摘要：
Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount ofresidual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights fortreatingAS.
期刊：
International Immunopharmacology,2024年142(Pt B):113188 ISSN：1567-5769
通讯作者：
Wang, Zong-Bao;Wang, SZ
作者机构：
[Yu, Mei-Ling; Wang, Shu-Zhi; Lei, Guan-Lan; Wang, Zong-Bao; Zeng, Tao; Zhang, Ting-Yu] Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Yu, Mei-Ling; Wang, Shu-Zhi; Lei, Guan-Lan; Wang, Zong-Bao; Zeng, Tao; Zhang, Ting-Yu] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;[Wang, SZ; Wang, ZB] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wang, SZ ; Wang, ZB] U;Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
关键词：
Atherosclerosis;Inflammation;Lipid metabolism;Oxidative stress;Trace elements
摘要：
Atherosclerosis is a slow and complex disease that involves various factors, including lipid metabolism disorders, oxygen-free radical production, inflammatory cell infiltration, platelet adhesion and aggregation, and local thrombosis. Trace elements play a crucial role in human health. Many trace elements, especially metallic ones, not only maintain the normal functions of organs but also participate in basic metabolic processes. The latest studies have revealed a close correlation between trace elements and the occurrence and progression of atherosclerosis. The imbalance of these trace elements can induce atherosclerosis or accelerate its progression through various mechanisms, which poses a significant threat to human health. Therefore, exploring the specific mechanism of trace elements on atherosclerosis is highly significant. In this review, we summarized the roles and mechanisms of iron, copper, zinc, magnesium, and selenium homeostasis and imbalance in atherosclerosis development, in order to identify novel targets and therapeutic strategies for treating atherosclerosis.
摘要：
With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome.
期刊：
Journal of Pharmacy and Pharmacology,2023年75(3):363-369 ISSN：0022-3573
通讯作者：
Shu-zhi Wang
作者机构：
[Liu, Shu-ting; Wang, Shu-zhi; Wang, Zong-bao; Chen, Ming-xin; Deng, Bo-yan] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Liu, Shu-ting; Wang, Shu-zhi; Wang, Zong-bao; Chen, Ming-xin; Deng, Bo-yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
通讯机构：
[Shu-zhi Wang] I;Institute of Pharmacy and Pharmacology, University of South China , Hengyang , China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China
摘要：
Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.
期刊：
MINI-REVIEWS IN MEDICINAL CHEMISTRY,2023年23(19):1905-1911 ISSN：1389-5575
作者机构：
Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China;Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of
South China, Hengyang, 421001, China;[Chen, Ke-qian] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China;[Ke, Bo-yi; Cheng, Lu; Guan, Meng-ting; Wang, Zong-bao; Wang, Shu-zhi] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of
South China, Hengyang, 421001, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China
关键词：
placebo;probucol;antioxidant;cholesterol;probucol;Alzheimer disease;antimalarial activity;area under the curve;contrast induced nephropathy;diabetic retinopathy;drug absorption;drug bioavailability;drug blood level;drug efficacy;drug half life;drug mechanism;drug solubility;drug structure;eye protection;human;lung injury;malaria;maximum concentration;neuroprotection;nonalcoholic fatty liver;nonhuman;Parkinson disease;randomized controlled trial (topic);renal protection;Short Survey;time to maximum plasma concentration;liver;Antioxidants;Cholesterol;Humans;Liver;Non-alcoholic Fatty Liver Disease;Probucol
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2022年237(1):86-97 ISSN：0021-9541
通讯作者：
Tang, C.-K.
作者机构：
[Qin, Yu-Sheng; Tang, Chao-Ke; Li, Heng] Univ South China, Hengyang Med Coll,Inst Cytol & Genet,Hengyang Key, Inst Cardiovasc Dis,Med Instrument & Equipment Te, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang, Hunan, Peoples R China.;[Wang, Shu-Zhi; Wang, Zong-Bao] Univ South China, Inst Pharm & Pharmacol, Sch Pharm, Hengyang, Hunan, Peoples R China.;[Wang, Shu-Zhi; Wang, Zong-Bao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Hunan, Peoples R China.
通讯机构：
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province,Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic disease, Medical Instrument and equipment technology laboratory of Hengyang medical college, Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, University of South China, Hunan, Hengyang, China
摘要：
It is well-recognized that hyperlipidemia and lipid peroxidation contribute to the progression of diabetic nephropathy (DN), which is associated with oxidative stress (OS) and fibrotic lesions. Ibrolipim, a specific lipoprotein lipase activator, has been proved to reduce hyperglycemia and hyperlipidemia, suppress renal lipid deposition, and also protect renal damage. However, the underlying mechanisms of its renoprotective effect are not clearly elaborated. Herein, the present study was to identify whether the putative mechanism of Ibrolipim was related to OS and fibrogenesis in diabetic minipigs fed by high-sucrose and high-fat diet (HSFD) with or without Ibrolipim for 5 months. Compared with the normal control diet, nutrient stress induced by HSFD caused moderate glomerulosclerosis and tubulointerstitial fibrosis, and promoted renal ultrastructural and functional abnormalities. These abnormalities were correlated with renal OS and fibrogenesis characterized by the increased levels of reactive oxygen species (ROS), malondialdehyde, hydroxyproline, collagen type Ⅳ alpha 1 and fibronectin, and decreased contents of reduced glutathione and total antioxidant capacity in kidneys. Ibrolipim significantly ameliorated these abnormalities in HSFD-fed minipigs. In addition, Ibrolipim diminished HSFD-induced nicotinamide-adenine dinucleotide phosphate oxidase-4 activation to reduce ROS production, and enhanced the expression and activity of antioxidant enzymes (i.e. superoxide dismutase 1, catalase and glutathione peroxidase 1) to increase ROS elimination, resulting in obvious suppression of renal OS. Meanwhile, Ibrolipim not only inhibited the upregulation of transforming growth factor-β1 but also partially reversed the downregulation of matrix metalloproteinase 2, and then prevented extracellular matrix (ECM) accumulation. Taken together, Ibrolipim exhibits anti-oxidative and anti-fibrotic effects via modulating the rebalance of renal ROS and ECM metabolism, and ultimately attenuates the progression of nephropathy in diet-induced diabetic minipigs.
摘要：
Cholesterol is one of the major components of biological membranes and has an important function in osteoclast formation and survival. It has been reported that high-density lipoprotein (HDL) promotes cholesterol efflux from osteoclasts and induces their apoptosis, but the underlying mechanisms are unclear. In this study, we investigated how HDL promotes osteoclast cholesterol efflux and explored its effect on osteoclast formation and survival. Our results showed that the maximum diameter and fusion index of osteoclasts were decreased, while the ratios of osteoclasts with pyknotic nuclei were increased when cells were treated with HDL (600 ng/ml), as revealed by tartrate-resistant acid phosphatase-positive staining and microscopy assay. HDL enhanced cellular cholesterol efflux from osteoclasts in both concentration- and time-dependent manners. The ability of HDL3 to stimulate cholesterol efflux was stronger than preβ-HDL, HDL2, and ApoAI. Knockdown of ABCG1 expression reduced HDL-mediated cholesterol efflux and restored the HDL-induced reduction in osteoclast formation. Finally, HDL3 promoted sphingomyelin efflux from osteoclasts and reduced the expression of caveolin-1. Together, the findings demonstrate that HDL3 upregulates ABCG1 expression and promotes cholesterol efflux from osteoclast, impairs cholesterol homeostasis in osteoclasts, and consequently enhances osteoclast apoptosis.
