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.
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
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：
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.
期刊：
JOURNAL OF MEMBRANE BIOLOGY,2020年253(2):101-108 ISSN：0022-2631
通讯作者：
Long, Shi-yin;Zhang, CP
作者机构：
[Wang, Chu-yao; Long, Shi-yin; Long, SY; Li, Bo-jie; Zhang, Cai-ping; Jiang, Su-su] Univ South China, Dept Biochem & Mol Biol, Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Chen, Hao] Univ South China, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.;[Tuo, Qin-hui] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Liao, Duan-fang] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Long, SY; Zhang, CP ] U;Univ South China, Dept Biochem & Mol Biol, Med Coll, Hengyang 421001, Hunan, Peoples R China.
关键词：
KIF16B;Kinesin;Endocytic trafficking;Cholesterol transport
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
期刊：
Chinese Medicine,2020年15(1):1-11 ISSN：1749-8546
通讯作者：
Liao, Duan-fang;Liu, Xin-min;Shi, Z;Liu, XM
作者机构：
[Peng, Zhuang; Liu, Xin-min; Huang, Lu; Liao, Duan-fang; Shi, Z; Shi, Zhe; Liao, DF] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha 410208, Hunan, Peoples R China.;[Huang, Lu] Jinan Univ, Guangdong Hongkong Macau Inst CNS Regenerat, Minist Educ, CNS Regenerat Collaborat Joint Lab, Guangzhou 510632, Peoples R China.;[Lu, Cong; Liu, Xin-min; Lv, Jing-wei] Chinese Acad Med Sci & Peking Union Med Coll, Res Ctr Pharmacol & Toxicol, Inst Med Plant Dev IMPLAD, Beijing 100193, Peoples R China.;[Chen, Ying] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.;[Peng, Zhuang; Qin, Meng] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China.
通讯机构：
[Liu, XM ] C;[Shi, Z ; Liu, XM; Liao, DF] H;Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha 410208, Hunan, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Res Ctr Pharmacol & Toxicol, Inst Med Plant Dev IMPLAD, Beijing 100193, Peoples R China.
摘要：
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. 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. 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. Our findings further provided a new strategy to treat chronic alcohol exposure induced adverse consequences.
摘要：
The uptake of modified low-density lipoprotein (LDL) and the accumulation of lipid droplets induce the formation of vascular smooth muscle cells (VSMCs)-derived foam cells, thereby promoting the development and maturation of plaques and accelerating the progression of atherosclerosis. Celastrol is a quinine methide triterpenoid isolated from the root bark of traditional Chinese herb Tripterygium wilfordii. It possesses various biological properties, including anti-obesity, cardiovascular protection, anti-inflammation, etc. In the present study, we found that celastrol significantly reduced lipid accumulation induced by oxidized LDL (ox-LDL) in VSMCs. Mechanistically, celastrol up-regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1 ) expression through activating liver X receptor alpha (LXR alpha) expression, which contributed to inhibit lipid accumulation in VSMCs. Meanwhile, celastrol decreased lipid accumulation by triggering autophagy in VSMCs. Therefore, these findings supported celastrol as a potentially effective agent for the prevention and therapy of atherosclerosis. (C) 2020 Elsevier Inc. All rights reserved.
期刊：
AMERICAN JOURNAL OF CHINESE MEDICINE,2020年48(3):559-577 ISSN：0192-415X
通讯作者：
Wang, Yong-Jun;Zhang, Y;Yuan, TF
作者机构：
[Wang, Yong-Jun; Sha, Nan-Nan; Shu, Bing; He, Ming-Chao; Sun, Yue-Li; Li, Yue; Zhang, Yan; Wang, YJ] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Spine Dis Res Inst, Room 908,Bldg 12,725 South Wanping Rd, Shanghai 200032, Peoples R China.;[Wang, Yong-Jun; Shu, Bing; He, Ming-Chao; Sun, Yue-Li; Li, Yue; Zhang, Yan] Minist Educ, Key Lab Theory & Therapy Muscles & Bones, Shanghai 200032, Peoples R China.;[Yuan, Ti-Fei; Shi, Zhe] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai 201108, Peoples R China.;[Liao, Duan-Fang; Shi, Zhe] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Changsha 410208, Peoples R China.;[Qin, Meng] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China.
通讯机构：
[Yuan, TF ; Zhang, Y ; Wang, YJ] S;Shanghai Univ Tradit Chinese Med, Longhua Hosp, Spine Dis Res Inst, Room 908,Bldg 12,725 South Wanping Rd, Shanghai 200032, Peoples R China.;Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai 201108, Peoples R China.
关键词：
Depression;Muscone;Microglia;Neuroinflammation;Renin-Angiotensin System
摘要：
<jats:p> Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1[Formula: see text]mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24[Formula: see text]h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1[Formula: see text], RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1[Formula: see text]. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade. </jats:p>
摘要：
<jats:sec>
<jats:title>Objective:</jats:title>
<jats:p>To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been
prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)-
Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying
mechanisms were demonstrated at the cellular, molecular, and in vivo levels.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal
inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)-
Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly
(ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP
expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation
mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase
in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression
of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic
protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn
resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation
of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation
of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in
the HepG2 nude mouse model.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion:</jats:title>
<jats:p>Pt(II)-Bpy is a potential candidate for cancer chemotherapy.</jats:p>
</jats:sec>
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.;[Liao, DF; Tian, Ying; Long, Shi-yin; Yang, Hui-xian; Zhang, Cai-ping; Zhang, Min] 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：
[Liao, DF ; Zhang, CP] 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.
