An argon atmospheric pressure plasma jet was employed to treat L929 murine fibroblasts cultured in vitro. Experimental results showed that, compared with the control cells, the treatment of fibroblasts with 15 s of plasma led to a significant increase of cell viability and collagen synthesis, while the treatment of 25 s plasma resulted in a remarkable decrease. Exploration of related mechanisms suggested that cold plasma could up-regulate CyclinD1 gene expression and down-regulate p27 gene expression at a low dose, while it could down-regulate CyclinD1 expression and up-regulate p27 expression at a higher dose, thus altering the cell cycle progression, and then affecting cell viability and collagen synthesis of fibroblasts.

Metformin, widely used for type 2 diabetes, raises concerns about its use in chronic kidney disease (CKD) due to risks like lactic acidosis and renal function impact. This study uses Mendelian randomization (MR) and summary data-based MR (SMR) to explore metformin’s potential causal relationship with CKD and associated genes. We employed MR methods (MR-Egger, weighted median, IVW) and sensitivity analyses to explore the causal relationship between metformin and CKD. SMR was used to analyze eQTL and CKD data from the UK Biobank and FinnGen, intersecting these with metformin drug targets to identify genes associated with CKD. MR analysis indicated that metformin may increase CKD risk (IVW model: OR = 144.67, p < 0.01). However, given the high OR value, additional studies are warranted to validate this finding. SMR identified genes ANPEP, STK11, ACACB, and RPS6KB as significantly associated with CKD risk. The study suggests metformin could elevate CKD risk and identifies relevant genes. Clinicians should exercise caution when prescribing metformin, particularly for patients with renal issues. Further research is needed to confirm these findings and guide clinical practices.

Mesangial proliferative glomerulonephritis (MesPGN) is a common renal disease that lacks effective drug intervention. Aconiti Lateralis Radix (Fuzi), a natural Chinese medical herb, is found with significant therapeutic effects on various diseases in the clinic. However, its effects on MesPGN have not been reported. This study is aimed to discuss the therapeutic effects of the aqueous extract of Aconiti Lateralis Radix (ALR) and the polysaccharides of Aconiti Lateralis Radix (PALR) on MesPGN as well as the underlying mechanism. In this study, we, firstly, studied the anti-MesPGN mechanism of ALR and PALR. ALR and PALR inhibit the proliferation of the mesangial cells through the PI3K/AKT/mTOR pathway, induce the G0/G1 phase of block and apoptosis, inhibit the activity of Cyclin E and CDK2, increase the expression of Bax, cleaved caspase-8/caspase-8, and cleaved caspase-3/caspase-3 proteins, and effectively inhibit the growth of the mesangial cells. Overall, our data suggest that ALR and PALR may be potential candidates for MesPGN and that PALR is more effective than ALR.

Background: Kidney transplant recipients (KTRs) are at an increased risk of osteoporosis, which negatively impacts their quality of life and transplant outcomes. However, the efficacy and safety of anti-osteoporosis treatments in this group remain uncertain. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials up to August 1, 2024. Randomized controlled trials (RCTs) examining anti-osteoporotic medications in KTRs were included. Primary outcomes were changes in bone mineral density (BMD) at femoral neck and lumbar spine, and adverse events. We performed a frequentist network meta-analysis using random-effects models. Evidence certainty was assessed using the GRADE approach. Results: Twenty-one RCTs involving 1,066 participants were included, published between 2000 and 2021. For femoral neck BMD, bisphosphonates significantly improved BMD compared to control (MD = 0.04, 95%CI=0.00-0.09, p<0.05) based on low certainty evidence, while calcitonin was significantly superior to calcium (MD=-0.14, 95%CI=-0.28 to -0.01). Most other comparisons showed no statistically significant differences based on very low to moderate certainty evidence. For lumbar spine BMD, bisphosphonates, calcitonin, and calcium demonstrated statistically significant inferiority compared to denosumab, with bisphosphonates showing MD=-4.98 (95%CI=-6.84 to -3.13), calcitonin showing MD=-4.35 (95%CI=-6.24 to -2.47), and calcium showing MD=-5.85 (95%CI=-7.72 to -3.98), while denosumab was superior to control (MD = 5.10, 95%CI=3.25-6.95), based on low to very low certainty evidence from one RCT. Calcitonin was also significantly superior to calcium (MD = 0.60, 95%CI=0.07-1.12). For safety outcomes, no statistically significant differences were observed between interventions based on low to moderate certainty evidence. Conclusion: Denosumab appears most effective for improving lumbar spine BMD in KTRs, while calcitonin shows promise for femoral neck BMD improvement. However, the low to moderate certainty of evidence necessitates individualized treatment approaches considering patient-specific factors including renal function and safety profiles. These findings suggest current guidelines emphasizing bisphosphonates as first-line therapy may require revision, though larger long-term studies with fracture endpoints are needed to confirm these results. Systematic review registration: https://www.crd.york.ac.uk/prospero/?utm_source=chatgpt.com , identifier PROSPERO CRD42024587203.

Introduction: Ulcerative colitis (UC) and diabetic kidney disease (DKD) are chronic disorders with multifaceted pathogenesis, posing significant challenges in clinical management. While substantial efforts have been made to investigate the individual causes of these diseases, the interplay between UC and DKD is not well understood. This study aims to elucidate the genetic association between UC and DKD through Mendelian randomization (MR) analysis, offering new insights into common biological pathways and potential clinical implications.Methods: We conducted a bidirectional two-sample MR study utilizing data from large-scale genome-wide association studies (GWAS) for both UC and DKD. Instrumental variables (IVs) were meticulously selected according to genome-wide significance and stringent statistical criteria, ensuring robust causal inference. Various MR methodologies, including inverse variance weighting (IVW), were employed to assess the causal relationships between UC and DKD. Sensitivity analyses were also performed to validate the robustness of our findings.Results: Our analysis revealed a significant causal relationship between genetic predisposition to UC and increased susceptibility to DKD. Specifically, individuals with a genetic susceptibility to UC exhibited a 17.3% higher risk of developing DKD. However, we found no evidence of a causal link between DKD and the risk of developing UC. Additionally, we identified shared genetic risk factors and molecular pathways linking UC and DKD, thereby highlighting potential therapeutic targets.Discussion: This study underscores the intricate genetic interplay between UC and DKD, suggesting that individuals with UC may be at an elevated risk for developing DKD. Understanding these shared genetic pathways could facilitate the development of early detection strategies and targeted interventions for individuals at risk of DKD. Ultimately, these insights could lead to improved clinical outcomes for patients suffering from both conditions.

The purpose of this study was to investigate the therapeutic effects and underlying mechanisms of Wenyang Huazhuo Formula (WYHZF) extract in diabetic kidney disease (DKD) in db/db mice. DKD mice were administered WYHZF extract by oral gavage, and glycolipid metabolism, renal function, and renal pathology were assessed. Renal histopathology was evaluated using H&E, PAS, and Masson’s trichrome staining. UPLC-QE-Orbitrap-MS, HPLC, and UV-Vis spectroscopy were employed to characterize prototype and potential blood-absorbed metabolites of WYHZF extract. Renal RNA-seq was conducted to identify differentially expressed genes and related pathways. Molecular docking and molecular dynamics simulations were used as supportive in silico analyses to assess the plausibility of interactions between representative metabolites and H2-Aa/H2-Ab1. Western blotting (WB) was performed to validate H2-Aa and H2-Ab1 regulation and to examine fibrosis-associated proteins TGF-β and α-SMA. Gut microbiota alterations were evaluated by 16S rRNA sequencing. WYHZF extract significantly improved hyperglycemia and dyslipidemia, reduced UACR, serum creatinine, and BUN, alleviated glomerular/tubular injury, and restored Nephrin and NGAL expression. Transcriptomic analysis indicated aberrant activation of MHC class II–related pathways in DKD kidneys, which was modulated after WYHZF treatment. Docking and molecular dynamics simulations suggested compatible binding modes and stable interaction patterns between several representative metabolites and H2-Aa/H2-Ab1 under simulated conditions. WB confirmed that H2-Aa and H2-Ab1 were upregulated in DKD and were reversed by WYHZF; notably, TGF-β and α-SMA were also reduced, consistent with attenuation of renal fibrotic features. In addition, WYHZF partially restored gut microbiota diversity and corrected key taxonomic imbalances. Collectively, WYHZF extract may exert multi-level benefits in DKD, accompanied by modulation of MHC class II-related molecules, reduced fibrosis-associated signals, and gut microbiota remodeling.