Proteomics analysis reveals age-related proteins in the urine of chronic kidney disease patients

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 6, 2025

Chronic kidney disease (CKD) is closely linked to the aging process, making identification of protein biomarkers that reflect in specific organs and tissues crucial for a deeper understanding this phenomenon. This study aimed identify potential aging-related proteins present urine CKD patients. Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis, we identified total 1,712 samples from both healthy controls patients our discovery cohort. Among 845 overlapped, found 161 were associated with aging. By applying threshold p < 0.05 |log2 (fold change) | > 1.5, classified 114 as differentially expressed (DEPs). The analyzes conducted using Gene Ontology Kyoto Encyclopedia Genes Genomes revealed DEPs significantly enriched several clusters related In validation cohort, demonstrated exhibited lower urinary levels L-selectin (SELL), uromodulin (UMOD), epidermal growth factor (EGF). Additionally, significant negative correlation was between age EGF levels. estimated glomerular filtration rate (eGFR) showed positive SELL, UMOD, EGF, while 24-h proteinuria UMOD EGF. Furthermore, negatively correlated tubulointerstitial fibrosis, glomerulosclerosis. conclusion, emphasizes promise LC-MS/MS-based proteomics analysis identifying markers. Specifically, have been recognized promising indicators CKD.

Язык: Английский

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The redox-sensitive GSK3β is a key regulator of glomerular podocyte injury in type 2 diabetic kidney disease

Redox Biology, Год журнала: 2024, Номер 72, С. 103127 - 103127

Опубликована: Март 16, 2024

Emerging evidence suggests that GSK3β, a redox-sensitive transducer downstream of insulin signaling, acts as convergent point for myriad pathways implicated in kidney injury, repair, and regeneration. However, its role diabetic disease remains controversial. In cultured glomerular podocytes, exposure to milieu type 2 diabetes elicited prominent signs podocyte injury degeneration, marked by loss homeostatic marker proteins like synaptopodin, actin cytoskeleton disruption, oxidative stress apoptosis, stress-induced premature senescence, shown increased staining senescence-associated β-galactosidase activity, amplified formation γH2AX foci, elevated expression mediators senescence p21 p16INK4A. These degenerative changes coincided with GSK3β hyperactivity, evidenced overexpression reduced inhibitory phosphorylation were averted tideglusib, highly-selective small molecule inhibitor GSK3β. agreement, post-hoc analysis publicly-available transcriptomics dataset from patients nephropathy revealed the curated nephropathy-related gene set was enriched high group. Mechanistically, GSK3β-modulated nuclear factor Nrf2 signaling is involved podocytopathy, because knockdown reinforced antioxidant response suppressed stress, resulting an improvement senescence. Conversely, ectopic constitutively active mutant impaired augmented culminating exacerbated Moreover, IRS-1 found be cognate substrate at IRS-1S332, which negatively regulates activity. hyperactivity promoted phosphorylation, denoting desensitized signaling. Consistently, vivo db/db mice nephropathy, hyperactive associated hyperphosphorylation, Our finding likely novel therapeutic target treating injury.

Язык: Английский

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Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Biomedicines, Год журнала: 2024, Номер 12(4), С. 718 - 718

Опубликована: Март 23, 2024

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it found in the body of most people because contaminant nearly all food types and readily absorbed. The burden Cd determined principally by its intestinal absorption rate as there mechanism for elimination. Most acquired accumulates within kidney tubular cells, where levels increase through to age 50 years but decline thereafter due release into urine injured cells die. This associated progressive disease, which signified sustained estimated glomerular filtration (eGFR) albuminuria. Generally, reductions eGFR after exposure are irreversible, likely further towards failure if persists. There evidence that elimination current environmental can reverse these effects theoretical reason believe such reversal possible. review aims provide an update on urinary blood were be GFR loss albuminuria general populations. A special emphasis placed mechanisms underlying albumin excretion Cd-exposed persons, accurate measure doses-response relationships between eGFR, must normalised creatinine clearance. difficult challenge establishing realistic guidelines human health protected, discussed.

Язык: Английский

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Vitamin C and/or garlic can antagonize the toxic effects of cadmium on growth performance, hematological, and immunological parameters of growing Japanese quail

Poultry Science, Год журнала: 2024, Номер 103(3), С. 103457 - 103457

Опубликована: Янв. 11, 2024

This study used 300 one-day-old, sexless, developing chicks of Japanese quail to estimate the ability vitamin C and/or garlic antagonize venomous influence cadmium (Cd) on hematological, immunological, and performance characteristics quail. The was separated into five similar groups 60 apiece, six duplicates (10 each) were given each sub-group. control group received a basal diet without any supplements. Cd nourished with + 80 mg chloride (CdCl2)/kg diet. 3rd fed CdCl2 /kg complemented 200 Vitamin (Cd+ C)/kg 4th by 500 dried powder G)/kg 5th diet, CG)/kg Results showed that in which added together Vit garlic, there an improvement both live weight gain (1-42 days) feed consumption (1-21 & 1-42 compared alone. addition alone seems completely improve cadmium-related increase alkaline phosphatase (ALP), Aspartate aminotransferase (AST) Malondialdehyde (MDA) levels when control. Compared cadmium-polluted diets, got additives significantly reduced residue. In addition, group's serum immunoglobulin M (IgM) level decreased significantly. These data imply dietary supplementation (C) or (G) may be beneficial retrogressing drop G (IgG) IgM caused minimizing Cd's deleterious immunity.

Язык: Английский

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Fucoidan Oligosaccharide Supplementation Relieved Kidney Injury and Modulated Intestinal Homeostasis in D-Galactose-Exposed Rats

Nutrients, Год журнала: 2025, Номер 17(2), С. 325 - 325

Опубликована: Янв. 17, 2025

Background/Objectives: A fucoidan oligosaccharide (FOS), a potent compound derived from algae, is known for its diverse biological activities, including prebiotic activity, anticancer and antioxidative properties, has demonstrated supportive therapeutic effects in treating kidney ailments. This study was conducted to explore the protective influence of FOS on damage due aging induced by D-galactose Sprague Dawley (SD) rats. Methods: The low-dose group administered (100 mg/kg) gavage, high-FOS received (200 gavage. Results: findings showed that could effectively mitigate improve pathological condition tissues caused D-gal enhance function. Intervention with significantly reduced serum creatinine, uric acid, urea nitrogen levels, compared model group. mechanism D-gal-induced injury may be inhibit oxidative stress impaired mitochondrial function downregulating AMPK/ULK1 signaling pathway. also modulate expression autophagy-related proteins (Beclin-1, P62, LC3II/LC3I), thereby excessive mitophagy kidney. Furthermore, protect against preserving intestinal homeostasis. decreased lipopolysaccharide levels enhanced mucosal barrier upregulated abundances Bacteroidota, Muribaculaceae, Lactobacillus, while it Firmicutes, NK4A136_group, Lachnospiraceae_NK4A136_group. supplementation modulated gut microbiota composition, increasing beneficial bacteria reducing detrimental ones, potentially contributing improved Conclusions: safeguard renal D-gal-exposed rats inhibiting mitophagy, function, regulating

Язык: Английский

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CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets

Cells, Год журнала: 2024, Номер 13(9), С. 749 - 749

Опубликована: Апрель 25, 2024

With the increasing proportion of aging population, neurodegenerative diseases have become one major health issues in society. Neurodegenerative (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's (PD), and amyotrophic lateral (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline cognitive, emotional, motor functions patients. The process is normal physiological human life accompanied immune system, which known as immunosenescence. T-cells an important part their senescence main feature appearance senescent has been shown potentially lead chronic inflammation tissue damage, some studies indicating direct link between T-cell senescence, inflammation, neuronal damage. role these subsets different NDs still under debate. A growing body evidence suggests that people ND, there prevalence CD4

Язык: Английский

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Kidney Aging and Chronic Kidney Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6585 - 6585

Опубликована: Июнь 14, 2024

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state accelerated and premature aging. Aging have numerous common characteristic features, ranging from pathological presentation clinical manifestation underlying mechanisms. shared mechanisms the development include cellular senescence, decrease autophagy, mitochondrial dysfunction, alterations epigenetic regulation, suggesting existence potential therapeutic targets that are applicable both conditions. this review, we provide comprehensive overview characteristics between CKD, encompassing morphological changes, functional alterations, recent advancements understanding Moreover, discuss strategies for targeting senescent cells CKD.

Язык: Английский

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A Network Meta-Analysis of Different Psychological Therapies for Death Anxiety in Older Adults

OMEGA - Journal of Death and Dying, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Objective: The purpose of this research was to assess and contrast the impact psychosocial therapies on older individuals' death anxiety offer evidence-based recommendations both adults healthcare professionals. Methods: Randomized controlled trials (RCTs) were collected through a thorough search multiple databases such as PubMed, Embase, Cochrane Library, Web Science, Scopus, etc. Review Manager 5.4 employed evaluate caliber included studies, STATA (15.1) used for data analysis. Results: This study seven randomized with total 266 adults, time ranged from earliest possible date July 2024. results Network Meta-Analysis (NMA) showed that teaching components spiritual intelligence therapy significantly reduced in elderly (SUCRA: 99.6%). Conclusion: network ranking chart psychotherapeutic method, had most superior efficacy reducing elderly.

Язык: Английский

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The boundaries of normal kidney tissue for biomedical research

Current Opinion in Nephrology & Hypertension, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Purpose of review In this review, we highlight the importance understanding inherent biological variability in normal kidney, or healthy reference tissue, to establish an accurate point for biomedical research. We explore and advantages limitations various sources tissue suitable structural omics-level studies. Recent findings Several large consortia are employing omic technologies diseased kidney underscoring utilizing these Emerging approaches, such as artificial intelligence multiomic analyses, expanding our molecular heterogeneity uncovering new insights. Summary Biological at functional, structural, level is complex remains active area study. Thoughtful selection critical, providing greatest potential producing high-quality research outcomes.

Язык: Английский

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Senotherapeutic approach to age-related endocrine diseases

Advances in pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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