Purpose:This study aimed to investigate the protective effects and underlying mechanisms of Yiqi Huoxue Yangyin Decoction (YHY), a multi-herb formula composed of Astragalus membranaceus, Ligusticum chuanxiong, Pueraria lobata, Rehmannia glutinosa, and Trichosanthes kirilowii, against diabetic nephropathy (DN), focusing on its role in modulating autophagy and attenuating podocyte senescence via the AMPK/mTOR signaling pathway. Materials and Methods:Using network pharmacology and UPLC-Q-TOF-MS, this study examined the active constituents and targets of YHY. The type 2 diabetes db/db mouse model (leptin receptor-deficient BKS.Cg-Lepr/+ mice, random blood glucose ≥ 16.7 mmol/L) was used to construct a DN model in vivo. Mice received daily oral gavage of YHY or vehicle for 4 weeks (n=10). YHY's protective benefits were assessed by physiological measurements, serum insulin and HbA1c by ELISA, histopathological evaluation of glomerular and tubular regions, glomerular basement membrane thickness by TEM, and protein expression in renal cortex by immunohistochemistry, immunofluorescence, and Western blot. In vitro, using a high-glucose-induced MPC-5 model, CCK-8, wound healing assays, qRT-PCR, and Western blot were performed (n=3-6) to investigate the mechanisms of YHY. Results:YHY demonstrated significant protective effects against DN. The expression levels of autophagy markers (ULK1, P62, and LC3B) in renal tissue were restored following YHY intervention. Through the AMPK/mTOR pathway, YHY regulated the expression of autophagy-related genes (ULK1, Beclin-1, P62, LC3B, ATG5, ATG7) and senescence-related genes (P21, P53), and improved the survival and migratory capabilities of high-glucose-induced MPC-5 cells. Furthermore, YHY enhanced the expression of podocyte structural proteins, including Nephrin, NPHS2, and SYNPO. Conclusion:YHY treatment was associated with activation of autophagy and attenuation of podocyte senescence, potentially through modulation of the AMPK/mTOR signaling pathway, a finding that requires validation in future mechanistic studies.
Background:Lipoprotein(a) [Lp(a)] is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Although both obesity and elevated Lp(a) are highly prevalent, their interrelationship and combined impact on ischemic heart disease (IHD) remain incompletely understood, particularly in Latin American populations. Objective:To evaluate the distribution of elevated Lp(a) across body mass index (BMI) categories, assess its association with ischemic heart disease (IHD), and determine whether this association differs across BMI categories. Methods:We conducted a multicenter observational study including 2975 adults from specialized centers in Argentina. Patients were stratified into BMI categories: Group 1: <25, Group 2 BMI: 25-29.9, Group 3: 30-34.9 kg/m2, with exploratory subgroups ≥35 and ≥40 kg/m2. Elevated Lp(a) was defined as >50 mg/dL or >125 nmol/L. Results:Median Lp(a) levels decreased across higher BMI categories. The prevalence of elevated Lp(a) declined across increasing BMI categories (34.6% in BMI <25 kg/m2, 29.8% in BMI 25-29.9, 30.1% in BMI ≥30, 26.4% in BMI ≥35 and 24.6% in BMI ≥40). However, after adjustment for demographic and cardiometabolic factors, overweight and obesity were associated with higher odds of elevated Lp(a) compared with normal weight (BMI 25-29.9: OR 1.97, 95% CI 1.38-2.82; BMI ≥30: OR 1.85, 95% CI 1.22-2.81) suggesting that crude prevalence estimates and adjusted associations were influenced by differences in baseline risk profiles across BMI categories. Elevated Lp(a) was independently associated with IHD across all BMI categories, without significant interaction between BMI and Lp(a). Conclusions:In this cross-sectional study, elevated Lp(a) was associated with prevalent ischemic heart disease across BMI categories despite lower crude prevalence among individuals with higher BMI. Because of the observational cross-sectional design, causal inferences cannot be made. Nevertheless, these findings support consideration of Lp(a) assessment across the BMI spectrum.
Background:Diabetic retinopathy (DR), a leading cause of blindness, is driven by redox imbalance and ferroptosis in retinal endothelial cells. While 6-Gingerol exhibits antioxidant properties, its role in modulating exosome-mediated redox signaling in DR remains unexplored. This study investigates whether 6-Gingerol protects against DR by regulating ferroptosis via the exosomal miR-148b-3p/ACSL4 axis. Methods:Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) ± 6-Gingerol. Ferroptosis was assessed via lipid ROS, intracellular iron, and key markers (GPX4, ACSL4, FTH1). Exosomal miRNAs were profiled by sequencing, with miR-148b-3p validated as a regulator of ACSL4 through luciferase assays. Functional rescue experiments confirmed pathway specificity. Results:6-Gingerol suppressed HG-induced ferroptosis, reducing lipid ROS by 2.1-fold (P<0.01) and iron accumulation by 1.8-fold (P<0.05), while upregulating GPX4 (3.2-fold, P<0.001). Exosomal miR-148b-3p was downregulated under HG but restored by 6-Gingerol (4.5-fold, P<0.001). miR-148b-3p directly targeted ACSL4, whose knockdown mimicked 6-Gingerol's effects, whereas ACSL4 overexpression or miR-148b-3p inhibition abolished protection. Conclusions:6-Gingerol mitigates DR progression by inhibiting ferroptosis through exosomal miR-148b-3p/ACSL4-dependent redox regulation. These findings unveil a novel crosstalk between exosomal miRNAs and iron metabolism, positioning 6-Gingerol as a potential redox-targeted therapy for DR. Nonetheless, as the data are exclusively obtained from an in vitro model, in vivo validation is essential prior to making any translational inferences.
Objective:To translate and psychometrically validate the Persian version of the Instrument for Self-care in Preventing Diabetic Foot (P-ISPDF) as a reliable, culturally appropriate tool for assessing foot-specific self-care behaviors among Persian-speaking adults, predominantly those with type 2 diabetes mellitus. Methods:The ISPDF was translated using a forward-backward procedure, followed by expert review (n=5) and cognitive debriefing with patients (n=10). A split-sample design was used: exploratory factor analysis (EFA; n=289) and a series of confirmatory factor analyses (CFAs), including first-order, second-order, and a hierarchical general-factor model in an independent sample (n=250). Items were rated on a 5-point Likert scale (1-5). Reliability (Cronbach's alpha, McDonald's omega, intraclass correlation coefficient [ICC]) and validity (EFA, CFA) were evaluated using SPSS 25, AMOS 24, and JASP. Results:EFA supported a three-factor structure: self-care maintenance (10 items), monitoring (9 items), and management (7 items). The hierarchical measurement model showed good fit (χ 2/df=2.80, CFI=0.974, TLI=0.954, RMSEA=0.060). Cronbach's alpha was 0.93 for the total scale, with subscale alphas ranging from 0.81 to 0.92. Test-retest reliability was excellent (two-way mixed-effects, absolute agreement ICCs 0.93-0.98 with 95% CIs reported). Conclusion:The P-ISPDF demonstrated strong reliability and preliminary structural validity. However, due to mixed evidence regarding convergent validity and the absence of external validation, the findings should be interpreted with caution. Further psychometric refinement and longitudinal studies are needed to establish its clinical utility.
Studies suggest that alterations of intestinal barrier function and a subsequent increased translocation of bacterial endotoxins may be critical in type 1 diabetes mellitus (T1DM) and may contribute to the proinflammatory state of patients. If Gram-positive derived bacterial toxins are also altered in the setting of T1DM is not yet clarified. In the present study, using a SEAP reporter assay and ELISA, markers of intestinal permeability, concentration of Toll like receptor (TLR) 2 ligands and soluble CD14 (sCD14) were assessed in serum of individuals with T1DM (n=19, m: 10/ f: 9) and age-matched healthy controls (n=18, m: 3/ f: 15) from the LatDiane study. BMI and HbA1c were significantly higher in individuals with T1DM. Serum concentrations of intestinal fatty acid binding protein (I-FABP) were significantly higher in individuals with T1DM than in controls as were concentrations of TLR2 ligands and sCD14 protein. A multivariable linear regression analysis revealed an independent association of T1DM with higher TLR2 ligand levels. Our findings indicate that not only bacterial endotoxin but also TLR2 ligands are elevated in patients with T1DM.
