Ageing – Oxidative stress, PTMs and disease

Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 86, P. 101099 - 101099

Published: June 8, 2022

Post-translational modifications (PTMs) have been proposed as a link between the oxidative stress-inflammation-ageing trinity, thereby affecting several hallmarks of ageing. Phosphorylation, acetylation, and ubiquitination cover >90% all reported PTMs. Several main PTMs are involved in normal "healthy" ageing different age-related diseases, for instance neurodegenerative, metabolic, cardiovascular, bone well cancer chronic kidney disease. Ultimately, data from human rare progeroid syndromes, but also long-living animal species, imply that critical regulators process. Mechanistically, target epigenetic non-epigenetic pathways during In particular, histone modification has implications process can modulate lifespan. Therefore, PTM-based therapeutics appear to be attractive pharmaceutical candidates reduce burden ageing-related diseases. phosphorylation acetylation inhibitors already FDA-approved treatment other diseases offer unique potential investigate both beneficial effects possible side-effects. As an example, most well-studied senolytic compounds dasatinib quercetin, which tested Phase 1 pilot studies, act kinase inhibitors, targeting cellular senescence increasing Future studies need carefully determine best "diseasome ageing".

Language: Английский

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Cerium–Luteolin Nanocomplexes in Managing Inflammation-Related Diseases by Antioxidant and Immunoregulation

ACS Nano, Journal Year: 2024, Volume and Issue: 18(8), P. 6229 - 6242

Published: Feb. 12, 2024

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a pivotal role in inflammation-related diseases. Excessive ROS levels can induce cellular damage impair normal physiological functions, triggering release of inflammatory mediators exacerbating response, ultimately leading to irreversible tissue damage. In this study, we synthesized cerium ion–luteolin nanocomplexes (CeLutNCs) coordinating Ce ions with natural product luteolin, aiming develop therapeutic agent excellent immunoregulation properties for ROS-related inflammation treatment. vitro experiments demonstrated that prepared CeLutNCs effectively scavenged excess ROS, prevented cell apoptosis, down-regulated important cytokines, regulated response macrophages, suppressed activation nuclear factor-κ-gene binding (NF-κB) pathway. acute kidney injury (AKI) animal model, exhibited significant efficacy improving function, repairing damaged renal tissue, reducing oxidative apoptosis. Moreover, potential lung (ALI) model was confirmed through assessment responses histopathological studies. This study emphasizes effectiveness these metal–natural coordination as promising approach preventing AKI other diseases associated stress.

Language: Английский

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Association of systemic immune-inflammation index and systemic inflammation response index with chronic kidney disease: observational study of 40,937 adults

Inflammation Research, Journal Year: 2024, Volume and Issue: 73(4), P. 655 - 667

Published: March 15, 2024

Language: Английский

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Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: evidence from NHANES (2001–2018)

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

Published: March 15, 2024

Objective To examine the correlation between SIRI and probability of cardiovascular mortality as well all-cause in individuals with chronic kidney disease. Methods A cohort 3,262 participants from US National Health Nutrition Examination Survey (NHANES) database were included study. We categorized into five groups based on stage weighted Cox regression model was applied to assess relationship mortality. Subgroup analyses, Kaplan–Meier survival curves, ROC curves conducted. Additionally, restricted cubic spline analysis employed elucidate detailed association hazard ratio (HR). Results This study a individuals, whom 1,535 male (weighted proportion: 42%), 2,216 aged 60 or above 59%). Following adjustments for covariates like age, sex, race, education, elevated remained significant independent risk factor (HR=2.50, 95%CI: 1.62-3.84, p<0.001) (HR=3.02, 2.03-4.51, CKD patients. The indicated nonlinear mortality, SIRI>1.2 identified an Conclusion Heightened independently poses both disease patients, potentially heightened significance early stages (Stage I Stage III)

Language: Английский

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Association between systemic inflammatory indicators with the survival of chronic kidney disease: a prospective study based on NHANES

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

Published: April 8, 2024

Background systemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the inflammatory indicators could be optimal predictors for survival of CKD remains less studied. Methods In this study, participants selected from datasets National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years. Four evaluated by peripheral blood tests including immune-inflammation index (SII, platelet*neutrophil/lymphocyte), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR). Kaplan-Meier curves, restricted cubic spline (RCS), Cox regression analysis used evaluate association with all-cause mortality CKD. Receiver operating characteristic (ROC) concordance (C-index) determine predictive accuracy varied indicators. Sensitive analyses conducted validate robustness main findings. Results A total 6,880 included study. The mean age was 67.03 years old. Among study population, levels 588.35 SII, 2.45 NLR, 133.85 PLR, 3.76 LMR, respectively. PLR all significantly positively associated patients, whereas high value LMR played a protectable role patients. NLR leading patients [Hazard (HR) =1.21, 95% confidence interval (CI): 1.07-1.36, p = 0.003 (3 rd quartile), HR 1.52, 95%CI: 1.35-1.72, p<0.001 (4 th quartile) 0.83, 0.75-0.92, (2 nd 0.73, 0.65-0.82, 0.74, 0.65-0.83, LMR], C-index 0.612 0.624, RCS curves showed non-linearity risk population. Conclusion Our highlights that are important predicting U.S. population would add additional clinical health care

Language: Английский

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Dapagliflozin in Chronic Kidney Disease: Insights from Network Pharmacology and Molecular Docking Simulation

Life, Journal Year: 2025, Volume and Issue: 15(3), P. 437 - 437

Published: March 11, 2025

Chronic kidney disease (CKD) involves inflammation, oxidative stress, and fibrosis, leading to renal dysfunction. Dapagliflozin, an SGLT2 inhibitor, shows renoprotective effects beyond glucose control, but its precise molecular mechanisms remain unclear. This study utilizes network pharmacology docking elucidate multi-target in CKD. Dapagliflozin’s SMILES structure was analyzed for ADMET properties. Potential targets were identified via SwissTargetPrediction, GeneCards, SEA, common CKD-related determined. A protein–protein interaction (PPI) constructed, key pathways using GO KEGG enrichment analyses. Molecular conducted validate dapagliflozin’s binding affinities with hub proteins. total of 208 identified, including EGFR, GSK3β, IL-6. analyses highlighted pathways, such as PI3K-Akt, MAPK, AGE-RAGE, involved metabolic regulation. confirmed strong EGFR (−8.42 kcal/mol), GSK3β (−7.70 IL-6 (−6.83 kcal/mol). Dapagliflozin exhibits therapeutic potential CKD by modulating pathways. integrative approach enhances the understanding mechanisms, supporting future experimental validation clinical application management.

Language: Английский

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Vitamin E (Alpha-Tocopherol) Metabolism and Nutrition in Chronic Kidney Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(5), P. 989 - 989

Published: May 18, 2022

Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function gene modulation effects. The metabolism of depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL tissue distribution together esterified cholesterol triglycerides. Chronic kidney disease (CKD) a condition oxidative stress increased peroxidation, are associated alterations function. Specific changes have been reported the levels its enzymatic metabolites, including both short-chain long-chain latter being endowed regulatory functions expression processes lipids xenobiotics detoxification, as well control immune inflammatory processes. therapy investigated CKD using oral protocols E-coated hemodialyzers, showing promising results secondary prevention cardiovascular disease, hematological complications. These therapeutic approaches reviewed present article, narrative excursus main findings indicating relative deficiency impaired E.

Language: Английский

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Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1112 - 1112

Published: June 3, 2022

The nuclear factor erythroid 2-related 2 (Nrf2) protects the cell against oxidative damage. Nrf2 system comprises a complex network that functions to ensure adequate responses redox perturbations, but also metabolic demands and cellular stresses. It must be kept within physiologic activity range. Oxidative stress alterations in Nrf2-system are central for chronic-kidney-disease (CKD) progression CKD-related morbidity. Activation of CKD is multiple ways related inflammation, kidney fibrosis, mitochondrial effects. In human CKD, both endogenous activation repression exist. state varies with cause disease, comorbidities, stage severity uremic toxin accumulation inflammation. An earlier stage, rapid inflammatory processes associated more robust activation. Advanced stronger repression. moderate kappa B (NF-κB) elevations. relates high NF-κB concentrations, may Kelch-like ECH-associated protein 1 (Keap1)-independent degradation. Furthermore, we review effects pharmacological by bardoxolone methyl, curcumin, resveratrol outline strategies how adapt future Nrf2-targeted therapies requirements patients CKD.

Language: Английский

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Cellular senescence of renal tubular epithelial cells in renal fibrosis

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 28, 2023

Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one major causes end-stage renal disease (ESRD), but pathogenesis which still unclear. tubulointerstitial lesions have been identified as a key hallmark RF pathology. tubular epithelial cells are resident tubulointerstitium play an important role in recovery versus following injury. Studies recent years shown that senescence can accelerate progression fibrosis. Oxidative stress(OS), telomere attrition DNA damage cell senescence. Current interventions therapeutic strategies for cellular include calorie restriction routine exercise, Klotho, senolytics, senostatics, other related drugs. This paper provides overview mechanisms signaling pathways including Wnt/β-catenin/RAS, Nrf2/ARE STAT-3/NF-κB pathway involved therapies targeting future potential patients. These findings may offer promise further treatment CKD.

Language: Английский

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Involvement of Inflammasome Components in Kidney Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 246 - 246

Published: Jan. 27, 2022

Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results caspase-1 and maturation cytokines interleukin-1β -18. These can elicit their effects through receptor activation, both locally within a certain tissue systemically. Animal models kidney diseases have shown inflammasome involvement inflammation, pyroptosis fibrosis. In particular, component nucleotide-binding domain-like family pyrin domain containing 3 (NLRP3) related canonical mechanisms been investigated. However, it has become increasingly clear that other components also importance disease. Moreover, is becoming obvious range molecular interaction partners wide. This review provides insights into these current areas research, special emphasis on redox signalling, endoplasmic reticulum stress, mitochondrial function. We present our findings separately for acute injury chronic As we strictly divided preclinical clinical data, this enables comparison from those complementary research specialities. reveals knowledge gaps exist, especially research. Furthermore, patient comorbidities treatments seem drivers alterations human

Language: Английский

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