Metabolic associated fatty liver disease (MAFLD), characterized by hepatic steatosis and metabolic dysregulation, is the most prevalent chronic liver disease worldwide, yet effective therapeutic strategies remain limited due to its complex pathogenesis. Astragaloside IV (AST IV), a bioactive saponin derived from Astragalus membranaceus, has demonstrated hypoglycemic, lipid-modulating, antioxidative, and hepatoprotective properties—though its specific mechanisms against MAFLD are not fully elucidated. In this study, we established high-fat diet-induced mouse and free fatty acid-induced HepG2 cell models of MAFLD to evaluate the efficacy of AST IV. Serum biochemical analyses revealed that AST IV significantly improved glucolipid metabolism and reduced hepatic injury. Combining network pharmacology prediction with experimental validation, we identified ferroptosis as a key pathway targeted by AST IV. Specifically, AST IV upregulates SLC7A11 and GPX4 expression while downregulating ACSL4, thereby inhibiting ferroptosis. Molecular docking further confirmed strong binding affinities between AST IV and these core proteins. In conclusion, our findings demonstrate that AST IV alleviates MAFLD by suppressing ferroptosis, highlighting its potential as a novel phytochemical candidate for MAFLD intervention.

Cardiovascular disease (CVD) remains the leading cause of global mortality and disability. As an inevitable risk factor, cardiac aging significantly exacerbates the incidence and progression of age-related cardiovascular pathologies, including coronary artery disease, cardiomyopathies, and heart failure in the elderly population. Mitochondria function as central organelles in cardiac energy metabolism. Dysregulation of functional homeostasis, characterized by impaired quality control mechanisms, such as diminished energy production efficiency and exacerbated oxidative stress, is a primary driver of the cardiac aging process. Accumulating evidence in recent years indicates that sirtuin 1 (SIRT1) plays a crucial role in regulating cardiac aging. A range of therapeutic agents, including natural compounds and synthetic molecules, ameliorate cardiac aging and related pathologies by activating SIRT1 to modulate mitochondrial function. This review systematically summarizes the emerging roles of SIRT1 in cardiac aging, with a focus on the molecular mechanisms through which SIRT1 governs mitochondrial homeostasis. We also highlight recent advances in SIRT1-targeted therapeutic strategies, thereby providing a theoretical basis and translational perspectives for preventing and treating cardiac aging-related diseases.

Numerous studies have demonstrated a significant association between serum copper (Cu) levels and abnormal glucose metabolism. However, there is a notable lack of research specifically examining the relationship between serum Cu concentration and type 2 diabetes mellitus (T2DM) in the elderly population. Consequently, this study aims to investigate the potential association between serum Cu concentration and T2DM in elderly adults. A total of 565 participants were recruited from the outpatient and inpatient geriatric departments of the First Hospital of Jilin University between July 2021 and July 2023. Logistic regression models were employed to explore the association between serum Cu concentration and the risk of diabetes mellitus, with odds ratios (ORs) and 95

Background:Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults. Methods:The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated. Results:There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (P<0.05). Iron (rZinc = 0.147, rSOD = 0.180, rT-AOC = 0.193, P < 0.05) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (rMDA = -0.146, P < 0.05). Magnesium was positively correlated with SOD (rMagnesium = 0.147, P < 0.05). Zinc (rSOD = 0.616, rT-AOC = 0.575, P < 0.01) was positively correlated with SOD and T-AOC. Zinc (rMDA =-0.636, rNO=-0.616, P<0.01) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], P <0.01), FBG (1.265, [1.059; 1.511], P <0.05), HbAlc (1.545, [1.431; 1.680], P <0.01), MDA (2.989, [1.900; 4.702], P <0.01) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], P < 0.05) and SOD (0.820, [0.698; 0.964], P < 0.05) were protective factors for the severity of diabetic microvascular complications. Conclusion:Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.

OBJECTIVE:Diabetes-related kidney disease reduces patients' quality of life, increases the risk of death, and is associated with insulin resistance (IR). The triglyceride-glucose (TyG) index is a simple and inexpensive alternative to IR measurement. Furthermore, the relationship between albuminuria and chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we aimed to investigate the association of TyG index with albuminuria and CKD in patients with T2DM. METHODS:Data from 01/2013-12/2017 period were obtained from the Population Health Data Archive's Diabetes Complications Data Set. A total of 1048 patients with T2DM were included in this study. CKD is defined as an estimated glomerular filtration rate < 60 ml/min-1.1.73 m-2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Albuminuria is defined as a UACR ≥ 30 mg/g. The TyG index is calculated by measuring the triglyceride and fasting blood glucose levels. Logistic regression models were used to analyze the association between albuminuria, CKD with T2DM and TyG index. RESULTS:We identified 1048 subjects, 63.03% of whom were men. The mean age was 46.21 years, and the mean body mass index was 26.742 kg/m2. CKD and albuminuria detection rates showed an increasing trend in the different TyG subgroups. (p = 0.008, p = 0.006). Using the Q1 group as a baseline, the risk of albuminuria and CKD was significantly greater in the group Q3 (OR = 1.514, 95% CI 1.121-2.047 P = 0.05), and the same result was obtained after adjusting for covariates (OR = 2.241, 95% CI 1.245-4.034, P = 0.007). Subgroup analyses revealed a significant increase in the incidence of albuminuria and CKD in the group Q3 compared to that in the Q1 group. CONCLUSIONS:The TyG index is positively associated with albuminuria and CKD in patients with T2DM and may be a marker for predicting the occurrence of early kidney injury in patients with T2DM. Clinicians should test this indicator early to detect lesions and improve patient prognosis.

Background and Objectives Sacubitril/valsartan has shown effectiveness in reducing hospitalization compared with valsartan in HFpEF patients with heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the cost effectiveness of sacubitril/valsartan as an alternative to valsartan in Chinese patients with heart failure with HFpEF. Methods A Markov model was built to investigate the cost effectiveness of sacubitril/valsartan as an alternative to valsartan in Chinese patients with HFpEF, from the healthcare system perspective. The time horizon was a lifetime, with a cycle length of 1 month. Costs were obtained from local information or published papers, discounted at a rate of 0.05 for future costs. The transition probability and utility were based on other studies. The primary outcome of the study was the incremental cost-effectiveness ratio (ICER). Sacubitril/valsartan was considered cost effective if the ICER obtained was lower than the willingness-to-pay threshold of US dollars (US$) 12,551.5 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses, as well as scenario analysis, were performed to test robustness. Results Over a lifetime simulation, a 73-year-old Chinese patient with HFpEF could gain 6.44 QALYs (9.15 life-years) if sacubitril/valsartan plus standard treatment was administered, and 6.37 QALYs (9.07 life-years) if valsartan plus standard treatment was prescribed. The corresponding costs in both groups were US$12,471 and US$8663, respectively. The ICER was US$49,019/QALY (US$46,610/life-year), higher than the willingness-to-pay threshold. Sensitivity analyses and scenario analysis showed that our results were robust. Conclusion Adding sacubitril/valsartan to standard treatment as an alternative to valsartan for the treatment of HFpEF resulted in more effectiveness but higher costs. Sacubitril/valsartan was likely to not be cost effective in Chinese patients with HFpEF. The cost of sacubitril/valsartan needs to reduce to 34% of its current price to be cost effective in this population. Studies based on real-world data are needed to confirm our conclusions.

Dysregulation of reactive oxygen species (ROS) production and ROS-regulated pathways in cancer cells leads to abnormal accumulation of reactive oxygen species, displaying a double-edged role in cancer progression, either supporting transformation/proliferation and stimulating tumorigenesis or inducing cell death. Cancer cells can accommodate reactive oxygen species by regulating them at levels that allow the activation of pro-cancer signaling pathways without inducing cell death via modulation of the antioxidant defense system. Therefore, targeting reactive oxygen species is a promising approach for cancer treatment. Ginsenosides, their derivatives, and related drug carriers are well-positioned to modulate multiple signaling pathways by regulating oxidative stress-mediated cellular and molecular targets to induce apoptosis; regulate cell cycle arrest and autophagy, invasion, and metastasis; and enhance the sensitivity of drug-resistant cells to chemotherapeutic agents of different cancers depending on the type, level, and source of reactive oxygen species, and the type and stage of the cancer. Our review focuses on the pro- and anticancer effects of reactive oxygen species, and summarizes the mechanisms and recent advances in different ginsenosides that bring about anticancer effects by targeting reactive oxygen species, providing new ideas for designing further anticancer studies or conducting more preclinical and clinical studies.

BACKGROUND:Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology commonly associated with comorbidities such as diabetes mellitus, obesity, hypertension and renal disease. Various diseases induce systemic, chronic and low-grade inflammation; microvascular dysfunction; metabolic stress; tissue ischemia; and fibrosis, leading to HFpEF. An effective treatment for HFpEF is lacking, largely owing to its pathophysiological heterogeneity. Recent studies have revealed that microRNAs (miRNAs) play crucial roles in regulating the pathogenesis of HFpEF and its comorbidities.METHODS:This narrative review included original articles and reviews published over the past 20 years found through 'PubMed' and 'Web of Science'. The search terms included "HFpEF," "MicroRNAs," "comorbidities," "Microvascular Dysfunction (MVD)," "inflammation," "pathophysiology," "endothelial dysfunction," "energy metabolism abnormalities" "cardiac fibrosis" and "treatment."RESULTS:Inflammation, MVD, abnormal energy metabolism, myocardial hypertrophy and myocardial fibrosis are important pathophysiological mechanisms underlying HFpEF. As gene expression regulators, miRNAs may contribute to the pathophysiology of HFpEF and are expected to serve in the stratification of patients with HFpEF and as prognostic indicators for monitoring treatment responses.CONCLUSIONS:A customized strategy based on miRNAs has emerged as an effective treatment for HFpEF. In this review, we discuss recent research surrounding miRNAs and HFpEF and propose potential miRNA targets for the pathophysiology of HFpEF and its comorbidities. Although current research concerning miRNAs and their therapeutic potential is in its early stages, miRNA-based diagnostics and therapeutics hold great promise in the future.

Oxidation of low-density lipoproteins (ox-LDL) plays a critical role in endothelial dysfunction and the pathological progression of atherosclerosis by causing leukocyte attachment to endothelial surfaces. Omentin-1, an important adipokine primarily secreted by stromal vascular cells, has displayed various biological functions in diverse tissues. However, little information regarding the effects of omentin-1 on ox-LDL- induced endothelial dysfunction has been reported before. In the current study, we found that omentin-1 significantly reduced the attachment of the leukocyte THP-1 cells to human umbilical vein endothelial cells (HUVECs) in a dose dependent manner. Additionally, omentin-1 treatment prevented the expression of cell adhesion molecules such as VCAM-1 and E-selectin at both the mRNA level and the protein level. Notably, we found that omentin-1 significantly restored ox-LDL-induced reduction of KLF2, an important transcriptional factor and regulator of endothelial function. Also, omentin-1 promoted the expression of KLF2 target genes eNOS and PAI-1. Mechanistically, our results indicate that the effects of omentin-1 on KLF2 expression are mediated by p53. These results highlight the potential of omentin-1 in preventing endothelial dysfunction and atherosclerosis.