptor, interleukin 1 receptor-II and interleukin 6 (IL-6) receptor from cells, thereby mediating the signalling pathways induced by corresponding proinflammatory cytokines. This study aimed to determine whether GKT137831 prevents hypertensive cardiac remodelling and its mechanisms of action in the rats with abdominal artery coarctation (AAC). The rats subjected to AAC were orally given GKT137831 for a consecutive period of 28 days. Echocardiography and histological analysis were performed to evaluate cardiac remodelling; and immunohistochemistry and real-time PCR were used to detect the expression of proinflammatory cytokines. GKT137831 significantly suppressed hypertensive cardiac remodelling in AAC-induced hypertensive rats. Concurrently, Nox1/4 dual inhibitor GKT137831 reduced the protein and mRNA levels of proinflammatory cytokines interleukin 1 beta (IL-1 beta), IL-6, and TNF-alpha in the left ventricle of AAC-induced hypertensive rats. Moreover, the treatment with GKT137831 markedly diminished the protein and mRNA levels of ADAM17 in the left ventricle of AAC-induced hypertensive rats. In summary, Nox1/4 dual inhibitor GKT137831 protects against hypertensive cardiac remodelling in AAC-induced hypertensive rats, and the inhibition of ADAM17-dependent proinflammatory cytokines-induced signalling pathways are related to its beneficial effect on hypertensive cardiac remodelling.
摘要：
Chlamydia trachomatis, the most common human pathogen that causes trachoma and sexually transmitted disease, has developed various strategies for inhibiting host cell apoptosis. Activation of the PI3K (phosphoinositide 3-kinase)/AKT-mediated MDM2 (murine double minute 2)-p53 pathway plays a prominent role in the apoptosis resistance arising from C. trachomatis infection. However, the precise upstream mechanisms by which C. trachomatis activates this pathway have not been adequately investigated. Here, we reveal that the secreted C. trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis in HeLa cells. This process requires the activation of the PI3K/AKT signaling pathway, thereby leading to phosphorylation and nuclear entry of MDM2, and p53 degradation. PI3 K inhibitor LY294002 and MDM2 inhibitor Nutlin-3a block Pgp3-induced inhibition of HeLa cell apoptosis, suggesting a critical role for the PI3K/AKT pathway and its effect on the MDM2-p53 axis in Pgp3 anti-apoptotic activity.
摘要：
The Sertoli cell, which is the supporting cell of spermatogenesis, has an important role in the endocrine and paracrine control of spermatogenesis. Functionally, it provides the cells of the seminiferous epithelium with nutrition, conveys mature spermatids to the lumen of seminiferous tubules, secretes androgen-binding protein and interacts with endocrine Leydig cells. In addition, the levels of cholesterol, as well as its intermediates, vary greatly between nongonadal tissues and the male reproductive system. Throughout spermatogen-esis, a dynamic and constant alteration in the membrane lipid composition of Sertoli cells occurs. In several mammalian species, testis meiosis-activating sterol and desmosterol, as well as other cholesterol precursors, accumulate in the testes and spermatozoa. In addition, certain cholesterogenic genes exhibit stage-specific expression patterns during spermato-genesis, including the cytochrome P450 enzyme lanosterol 14α-demethylase. Inconsistency in the patterns of gene expression during spermatogenesis indicates a cell-type specific and complex temporary modulation of lipids and cholesterol, which also implicates the dynamic interactions between Sertoli cells and germ cells. Furthermore, in the female reproductive tract and during epididymal transit, which is a prerequisite for valid fertilization, the modulation of cholesterol occurring in spermatozoal membranes further indicates the functional importance of sterol compounds in spermatogenesis. However, the exact role of cholesterol metabolism in Sertoli cells in sperm production is unknown. The present review article describes the progress made in the research regarding the characteristics of the Sertoli cell, particularly the regulation of its cholesterol metabolism during spermatogenesis.
摘要：
The aim of the present study was to determine the role of hydrogen sulfide (H2S) in improving myocardial fibrosis and its effects on oxidative stress, endoplasmic reticulum (ER) stress and cell apoptosis in diabetic rats, by regulating the Janus kinasesignal transducer and activator of transcription (JAKSTAT) signaling pathway. A total of 40 male SpragueDawley rats were randomly divided into four groups (n=10) as follows: normal (control group), diabetes mellitus [streptozotocin (STZ) group], diabetes mellitus treated with H2S (STZ + H2S group), and normal rats treated with H2S (H2S group). Diabetes in rats was induced by intraperitoneal (i.p.) injection of STZ at a dose of 40 mgkg. NaHS (100 micromolkg, i.p.), which was used as an exogenous donor of H2S, was administered to rats in the STZ + H2S and H2S groups. After 8 weeks, the pathological morphological changes in myocardial fibers were observed following hematoxylin and eosin and Masson's trichrome staining. Apoptosis of myocardial tissue was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Oxidative stress was evaluated through detecting the content of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione (GSH) and superoxide dismutase (SOD) in the myocardial cells by ELISA. The expression of collagen III, matrix metalloproteinase (MMP)8, MMP14, tissue inhibitor of metalloproteinase (TIMP)2, transforming growth factor (TGF)-beta, cystathioninegammalyase (CSE), eukaryotic initiation factor 2alpha (eIF2alpha), GRP94, Bcl-2, caspase-3, tumor necrosis factor (TNF)-alpha, nuclear factorkappaB (NFkappaB) and proteins related to the JAKSTAT pathway, was detected by western blot analysis. The results indicated that the array of myocardial cells was markedly disordered in STZ group rats; compared with the control group, both myocardial interstitial fibrosis and the deposition of collagen III were increased. Furthermore, the expression ratio of MMPsTIMPs was dysregulated, while the expression levels of TGF-beta, eIF2alpha, GRP94, caspase-3, TNF-alpha, NF-kappaB, MDA and 4-HNE were significantly increased. Furthermore, the expressions of JAK-12 and STAT1356 were also markedly upregulated, while those of CSE, SOD, GSH and Bcl-2 were downregulated. Compared with the STZ group, these changes were reversed in the STZ + H2S group. The results of the present study demonstrated that H2S can improve myocardial fibrosis in diabetic rats, and the underlying mechanism may be associated with the downregulation of the JAKSTAT signaling pathway, thereby suppressing oxidative stress and ER stress, inflammatory reaction and cell apoptosis.
作者机构：
[Wang, Ai-Ping; Wei, Hai-Jun; Wang, Chun-Yan; Li, Man-Hong; Tang, Xiao-Qing; Zou, Wei; Li, Xiang; Tang, Yi-Yun; Zhang, Ping] Univ South China, Inst Neurosci, Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Wei, Hai-Jun; Tang, Xiao-Qing; Tang, Yi-Yun] Univ South China, Dept Physiol, Med Coll, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Ai-Ping] Univ South China, Dept Anat, Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Li, Man-Hong; Tang, Xiao-Qing; Zou, Wei; Zhang, Ping] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, 336 E Dongfeng Rd, Hengyang 421001, Hunan, Peoples R China.;[Li, Xiang] Univ South China, Dept Anaesthesiol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, Xiao-Qing; Zou, Wei] U;Univ South China, Dept Physiol, Med Coll, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Nanhua Affiliated Hosp, Dept Neurol, 336 E Dongfeng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Neurosci, Med Coll, 28 W Changsheng Rd, Hengyang, Hunan, Peoples R China.
关键词：
Hydrogen sulfide;Homocysteine;Silent mating type information regulation 2 homolog 1;Endoplasmic reticulum stress;Cognitive dysfunction
摘要：
Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H2S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H2S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H2S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H2S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H2S in Hcy-induced cognitive dysfunction.
作者：
Ye, Qiong;Tian, Guo-Ping;Cheng, Hai-Peng;Zhang, Xin;Ou, Xiang;...
期刊：
Journal of Atherosclerosis and Thrombosis,2018年25(3):244-253 ISSN：1340-3478
通讯作者：
Tang, Chao-Ke
作者机构：
[Zhang, Xin; Gong, Duo; Cheng, Hai-Peng; Ye, Qiong; Xia, Xiao-Dan; Zhang, Min; Tang, Chao-Ke; Zhao, Zhen-Wang; Yu, Xiao-Hua; Li, Liang; Xie, Wei; Huang, Chong; Chen, Ling-Yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang, Hunan, Peoples R China.;[Tan, Ru-Qi; Ye, Qiong; Tian, Guo-Ping; Yang, Feng-Yun; Pan, Yan-Jun] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Ou, Xiang] First Hosp Changsha, Dept Endocrinol, Changsha, Hunan, Peoples R China.;[Zhang, Jie] Univ South China, Affiliated Hosp 2, Dept Spinal Surg, Hengyang, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Cumming Sch Med,Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB, Canada.
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
关键词：
MiR-134;ANGPTL4;LPL;Atherosclerosis
摘要：
Aims: Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. Methods: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Results: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. Conclusions: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.
期刊：
International Journal of Pharmaceutics,2018年535(1-2):253-260 ISSN：0378-5173
通讯作者：
Zheng, Xing;Tang, Guotao
作者机构：
[Wang, Zhe; Deng, Xiangping; Tang, Guotao; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Ding, Jinsong; Zhou, Wenhu] Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha, Hunan, Peoples R China.;[Zheng, Xing; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zheng, X; Tang, GT] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
关键词：
pH-sensitive micelles;pH-sensitive release;release mechanism;targeted drug delivery system
摘要：
During the past decades, chemotherapy has been regarded as the most effective method for tumor therapy, but still faces significant challenges, such as poor tumor selectivity and multidrug resistance. The development of targeted drug delivery systems brings certain dramatic advantages for reducing the side effects and improving the therapeutic efficacy. Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for targeted therapy. Among these approaches, pH-sensitive micelles are regarded as the most general strategy with advantages of increasing solubility of water-insoluble drugs, pH-sensitive release, high drug loading, etc. This review will focus on the potential of pH-sensitive micelles in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations. Sufficient understanding of these mechanisms will help us to design more efficient pH-sensitive drug delivery system to address the challenges encountered in targeted drug delivery systems for tumor therapy.
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2018年233(3):2075-2090 ISSN：0021-9541
通讯作者：
Li, Lanfang
作者机构：
[Li, Lanfang; Xu, Jin; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang, Peoples R China.;[Li, Lanfang] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
通讯机构：
[Li, Lanfang] U;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
ATP;oxidative stress;pannexins
摘要：
Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels. It is also reported that pannexins regulate the production of ROS which in turn may increase the opening of pannexin hemichannels. In this paper, we review recent researches about the important role of pannexin hemichannels in oxidative stress related diseases. Thus, pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases.
