March6 Protects Against Acute Kidney Injury by Suppressing Renal Tubular Epithelial Cell Ferroptosis Through the Destabilization of P53 and ACSL4 Proteins DOI Creative Commons
Jie Feng, Ranran Kong, Yitian Yang

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: May 30, 2025

Acute kidney injury (AKI) progression involves significant contributions from renal tubular epithelial cell ferroptosis. Membrane associated RING finger protein 6 (March6) is implicated in modulating ferroptosis by regulating the stability of related proteins, yet its specific role and AKI remains unknown. This work seeks to clarify regulatory March6 cells involvement using ischemia-reperfusion (IRI)-induced animal models hypoxia/reoxygenation (H/R)-induced cellular models. Our results demonstrated a reduction expression tissues IRI mice H/R cells, accompanied elevated PTGS2 reduced GPX4 levels, two marker proteins. Overexpression HK-2 significantly counteracted Erastin-induced ferroptosis, whereas silencing increased susceptibility. In models, overexpression enhanced viability lowered death, reversing ferroptosis-related changes, exhibited opposite effects. Tubular-specific with IRI-induced notably mitigated damage suppressed ferroptotic changes. Mechanistically, inhibited accelerating degradation key pro-ferroptotic proteins ACSL4 p53. Co-immunoprecipitation (Co-IP) experiments validated direct interaction between p53 or ACSL4. Overexpressing March6-overexpressing markedly reversed March6's protective effects against H/R-induced Collectively, mitigates promoting p53, thereby alleviating progression. study not only uncovers novel mechanism but also provides potential therapeutic target for treatment.

Language: Английский

Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury DOI Creative Commons
Pengfei Huang, Yanqi Liu, Yue Li

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 11, 2025

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and associated high mortality. Therefore, early recognition of SA-AKI essential for administering supportive treatment preventing further damage. This study aimed to identify validate metabolite biomarkers assist clinical diagnosis. Methods Untargeted renal proteomic metabolomic analyses were performed on the tissues LPS-induced mice. Glomerular filtration rate (GFR) monitoring technology was used evaluate real-time function To elucidate distinctive characteristics SA-AKI, multi-omics Spearman correlation network constructed integrating core metabolites, proteins, function. Subsequently, metabolomics analysis explore dynamic changes metabolites serum mice at 0, 8, 24 h. Finally, cohort (28 vs. 28 sepsis) quantitative carried out build diagnostic model via logistic regression (LR). Results Thirteen differential 112 proteins identified through highlight five i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric creatine, myristic inosine, which then observed time series experiments The levels creatine increased significantly h, acid 8 while inosine decreased Ultimately, based we recruited 56 named IC3, using (AUC = 0.90). Conclusions We proposed blood consisting screening SA-AKI. Future studies will observe performance these other populations their role.

Language: Английский

Citations

3
Significance of FXR agonists in MASLD treatment: a deep dive into lipid alteration by analytical techniques DOI Creative Commons
Pirangi Srikanth, Khaja Moinuddin Shaik,

Vijay Patibandla

et al.

Published: March 25, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known non-alcoholic fatty (NAFLD), reflects deeper understanding intricate interplay between metabolic dysfunction health. At heart MASLD lies troubling accumulation triglycerides (TGs) in hepatocytes, which precipitates insulin resistance oxidative stress, ultimately leading to more severe forms like steatohepatitis (MASH). Excitingly, recent research has spotlighted farnesoid X receptor (FXR) groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation resistance, making it potential game-changer fight against MASLD. With one FDA-approved drug, resmetirom, currently available, exploration agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing power restore balance integrating advanced strategies lipidomics acid profiling, we stand on brink transforming how approach its associated complications, paving way healthier future. review delves into promising role combating implications related disorders, emphasizing urgency detect manage this burgeoning epidemic.

Language: Английский

Citations

0
Association between triglyceride glucose body mass index and 1 year all cause mortality in stage 4 CKM syndrome patients DOI Creative Commons
Wen Pan, Tengfei Ji, Bing Hu

et al.

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

Published: May 16, 2025

The triglyceride-glucose body mass index (TyG-BMI) is acknowledged as a dependable surrogate biomarker for the evaluation of insulin resistance (IR). Current research indicates significant correlation between TyG-BMI and risk subsequent cardiovascular events in individuals diagnosed with cardiovascular-kidney-metabolic syndrome (CKM) at stages 0-3. Nevertheless, prognostic significance patients CKM stage 4 has not been extensively investigated, there paucity evidence available on this topic. study utilized patient data from Medical Information Mart Intensive Care (MIMIC-IV) database, categorizing into quartiles based index. primary outcomes interest were all-cause mortality 180 days one year. To assess relationship these CKM, Cox proportional hazards model was employed. Additionally, restricted cubic splines(RCS) applied to further investigate associations specified outcomes. A total 1,885 participated study, 62.49% cohort being male. rates recorded 30.50% 35.12% Analysis using multivariate revealed that an increase significantly correlated reduction both 180-day one-year marks. Specifically, each standard deviation index, decreased by 17% within (HR = 0.83, 95% CI: 0.76-0.91) 21% year 0.79, 0.71-0.87). Furthermore, regression analysis utilizing RCS indicated linear decrease associated increasing values over periods (P nonlinearity 0.171 P 0.141, respectively). In syndrome, reduced found be heightened Consequently, may effective instrument stratification assessment population.

Language: Английский

Citations

0
March6 Protects Against Acute Kidney Injury by Suppressing Renal Tubular Epithelial Cell Ferroptosis Through the Destabilization of P53 and ACSL4 Proteins DOI Creative Commons
Jie Feng, Ranran Kong, Yitian Yang

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: May 30, 2025

Acute kidney injury (AKI) progression involves significant contributions from renal tubular epithelial cell ferroptosis. Membrane associated RING finger protein 6 (March6) is implicated in modulating ferroptosis by regulating the stability of related proteins, yet its specific role and AKI remains unknown. This work seeks to clarify regulatory March6 cells involvement using ischemia-reperfusion (IRI)-induced animal models hypoxia/reoxygenation (H/R)-induced cellular models. Our results demonstrated a reduction expression tissues IRI mice H/R cells, accompanied elevated PTGS2 reduced GPX4 levels, two marker proteins. Overexpression HK-2 significantly counteracted Erastin-induced ferroptosis, whereas silencing increased susceptibility. In models, overexpression enhanced viability lowered death, reversing ferroptosis-related changes, exhibited opposite effects. Tubular-specific with IRI-induced notably mitigated damage suppressed ferroptotic changes. Mechanistically, inhibited accelerating degradation key pro-ferroptotic proteins ACSL4 p53. Co-immunoprecipitation (Co-IP) experiments validated direct interaction between p53 or ACSL4. Overexpressing March6-overexpressing markedly reversed March6's protective effects against H/R-induced Collectively, mitigates promoting p53, thereby alleviating progression. study not only uncovers novel mechanism but also provides potential therapeutic target for treatment.

Language: Английский

Citations

0