Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk.Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models).Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082–1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095–5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055–2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148–3.257, p = 0.013) with random effects model. After omitting Gouda’s study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I² = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004–1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model.Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.

Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low‐density lipoprotein cholesterol (LDL‐C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804–0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non‐hypertensive population (HR: 1.251; 95% CI: 1.100–1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension.

Background: Pseudoprotodioscin (PPD) is a prominent active steroidal saponin isolated from plants of the genus Dioscorea. Investigations have shown that PPD exhibits considerable biological activity and has great clinical potential. Methods: Dioscorea plants and pseudoprotodioscin were used as search terms for study retrieval. Studies involving PPD were collected from a wide range of databases, including China National Knowledge Infrastructure, PubMed, Web of Science, and Elsevier, as well as relevant scientific websites. Results: PPD possesses multiple bioactive properties, such as anticancer, anti-inflammatory, hepatoprotective, and cardioprotective effects. Pharmacokinetic studies in rats indicated that PPD undergoes rapid excretion and has low bioavailability (5.7%), which need to develop a more effective drug delivery system to modify, such as lipid-based nanoparticles. Additionally, Chinese patent medicines containing PPD have shown promising clinical applications in related diseases. Conclusions: This review highlights the therapeutic potential of PPD and its related Chinese patent medicines, providing a foundation for future research and clinical development. Further studies are required to optimize the pharmacokinetic profile of PPD and explore its full pharmacological potential and underlying mechanisms.

Background: This study explores the causal links between genetically predicted lifestyle factors, socioeconomic status, and coronary artery disease (CAD) risk in individuals with diabetes using a bidirectional Mendelian-randomization approach.Methods: This study explored the potential causal relationships of lifestyle factors and socioeconomic status with the risk of CAD in diabetes patients by a bidirectional, two-sample Mendelian-randomization (MR) analysis.Results: Genetically predicted smoking initiation (p = 0.005, 95% CI: 1.08–1.55) and insomnia (p = 0.001, 95% CI: 1.06–1.29) were associated with a higher risk of CAD in individuals with diabetes, whereas educational attainment (p = 0.0001, 95% CI: 0.47–0.78) was associated with a lower risk of CAD. The lifetime smoking index (p = 0.016, 95% CI: 1.12–3.03) was suggestively associated with a higher risk of CAD, while household income before taxes (p = 0.048, 95% CI: 0.41–1.00) was suggestively associated with a lower risk of CAD. In addition, we observed a suggestive negative association between the genetically predicted risk of CAD and the lifetime smoking index (p = 0.016, 95% CI: 0.98–0.99) and a significant causal relationship between the risk of CAD and household income before taxes (p = 0.006, 95% CI: 0.97–0.99).Conclusion: The results of this study provide evidence that smoking initiation, lifetime smoking index and insomnia are associated with an increased risk of CAD in individuals with diabetes, educational attainment and household income before taxes are associated with a reduced risk of CAD in individuals with diabetes, and the possible role of lifetime smoking index and household income before taxes on the risk of CAD in individuals with diabetes. It provides an opportunity for the prevention and management of CAD in individuals with diabetes.

Background/Objectives: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture. It has become a major clinical challenge due to the limitations of current therapeutic approaches. Isoimperatorin (ISO), a naturally occurring and biologically active furanocoumarin extracted from various traditional herbals, exhibits therapeutic potential in combating osteoporosis. However, toxicity limits its application. Methods: In vivo, compound B15 was evaluated in an Ovariectomy (OVX) mice model, where treatment was associated with changes in bone microarchitecture parameters, modulation of serum bone metabolism markers, and alterations in the histopathological features of bone tissue. Results: In this study, a new series of furanocoumarin derivatives was designed and synthesized for the treatment of osteoporosis. Compared with ISO, compound B15 has less toxicity and better ability to inhibit osteoclast formation in vitro. Compound B15 could decelerate the progression of osteoporosis in ovariectomized mice. It is worth mentioning that the expression of estradiol in the serum of mice with excised ovaries was significantly increased by compound B15. Conclusions: These results imply that the novel furanocoumarin derivative B15 is a promising therapeutic option for osteoporosis.

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has garnered attention for its cardiovascular benefits beyond glycemic control. Ferroptosis, a novel form of regulated cell death, contributes to the pathogenesis of diabetic cardiomyopathy (DCM). However, whether EMPA mitigates DCM by suppressing ferroptosis remains unclear. Here, Type 2 diabetic db/db mice were used to establish a DCM model and treated with EMPA (10 mg/kg/day) for 12 weeks. EMPA significantly improved cardiac function, reduced myocardial fibrosis, and attenuated ferroptosis, concomitant with upregulated silent information regulator 3 (SIRT3) expression. In the rat cardiomyocytes (H9c2 cells) exposed to high glucose and palmitic acid, EMPA treatment or SIRT3 overexpression alleviated oxidative stress, mitochondrial dysfunction, and ferroptosis. Mechanistically, molecular docking, molecular dynamics simulation, cellular thermal shift assay and drug affinity responsive target stability assay confirmed that SIRT3 is the drug target of EMPA, stabilizing its protein levels and reducing acetylated p53 expression. Notably, SIRT3 silencing abolished EMPA’s beneficial effects on oxidative stress and ferroptosis. Our findings demonstrate that EMPA exerts cardioprotective effects by inhibiting oxidative stress and ferroptosis in cardiomyocytes, which is mediated by SIRT3. This study provides novel insights into the mechanisms underlying EMPA’s therapeutic effects in DCM.