Mitochondrial dysfunction and therapeutic perspectives in osteoporosis

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Фев. 2, 2024

Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration of tissue, resulting in heightened vulnerability to fractures due increased fragility. This condition primarily arises from an imbalance between the processes resorption formation. Mitochondrial dysfunction has been reported potentially constitute one most crucial mechanisms influencing pathogenesis osteoporosis. In essence, mitochondria play role maintaining delicate equilibrium formation resorption, thereby ensuring optimal health. Nevertheless, disruption this balance can arise as consequence mitochondrial dysfunction. dysfunctional mitochondria, electron transport chain (ETC) becomes uncoupled, ATP synthesis generation reactive oxygen species (ROS). Reinforcement further exacerbated accumulation aberrant mitochondria. review, we investigated analyzed correlation dysfunction, encompassing DNA (mtDNA) alterations, oxidative phosphorylation (OXPHOS) impairment, mitophagy dysregulation, defects biogenesis dynamics, well excessive ROS accumulation, with regards OP ( Figure 1 ). Furthermore, explore prospective strategies currently available for modulating ameliorate Undoubtedly, certain therapeutic still require investigation ensure their safety efficacy clinical treatments. However, perspective, potential establishing effective safe approaches osteoporosis appears promising.

Язык: Английский

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Circulating PGC-1α and MOTS-c Peptide as Potential Mitochondrial Biomarkers in Patients Undergoing Aortic Valve Replacement

Biologics, Год журнала: 2025, Номер Volume 19, С. 87 - 96

Опубликована: Март 1, 2025

Aortic valve disease (AVD) is a common condition that leads to pressure and/or volume overload in the left ventricle. replacement standard treatment, as no pharmacological therapies are currently available. The incidence of AVD increasing developed countries, making discovery new biomarkers for early detection crucial. importance mitochondria heart function well established, and various cardiovascular pathologies associated with mitochondrial dysfunction. In this cross-sectional study, we evaluated first time role AVD, aiming identify pathways involved discover potential biomarkers. We recruited 17 patients diagnosed scheduled aortic replacement, 22 healthy controls. Plasma levels peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) open reading frame 12S rRNA type-c peptide (MOTS-c) were measured by ELISA. observed significantly reduced both proteins patients, suggesting substantial dysfunction occurs independent sex or age, but directly related disease. Mitochondria may represent promising target studying AVD. propose PGC1α MOTS-c plasma detection. Further studies, including early-stage necessary confirm significance our findings.

Язык: Английский

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The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism

Antioxidants, Год журнала: 2024, Номер 13(5), С. 613 - 613

Опубликована: Май 17, 2024

Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating injury. C57BL/6 mice were exposed 20 Gy irradiation (IR) received daily intraperitoneal injections for 2 weeks. significantly ameliorated tissue damage, inflammation, oxidative stress caused radiation. Meanwhile, reversed apoptosis damage alveolar cells mice. Furthermore, inhibited MLE-12 primary mouse Mechanistically, increased nuclear factor erythroid 2-related (Nrf2) level promoted its translocation. Notably, Nrf2 deficiency abolished function with RP. In conclusion, alleviates protecting through an Nrf2-dependent mechanism, indicating that may be novel potential agent

Язык: Английский

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Potential of extracellular vesicle cargo as molecular signals in Schizophrenia: a scoping review

Schizophrenia, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 12, 2025

Abstract The diagnosis of schizophrenia (SCZ) primarily relies on clinical history and mental status assessments by trained professionals. There has been a search for biomarkers to facilitate laboratory diagnosis. Since extracellular vesicles (EVs) communicate with brain cells can easily cross blood-brain barrier, there is increased interest among experts explore them as potential molecular signals disease detection. A scoping review was conducted provide comprehensive summary the existing literature identify differentially expressed in EVs isolated from SCZ patients. methodological framework outline provided Arksey O’Malley employed conduct this review. systematic using string across four databases, ultimately leading selection 24 relevant studies. Over 1122 biomolecules were identified extracted biological fluids tissues that be categorized RNAs, proteins, metabolites. Among them, 83 validated signals, which included metabolites, circRNAs, lncRNAs, miRNAs, proteins. These found affect cellular receptors intracellular pathways, neurotransmitters, mitochondrial functions, immune-related metabolic could serve

Язык: Английский

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The mitochondrial-derived peptide MOTS-c suppresses ferroptosis and alleviates acute lung injury induced by myocardial ischemia reperfusion via PPARγ signaling pathway

European Journal of Pharmacology, Год журнала: 2023, Номер 953, С. 175835 - 175835

Опубликована: Июнь 7, 2023

Acute lung injury (ALI) is a life-threatening complication of cardiac surgery that has high rate morbidity and mortality. Epithelial ferroptosis believed to be involved in the pathogenesis ALI. MOTS-c been reported play role regulating inflammation sepsis-associated The purpose this study observe effect on myocardial ischemia reperfusion (MIR)-induced ALI ferroptosis. In humans, we used ELISA kits investigate malondialdehyde (MDA) levels patients undergoing off-pump coronary artery bypass grafting (CABG). vivo, pretreated Sprague-Dawley rats with MOTS-c, Ferrostatin-1 Fe-citrate(Ⅲ). We conducted Hematoxylin Eosin (H&E) staining detection ferroptosis-related genes MIR-induced rats. vitro, evaluated hypoxia regeneration (HR)-induced mouse epithelial-12 (MLE-12) analyzed expression PPARγ through western blotting. found circulating were decreased postoperative after CABG, contributed induced by MIR suppressed alleviated MIR, protective MOTS-c- was dependent signaling pathway. Additionally, HR promoted MLE-12 cells, inhibited against These findings highlight therapeutic potential for improving surgery.

Язык: Английский

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AagingBase: a comprehensive database of anti-aging peptides

Database, Год журнала: 2024, Номер 2024

Опубликована: Янв. 1, 2024

Abstract The process of aging is an intrinsic and inevitable aspect life that impacts every living organism. As biotechnological advancements continue to shape our understanding medicine, peptide therapeutics have emerged as a promising strategy for anti-aging interventions. This primarily due their favorable attributes, such low immunogenicity cost-effective production. Peptide-based treatments garnered widespread acceptance interest in research, particularly the context age-related therapies. To effectively develop treatments, comprehensive physicochemical characteristics peptides essential. Factors amino acid composition, instability index, hydrophobic areas other relevant properties significantly determine efficacy potential therapeutic agents. Consequently, creation ‘AagingBase’, database peptides, aims facilitate research on by leveraging AagingBase houses experimentally validated 282 collected from 54 articles 236 patents. Employing state-of-the-art computational techniques, acquired sequences undergone rigorous calculations. Furthermore, presents users with various informative analyses highlighting atomic compositions, secondary structure fractions, tertiary structure, compositions frequencies. also offers advanced search filtering options similarity search, thereby aiding researchers biological functions. Hence, enables efficient identification prioritization candidates geriatric medicine holds immense advancing innovations. can be accessed without any restriction. Database URL: https://project.iith.ac.in/cgntlab/aagingbase/

Язык: Английский

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Comparative Analysis of Biomarkers in Type 2 Diabetes Patients With and Without Comorbidities: Insights Into the Role of Hypertension and Cardiovascular Disease

Biomarker Insights, Год журнала: 2024, Номер 19

Опубликована: Янв. 1, 2024

Background: Type 2 diabetes mellitus (T2DM) are 90% of cases, and its prevalence incidence, including comorbidities, rising worldwide. Clinically, associated comorbidities identified by biochemical physical characteristics glycemia, glycated hemoglobin (HbA1c), tests for cardiovascular, eye kidney disease. Objectives: Diabetes may have a common etiology based on inflammation oxidative stress that provide additional information about disease progression treatment options. Thus, identifying high-risk individuals can delay or prevent complications. Design: In patients with without hypertension cardiovascular disease, as part from no to T2DM, this research studied the changes in biomarkers between control prediabetes, prediabetes classified first-attendance data. Control hypertension, both diseases 156, 148, 61, 216, respectively. Methods: Linear discriminant analysis is used classification method feature importance, This study examined relationship Humanin mitochondrial protein (MOTSc), peptides stress, progression, Results: MOTSc, reduced glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), 8-isoprostane were significant ( P < .05) transition t2dm, highlighting importance involvement. complement component 5a (c5a) biomarker gsh gssg, monocyte chemoattractant protein-1 (mcp-1), being most important biomarkers. Conclusions: Comorbidities affect hypothesized progresses. Mitochondrial indicators, coagulation, inflammatory markers help assess development appropriate medications. Future studies will examine longitudinal evolution.

Язык: Английский

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Cellular and Molecular Biology of Mitochondria in Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7780 - 7780

Опубликована: Июль 16, 2024

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by enduring airflow limitation and chronic inflammation. Growing evidence highlights mitochondrial dysfunction as critical factor in COPD development progression. This review explores the cellular molecular biology of mitochondria COPD, focusing on structural functional changes, including alterations shape, behavior, chain complexes. We discuss impact signaling pathways, apoptosis, aging. Therapeutic strategies targeting dysfunction, such antioxidants biogenesis inducers, are examined for their potential to manage COPD. Additionally, we consider role biomarkers diagnosis, evaluating progression, monitoring treatment efficacy. Understanding interplay between crucial developing targeted therapies slow progression improve patient outcomes. Despite advances, further research needed fully elucidate mechanisms, discover new biomarkers, develop therapies, aiming comprehensive management that preserves lung function enhances quality life patients.

Язык: Английский

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The mitochondrial-derived peptide MOTS-c may refine mortality and cardiovascular risk prediction in chronic hemodialysis patients: a multicenter cohort study

Blood Purification, Год журнала: 2024, Номер 53(10), С. 824 - 837

Опубликована: Авг. 7, 2024

Introduction: Uremic patients exhibit remarkably increased rates of mortality and cardiovascular (CV) events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive end-stage kidney disease may contribute to CV complications. We tested the clinical significance circulating MOTS-c, a small mitochondrial-derived peptide, as biomarker for improving hemodialysis (HD) patients. Methods: conducted prospective, observational, multicenter study on 94 prevalent HD The endpoint was composite all-cause non-fatal events. diagnostic prognostic capacities predictive models based cohort-related factors were before after inclusion MOTS-c. Results: MOTS-c levels higher than controls (p &lt; 0.001) even more elevated = 0.01) 53 individuals experiencing combined during follow-up (median duration: 26.5 months). independently associated with at either multivariate logistic (OR 1.020; 95% CI: 1.011–1.109; p 0.03) or Cox regression analyses (HR 1.004; 1.000–1.025; 0.05) addition including other predictors (age, left ventricular mass, evidence diastolic dysfunction, diabetes, pulse pressure) significantly improved calibration, variability explanation, discrimination (receiver operating characteristic area under curve from 0.727 0.743; C-index 0.658 0.700), particularly, overall reclassification capacity (NRI 15.87%; 0.01). Conclusions: In patients, peptide impart significant information refine prediction, beyond factors. Future investigations are needed generalize these findings larger heterogeneous cohorts.

Язык: Английский

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Transcription Factor Nrf2 and Mitochondria – Friends or Foes in the Regulation of Aging Rate

Biochemistry (Moscow), Год журнала: 2022, Номер 87(12-13), С. 1477 - 1486

Опубликована: Дек. 1, 2022

Язык: Английский

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