Methylglyoxal-Stimulated Mesothelial Cells Prompted Fibroblast-to-Proto-Myofibroblast Transition

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 813 - 813

Опубликована: Янв. 19, 2025

During long-term peritoneal dialysis, fibrosis (PF) often happens and results in ultrafiltration failure, which directly leads to the termination of dialysis. The accumulation extracellular matrix produced from an increasing number myofibroblasts was a hallmark characteristic PF. To date, glucose degradation products (GDPs, i.e., methylglyoxal (MGO)) that appeared during heating storage dialysate are considered be key components initiating PF, but how GDPs lead activation myofibroblast fibrotic peritoneum has not yet been fully elucidated. In this study, mesothelial cell line (MeT-5A) fibroblast (MRC-5) were used investigate transcriptomic proteomic changes unveil underlying mechanism MGO-induced Our data MGO-stimulated cells showed upregulation genes involved pro-inflammatory, apoptotic, pathways. While no phenotypic noted on fibroblasts after direct MGO, supernatant promoted change into proto-myofibroblasts, activated first stage toward myofibroblasts. conclusion, study fibroblast-to-proto-myofibroblast transition; however, additional involvement other factors or (e.g., macrophages) may needed complete transformation

Язык: Английский

---

Relationship between glucose to lymphocyte ratio and the first peritonitis episode in patients treated with peritoneal dialysis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 26, 2025

This study aimed to investigate the potential relationship between baseline glucose lymphocyte ratio (GLR) levels and first episode of peritonitis in patients treated with peritoneal dialysis (PD). A total 314 PD were included divided into three groups based on GLR tertiles: tertile 1 (GLR ≤ 4.23); 2 (4.23 < 5.96), 3 > 5.96). The relationships analyzed using Kaplan–Meier curves multivariable Cox regression models. Competitive risk analysis, subgroup sensitivity analyses performed validate robustness findings. During a median follow-up 27 months, 123 (39.17%) developed peritonitis. incidence increased higher tertiles (tertile 1: 32.08%, 2: 37.50%, 3: 48.08%). revealed significant differences cumulative among (Log-Rank test, P = 0.018). After full adjustment for confounding factors, remained at significantly compared those (HR 2.633, 95% CI 1.223–5.668, 0.013). models analysis further confirmed this association. Our suggests that elevated is associated an PD.

Язык: Английский

---

Metabolic reprogramming of peritoneal mesothelial cells in peritoneal dialysis–associated fibrosis: therapeutic targets and strategies

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 27, 2025

Peritoneal dialysis (PD) is considered a life-saving treatment for end-stage renal disease. However, prolonged PD use can lead to the development of peritoneal fibrosis (PF), diminishing its efficacy. mesothelial cells (PMCs) are key initiators PF when they become damaged. Exposure high glucose‑based fluids (PDFs) contributes by directly affecting highly metabolically active PMCs. Recent research indicates that PMCs undergo metabolic reprogramming exposed high-glucose PDFs, including enhanced glycolysis, impaired oxidative phosphorylation, abnormal lipid metabolism, and mitochondrial dysfunction. Although this transition temporarily compensates cellular damage maintains energy levels, long-term impact on tissue concerning. Multiple studies have identified close association between shift in metabolism PF, may promote progression through various molecular mechanisms. This review explores recent findings regarding role mechanism PMC progression. Moreover, it provides summary potential therapeutic strategies aimed at processes, glucose function. The establishes targeting be novel strategy preventing treating PD-associated fibrosis. Overview associated with implications. Under physiological conditions, primarily produce ATP OXPHOS FAO maintain functions. High-glucose PDFs induce PMCs, characterized increased polyol pathway, PPP, inhibited OXPHOS, FAO, exocytosis deposition, These changes multiple pathways. Potential target absorption, restoration, fatty acid oxidation; phosphorylation; PD, dialysis, PDF, fluid; PMC, cell; pentose phosphate pathway.

Язык: Английский

---

Shenbing Decoction III and Apigenin Improve Peritoneal Fibrosis Mediated by Epithelial–Mesenchymal Transition Through TAK1/p38MAPK/NF‐κB Pathways

Journal of Food Biochemistry, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Background: This study aimed to evaluate the effect of Shenbing Decoction III (SBD III) and its key Apigenin on peritoneal dialysis (PD)–induced fibrosis explore underlying mechanisms. Methods: Liquid chromatography–mass spectrometry confirmed presence in SBD III. Human mesothelial cells (HMrSV5) were stimulated with PD solution (PDS) induce fibrosis, treatment was administered. Results: PDS decreased cell viability increased migration invasion capabilities HMrSV5 cells. It also reduced E‐cadherin expression, while increasing expression α‐SMA, fibronectin, collagen I, TGF‐β1. effectively counteracted these effects. Additionally, inhibited PDS‐induced upregulation phosphorylation transforming growth factor‐β‐activated kinase 1 (TAK1), p38, nuclear factor‐κB (NF‐κB), similar effects 5z‐7‐oxozeaenol. Chronic kidney disease (CKD) induced mice by 5/6 nephrectomy, followed treatment. The therapeutic evaluated. CKD exhibited body weight indices, along elevated blood urea nitrogen, urinary creatinine, protein levels. Fibrosis observed kidneys peritoneum. significantly alleviated Notably, further augmented when Conclusion: ameliorated inhibiting epithelial–mesenchymal transition via TAK1/p38MAPK/NF‐κB pathway, indicating promising pharmaceutical candidates for CKD.

Язык: Английский

---

The Versatility of Biological Field-Effect Transistor-Based Biosensors (BioFETs) in Point-of-Care Diagnostics: Applications and Future Directions for Peritoneal Dialysis Monitoring

Biosensors, Год журнала: 2025, Номер 15(3), С. 193 - 193

Опубликована: Март 18, 2025

Peritoneal dialysis (PD) is a vital treatment for end-stage renal disease patients, but its efficacy often compromised by complications such as infections and peritoneal fibrosis. Biological field-effect transistors (BioFETs) present promising solution rapid, sensitive, non-invasive detection of indicators biomarkers associated with these complications, potentially enabling early intervention. However, BioFETs are yet to be adopted PD monitoring. This review presents forward-looking analysis the capacity potential integration into management systems, highlighting their monitor both routine efficiency metabolic status, well specific inflammation We examine challenges in adapting applications, focusing on key areas improvement, including sensitivity, specificity, stability, reusability, clinical integration. Furthermore, we discuss various approaches address challenges, which crucial developing point-of-care (PoC) multiplexed wearable devices. These advancements could facilitate continuous, precise, user-friendly monitoring, revolutionizing complication enhancing patient care.

Язык: Английский

---

Text mining for case report articles on “peritoneal dialysis” from PubMed database

Therapeutic Apheresis and Dialysis, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

The number of published medical articles on peritoneal dialysis (PD) has been increasing, and efficiently selecting information from numerous can be difficult. In this study, we examined whether artificial intelligence (AI) text mining a good support for collecting PD information. We performed analyzed all the abstracts case reports in PubMed database. total, 3137 with related to "peritoneal dialysis" 1970 2021 were identified. A total 280 347 relevant words extracted abstracts. Word frequency analysis, word dependency transition analysis showed that peritonitis, encapsulating sclerosis, child have important keywords. Theseanalyses not only reflected historical background but also anticipated future trends study. These suggest

Язык: Английский

---

Type 2 diabetes as a risk factor for promoting hypertrophic scar formation after wound healing: a two-sample mendelian randomization study

Archives of Dermatological Research, Год журнала: 2025, Номер 317(1)

Опубликована: Апрель 1, 2025

Individuals with type 2 diabetes mellitus (T2DM) not only face the risk of difficult wound healing after trauma or surgery but also struggle scar formation healing. However, relationship between T2DM and hypertrophic scars (HS) remains unclear. First, data sets related to HS were downloaded from OpenGWAS database. Second, inverse variance-weighted (IVW) technique was employed assess causal impact on utilizing mendelian randomization (MR). Finally, sensitivity analyses reverse MR performed determine robustness findings examine potential for causation. A positive observed. Three suitable datasets analysis obtained using ids ebi-a-GCST006867, ebi-a-GCST007515, ebi-a-GCST007516 (A total 206,572 cases 753,191 controls included). The (finn-b-L12_HYPETROPHICSCAR) dataset comprised 766 207,482 controls. IVW model results showed odds ratio (OR) 1.213 (95% confidence interval (CI): 1.04-1.41, p = 0.0137), 1.300 CI: 1.05-1.61, 0.017), 1.284 1.03-1.60, 0.0276), respectively. stable without any significant bias causality. This study systematically explored first time, provided a quantitative effect assessment. consistency, which indicated biological mechanism clinical intervention direction.

Язык: Английский

---

A Novel Inhibitor of Methyltransferase SMYD2, AZ505 Protects Against Peritoneal Fibrosis in Mice

Clinical and Experimental Pharmacology and Physiology, Год журнала: 2025, Номер 52(7)

Опубликована: Май 25, 2025

ABSTRACT AZ505, a highly selective inhibitor of SMYD2, exhibits an antifibrotic effect in renal fibrosis. Its on peritoneal fibrosis remains unexplored. In this study, we investigated its effects the development induced by chlorhexidine gluconate (CG) murine model. We found that SMYD2 and trimethylated histone substrate H3K36 (H3K36me3) were expressed tissue following CG injection, administration AZ505 remarkably inhibited their expression, along with attenuating CG–induced expression collagen I fibronectin. Moreover, also significantly reduced CD31 (marker angiogenesis) CD68‐positive macrophage infiltration CG‐injured peritoneum. further CG‐induced epithelial‐to‐mesenchymal transition (EMT) mesothelial cells, manifested decreasing α‐smooth muscle antigen (α‐SMA) Vimentin restoring E‐cadherin accompanied suppressing two transcription factors, Snail Twist. Finally, phosphorylation AKT increased phosphatase tensin (PTEN), key phosphatase. These data suggest may protect against inhibiting EMT, inflammation angiogenesis, due to blockade methylation modification catalysed SMYD2.

Язык: Английский

---

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis

Peritoneal Dialysis International, Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity metabolic alterations. Indeed, almost all fluids exploit glucose as an osmotic agent that rapidly diffuses across the membrane, potentially resulting in abnormalities such hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than itself, induce significant morphological functional changes peritoneum leading ultrafiltration failure. The partial substitution of with agents characterized a better local systemic biocompatibility has been suggested potential strategy innovate fluids. approach aims minimize glucose-associated toxicity, preserving welfare counteracting common comorbidities. In this work, we report clinical trial design ELIXIR, phase III randomized, controlled, blinded outcome assessment study comparing Xylocore

Язык: Английский

---

Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes

Biomedicines, Год журнала: 2024, Номер 12(10), С. 2377 - 2377

Опубликована: Окт. 17, 2024

Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy due to insufficient evidence its benefits on mortality. However, the impact dyslipidemia PD may extend beyond concerns, influencing PD-related outcomes such as ultrafiltration rate, residual kidney function, technique survival, overall This review challenges traditional perspective by discussing dyslipidemia’s potential role complications, which account for observed link between increased all-cause mortality patients. It explores pathophysiology PD, molecular mechanisms linking membrane dysfunction, summarizes clinical supporting this hypothesis. In addition, paper examines therapeutic strategies manage improve function patient outcomes. The calls future research investigate contributor dysfunction develop targeted interventions

Язык: Английский

---