Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights importance of metabolic homeostasis protecting against oxidative large intestine. By developing low-input user-friendly pipeline for simultaneous profiling five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S -nitrosylation (SNO), -glutathionylation (SSG), we shed light on redox modification stoichiometries signaling with regional resolution gut monkeys. Notably, proteins modified by SOH SSG were associated primarily cell adhesion. In contrast, SNO-modified immunity. Interestingly, observed that Sto levels ranged from 0.97% to 99.88%, exhibiting two peaks increasing age. Crosstalk analysis revealed numerous age-related metabolites potentially modulating modifications. elucidated fumarate alleviating intestinal dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed treatment promotes recovery several types, pathways, genes regulation. Calorie restriction (CR) is known strategy stress. Two-month CR intervention led many antioxidative reshaped redoxome. decodes complexities redoxomics during non-human primates identifies key signaling.

Language: Английский

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Dietary Restrictions and Cancer Prevention: State of the Art

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 503 - 503

Published: Jan. 29, 2025

Worldwide, almost 10 million cancer deaths occurred in 2022, a number that is expected to rise 16.3 by 2040. Primary prevention has long been acknowledged as crucial approach reducing incidence. In fact, between 30 and 50 percent of all tumors are known be preventable eating healthy diet, staying active, avoiding alcohol, smoking, being overweight. Accordingly, many international organizations have created tumor guidelines, which underlie the importance following diet emphasizes plant-based foods while minimizing consumption red/processed meat, sugars, processed foods, alcohol. However, further research needed define relationship effect specific diets or nutritional components on prevention. Interestingly, reductions food intake dietetic restrictions can extend lifespan yeast, nematodes, flies, rodents. Despite controversial results humans, those approaches potential ameliorate health via direct indirect effects signaling pathways involved onset. Here, we describe latest knowledge cancer-preventive dietary biochemical processes involved. Molecular, preclinical, clinical studies evaluating different fasting strategies will also reviewed.

Language: Английский

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Rehabilitation of the Elderly in Primary Healthcare

Balneo and PRM Research Journal, Journal Year: 2025, Volume and Issue: 16(Vol 16 No. 1), P. 791 - 791

Published: March 31, 2025

Rehabilitation is a fundamental pillar of universal health coverage, alongside promotion, disease prevention, treatment, and palliative care. As crucial indicator following mortality morbidity, functional optimization key outcome rehabilitation. Traditionally associated with tertiary healthcare facilities due to its complex multidimensional nature, various models have been proposed integrate rehabilitation seamlessly into primary services. The goal enhance, maintain, and, when possible, improve an individual's capacity. This review explores aspects elderly patient assessments conducted by family physicians recommend appropriate programs. Additionally, it highlights the components integrated preventive consultations for older adults suggests tailored approaches based on evaluation outcomes.Collaboration between medical specialists essential prevention treatment patients. A holistic, patient-centered approach ensures comprehensive care, promoting physical independence, mental well-being, improved quality life.

Language: Английский

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The effect of Ramadan intermittent fasting on anthropometric, hormonal, metabolic, inflammatory, and oxidative stress markers in pre-and post-menopausal women: a prospective cohort of Saudi women

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 4, 2024

The menopausal transition significantly affects cardiometabolic health, primarily due to changes in reproductive hormones, particularly decreased estrogen levels and relative androgen excess. Adult Muslim women, both pre-and post-menopausal, are mandated observe Ramadan intermittent fasting (RIF) every year. Therefore, the current study was designed investigate RIF's effects on pre-menopausal (PRE-M) post-menopausal (POST-M) healthy women's health markers. This further evaluated relationship between tested markers participant's basic variables, such as BMI body fatness. Due differences physiological metabolic biomarkers groups, RIF is likely impact PRE-M POST-M women differently.

Language: Английский

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Resveratrol and Its Derivatives Diminish Lipid Accumulation in Adipocytes In Vitro—Mechanism of Action and Structure–Activity Relationship

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3869 - 3869

Published: Nov. 13, 2024

Background and Objectives: Expansion of white adipose tissue causes systemic inflammation increased risk metabolic diseases due to its endocrine function. Resveratrol was suggested be able prevent obesity-related disorders by mimicking caloric restriction; however, structure–activity relationships molecular targets are still unknown. We aimed compare the effects resveratrol analogues on adipocyte metabolism lipid accumulation in vitro. Methods: Mouse embryonic fibroblasts were differentiated adipocytes absence or presence derivatives (oxyresveratrol, monomethylated resveratrol, trimethylated resveratrol). Intracellular content assessed Oil Red O staining. Glucose uptake response insulin estimated 2-NBDG, mitochondrial activity assayed via resazurin reduction. Involvement potential pathways investigated concurrent treatment with their inhibitors. Results: Although significantly reduced all without altering protein content, oxyresveratrol most potent (IC50 = 4.2 μM), while lowest potency observed 27.4 μM). Increased insulin-stimulated glucose restored each analogue comparable efficiency. The enhanced normalized methylated derivatives, had a minor impact it. Among examined pathways, inhibition SIRT1, PGC-1α, JNK diminished lipid-reducing effect compounds. Autophagy appeared play key role compounds but oxyresveratrol. Conclusions: can mimic restriction complex mechanisms, including activation JNK, making them possible drug candidates treat diseases.

Language: Английский

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Causal and mediating effects of lipid and facial aging: association study integrating GWAS, eQTL, mQTL, and pQTL data

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 21, 2024

Increasing evidence suggests a potential causal association between lipid levels and facial aging. The aim of this study was to investigate the relationship specific lipids aging via Mendelian randomization methods. Additionally, aimed identify mediators explore relevant genes drug targets. In study, genome-wide data on plasma from 7,174 Finnish individuals in UK Biobank were used. Two-sample applied assess effects Sensitivity pleiotropy analyses conducted ensure robustness reliability results. Multivariate account for impact confounding factors. Furthermore, summary-data-based used genes, which validated through multiomics data. Finally, drug‒gene interactions explored molecular docking techniques. analysis revealed According multivariate results, smoking found mediate association, these remained significantly associated with aging, even after accounting environmental confounders. Using randomization, CYP21A2, CCND1, PSMA4, MED1 identified as gene targets, further pQTL mQTL protein bind spontaneously astragalin, fenofibrate, ginsenoside. results revealing key targets that still controlling certain drugs may indicate pathways therapeutic interventions related

Language: Английский

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Caffeine-Induced Upregulation of pas-1 and pas-3 Enhances Intestinal Integrity by Reducing Vitellogenin in Aged Caenorhabditis elegans Model

Nutrients, Journal Year: 2024, Volume and Issue: 16(24), P. 4298 - 4298

Published: Dec. 12, 2024

Background: Intestinal aging is characterized by declining protein homeostasis via reduced proteasome activity, which are hallmarks of age-related diseases. Our previous study showed that caffeine intake improved intestinal integrity with age reducing vitellogenin (VIT, yolk protein) in C. elegans. In this study, we investigated the regulatory mechanisms improves and reduces (VIT) production aged Caenorhabditis Methods: We performed RNA-seq analysis, qRT-PCR to validate confirm results. Transgenic worms VIT-2::GFP VIT-6::GFP were used for measuring VIT production. dsRNAi was conducted elucidate roles pas-1 pas-3 genes. Results: pas-3, a elegans ortholog human PASM4, upregulated intake. They repressing unc-62, transcriptional activator vit expression. Interestingly, vit-2 required expression, RNAi promoted atrophy colonization, suggesting balancing mechanism levels health. Additionally, lifespan extended (2 ± 0.05 days), however, effect not observed but RNAi, mode action an anti-aging through distinctive. The mediated SKN-1 activation. Conclusions: Caffeine enhances health activity extends upregulating pas-3. These findings suggest consumption mitigates impairment maintains during aging.

Language: Английский

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Intermittent Fasting (IF) Reduces Tumor Metastasis via Ras/MAPK, PI3K/AKT/mTOR, Wnt/<i>&#946;</i>-Catenin, and HGF/c-Met Pathways

Open Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: 14(12), P. 1827 - 1840

Published: Jan. 1, 2024

Language: Английский

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