Sodium Tanshinone IIA Sulfonate alleviates vascular senescence in diabetic mice by modulating the A20-NFκB-NLRP3 inflammasome-catalase pathway.

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence ß-Galactosidase Staining (SA-ß-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-ß-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Chemical Constituents from the deep-sea-derived Fungus Aureobasidium melanogenum LUO5.

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.

Associations between Physical Activity Trajectories and Incident Hypertension.

Purpose: We aimed to characterize physical activity (PA) trajectories across adulthood and to estimate their association with incident hypertension risk. Methods: Data were obtained from the China Health and Nutrition Survey (CHNS) conducted during 2004-2011. Group-based trajectory modeling (GBTM) was used to identify distinct groups of PA trajectories. The Cox proportional hazards model was used to investigate the association. Results: A total of 11,162 participants whose PA was repeatedly estimated by self-report from questionnaires two to four times in the CHNS were included in our study. During the 5.4 years of follow-up, 3824 incident hypertension cases were identified. Five distinct PA trajectories were identified in men: light and slight decline, light and gradual decline then sharp rise, light to medium-heavy then decline, medium-heavy and gradual decline, and heavy and sharp decline. Two distinct PA trajectories were identified in women: light and stable, and medium and gradual decline. The PA trajectory of medium-heavy and gradual decline was significantly associated with decreased risk of hypertension in men, with the hazard ratios and 95% confidence intervals (CI) being 0.80 (0.63, 0.99), 0.74 (0.59, 0.93), 0.76 (0.60, 0.96), and 0.70 (0.55, 0.88) in models 1-4, respectively. Conclusions: Our study identified five distinct long-term PA trajectories in men and two distinct trajectories in women. The PA trajectory of medium-heavy PA in early adulthood followed by gradual decline was found to be significantly associated with a decreased risk of hypertension in later life in men.

Precise selection of aptamers targeting PD-L1 positive small extracellular vesicles on magnetic chips.

A donor-cell-assisted membrane biotinylation strategy was used to modify small extracellular vesicles (sEVs) while minimizing protein damage, and allowed the sEVs to be loaded onto carriers. Biotinylated programmed death-ligand 1 (PD-L1) positive sEVs were used to select for aptamers from a DNA library. PD-L1 negative sEVs from a homologous cell line were found to remove non-specific aptamer sequences to increase the specificity. After just four rounds, high-affinity aptamers for PD-L1 positive sEVs were selected as novel affinity reagents.