This study aimed to investigate the role of Mep1a in unilateral ureteral obstruction (UUO)-induced renal injury and the underlying mechanisms. A UUO model was established in Mep1a knockout (KO) mice and wild-type littermates. Primary renal tubular epithelial cells were isolated and treated with transforming growth factor-β1 (TGF-β1), and Mep1a was knocked down by small interfering RNA. Macrophages were induced with interleukin-4 (IL-4). Renal fibrosis and pathological injury were evaluated by Masson’s trichrome staining, hematoxylin-eosin (H E) staining, and Western blotting. Glycolysis was assessed by measuring extracellular acidification rate (ECAR) and lactate production. The AKT/HIF-1α pathway was examined by Western blotting, and AKT was reactivated with SC79. Mep1a was upregulated in UUO-injured kidney tissues and TGF-β1-induced renal tubular epithelial cells, but showed no significant change in IL-4-induced macrophages. Mep1a knockout mice exhibited attenuated renal fibrosis and improved renal pathological injury compared with wild-type controls after UUO. In vitro, Mep1a knockdown reduced TGF-β1-induced upregulation of Collagen I, Collagen III, α-SMA, and vimentin in renal tubular epithelial cells. Mechanistically, Mep1a deficiency suppressed glycolysis and lactate accumulation during renal injury. Mep1a deficiency also downregulated AKT phosphorylation and HIF-1α expression in TGF-β1-induced renal tubular epithelial cells, and reactivation of AKT by SC79 abolished the inhibitory effects of Mep1a deficiency on Pfkfb3, Ldha, and Pfk1 mRNA levels. Mep1a deficiency alleviates UUO-induced renal injury by inhibiting EMT via blockade of glycolysis in an HIF-1α-dependent manner.
Insulin resistance (IR) is central to cardiovascular–kidney–metabolic (CKM) syndrome, but the best IR-related marker for identifying CKM patients at high risk of diabetes remains uncertain. This study examined associations between IR-related markers and new-onset diabetes and compared their predictive performance. We analyzed 6,307 CKM participants from the China Health and Retirement Longitudinal Study (CHARLS) and 6,388 from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and restricted cubic spline analyses were used to assess associations of triglyceride-glucose (TyG), TyG-body mass index (TyG-BMI), TyG-waist-to-height ratio (TyG-WHtR), metabolic score for IR (METS-IR), and estimated glucose disposal rate (eGDR) with diabetes. Subgroup analyses and receiver operating characteristic curves were employed to evaluate robustness and discrimination. Over 7 years, diabetes developed in 736 CHARLS participants (11.67
Pulsed electromagnetic fields (PEMFs) are a noninvasive, safe, and well-tolerated physical therapy modality with established applications in musculoskeletal disorders. Their potential role in oncology has attracted increasing interest. This review synthesizes current evidence on the antitumor mechanisms and experimental effects of PEMFs across diverse cancer models. Reported biological effects include the induction of apoptosis, regulation of intracellular calcium homeostasis, inhibition of angiogenesis, modulation of immune responses, induction of oxidative stress, regulation of autophagy and cellular metabolism, and enhancement of sensitivity to radiotherapy and chemotherapy. Preclinical studies suggest that PEMFs can selectively suppress proliferation and promote cell death in malignant cells while exerting comparatively limited cytotoxicity in normal cells. Evidence has been reported in models of breast cancer, glioma, hepatocellular carcinoma, melanoma, and other malignancies. Although clinical investigations remain preliminary, studies conducted over the past two decades support a favorable safety profile and suggest potential therapeutic efficacy, particularly in combination with chemotherapy, radiotherapy, or immunotherapy. Artificial intelligence and machine learning may facilitate parameter optimization and the development of individualized treatment regimens. Ultimately, the integration of PEMFs into routine oncology practice will require well-designed, large-scale randomized controlled trials to standardize treatment protocols, define clinical indications, and establish their role in multimodal cancer care.
Clinical data on the efficacy and safety of tenofovir alafenamide fumarate (TAF) in chronic hepatitis B (CHB) patients with suboptimal response to entecavir (ETV) are limited. This study was designed to investigate the efficacy and safety of switching to TAF in CHB patients with low-level viremia (LLV). CHB patients with LLV who received ETV treatment for more than 52 weeks were divided into TAF group (n = 104) and ETV group (n = 395). Propensity score matching (PSM) was performed to adjust for baseline differences in age between the two groups. The outcomes included complete virological response (CVR) at weeks 12 and 24, normalization rates of aminotransferase (ALT) and aspartate aminotransferase (AST), and renal function and blood lipid levels. Compared with the ETV group, the TAF group had significantly higher rates of CVR at week 12 and week 24 in both the raw cohort and the PSM cohort (all P < 0.05). In the PSM cohort, the superiority of TAF over ETV in achieving CVR remained statistically significant at both time points (all P < 0.05). ALT and AST normalization rates were also significantly greater in the TAF group than in the ETV group at week 24 (all P < 0.05). No significant differences in creatinine (Cr) levels or estimated glomerular filtration rate (eGFR) were observed between week 24 and baseline in the raw cohort. No significant changes in blood lipid levels were detected in the TAF group at week 24 (all P > 0.05). Switching to TAF may be beneficial for patients with LLV after prolonged ETV therapy, as it is associated with a significantly higher rate of CVR. No lipid metabolism-related disorders were observed following the switch to TAF.
