Mitochondrial Calcium Homeostasis and Atrial Fibrillation: Mechanisms and Therapeutic Strategies Review

Current Problems in Cardiology, Journal Year: 2025, Volume and Issue: 50(3), P. 102988 - 102988

Published: Jan. 17, 2025

Language: Английский

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L-Arginine and Nitric Oxide in Vascular Regulation—Experimental Findings in the Context of Blood Donation

Nutrients, Journal Year: 2025, Volume and Issue: 17(4), P. 665 - 665

Published: Feb. 13, 2025

This narrative review provides an analysis of the role nitric oxide (NO) and its precursors, particularly L-arginine, in vascular regulation health, with emphasis on findings from our experimental research animal models. NO serves as a critical mediator function, contributing to vasodilation, blood flow, prevention thrombosis. As primary precursor NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial reducing oxidative damage. synthesises data contextualises these within physiological challenges faced by donors, such repeated donation associated stress. It examines effects supplementation respiration, lipid peroxidation, microsomal oxidation different conditions, including differences age, gender, dietary interventions. The mechanisms which enhances production, improves elasticity, alleviates dysfunction caused reduced bioavailability are also investigated. By integrating insights existing literature, this perspective potential address specific needs donors. highlights importance personalised nutritional approaches enhancing donor recovery resilience. In addition, assesses wider implications mitigating stress preserving function. interplay between bioavailability, factors, adaptation donors highlighted, along identification current knowledge gaps recommendations future research. presenting both original evidence synthesis article therapeutic promoting health context donation.

Language: Английский

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In ovo feeding of α-ketoglutaric acid improves hepatic antioxidant-gene expression, plasma antioxidant activities and decreases body temperature without affecting broiler body weight under cyclic heat stress

Poultry Science, Journal Year: 2024, Volume and Issue: 103(6), P. 103749 - 103749

Published: April 9, 2024

The broiler industry is adversely affected by the rise in global temperature. This study investigated effects of ovo feeding α-ketoglutaric acid (AKG) on growth performance, organ weight, plasma metabolite, oxidative stress, rectal temperature (RT), and hepatic mRNA expression antioxidant-related genes Arbor Acres broilers subjected to cyclic heat stress (HS). Three hundred fifty fertile eggs during incubation were divided into five groups according AKG concentrations conditions. After dissolving distilled water at 0%, 0.5%, 1.0%, 1.5%, 0% was administered two whereas remaining three received respectively. From days 29 34 age, 4 birds (HS) 31°C ± 1°C for 6 h per day while other group kept room (21 1°C; NT). So, treatment were: (i) 0AKG-NT, where chicks hatched from receiving reared under thermoneutral (ii) 0AKG-HS, HS (iii) 0.5% (iv) 1.0% (v) 1.5% significantly reduced body weight change (ΔBW %) average daily gain (ADG) without affecting feed intake (ADFI). Feed conversion ratio (FCR) increased (p = 0.003) all HS-treated groups. A significant linear decrease final RT 0.005) a detected with increasing concentration. Total antioxidant capacity 0.029) balance 0.001) linearly concentration malondialdehyde decreased 0.001). Hepatic gene CAT 0.026) GPX1 dose-dependently upregulated nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, HSP70 downregulated < 0.05). Hence, injection effective mitigating HS-induced attenuating adverse growth.

Language: Английский

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Recent Issues in the Development and Application of Targeted Therapies with Respect to Individual Animal Variability

Animals, Journal Year: 2025, Volume and Issue: 15(3), P. 444 - 444

Published: Feb. 6, 2025

This literature review explores the impact of molecular, genetic, and environmental factors on efficacy targeted therapies in veterinary medicine. Relevant studies were identified through systematic searches PubMed, Web Science, Scopus, ScienceDirect using keywords such as “species-specific treatment strategies”, “signalling pathways”, “epigenetic paragenetic influences”, “targeted therapies”, “veterinary medicine”, “genetic variation”, “free radicals oxidative stress”. Inclusion criteria included focusing species-specific therapeutic responses, genetic influences, stress. To ensure that only most recent relevant evidence was included, peer-reviewed publications from last two decades considered. Each study selected for analysis critically appraised, with a particular emphasis methodological quality, experimental design, scientific contribution to understanding how biological influence outcomes. A special placed used comparative, cross-species approach assess variability responses potential adverse effects. The synthesises role epigenetic highlights importance understand By highlighting variation, stress, individual species differences, argues personalised approaches. emphasises an would improve care inform future research aimed at optimising therapies, ultimately leading better animal health efficacy. key is its need more protocols take into account profiles factors; it also calls greater integration studies.

Language: Английский

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Investigating the bidirectional interactions between senotherepeutic agents and human gut microbiota

European Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 107098 - 107098

Published: April 1, 2025

Biological ageing is a time-dependent process that has implications for health and disease. Cellular senescence key driver in age-related diseases. Senotherapeutic agents have been shown to slow biological by eliminating senescent mammalian cells. Given the increasing awareness of gut microbiome regulating human health, this study aimed investigate effects senotherapeutic as pharmacological interventions on microbiota. In study, bidirectional four agents, quercetin, fisetin, dasatinib, sirolimus, with microbiota sourced from healthy donors were investigated. The results revealed quercetin was completely biotransformed within six hours, while dasatinib most stable compounds. Additionally, metagenomic analysis confirmed all compounds increased abundance bacterial species associated (e.g., Bacteroides fragilis, Bifidobacterium longum, Veillonella parvula), decreased pathogenic bacteria primarily diseases Enterococcus faecalis Streptococcus spp.). findings provide comprehensive understanding pharmacobiomics interventions, highlighting potential microbiome-targeted senolytics promoting ageing.

Language: Английский

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Elucidation of the Role of L-Arginine and Nω-Nitro-L-Arginine in the Treatment of Rats with Different Levels of Hypoxic Tolerance and Exposure to Lead Nitrate

Cellular Physiology and Biochemistry, Journal Year: 2024, Volume and Issue: 58(4), P. 336 - 360

Published: July 30, 2024

Background/Aims: Individual resistance to hypoxia is an important feature of the physiological profile organism, particularly in relation lead-induced toxicity. Methods: Our study focused on evaluating parameters mitochondrial oxygen consumption, microsomal oxidation, intensity lipoperoxidation processes and antioxidant defences liver rats with low (LR) high (HR) elucidate mechanisms action L-arginine NO synthase inhibitor L-NNA before or after exposure lead nitrate. Results: suggests that redistribution oxygen-dependent towards under influence nitric oxide precursor amino acid mechanism for maintaining respiratory chain function during per os nitrate (3.6 mg nitrate/kg bw day 30 days). Animals were given at a dose 600 mg/kg (i.p., min) Nω-nitro-L-arginine (L-NNA) 35 experiments demonstrated efficacy using simulate lead-related toxic via Pb levels tissue; we significantly reduced nitrites nitrates, i.e. stable metabolites system, both LR HR animals. The effect stabilised negative effects groups rats. We observed efficiency energy supply showed greater vulnerability NADH-dependent oxidation Conclusion: initiated substrates group, whereas group this directionality was more effective when role system (use L-NNA). key enzyme activities rat tissue revealed changes catalase-peroxidase activity ratio. found different enzymes treated L-NNA, significant increase GPx administered

Language: Английский

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Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 898 - 898

Published: July 24, 2024

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung (NSCLC) accounting for over 85% cases and poor prognosis in advanced stages. This study explored shifts circulating metabolite levels NSCLC patients versus healthy controls examined effects conventionally fractionated radiation therapy (CFRT) stereotactic body (SBRT). We enrolled 91 (38 CFRT 53 SBRT) 40 controls. Plasma were assessed using semi-targeted metabolomics, revealing 32 elevated 18 reduced metabolites patients. Key discriminatory included ethylmalonic acid, maltose, 3-phosphoglyceric taurine, glutamic glycocolic d-arabinose, a combined Receiver Operating Characteristics curve indicating perfect discrimination between SBRT affected different metabolites, but both changes suggested partial normalization energy amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures potential as diagnostic biomarkers. The differing responses to reflect their unique therapeutic impacts, underscoring utility this technique enhancing diagnosis treatment monitoring.

Language: Английский

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Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy

Published: June 17, 2024

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung (NSCLC) accounting for over 85% cases and poor prognosis in advanced stages. This study explored shifts circulating metabolite levels NSCLC patients versus healthy controls examined effects conventionally fractionated radiation therapy (CFRT) stereotactic body (SBRT). We enrolled 91 (38 CFRT 53 SBRT) 40 controls. Plasma were assessed using semi-targeted metabolomics, revealing 32 elevated 18 reduced metabolites patients. Key discriminatory included ethylmalonic acid, maltose, 3-phosphoglyceric taurine, glutamic glycocolic d-arabinose, a combined Receiver Operating Characteristics curve indicating perfect discrimination between SBRT affected different metabolites, but both changes suggested partial normalization energy amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures potential as diagnostic biomarkers. The differing responses to reflect their unique therapeutic impacts, underscoring utility this technique enhancing diagnosis treatment monitoring.

Language: Английский

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Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3968 - 3968

Published: Nov. 20, 2024

AKG, a central metabolite in the Krebs cycle, plays vital role cellular energy production and nitrogen metabolism. This review explores AKG's potential therapeutic applications skeletal muscle health exercise performance, focusing on its mechanisms for promoting regeneration counteracting atrophy. A literature search was conducted using PubMed, Web of Science, Scopus databases, yielding 945 articles published up to 31 October 2024. Of these, 112 peer-reviewed met inclusion criteria formed basis this review. AKG supports recovery by stimulating satellite cells (MuSCs) macrophage polarization, aiding repair reducing fibrosis. Additionally, shows promise preventing atrophy enhancing protein synthesis, inhibiting degradation pathways, modulating inflammatory responses, making it relevant conditions like sarcopenia, cachexia, injury recovery. For athletes active individuals, supplementation has enhanced endurance, reduced fatigue, supported faster post-exercise Despite promising preliminary findings, research gaps remain understanding long-term effects, optimal dosage, specific particularly across diverse populations. Further research, including large-scale clinical trials, is essential clarify optimize application as agent diseases an enhancer physical performance. aims provide comprehensive overview benefits identify future directions both sports settings.

Language: Английский

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Identifying Metabolomic and Proteomic Biomarkers for Age-Related Morbidity in a Population-Based Cohort - the Cooperative Health Research in South Tyrol (CHRIS) study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 15, 2024

Abstract Identifying biomarkers able to discriminate individuals on different health trajectories is crucial understand the molecular basis of age-related morbidity. We investigated multi-omics signatures general and organ-specific morbidity, as well their interconnectivity. examined cross-sectional metabolome proteome data from 3,142 adults Cooperative Health Research in South Tyrol (CHRIS) study, an Alpine population study designed investigate how human biology, environment, lifestyle factors contribute people’s over time. had 174 metabolites 148 proteins quantified fasting serum plasma samples. used Cumulative Illness Rating Scale (CIRS) Comorbidity Index (CMI), which considers morbidity 14 organ systems, assess status (any vs. healthy). Omics-signatures for were identified using random forest (RF) classifiers. Linear regression models fitted directionality omics markers associations, identify related Next age, we 21 10 relevant predictors results confirmed associations serotonin glutamate be age-independent. Considering several jointly endocrine, cardiovascular, renal To conclude, circulating was a potential novel predictor overall

Language: Английский

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