miR-181c-5p suppresses neuronal pyroptosis via NLRP1 in Alzheimer's disease.

Alzheimer's disease (AD) is neurodegenerative disease common in the elderly, whose pathological mechanism is the deposition of amyloid-ß (Aß) plaques and neurofibrillary tangles in the brain. Pyroptosis is a programmed cell death mediated by Gasdermin protein. After the activation of inflammasomes, the cleaved caspase⁃ 1/4/5/11 activates GSDMD, which promotes the release of inflammatory substances and eventually causes cell swelling and death. Pyroptosis caused by inflammasomes plays a role in AD. However, the specific regulatory mechanism of pyroptosis in AD still needs more experimental studies. To further study the effects of NLRP1-induced pyroptosis on AD, miR-181c-5p, which could targeted bind to NLRP1, was knocked down or overexpression in HT22 cells to detect cell apoptosis with Tunel assay, the expression of inflammasome-related proteins with Western blot and the content of inflammatory factors with ELISA. miR-181c-5p was overexpressed in AD model mice to detect the learning and cognitive ability with morris water maze testing and the expression of inflammasoma-related proteins with Western blot. The results showed that miR-181c-5p mimic attenuated Aß1-42-induced neuronal pyroptosis in HT22 cells, while up-regulation of NLRP1 aggravated neuronal pyroptosis in HT22 cells. In mice, miR-181c-5p agomir attenuated neuronal pyroptosis in both hippocampal and cortical tissues, and miR-181c-5p antagomir improved neuronal pyroptosis and cognitive impairment through NLRP1. Therefore, the study suggests that miR-181c-5p can alleviated AD process by targeted downregulation of NLRP1, which is expected to be a target site for AD treatment.

Identification of the Key Immune-Related Genes in Chronic Obstructive Pulmonary Disease Based on Immune Infiltration Analysis.

Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity worldwide. A better understanding of new biomarkers for COPD patients and their complex mechanisms in the progression of COPD are needed. Methods: An algorithm was conducted to reveal the proportions of 22 subsets of immune cells in COPD samples. Differentially expressed immune-related genes (DE-IRGs) were obtained based on the differentially expressed genes (DEGs) of the GSE57148 dataset, and 1509 immune-related genes (IRGs) were downloaded from the ImmPort database. Functional enrichment analyses of DE-IRGs were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Ingenuity Pathway Analysis (IPA). We defined the DE-IRGs that had correlations with immune cells as hub genes. The potential interactions among the hub genes were explored by a protein-protein interaction (PPI) network. Results: The CIBERSORT results showed that lung tissue of COPD patients contained a greater number of resting NK cells, activated dendritic cells, and neutrophils than normal samples. However, the fractions of follicular helper T cells and resting dendritic cells were relatively lower. Thirty-eight DE-IRGs were obtained for further analysis. Functional enrichment analysis revealed that these DE-IRGs were significantly enriched in several immune-related biological processes and pathways. Notably, we also observed that DE-IRGs were associated with the coronavirus disease COVID-19 in the progression of COPD. After correlation analysis, six DE-IRGs associated with immune cells were considered hub genes, including AHNAK, SLIT2 TNFRRSF10C, CXCR1, CXCR2, and FCGR3B. Conclusion: In the present study, we investigated immune-related genes as novel diagnostic biomarkers and explored the potential mechanism for COPD based on CIBERSORT analysis, providing a new understanding for COPD treatment.

Delphinidin-3-sambubioside from Hibiscus sabdariffa. L attenuates hyperlipidemia in high fat diet-induced obese rats and oleic acid-induced steatosis in HepG2 cells.

Hibiscus sabdariffa. L is folk medicine that is often used for its hypolipidemic and antihypertensive effects; however, the active compound responsible for its anti-obesity effect is presently unknown. Delphinidin-3-sambubioside (Dp3-Sam) is an anthocyanin, was extracted from Hibiscus sabdariffa L. The present research aimed to investigate the role of Dp3-Sam in the prevention of hyperlipidemia in vivo and in vitro. Rats were fed with a standard chow diet (Control group) or high-fat diet (HFD and DP group) for eight weeks. Besides, HepG2 cells were stimulated with 0.2 mM oleic acid, with or without Dp3-Sam (100-200 µg/ml). Lipid profiles were measured by commercial kits. Oil Red O staining was performed to measure the hepatic and intracellular lipid levels. The key genes of lipid metabolism were measured by RT-PCR. In HFD-fed rats, Dp3-Sam reduced the body weight gain, visceral fat, and abdominal fat and decreased hepatic lipid deposits. Dp3-Sam decreased intracellular TG levels and lipid accumulation in oleic acid-treated HepG2 cells. Besides, Dp3-Sam downregulated the mRNA expression of HMG-CoA reductase (HMGCR), sterol regulatory element-binding protein-1 c (SREBP-1 C), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) and upregulated the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1), carnitine palmitoyltransferase1 (CPT1), acyl-coenzyme A oxidase (ACOX), and peroxisome proliferator-activated receptor alpha (PPARα). Dp3-Sam up-regulated the expression of phosphorylation of AMP-activated protein kinase (pAMPK) in HFD-fed rats. Our findings indicated that Dp3-Sam possesses the potential to improve lipid metabolism dysfunction and our results offered evidence for the use of Dp3-Sam as therapy for the prevention of obesity and dyslipidemia.