1.Research progress on the role and mechanism of copper overload mediating athero-sclerosis
Tian WANG ; Hongfei WU ; Min DAI ; Yarong LIU
Chinese Journal of Arteriosclerosis 2024;32(8):719-727
Atherosclerosis(As)is a chronic inflammatory disease associated with lipid deposition.Copper is con-sidered to be an important trace element and is closely related to the occurrence and development of As.Excessive accu-mulation of copper ions in cells can induce cell death,a new type of cell death named"cuproptosis".Under normal con-ditions,the body's copper metabolism can control the copper level in a stable range.When the disease occurs,copper ho-meostasis is destroyed,intracellular copper overload produces cytotoxicity,induces oxidative stress,inflammation,cell py-roptosis and cuproptosis,and promotes the occurrence and development of As.This article summarizes the relationship between copper levels and As,and discusses the mechanism of cuproptosis and the pathological mechanism of copper over-load promoting As from the perspective of the body's copper regulation,and reviews the relevant drug intervention,expec-ting to provide a new therapeutic target for As.
2.Methods for mammalian single cell research - a review.
Wenqian JIANG ; Yarong TIAN ; Rui ZUO ; Jun LIN
Chinese Journal of Biotechnology 2019;35(1):27-39
Basic research in life science and medicine has dug into single cell level in recent years. Single-cell analysis offers to understand life from diverse perspectives and is used to profile cell heterogeneity to investigate mechanism of diseases. Single cell technologies have also found applications in forensic medicine and clinical reproductive medicine, while the techniques are rapidly evolving and have become more and more sophisticated. In this article, we reviewed various single cell isolation techniques and their pros and cons, including manual cell picking, laser capture microdissection and microfluidics, as well as analysis methods for DNA, RNA and protein in single cell. In addition, we summarized major up-to-date single cell research achievements and their potential applications.
Animals
;
Cell Separation
;
DNA
;
Laser Capture Microdissection
;
RNA
;
Single-Cell Analysis
3.Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice.
Yarong LIU ; Hongfei WU ; Tian WANG ; Xiaoyan SHI ; Hai HE ; Hanwen HUANG ; Yulong YANG ; Min DAI
Chinese Journal of Natural Medicines (English Ed.) 2023;21(10):759-774
Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Animals
;
Mice
;
Atherosclerosis/drug therapy*
;
Diet, High-Fat
;
Endothelial Cells
;
Inflammation/drug therapy*
;
Mice, Inbred C57BL
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Reactive Oxygen Species