Mechanism of action of quercetin in regulating cellular autophagy in multiple organs of Goto-Kakizaki rats through the PI3K/Akt/mTOR pathway.

Objective: This experimental study investigated the protective function of quercetin on the liver, spleen, and kidneys of Goto-Kakizaki (GK) rats and explores its mechanism of action on autophagy-related factors and pathways. Materials and methods: GK rats were randomly divided into three groups: DM, DM + L-Que, and DM + H-Que, with age-matched Wistar rats serving as the control group. The control and DM groups were gavaged with saline, and the quercetin-treated group was gavaged with quercetin for 8 weeks each. Weekly blood glucose levels were monitored. Upon conclusion of the experiment, blood samples were gathered for lipid and hepatic and renal function analyses. The histopathologic morphology and lipid deposition in rats were examined. Disease-related targets were identified using molecular docking methods and network pharmacology analysis. Subsequently, immunohistochemical analysis was performed, followed by Western blotting to evaluate the levels of autophagy-related proteins and proteins in the AKT/PI3K/mTOR pathway, as well as their phosphorylation levels. Results: The results showed that, compared with the control group, the DM group exhibited significant increases in blood glucose, serum liver and kidney markers, liver fat vacuoles, and inflammatory cell infiltration. Immunohistochemistry (IHC) results indicated that quercetin reduced the extensive expression of AKT, P62, and mTOR in the liver and spleen of diabetic rats. The expression of autophagy and pathway-related proteins, such as P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR, was upregulated, while the expression of LC3A/LC3B, Beclin-1, Pink-1, and Parkin was downregulated. Conversely, the quercetin group showed a reduction in liver and kidney injury serum markers by decreasing lipid deposition and cell necrosis, indicating that quercetin has protective effects on the liver, spleen, and kidneys of GK rats. Additionally, in the quercetin group, the expression of autophagy and pathway-related proteins such as LC3A/LC3B, Beclin-1, Pink-1, and Parkin was upregulated, while the expression of P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR was downregulated, with statistically significant correlations. Conclusion: Quercetin markedly ameliorates liver, spleen, and kidney damage in GK rats, potentially through the inhibition of the PI3K/Akt/mTOR pathway, promoting autophagy. This research offers a rationale to the therapeutic potential of quercetin in mitigating organ damage associated with diabetes.

Insight into the mechanism of solution organic fractions on soot oxidation activity enhancement.

The particulate matter and soluble organic fraction emitted by diesel engine are hazardous to environment and human health. Exploring the effect mechanism of soluble organic fraction on soot oxidation is beneficial for reducing the emissions. In this study, the effects of four different types of soluble organic fractions on the soot oxidation activity and physicochemical properties are investigated. The results show that the attachment of oxygen-containing soluble organic fractions enhances the soot oxidation and reduces the peak characteristic temperature. However, the low volatility soluble organic fractions without oxygen element inhibit soot oxidation. Additionally, the high volatility soluble organic fractions without oxygen element elicit limited effects on soot oxidation. the contents of aliphatic C-H functional groups, carbonyl CO functional groups, and carboxylic acid O-CO functional groups significantly increase after adding oxygen-containing soluble organic fractions, while the limited increase in functional groups is observed in soluble organic fractions without oxygen element. Solid soluble organic fractions adhere to soot particles in the form of small particles, leading a reduction in the initial particle size distribution, while liquid soluble organic fractions exhibit block and chain shapes around the soot particles, which makes the initial particle size distribution increasing. Moreover, the attachment of all soluble organic fractions disrupts the surface order of soot particle, leading to a decrease in soot graphitization. This study is beneficial for revealing the interaction mechanism between soot and soluble organic fractions.

Macrophage fatty acid oxidation in atherosclerosis.

Atherosclerosis significantly contributes to the development of cardiovascular diseases (CVD) and is characterized by lipid retention and inflammation within the artery wall. Multiple immune cell types are implicated in the pathogenesis of atherosclerosis, macrophages play a central role as the primary source of inflammatory effectors in this pathogenic process. The metabolic influences of lipids on macrophage function and fatty acid ß-oxidation (FAO) have similarly drawn attention due to its relevance as an immunometabolic hub. This review discusses recent findings regarding the impact of mitochondrial-dependent FAO in the phenotype and function of macrophages, as well as transcriptional regulation of FAO within macrophages. Finally, the therapeutic strategy of macrophage FAO in atherosclerosis is highlighted.

LncRNA PVT1 inhibits endothelial cells apoptosis in coronary heart disease through regulating MAPK1 expression via miR-532-3p.

Background: Coronary atherosclerotic heart disease (CAD) is an inflammatory vascular disease caused by atherosclerosis. Long non-coding RNAs are involved in the pathophysiological process of coronary heart disease. Here we investigated the regulatory effects of lncRNA PVT1 (PVT1) in human coronary artery endothelial cells (HCAECs).Methods: qRT-PCR and western blot were performed to detect gene and protein expressions. CCK-8, flow cytometry and wound healing assays were used to determine cell viability, apoptosis and migration of HCAECs. The binding relationship among miR-532-3p, PVT1 and MAPK1 was verified by dual luciferase reporter assay.Results: Overexpression of PVT1 markedly reduced cell apoptosis and increased cell proliferation and migration. However, miR-532-3p upregulation suppressed cell proliferation and migration and promoted apoptosis of HCAECs. PVT1 suppressed the expression of miR-532-3p via directly targeting miR-532-3p. And miR-532-3p overexpression abolished the effect of PVT1 upregulation on proliferation and apoptosis in HCAECs. Furthermore, MAPK1 acted as a target gene of miR-532-3p and miR-532-3p inhibited MAPK1 expression.Conclusion: PVT1 promoted MAPK1 expression by targeting miR-532-3p, thus inhibiting HCAECs apoptosis and promoting cell proliferation, suggesting PVT1 might have great potential as a therapeutic target for CAD.

MiR-181a-5p is involved in the cardiomyocytes apoptosis induced by hypoxia-reoxygenation through regulating SIRT1.

MiR-181a-5p's mechanism in hypoxia-reoxygenation (H/R)-induced cardiomyocytes apoptosis has not been clarified. This study verified that SIRT1 was the target of miR-181a-5p. MiR-181a-5p expression was up-regulated or down-regulated in H/R-induced cardiomyocytes, and SIRT1 was transfected into cells alone or in combination with miR-181a-5p. Cell viability, apoptosis, levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the Bcl-2, Bax, and Caspase 3 levels in treated cells were tested. On the one hand, down-regulated miR-181a-5p promoted cell viability, reduced released LDH and MDA, and increased SOD level in H/R-induced cardiomyocytes. On the other hand, miR-181a-5p inhibited apoptosis and elevated Bcl-2 expression while decreasing the expressions of Bax and Caspase 3 in treated cells, but the effects of miR-181a-5p could be rescued by SIRT1. In conclusion, miR-181a-5p involved in H/R-induced cardiomyocytes apoptosis through regulating SIRT1, which might become a novel direction for related diseases.