This study aims to investigate the molecular mechanism of Adenovirus type 36 (Ad36) in adipocyte differentiation and glucolipid metabolism. Rat obesity model was established by Ad36 infection and high-fat diet, respectively. Comparison of the body weight, clinical biochemical indicators, insulin sensitivity and lipid heterotopic deposition between these two models was performed. Ad36-induced adipocyte in vitro model was also established. The binding rate of FoxO1, PPARγ and its target gene promoter was detected using ChIP. The mRNA and protein expression levels of PPARγ and downstream target genes were detected by RT-PCR and Western blot, respectively. Oil red O staining was used to measure differentiation into adipocyte. Wortmannin (WM), inhibitor of PI3K, was used to act on Ad36-induced hADSCs. Ad36-induced obese rats did not exhibit disorders in blood glucose and blood TG, insulin resistance and lipid ectopic deposition. The expression of Adipoq, Lpin1 and Glut4 in the adipose tissue increased. Oil red O staining showed that Ad36 induced the differentiation of hAMSCs into human adipocytes in vitro. During this process, the binding rate of FoxO1 and PPARγ promoter regions was weakened. However, the binding rate of the transcription factor PPARγ to its target genes Acc, Adipoq, Lpin1 and Glut4 was enhanced, and thus increased the protein expression of P-FoxO1, PPARγ2, ACC, LPIN1, GLUT4 and ADIPOQ. The PI3K inhibitor Wortmannin reduced the expression of P-Akt, P-FoxO1 and PPARγ2, thereby inhibiting adipogenesis of hADSC. Ad36 may promote fatty acid and triglyceride synthesis, and improve insulin sensitivity by affecting the PI3K/Akt/FoxO1/PPARγ signaling pathway.

Fibrosis is the final common pathway leading to end-stage chronic kidney disease (CKD). However, the function of protein palmitoylation in renal fibrosis and the underlying mechanisms remain unclear. In this study, we observed that expression of the palmitoyltransferase ZDHHC18 was significantly elevated in unilateral ureteral obstruction (UUO) and folic acid–induced (FA-induced) renal fibrosis mouse models and was significantly upregulated in fibrotic kidneys of patients with CKD. Functionally, tubule-specific deletion of ZDHHC18 attenuated tubular epithelial cells’ partial epithelial-mesenchymal transition (EMT) and then reduced the production of profibrotic cytokines and alleviated tubulointerstitial fibrosis. In contrast, ZDHHC18 overexpression exacerbated progressive renal fibrosis. Mechanistically, ZDHHC18 catalyzed the palmitoylation of HRAS, which was pivotal for its translocation to the plasma membrane and subsequent activation. HRAS palmitoylation promoted downstream phosphorylation of MEK/ERK and further activated Ras-responsive element–binding protein 1 (RREB1), enhancing SMAD binding to the Snai1 cis -regulatory regions. Taken together, our findings suggest that ZDHHC18 plays a crucial role in renal fibrogenesis and represents a potential therapeutic target for combating kidney fibrosis.

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, affects 30– 40% of patients and is the leading cause of end-stage renal disease. The Wnt/β-catenin signaling pathway plays a dual role in DKD pathogenesis: its moderate activation protects against hyperglycemia-induced mesangial apoptosis, while chronic overactivation exacerbates renal fibrosis, podocyte injury, and tubular dysfunction. This review synthesizes current evidence on the pathway’s context-dependent mechanisms. Emerging therapeutic strategies—including small-molecule inhibitors (eg, Dickkopf-1), monoclonal antibodies, and natural compounds like curcumin and Salvia miltiorrhiza extracts—show preclinical promise in modulating Wnt/β-catenin activity. However, clinical translation faces challenges such as pathway redundancy, off-target effects, and the need for precise dosing to balance protective and injurious outcomes. Recent advances in biomarker discovery (eg, urinary β-catenin) and ongoing clinical trials highlight the pathway’s potential as a therapeutic target. Future research must prioritize patient stratification, combination therapies (eg, Wnt inhibitors + RAAS blockers), and mechanistic studies to address unresolved controversies in Wnt signaling dynamics. This work underscores the therapeutic implications of targeting Wnt/β-catenin in DKD while advocating for a nuanced approach to harness its protective roles.

Background: Diabetes mellitus is a prevalent chronic disease that is becoming increasingly common worldwide and can lead to a number of dangerous complications. The Wnt signaling pathway is important for the onset and progression of diabetes. Wnt3a is a typical Wnt ligand that can increase the stability of β-catenin, control TCF7L2 expression, promote β-cell proliferation, and reduce apoptosis. Summary: The involvement of the Wnt3a/β-catenin/TCF7L2 signaling pathway in the development of diabetes and associated problems related to the kidneys is reviewed in this article. Key message: We believe that a thorough comprehension of the molecular connections between diabetes and signaling pathways will eventually lead to improved diabetes management.

Background Acarbose and repaglinide are widely used either by themselves or in combination with other medications. However, their efficacy in diabetes control has not been compared when used in combination with metformin. Methods The present study aimed to compare their effects on glycemic variability (GV) control when taken with metformin for type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. In this retrospective cohort study, T2DM patients who were treated with either acarbose-metformin or repaglinide-metformin combination were recruited. Either acarbose 100 mg or repaglinide 2 mg triple daily was taken for the subsequent 12 weeks in combination with metformin. Demographic data, biochemical data and 7-point glycemic self-monitoring conducted with capillary blood (SMBG) data were reviewed after one week and 12 weeks. The primary outcome including glucose control and changes in GV as well as other factors affecting GV and the incidence of hypoglycemia were also analyzed. Results Of the 305 T2DM patients enrolled, data from 273 subjects, 136 in the acarbose-metformin group (M+A) and 137 in the repaglinide-metformin group (M+R) were analyzed. Both regimens improved glycemic control at 12 weeks post commencement of new medications. GV, expressed as the mean amplitude of plasma glycemic excursions (MAGE, 5.0 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.1 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R), standard deviation of blood glucose (SDBG, 3.6 ± 1.3 vs. 2.0 ± 0.9 mmol/L, p < 0.001 in M+A; 3.7 ± 1.3 vs. 2.4 ± 1.3 p < 0.001 in M+R), coefficient of variation of blood glucose (CVBG, (0.30 ± 0.09 vs. 0.21 ± 0.1, p < 0.001 in M+A; 0.31 ± 0.09 vs. 0.24 ± 0.12, p < 0.001 in M+R), postprandial amplitude of glycemic excursions (PPGE, 5.2 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.3 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R) or largest amplitude of glycemic excursions (LAGE, 9.8 ± 3.6 vs. 5.4 ± 2.4 mmol/L, p < 0.001 in M+A; 10.1 ± 3.4 vs. 6.3 ± 3.2 mmol/L, p < 0.001 in M+R) decreased significantly after the addition of acarbose or repaglinide (p < 0.05 respectively). Compared with repaglinide-metformin, acarbose-metformin was more effective in GV control at 12 weeks post commencement of new medications (p < 0.05). This study indicates that both acarbose-metformin and repaglinide-metformin combinations could effectively reduce GV and the acarbose-metformin combination seems to be more effective than the repaglinide-metformin combination. However, this conclusion should be confirmed by future large-scaled and more comprehensive studies due to the limitations of the present study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent in Xinjiang, with genetic factors influencing its pathogenesis. Keratin 23 (KRT23), a liver-enriched protein linked to metabolic regulation, remains understudied in MAFLD genetics. Objective: To investigate associations between KRT23 gene polymorphisms, expression, and MAFLD in Xinjiang. Methods: This study enrolled 1,795 MAFLD patients diagnosed via ultrasonography and metabolic criteria. KRT23 polymorphisms (rs72826004, rs2269859) were analyzed. GEO database screening identified MAFLD-related genes. KRT23 expression was assessed in human serum/liver tissues (ELISA, Western blot, qRT‒PCR, IHC) and murine models (high-fat diet-induced MAFLD and db/db mice). Results: Enrichment analysis identified 10 key MAFLD-associated genes, including KRT23. The rs72826004 TT genotype increased MAFLD risk (OR: 2.156, P=0.007), while rs2269859 TT conferred protection (OR: 0.306, P=0.002). MAFLD patients exhibited elevated KRT23 protein/mRNA levels in serum and liver versus controls. Murine models confirmed higher KRT23 expression in MAFLD and db/db mice compared to wild-type. Conclusion: KRT23 gene polymorphism was associated with the occurrence of MAFLD. The rs72826004 loci TT genotype may be a risk factor for MAFLD, whereas the rs2269859 loci TT genotype may be a protective factor against MAFLD. Higher KRT23 expression (protein and mRNA) is related to MAFLD. KRT23 is a potential target for the treatment of MAFLD.