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关键词： HLA   HLA-C*07:1173   novel allele   sequencing-based typing  

摘要： HLA-C*07:1173 differs from HLA-C*07:02:01:03 by one nucleotide substitution in codon 96 in exon 3.

关键词： myocardial ischemia   reperfusion   remimazolam   oxidative stress   inflammation  

摘要： Remimazolam (Rema) is a novel anesthetic that is widely used in anesthesia and sedation in critically ill patients. Notably, Rema exerts effects in patients through activation of the gamma-aminobutyric acid (GABA) receptor. GABA may alleviate myocardial ischemia/reperfusion (I/R) injury;however, the impact of Rema and underlying molecular mechanism in myocardial I/R injury remain to be fully understood. Therefore, the present study aimed to investigate the effects of Rema on cardiac I/R injury and to determine the underlying mechanisms. An acute myocardial I/R model was established by ligating the left anterior descending artery in adult male C57BL/6 mice (8-10 weeks). Cultured Raw264.7 cells treated with lipopolysaccharide (LPS) were also used to investigate the effect of Rema on macrophages. The results of the present study revealed that Rema improved I/R-induced cardiac dysfunction by increasing the ejection fraction value and reducing the myocardial infarction area. In addition, Rema also alleviated I/R-induced cardiac inflammatory cell infiltration based on H&E and immunofluorescence staining. Transmission electron microscopy and ROS measurements showed that Rema improved I/R-induced mitochondrial structural disruption and oxidative stress in cardiomyocytes. Transcriptomics analysis and reverse transcription-quantitative PCR revealed that Rema alleviated I/R-induced release of inflammatory factors and cytokines by inhibiting the expression of IL-1 beta, IL-6, C-C chemokine receptor 2 and C-X-C motif chemokine ligand 5. Rema also inhibited I/R-induced CD68+ cell proliferation, IL-1 beta release, and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and IL-1 beta expression. The results of in vitro assays revealed that Rema inhibited LPS-induced increases in IL-1 beta, IL-6 and TNF-alpha expression and release in cultured RAW264.7 macrophages. In conclusion, the present study revealed that Rema may alleviate I/R-induced cardiac dysfunction and

摘要： Multiple sclerosis (MS) is a chronic inflammatory disease characterized by immune-mediated demyelination of the central nervous system, resulting in extensive neurological deficit and remyelination impairment. We have previously found that interleukin-four induced one (IL4I1) protein modulates CNS inflammation and enhances remyelination in mouse models of experimental demyelination. However, it remained unclear if IL4I1 regulates lymphocyte activity in MS. To assess the therapeutic potential of IL4I1 in MS, we investigated the impact of IL4I1 treatment on human lymphocytes from peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and MS patients. We found that IL4I1 increased the relative densities of Th2 and regulatory T-cells, while reducing Th17 cell density in healthy control (HC) samples. Furthermore, IL4I1-treated lymphocytes promoted CNS remyelination when grafted into demyelinated spinal cord lesions in mice. We found that baseline endogenous IL4I1 expression was reduced in people with MS. However, unlike HCs, IL4I1 treatment had no significant effect on IL17 or TOB1 expression in lymphocytes derived from MS patients. These results suggest that IL4I1 skews CD4+ T-cells to a regulatory state in healthy human lymphocytes, which may be essential for promoting remyelination. However, IL4I1 appears unable to exert its influence on lymphocytes in MS, indicating that impaired IL4I1-mediated activity may underlie MS pathology.

关键词： Lian-Dou-Qing-Mai   PPAR gamma-LXR alpha-ABCA1/ABCG1   IL-10   Atherosclerosis  

摘要： . Background. To observe the effect of the Lian-Dou-Qing-Mai (LDQM) formula on lipid metabolism in mice and explore its mechanism from the perspective of regulating the PPAR gamma/LXR alpha/ ABCA1 signaling pathway. Methods. THP-1 cells were induced to transform into foam cells with ox-LDL. Atherosclerosis (AS) models were constructed using a high-fat diet in ApoE-/- mice. Detection kits were used to evaluate triglyceride (TG) and total cholesterol (TC) content;TNF-alpha, MCP-1, MMP-9, TMP-1, PPAR gamma, LXR alpha, ABCA1, and ABCG1 mRNA and protein expression were identified using real-time PCR and western blot. Aortic plaque development and lipid deposition were seen using hematoxylin and eosin (HE) and oil red O staining, respectively. Results. In the cell model, LDQM could inhibit the formation of THP-1 macrophage-derived foam cells and the expression of inflammatory factors, promote macrophage cholesterol efflux, increase the expression of IL-10, and activate the PPAR gamma-LXR alpha-ABCA1/ ABCG1 pathway. Additional IL-10 treatment further promotes LDQM-induced cholesterol efflux in THP-1 cells. In in vivo models, LDQM inhibited the area of atherosclerotic lesions, aortic lipid deposition, and inflammation levels in ApoE-/- mice through IL-10, and activated the expression level of the PPAR gamma-LXR alpha ABCA1/ABCG1 pathway. Conclusion. LDQM may affect the PPAR gamma/LXR alpha/ ABCA1 signaling pathway through IL-10, regulate lipid metabolism, reduce serum inflammatory expression lipid deposition, and improve the formation atheroplaques.

关键词： HLA   HLA-DQB1*03:568   new allele   next-generation sequencing  

摘要： Identification of the novel HLA-DQB1*03:568 allele that differs from HLA-DQB1*03:03:02:01 by a non-synonymous mutation within exon 1.

关键词： il-17   macrophage   autophagy   polarization   pink1/parkin   rheumatic heart disease  

摘要： Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.