摘要:
Chronic infection is considered a risk factor for atherosclerosis. The link between infectious agents and atherosclerosis is manifested by the presence of infection-induced pyroptotic cells in atherosclerotic lesions. Pyroptosis is an inflammatory form of programmed cell death that occurs most frequently upon infection. However, inflammation is not the only cause by which pyroptosis involved in atherosclerosis. During pyroptosis, a large amount of microparticles are released from pyroptotic cells, which not only transfer inflammatory mediators to arterial vessel, but also mediate the interaction between a variety of cells, leading to endothelial injury, macrophage infiltration, vascular smooth muscle cell migration and proliferation, thereby accelerating atherosclerosis. Thus, we proposed hypothesis that pyroptotic cell-derived microparticle is an atherogenic factor in infectious diseases.
作者机构:
[梁曜华; 李春; 刘晓谦; 王智民; 朱萱萱; 冯伟红] National Engineering Laboratory for Quality Control Technology of Chinese Herbal Medicines, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China;[林丽美; 廖端芳] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[白璐] Zhuzhou Qianjin Pharmaceutical Co. Ltd., Zhuzhou, 412000, China
通讯机构:
[Li, C.] N;[Liao, D.-F.] S;School of Pharmacy, China;National Engineering Laboratory for Quality Control Technology of Chinese Herbal Medicines, China
摘要:
Aldo-keto reductase 1B10 (AKR1B10) is downregulated in human ulcerative colitis (UC) and colorectal cancer, being a potential pathogenic factor of these diseases. Aldo-keto reductase 1B8 (AKR1B8) is the ortholog in mice of human AKR1B10. Targeted AKR1B8 deficiency disrupts homeostasis of epithelial self-renewal and leads to susceptibility to colitis and carcinogenesis. In this study, we found that in AKR1B8 deficient mice, Muc2 expression in colon was diminished, and permeability of colonic epithelium increased. Within 24 h, orally administered FITC-dextran penetrated into mesenteric lymph nodes (MLN) and liver in AKR1B8 deficient mice, but not in wild type controls. In the colon of AKR1B8 deficient mice, neutrophils and mast cells were markedly infiltrated, gamma delta T cells were numerically and functionally impaired, and dendritic cell development was altered. Furthermore, Th1, Th2, and Th17 cells decreased, but Treg and CD8T cells increased in the colon and MLN of AKR1B8 deficient mice. In colonic epithelial cells of AKR1B8 deficient mice, p-AKT (T308 and S473), p-ERK1/2, p-IKB alpha, p-p65 (S536), and IKK alpha expression decreased, accompanied with downregulation of IL18 and CCL20 and upregulation of IL1 beta and CCL8. These data suggest AKR1B8 deficiency leads to abnormalities of intestinal epithelial barrier and immunity in colon.
作者:
Li Kai;Pierre Sirois;Dai Ai-Guo;Liao Duan-Fang
期刊:
数字中医药(英文),2020年3(2):133-138 ISSN:2096-479X
通讯作者:
Dai Ai-Guo<&wdkj&>Liao Duan-Fang
作者机构:
Translational Medicine Institute, the First People’s Hospital of Chenzhou, Southern Medical University, Chenzhou, Hunan 423000, China;Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Pierre Sirois] CHUL Research Center, Laval University, Quebec, G1V 4G2, Canada;Department of Respiratory Diseases, School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Departmeng of Respiratory, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
通讯机构:
[Dai Ai-Guo; Liao Duan-Fang] K;Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Department of Respiratory Diseases, School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Department of Respiratory Diseases, School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Departmeng of Respiratory, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
摘要:
As a member of the kinesin-3 family, kinesin family member 16B (KIF16B) has a characteristic PhoX homology (PX) domain that binds to membranes containing phosphatidylinositol-3-phosphate (PI(3)P) and moves along microtubule filaments to the plus end via a process regulated by coiled coils in the stalk region in various cell types. The physiological function of KIF16B supports the transport of intracellular cargo and the formation of endosomal tubules. Ras-related protein (Rab) coordinates many steps of membrane transport and are involved in the regulation of KIF16B-mediated vesicle trafficking. Data obtained from clinical research suggest that KIF16B has a potential effect on the disease processes in intellectual disability, abnormal lipid metabolism, and tumor brain metastasis. In this review, we summarize recent advances in the structural and physiological characteristics of KIF16B as well as diseases associated with KIF16B disorders, and speculating its role as a potential adaptor for intracellular cholesterol trafficking. Graphic
摘要:
Atherosclerosis (AS) is characterized by lipids metabolism disorder and inflammatory response. Accumulating evidence has demonstrated that Wingless type 5a (Wnt5a) is implicated in cardiovascular diseases through non-canonical Wnt cascades. However, its precise role during the pathogenesis of AS is still unclear. Therefore, the present study aims to investigate the role and the underlying mechanism of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (Ror2) pathways in the promotion of AS process through affecting lipid accumulation and inflammation. In atherosclerotic clinical samples, Wnt5a levels were measured by using enzyme-linked immunosorbent assay (ELISA) assay. In vivo experiments were conducted by using apolipoprotein E knockout (apoE(-)(/)(-)) mice model. Vascular smooth muscle cells (VSMCs) were applied for in vitro studies. Wnt5a was highly expressed in both of atherosclerotic clinical samples and apoE(-)(/)(-) mice. The knockdown of Wnt5a significantly inhibited cholesterol accumulation and inflammatory response. Additionally, the lipopolysaccharide (LPS)-induced inflammation aggravated the cholesterol accumulation and decreased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression in VSMCs. Depletion of intracellular cholesterol by beta-cyclodextrin (beta-CD) led to the upregulation of ABCA1 and the inhibition of inflammation. Conversely, the overexpression of Wnt5a inhibited ABCA1 expression, facilitated cholesterol accumulation, impared cholesterol efflux, promoted NF-kappaB nuclear translocation and the inflammatory cytokines secretion. Moreover, the knockdown of Ror2 increased ABCA1 expression and reduced Wnt5a-induced cholesterol accumulation and inflammatory responses. Furthermore, the knockdown of ABCA1 enhanced cholesterol accumulation and inflammatory response. Therefore, Wnt5a/Ror2 pathway was critical in regulating cholesterol homeostasis and inflammatory response, which might be a promising therapeutic target for AS therapy.
摘要:
Background Chronic alcohol consumption disrupts psychomotor and cognitive functions, most of which are subserved by the dysfunction of hippocampus. Dysregulated excitatory glutamatergic transmission is implicated in repeated alcohol induced psychomotor and cognitive impairment. Ginsenoside Rg1, one of the main active ingredient of the traditional tonic medicine Panax ginseng C.A. Meyer (Araliaceae), has been used to treat cognitive deficits. Particularly, Rg1 has been demonstrated to improve hippocampus-dependent learning in mice and attenuate glutamate-induced excitotoxicity in vitro. Thus, in the present research, we sought to investigate the therapeutic effects of Ginsenoside Rg1 on repeated alcohol induced psychomotor and cognitive deficits in hippocampal-dependent behavioral tasks and unravel the underpinnings of its neuroprotection. Methods Male ICR (CD-1) mice were consecutively intragastrically treated with 20% (w/v) alcohol for 21 days. Then, behavior tests were conducted to evaluate repeated alcohol induced psychomotor and cognitive deficits. Histopathological changes, and biochemical and molecular alterations were assessed to determine the potential neuroprotective mechanism of Rg1. Results The results suggested that Rg1, at the optimal dose of 6 mg/kg, has the potential to ameliorate repeated alcohol induced cognitive deficits by regulating activities of NR2B containing NMDARs and excitotoxic signaling. Conclusion Our findings further provided a new strategy to treat chronic alcohol exposure induced adverse consequences.
作者机构:
[蒋素素; 龙石银; Shao J.-Q.; 张敏; 田英; 张彩平; 袁育林; 李博洁; 王楚瑶] Dept of Biochemistry & Molecular Biology, Medical College, University of South China, Hunan, Hengyang, 421001, China;[向德彪; 廖端芳] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[贺卫和; 杨慧仙] Institute of Cardiovascular Diseases, University of South China, Hunan, Hengyang, 421001, China
作者机构:
[Yang, Hui-xian] Univ South China, Med Coll, Inst Cardiovasc Dis, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang; Chen, Jian-xiong; Tuo, Qin-hui] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Tian, Ying; Long, Shi-yin; Yang, Hui-xian; Zhang, Cai-ping; Zhang, Min; Liao, DF] Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Jian-xiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, University, MS 38677 USA.
通讯机构:
[Zhang, CP; Liao, DF] U;Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Dyslipidemia;IDOL;LDL-C;LDLR;PCSK9;SREBP2
摘要:
The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.