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

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 813 - 813

Published: Jan. 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

Language: Английский

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

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 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.

Language: Английский

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

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 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.

Language: Английский

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

Journal of Food Biochemistry, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 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.

Language: Английский

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

Biosensors, Journal Year: 2025, Volume and Issue: 15(3), P. 193 - 193

Published: March 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.

Language: Английский

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

Therapeutic Apheresis and Dialysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 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

Language: Английский

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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, Journal Year: 2025, Volume and Issue: 317(1)

Published: April 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.

Language: Английский

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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, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 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

Language: Английский

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Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116905 - 116905

Published: June 12, 2024

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating sclerosis. Although mechanisms fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors proven be anti-fibrosis rodent models. To assess potential effects on larger animal model, novel porcine model induced by 40 mM methylglyoxal 2.5 % dialysate was established, two different doses (20 mg/kg 30 mg/kg) sorafenib were given orally evaluate their efficacy this study. Our results showed that effectively reduced adhesions between organs significantly diminished thickening both parietal visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, decreased glycocalyx resulting from stimulations also alleviated with sorafenib. However, ameliorating loss mesothelial cells, restoring volume, improving elevated small solutes transport rates limited. In conclusion, study demonstrated could potentially used for treatment, but applying alone might not sufficient fully rescue methylglyoxal-induced defects.

Language: Английский

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Peritoneal fibrosis: from pathophysiological mechanism to medicine

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

Peritoneal dialysis (PD) is currently one of the effective methods for treating end-stage renal disease (ESRD). However, long-term exposure to high concentration glucose in peritoneal environment could lead fibrosis (PF), impaired filtration function, decreased efficiency, and even withdrawal from patients. Considerable evidence suggests that after related crucial factors such as mesothelial-to-mesenchymal transition (MMT), inflammatory response, angiogenesis, etc. In our review, we summarize pathophysiological mechanisms further illustrate future strategies against PF.

Language: Английский

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