Muscle aging, characterized by the progressive loss of muscle mass and function, presents a significant clinical challenge, contributing to sarcopenia and age-related frailty. Recent research highlights metformin, a widely used anti-diabetic drug, as a promising candidate for mitigating muscle aging by targeting conserved molecular pathways. This review explores metformin’s mechanisms in Drosophila melanogaster, emphasizing its activation of AMP-activated protein kinase (AMPK) and inhibition of the mechanistic target of rapamycin (mTOR), pivotal regulators of cellular energy balance and proteostasis. Metformin enhances autophagy, reduces protein aggregation, and preserves muscle integrity by modulating autophagy-related genes, such as Atg1 and Atg8. Furthermore, the drug's suppression of ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF-4E) inhibits excessive protein synthesis, mitigating proteostatic stress. Studies in Drosophila reveal that metformin extends lifespan, reduces oxidative stress, and improves muscle function, offering insights into its translational potential for addressing sarcopenia. However, challenges remain in bridging the findings from Drosophila to humans due to species-specific differences and the need for long-term clinical studies. By elucidating the interplay of AMPK, mTOR, and autophagy pathways, this review underscores metformin’s therapeutic potential in age-related muscle decline, providing a molecular foundation for its application in geroprotective interventions. Future research should focus on optimizing dosing strategies, exploring synergistic therapies, and advancing biomarkers for muscle aging to fully harness metformin’s clinical utility in promoting healthy aging.

Low-grade glioma (LGG) is a common primary tumor in the central nervous system. The function of several types of cell death has been proved in tumorigenesis of low-grade glioma (LGG). Cuproptosis, a new form of cell death, has been defined in recent years. We put forward the function between cuproptosis and LGG for the first time. According to TCGA datasets, we performed a univariate Cox regression analysis and got 5 hub risk genes related to the survival of LGG. Then, we constructed a prognostic risk mode by using LASSO method and demonstrated that risk score is independent prognostic risk factor by using univariate and multivariate Cox regression analyses. The above results were verified in CGGA datasets. Next, we compared the immune characteristics by using CIBERSORT, ssGSEA and demonstrated that 5 hub genes play an important role in tumor immunotherapy. Finally, we performed GO term and KEGG pathway analyses and found 5 hub genes are likely to change the biological functions of LGG by regulating the metabolism related components. We believe that our results will provide a new strategy for tumor treatment.

Objective: Compound Danshen Dripping Pill (CDDP) is a marketed Chinese patent medicine, primarily efficacious in “promoting blood circulation to remove blood stasis, regulating Qi to relieve pain”. CDDP, as an anti-platelet aggregation drug, has been applied in clinic. However, the evidence has not been critically assessed, and the underlying mechanism has still not been fully understood.

Methods: A meta-analysis was conducted to collect randomized controlled trials (RCTs) from PubMed, Embase, Cochrane library, Web of Science, CNKI, Wanfang and VIP, and assess the efficacy and safety of CDDP against platelet aggregation. A network pharmacology analysis was performed to predict the potential mechanisms of CDDP against platelet aggregation. A series of in vitro and vivo experiments were conducted to reveal the potential mechanisms of CDDP against platelet aggregation.

Results: The pooled result of the meta-analysis involving 20 RCTs showed a more significant reduction in platelet aggregation rate after CDDP plus anti-platelet drugs treatment than anti-platelet drugs alone (SMD=1.27, 95 % CI: 0.97-1.57, P < 0.0001). The network pharmacology analysis found 86 overlapping target genes between CDDP and platelet aggregation that were closely related to lipid, atherosclerosis and inflammation signal pathways. The in vitro and vivo experiments found that CDDP inhibited carrageenan-induced thrombi in tissue vessels of mice. Especially, the combination of CDDP and aspirin/clopidogrel showed a better effect of inhibiting thrombus. CDDP also decreased the level of serum P-selectin and TXB2, and the expression of tumor necrosis factor α, P-selectin and activated matrix metalloproteinase 2 in tissues. CDDP protected human umbilical vein endothelial cells (HUVECs) against lipopolysaccharide (LPS)-induced cell death and reduced the expression of tumor necrosis factor-like cytokine 1 A and vascular endothelial growth factor-α. Meanwhile, CDDP reduced the adhesion of ox-LDL-induced platelets and LPS-induced THP-1 monocytes to HUVECs, and inhibited thrombin-induced human platelet clotting.

Conclusion: This integrated study suggests that CDDP have a potential anti-platelet aggregation effect. It may provide a new option for anti-platelet aggregation in clinical practice.

Background: Ferroptosis, an iron-dependent cell death, contributes to non-alcoholic fatty liver disease (NAFLD), but causal genes remain unclear. This study identifies ferroptosis-related genes driving NAFLD to fill this gap.

Methods: Summary data-based Mendelian Randomization (SMR) analyzed 564 ferroptosis-related genes for causal links to NAFLD by integrating mQTL/eQTL/pQTL data with GWAS, validated in FinnGen and the GWAS Catalog. To further substantiate our findings, expression of lead candidate genes was validated in independent human liver tissue datasets from the Gene Expression Omnibus (GEO). HepG2 cells were used to assess candidate gene expression, oxidative stress, and ferroptosis under free fatty acids (FFA) treatment. We evaluated cell viability, lipid ROS levels, gene expression, protein levels, and oxidative stress markers.

Results: SMR analysis revealed an association between SLC2A6 methylation/expression and NAFLD risk. Hypermethylation at cg02257517 was associated with increased NAFLD risk (OR=1.032, 95 % CI=1.013-1.051), while higher SLC2A6 expression correlated with lower risk (OR=0.919, 95 % CI=0.87-0.97). Multi-omics analysis confirmed an inverse relationship between SLC2A6 expression and cg02257517 methylation (OR=0.741, 95 % CI=0.66-0.832), suggesting hypermethylation downregulates SLC2A6, increasing NAFLD susceptibility. Those results were further validated in HepG2 cells, where the candidate gene demonstrated a protective role against FFA-induced oxidative stress and ferroptosis. Overexpression of the gene significantly mitigated these pathological effects, supporting its potential as a therapeutic target.

Conclusion: Multi-omics Mendelian randomization identified SLC2A6 hypermethylation as a causal NAFLD risk factor by suppressing its expression. Functional validation in disease-relevant models revealed SLC2A6-mediated protection against oxidative stress and ferroptosis, highlighting its potential as a therapeutic target for NAFLD through epigenetic or gene-based interventions.

Background: The pleiotropic effects of semaglutide make it a breakthrough therapy for managing diabetes and obesity, particularly in patients with comorbid cardiovascular diseases. However, its clinical application in heart failure (HF) remains under investigation.

Objective: To systematically evaluate the efficacy and safety of subcutaneous semaglutide in the treatment of HF, irrespective of obesity status or the presence of type 2 diabetes mellitus (T2DM).

Methods: A comprehensive search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases was conducted to identify randomized controlled trials (RCTs) of subcutaneous semaglutide in HF patients, from inception to November 2, 2024. RevMan 5.3 software was used for statistical analysis.

Results: A total of 4 RCTs involving 6109 patients were included. Four RCTs involving 6109 patients were included. Meta-analysis showed that, compared with placebo, subcutaneous semaglutide reduced the risks of cardiovascular death (RR = 0.75, 95 % CI: 0.61-0.92, P = 0.005), all-cause mortality (RR = 0.81, 95 % CI: 0.67-0.98, P = 0.03), and serious adverse events (RR = 0.53, 95 % CI: 0.41-0.68, P < 0.00001). Subgroup analysis revealed that semaglutide improved Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-CSS) (MD = 7.58, 95 % CI: 4.40-10.77, P < 0.00001) and 6-minute walk test (6-MWT) distances (MD = 16.91, 95 % CI: 8.98-24.83, P < 0.0001), and reduced the risk of HF rehospitalization (RR = 0.41, 95 % CI: 0.26-0.65, P = 0.0001) in obese patients with HFpEF. Among patients without T2DM, semaglutide was superior to placebo in reducing HF rehospitalization (RR = 0.16, 95 % CI: 0.04-0.68, P = 0.01) and cardiovascular mortality (RR = 0.76, 95 % CI: 0.60-0.97, P = 0.03). Furthermore, at a dose of 2.4 mg weekly, semaglutide reduced HF rehospitalization (RR = 0.29, 95 % CI: 0.14-0.58, P = 0.0005) and cardiovascular mortality (RR = 0.75, 95 % CI: 0.59-0.95, P = 0.02) compared with placebo, whereas no significant benefit was observed at a dose of 1.0 mg weekly.

Conclusion: Current evidence suggests that subcutaneous semaglutide safely and effectively reduces cardiovascular mortality, all-cause mortality, and serious adverse events in patients with HF, improves quality of life and exercise tolerance in obese HFpEF patients, and lowers the risk of HF rehospitalization. Nevertheless, given the limited number of included trials and patient populations, further high-quality studies are warranted to confirm these findings.

Objective: To analyze factors influencing the safety of blinatumomab based on real-world adverse drug event (ADE) reports collected from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) over the last decade since its market approval, thereby strengthening pharmacovigilance for high-risk populations.

Methods: Data from the FAERS database from the fourth quarter of 2014 to the third quarter of 2024 were retrieved. ADE positive signals were systematically classified, and six types of adverse events with high incidence, strong specificity, and high correlation were analyzed, including neurological disorders, cytokine release syndrome (CRS), immune system disorders, hematologic and lymphatic system disorders, infections and infestations, and lineage switch. For each type, statistical analyses were performed according to potential influencing factors, including age, sex, body weight, interval time, and continent of patient origin.

Results: A total of 18,728 ADE reports associated with blinatumomab were collected, from which 371 positive signals were identified, involving 20 system organ classifications (SOCs). The preferred term (PT) with the strongest signal was lineage switch leukemia, an adverse event not mentioned in the prescribing information. The SOC with the highest frequency was neurological disorders. Except for lineage switch leukemia, significant differences in influencing factors were observed across the other five adverse event categories. Analysis of the overall population of ADE suggested that Asian juvenile and elderly patients showed lower drug tolerability, and juvenile patients were more prone to delayed adverse events.

Conclusion: In clinical use of blinatumomab, particular attention should be paid to drug tolerability in Asian populations, with vigilance for early-onset and delayed adverse events. Given the short duration of blinatumomab's availability in China and limited local experience, enhanced drug monitoring and risk prevention are warranted for juvenile and elderly patients in clinical practice.