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Background: Cardiac hypertrophy is a significant complication of diabetes, often triggered by hyperglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists alleviate cardiac hypertrophy, but their efficacy diminishes under GLP-1 resistance. Syringaldehyde (SA), a natural phenolic compound, may activate GLP-1 receptors and mitigate hypertrophy. This study explores SA's therapeutic potential in hyperglycemia-induced cardiac hypertrophy in H9c2 cardiomyocytes. Methods: H9c2 cells were exposed to high glucose to induce hypertrophy. Cells were treated with varying SA concentrations, and hypertrophic biomarkers were analyzed using ELISA, qPCR, and Western blot. Results: SA reduced cell size and hypertrophic biomarkers in a dose-dependent manner while increasing GLP-1 receptor expression and cAMP levels. These effects were attenuated in GLP-1-resistant cells, highlighting the role of GLP-1 receptor activation. AMPK activation was essential, as its inhibition abolished SA's effects. SA also decreased O-linked N-acetylglucosamine transferase (OGT) expression via AMPK activation, contributing to reduced hypertrophy. Conclusions: SA alleviates hyperglycemia-induced cardiac hypertrophy in H9c2 cells by activating the GLP-1 receptor and AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Metabolic remodeling contributes to the pathological process of heart failure (HF). We explored the effects of cardiac contractility modulation (CCM) on myocardial metabolic remodeling in the rabbit model with HF. The HF in rabbit model was established by pressure uploading and then CCM was applied. We evaluated the cardiac structure and function by echocardiography, serum BNP level, and hematoxylin and eosin and Masson’s trichrome staining. We detected the accumulation of glycogen and lipid droplets in myocardial tissues by periodic acid-Schiff and Oil Red O staining. Then, we measured the contents of glucose, free fatty acid (FFA), lactic acid, pyruvate, and adenosine triphosphate (ATP) levels in myocardial tissues by corresponding kits and the expression levels of key factors related to myocardial substrate uptake and utilization by western blotting were analyzed. CCM significantly restored the cardiac structure and function in the rabbit model with HF. CCM therapy further decreased the accumulation of glycogen and lipid droplets. Furthermore, CCM reduced the contents of FFA, glucose, and lactic acid, and increased pyruvate and ATP levels in HF tissues. The protein expression levels related to myocardial substrate uptake and utilization were markedly improved with CCM treatment by further activating adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor-α signaling pathways.

Background: Oxidative stress has been implicated in the pathogenesis of uterine leiomyoma (ULM) with an increasing incidence. This study aimed to identify potential oxidative stress-related biomarkers in ULM using transcriptome data integrated with Mendelian randomization (MR) analysis. Methods: Data from GSE64763 and GSE31699 in the Gene Expression Omnibus (GEO) were included in the analysis. Oxidative stress-related genes (OSRGs) were identified, and the intersection of differentially expressed genes (DEGs), Weighted Gene Co-expression Network Analysis (WGCNA) genes, and OSRGs was used to derive differentially expressed oxidative stress-related genes (DE-OSRGs). Biomarkers were subsequently identified via MR analysis, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. Nomograms, regulatory networks, and gene-drug interaction networks were constructed based on the identified biomarkers. Results: A total of 883 DEGs were identified between ULM and control samples, from which 42 DE-OSRGs were screened. MR analysis revealed four biomarkers: ANXA1 , CD36 , MICB , and PRDX6. Predictive nomograms were generated based on these biomarkers. ANXA1 , CD36 , and MICB were significantly enriched in chemokine signaling and other pathways. Notably, ANXA1 showed strong associations with follicular helper T cells, resting mast cells, and M0 macrophages. CD36 was positively correlated with resting mast cells, while MICB was negatively correlated with macrophages. Additionally, ANXA1 displayed strong binding energy with amcinonide, and MICB with ribavirin. Conclusion: This study identified oxidative stress-related biomarkers (ANXA1, CD36, MICB, and PRDX6) in ULM through transcriptomic and MR analysis, providing valuable insights for ULM therapeutic research. [ABSTRACT FROM AUTHOR]

The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future. [ABSTRACT FROM AUTHOR]

To study the effect of different soil-to-rock thickness ratios on surface settlement in the excavation surface when shield tunnel crosses the upper soft and lower hard strata, a three-dimensional finite element model is established under seven working conditions based on an interval tunnel of Guiyang rail transit line 3 and with constant tunnel burial depth and the spacing between the two-lane tunnels, and the settlement law is obtained by comparing and analyzing the measured data. Using 44 sets of surface settlement data from the two-lane tunnel, a Peck segmentation formula applicable to the local composite strata is fitted. The research results show that the settlement curves of the numerical simulation are all W-shaped from the overall point of view, and the maximum settlement of the ground surface is located above the preceding tunnel; the ground surface is more likely to be disturbed resulting in uneven settlement when crossing the red clay layer, and the symmetry of the simulated curve increases as the soil-to-rock thickness ratio decreases, the settlement difference between the left and right tunnels decreases, and the overall settlement value basically shows a decreasing trend. The relationship between the soil-to-rock thickness ratio and the correction factor is summarized, and the graph shows that the Peck settlement pattern of the upper soft and lower hard strata in Guiyang. [ABSTRACT FROM AUTHOR]