The Spectrum of Minimal Change Disease/Focal Segmental Glomerulosclerosis: From Pathogenesis to Proteomic Biomarker Research

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2450 - 2450

Published: March 9, 2025

Podocyte injury plays a central role in both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Pathogenic mechanisms are diverse incompletely understood, partially overlap between FSGS MCD, not reflected by kidney biopsy. In order to optimize the current variable response treatment, personalized management should rely on pathogenesis. One promising approach involves identifying biomarkers associated with specific pathogenic pathways. With advancement of technology, proteomic studies could be valuable tool improve knowledge this area define valid biomarkers, as they have other areas glomerular disease. This work attempts cover discuss main podocyte injury, followed review recent literature biomarker podocytopathies. Most these been conducted biofluids, while tissue applied podocytopathies remain limited. While we recognize importance non-invasive biofluid propose sequential for their development: proteomics first identify proteins increased expression that may reflect underlying mechanisms; subsequently, validation urine or plasma pave way diagnostic prognostic biomarker-based approach.

Language: Английский

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Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

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Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2939 - 2939

Published: March 3, 2024

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is critical target for immunotherapy. This review focuses on the regulation of PD-L1 through dynamic processes ubiquitination deubiquitination, which are crucial its stability function. Here, we explored intricate mechanisms involving various E3 ubiquitin ligases deubiquitinating enzymes (DUBs) that modulate expression cells. Specific discussed detail, highlighting their roles tagging degradation. Furthermore, discuss actions DUBs stabilize by removing chains. The interplay these not only dictates levels but also influences progression patient response to immunotherapies. therapeutic implications targeting regulatory pathways propose novel strategies enhance efficacy PD-L1/PD-1-based therapies. Our underscores complexity significant impact tumor microenvironment immunotherapy outcomes.

Language: Английский

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Quercetin‐4′‐O‐β‐D‐glucopyranoside inhibits podocyte injury by SIRT5‐mediated desuccinylation of NEK7

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2024, Volume and Issue: 51(9)

Published: July 22, 2024

Abstract Diabetic kidney disease (DKD) is a complication of diabetic mellitus. New treatments need to be developed. This study aimed investigate the effects quercetin‐4′‐O‐β‐D‐glucopyranoside (QODG) on podocyte injury. Podocytes were cultured in high glucose (HG) medium, treated with QODG, and overexpressing or knocking down SIRT5. Oxidative stress indicators assessed using corresponding kits. Pyroptosis was detected by flow cytometry western blot analysis. Succinylation modification immunoprecipitation (IP) The interaction between NEK7 NLRP3 determined co‐IP. results indicated that QODG inhibited oxidative pyroptosis podocytes induced HG. Besides, suppressed succinylation levels HG‐induced podocytes, upregulation Knockdown SIRT5 reversed pyroptosis. Moreover, NEK7. In conclusion, upregulates inhibit NEK7, impedes NLRP3, then inhibits injury under HG conditions. findings suggested has potential treat DKD explore novel underlying mechanism function.

Language: Английский

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Rapid Characterization of the Potential Active of Sinomenine in Rats by Ultra‐High‐Performance Liquid Chromatography‐Quadrupole‐Exactive Orbitrap Mass Spectrometry and Molecular Docking

Journal of Separation Science, Journal Year: 2024, Volume and Issue: 47(19)

Published: Oct. 1, 2024

Sinomenium acutum (Thunb.) Rehd. et Wils is widely used in the treatment of rheumatoid arthritis, with its alkaloid compound sinomenine (SIN) being renowned for significant anti-inflammatory properties. However, despite widespread application, vivo mechanisms and metabolic pathways SIN remain incompletely understood. This study established a rapid reliable method based on an ultra-high-performance liquid chromatography coupled Quadrupole-Exactive Orbitrap mass spectrometry molecular docking to identify characterize 69 metabolites rat plasma, urine, feces, revealing primary hydroxylation, demethylation, sulfation, glucuronidation. Molecular results revealed that phase I reactions, including dedimethylation, dehydrogenation, dihydroxylation, along their composite were pivotal influencing SIN's activity. M28, M36, M59 are potentially most active vivo. comprehensive analysis unveils pathways, offering insights into biological processes suggesting novel approach exploring drug constituents. These findings pave way further understanding mechanisms, contributing significantly development new therapeutic strategies.

Language: Английский

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