Lycium barbarum polysaccharide's protective effects against PM2.5-induced cellular senescence in HUVECs.

Fine particulate matter (PM2.5) exposure is strongly associated with vascular endothelial senescence, a process implicated in cardiovascular diseases. While there is existing knowledge on the impact of Lycium barbarum polysaccharide (LBP) on vascular endothelial damage, the protective mechanism of LBP against PM2.5-induced vascular endothelial senescence remains unclear. In this study, we investigated the impact of PM2.5 exposure on vascular endothelial senescence and explored the intervention effects of LBP in human umbilical vein endothelial cells (HUVECs). We found that PM2.5 exposure dose-dependently reduced cell viability and proliferation in HUVECs while increasing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Additionally, PM2.5 exposure inhibited the activity of superoxide dismutase (SOD). Notably, PM2.5 exposure induced autophagy impairments and cellular senescence. However, LBP mitigated PM2.5-induced cell damage. Further studies demonstrated that correcting autophagy impairment in HUVECs reduced the expression of the senescence markers P16 and P21 induced by PM2.5. This suggests the regulatory role of autophagy in cellular senescence and the potential of LBP in improving HUVECs senescence. These findings provide novel insights into the mechanisms underlying PM2.5-induced cardiovascular toxicity and highlight the potential of LBP as a therapeutic agent for improving vascular endothelial health.

PM2.5-induced premature senescence in HUVECs through the SIRT1/PGC-1α/SIRT3 pathway.

Vascular endothelial cell senescence plays a pivotal role in the development of atherosclerosis. Recent studies have demonstrated that ambient fine particulate matter (PM2.5) induces stress-induced premature senescence (SIPS) in vascular endothelial cells. However, the precise mechanisms underlying this process remain to be fully elucidated. Cellular senescence is closely associated with reactive oxygen species (ROS), and emerging research has established a strong connection between the SIRT1/PGC-1α/SIRT3 signaling pathway and the antioxidant system in vascular endothelial cells. In this study, we aimed to investigate the impact of PM2.5 on vascular endothelial cell senescence and to elucidate the underlying mechanisms. Our findings revealed that PM2.5 exposure led to an increase in senescence-associated ß-galactosidase (SA-ß-gal) activity and the expression of the cell cycle-blocking proteins P53/P21 and P16 in human umbilical vein endothelial cells (HUVECs). Flow cytometry analysis demonstrated an elevated proportion of cells arrested in the G0/G1 phase after PM2.5 exposure. In addition, PM2.5-induced cellular senescence was attributed to the disruption of the cellular antioxidative defense system through the SIRT1/PGC-1α/SIRT3 signaling pathway. The expression of cellular senescence markers was reduced after targeted scavenging of mitochondrial ROS using MitoQ. Moreover, treatment with SRT1720, a SIRT1-specific activator, upregulated the SIRT1/PGC-1α/SIRT3 signaling pathway, restored the antioxidant system, and attenuated the expression of cellular senescence markers. Taken together, our results suggest that PM2.5 downregulates the SIRT1/PGC-1α/SIRT3 signaling pathway, resulting in impaired antioxidant defenses in HUVECs. This, in turn, allows for the accumulation of ROS, leading to inhibition of endothelial cell cycle progression and the onset of stress-induced senescence in HUVECs.

Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells.

Background: Fine particulate matter (PM2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs was exposed to PM2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 µg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected. Results: A remarkable decrease in cell viability is observed in the PM2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM2.5. Conclusions: Overall, our results indicate that PM2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM2.5-induced cardiovascular diseases.

Study on the Antibreast Cancer Mechanism and Bioactive Components of Si-Wu-Tang by Cell Type-Specific Molecular Network.

Si-Wu-Tang (SWT), a traditional Chinese herbal formula, has shown an effect on antibreast cancer. However, the mechanisms and bioactive components of SWT are still unclear. Fortunately, cell type-specific molecular network has provided an effective method. This study integrated the data of formula components, all types of biomolecules in the human body, and nonexpressed protein in breast cancer cells and constructed the breast cancer cell network and the biological network that SWT acted on the breast cancer-related targets by Entity Grammar System (EGS). Biological network showed 59 bioactive components acting on 15 breast cancer-related targets. The antibreast cancer mechanisms were summarized by enrichment analysis: regulation of cell death, response to hormone stimulation, response to organic substance, regulation of phosphorylation of amino acids, regulation of cell proliferation, regulation of signal transmission, and affection of gland development. In addition, we discovered that verbascoside played the role of antibreast cancer by inhibiting cell proliferation, but there was not a report on this effect. The results of CCK8 and western blot were consistent with the antibreast cancer effect of verbascoside based on biological network. Biological network modeling by EGS and network analysis provide an effective way for uncovering the mechanism and identifying the bioactive components of SWT.

[Mechanism of anti-aging therapy on Parkinson's disease].

Many studies have shown that anti-aging treatment has value to prevention and treatment of some diseases. For the treatment of Parkinson' s disease, clinical and experimental researches have proved the potential value of anti-aging treatment, yet the mechanism remains unclear. For this reason, this work used the anti-aging prescriptions of Buyang Huanwu decoction in traditional Chinese medicines example to discover the anti-aging treatment mechanism on Parkinson's disease. The results showed that the mechanism of mitochondrial damage, apoptosis, free radicals and oxidative stress could contribute to the treatment of Parkinson' s disease. Buyang Huanwu decoction is more than as the carrier in this article, the discovered anti-aging treatment mechanism Parkinson's disease is not confined to Buyang Huanwu decoction, could also be used to understand the anti-aging treatment mechanism using other prescription. The main contribution of this paper is to clarify the mechanism of anti-aging treatment of Parkinson's disease, and provide a new strategy for the treatment and prevention of Parkinson's disease.

[Elucidating hypoglycemic mechanism of Dendrobium nobile through auxiliary elucidation system for traditional Chinese medicine mechanism].

To build the Dendrobium nobile -T2DM network, and elucidate the molecular mechanism of D. nobile to type 2 diabetes (T2DM). Collect the chemical composition of D. nobile and the targets on T2DM by retrieving database and documents, build the network of D. nobile to T2DM using the entity grammar systems inference rules. The molecular mechanism of D. nobile to T2DM includes: (1) regulating lipid metabolism by lowering triglyceride; (2) reducing insulin resistance; (3) protecting islet cells; (4) promoting the glucose-dependent insulin tropic peptide (GIP) secretion; (5) inhibiting calcium channel. Under the guidance of network pharmacology, through entity grammar systems inference rules we elucidate the molecular mechanism of D. nobile to T2DM, and provide the basis for the further development of health care products based on D. nobile.