Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 197, P. 106520 - 106520

Published: May 3, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental affecting 1 in 36 children and associated with physiological abnormalities, most notably mitochondrial dysfunction, at least subset of individuals. This systematic review meta-analysis discovered 204 relevant articles which evaluated biomarkers dysfunction ASD Significant elevations (all p < 0.01) the prevalence lactate (17%), pyruvate (41%), alanine (15%) creatine kinase (9%) were found ASD. Individuals had significant differences moderate to large effect sizes (Cohen's d' ≥ 0.6) compared controls mean pyruvate, lactate-to-pyruvate ratio, ATP, kinase. Some studies abnormal TCA cycle metabolites Thirteen controlled reported DNA (mtDNA) deletions or variations group blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, brain. Meta-analyses (p copy number mtDNA overall ND1, ND4 CytB genes. Four linked specific haplogroups A series subgroup elevated respiration was increased sensitivity mitochondria stressors regression. Lactate, carnitine, acyl-carnitines clinical features such as delays language, social interaction, cognition, motor skills, repetitive behaviors gastrointestinal symptoms, although not all an association. acyl-carnitines, CoQ10, well variants, heteroplasmy, severity. Variability across biomarker primarily due collection processing techniques intrinsic heterogeneity population. Several alterations metabolism mothers neonates who develop Treatments targeting mitochondria, particularly carnitine ubiquinol, appear beneficial The link between common abnormalities individuals including disorders, oxidative stress, immune outlined. subtypes are discussed, one related regression, another microbiome metabolites, acyl-carnitines. Mechanisms linking function prenatal brain development postnatal Given multisystem complexity some ASD, this presents evidence for being central by contributing development, comorbidities diagnostic approach identify From evidence, it clear that many have may need be addressed order achieve optimal outcomes. fact during pregnancy early life eventually provides promise predictive Further improve understanding role better defining subgroups molecular mechanisms driving unique changes those

Language: Английский

---

High-Resolution Tracking of Aging-Related Small Molecules: Bridging Pollutant Exposure, Brain Aging Mechanisms, and Detection Innovations

Biosensors, Journal Year: 2025, Volume and Issue: 15(4), P. 242 - 242

Published: April 11, 2025

Brain aging is a complex process regulated by genetic, environmental, and metabolic factors, increasing evidence suggests that environmental pollutants can significantly accelerate this interfering with oxidative stress, neuroinflammation, mitochondrial function-related signaling pathways. Traditional studies have focused on the direct damage of macromolecules (e.g., proteins, DNA), while central role senescence-associated small molecules ROS, PGE2, lactate) in early regulatory mechanisms has been long neglected. In study, we innovatively proposed cascade framework "small molecule imbalance-signaling pathway dysregulation-macromolecule collapse", which reveals exacerbate dynamics brain through activation NLRP3 inflammatory vesicles inhibition HIF-1α. Meanwhile, to address technical bottleneck spatiotemporal monitoring, paper systematically reviews cutting-edge detection tools such as electrochemical sensors, genetically encoded fluorescent probes antioxidant quantum dots (AQDs). Among them, AQDs show unique advantages real-time monitoring ROS fluctuations intervention virtue their ultra-high specific surface area, controllable modification, free radical scavenging ability. By integrating multimodal techniques mechanism studies, work provides new perspective for analyzing pollutant-induced lays methodological foundation strategies based networks.

Language: Английский

---

Bioenergetic signatures of neurodevelopmental regression

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

Published: Feb. 19, 2024

Studies have linked autism spectrum disorder (ASD) to physiological abnormalities including mitochondrial dysfunction. Mitochondrial dysfunction may be a subset of children with ASD who neurodevelopmental regression (NDR). We developed cell model which demonstrates unique profile respiration higher than normal and sensitive stress. previously shown similar profiles in individuals NDR.

Language: Английский

---

Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(21), P. 9884 - 9884

Published: Oct. 29, 2024

Oxidative stress is an imbalance between reactive oxygen species production and antioxidant defense that can lead to reproductive disorders poor pregnancy outcomes. Environmental pollution under climate change involved in formation may cause various dysfunctions of the system. a widespread factor affects physiology male female systems, leading high levels DNA damage infertility. Miscarriage, preeclampsia, premature birth are all linked oxidative stress. induces excesses by expanding ROS generation or overwhelming physiological responses This increases cellular damage, inflammation, development numerous diseases. Here, we present brief outline developmental roles plays during pregnancy. We also offer some insights into underlying mechanisms have been put forth, which culminate summary harmful effects environmental origin pregnancy-related complications. The current work motivate design more focused wellbeing measures order prevent promote human health anticipate unfavorable

Language: Английский

---

Use of Tocolytic Agents in Preterm Labor: A Cross‐Sectional Analysis from a Chinese Real‐World Study from 2016 to 2021

Journal of Clinical Pharmacy and Therapeutics, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

What Is Known and Objective . Tocolytic agents are used to prolong gestational age prevent immediate preterm birth (PTB). This study aims provide an overview of the use tocolytics among patients with PTB in China through retrospectively analyzing trends application, influencing factors, inappropriate prescriptions. Methods The prescription data five tocolytic from 2016 2021 were extracted database Hospital Prescription Analysis Cooperation Project. Drug consumption was expressed as number prescriptions, cost DDDs (defined daily doses). Pearson correlation analysis examine association between DDC cost). appropriateness prescriptions analyzed terms drug dosage form, administration, clinical diagnosis, combined medication. Results total increased by 6.12% 387.58%, respectively, over six‐year duration study. From 2021, ranking magnesium sulfate > ritodrine nifedipine indomethacin atosiban. During period, significantly, which mainly related costs 2017 atosiban 2018 2019. DDCs = 2021. For atosiban, negatively correlated DDDs. Inappropriate prescription, accounted for 14.84% all manifested selection low frequency indomethacin, overdosing ritodrine. Furthermore, 22.87% remained active after 34 weeks gestation, 7.24% authorized combination drugs, being most commonly prescribed combination. New Conclusion Magnesium sulfate, ritodrine, top three agents. As continues persist, it is important intensify efforts ensure safety maternal

Language: Английский

---

Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9297 - 9297

Published: Aug. 27, 2024

The goal of our study was to identify and assess the functionally significant SNPs with potentially important roles in development type 2 diabetes mellitus (T2DM) and/or their effect on individual response antihyperglycemic medication metformin. We applied a bioinformatics approach regulatory (rSNPs) associated allele-asymmetric binding expression events paired ChIP-seq RNA-seq data for peripheral blood mononuclear cells (PBMCs) nine healthy individuals. rSNP outcomes were analyzed using public from GWAS (Genome-Wide Association Studies) Genotype-Tissue Expression (GTEx). differentially expressed genes (DEGs) between T2DM individuals (GSE221521), including metformin responders non-responders (GSE153315), searched GEO data. DEGs harboring rSNPs Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG). identified 14,796 promoters 5132 human PBMCs. found 4280 associate both phenotypic traits (GWAS) quantitative trait loci (eQTLs) GTEx. Between patients controls, 3810 detected 1284 DEGs. Based protein-protein interaction (PPI) network, we 31 upregulated hub genes, involved inflammation, obesity, insulin resistance. top-ranked 10 enriched KEGG pathways these hubs included insulin, AMPK, FoxO signaling pathways. non-responders, 367 131 encoding transcription factors regulators most widely represented group many shown be pathogenesis. have formed list that add functional interpretation T2DM-association signals GWAS. results suggest candidate causal variants T2DM, strong enrichment related glucose metabolism, effects

Language: Английский

---

Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II

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

Published: Sept. 16, 2024

Background The standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim safeguarding liver against deleterious effects various toxic substances. However, role silibinin Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate impact on PM2.5-induced and elucidate potential underlying mechanisms. Methods A model was established male C57BL/6J mice through intratracheal instillation PM2.5, followed by assessment weight, body index, measurements triglycerides cholesterol after treatment capsules. Hep G2 cells were exposed PM2.5 suspension create an intracellular model, cell viability, cholesterol, fluorescence staining Nile Red (lipid droplets), DCFH-DA (Reactive Oxygen Species, ROS), well proteomics, real-time PCR, mitochondrial function assays, performed mechanisms involved reducing triglycerides. Results exposure leads accumulation, increased ROS production, elevated expression inflammatory factors, decreased antioxidant downstream genes aryl hydrocarbon receptor. Silibinin can partially or fully reverse these thereby protecting animal livers from damage. In vitro studies show that exerts its protective preserving oxidative phosphorylation complexes I II, particularly significantly enhancing complex II. Succinate dehydrogenase (mitochondrial II) is a direct target but B exhibit different affinities subunits Conclusion improved induced this was, at least part, explained enhancement Complexes

Language: Английский

---