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Biochemical Pharmacology Dec 2023Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against... (Review)
Review
Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against Metabolic-associated Fatty Liver Disease (MAFLD) and Nonalcoholic Steatohepatitis (NASH). However, the pharmacological limitations of the intact protein have prompted a focus on alternative options, specifically peptidic and small molecule agonists targeting the adiponectin receptor. AdipoRon is an extensively researched non-peptidic drug candidate in adiponectin replacement therapy. In turn, ADP355 is an adiponectin-based active short peptide. They have garnered significant attention due to their potential as substitutes for adiponectin. Researchers have studied AdipoRon's and ADP355's efficacy and therapeutic applications in various disease conditions. However, the effects of AdipoRon and ADP355 against NAFLD and NASH models advanced more, and no systematic review explored this area before. This systematic review was conceived to address the deficiency mentioned above and consider the lack of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. To assess the risk of bias in systematic review, The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed. Results from pre-clinical evidence show that AdipoRon and ADP355 represent promising effects in NAFLD and NASH-related models, including reducing hepatic steatosis, modulating inflammation, improving insulin sensitivity, enhancing mitochondrial function, and protecting against liver fibrosis. While AdipoRon and ADP355 exhibit promise in pre-clinical studies and experimental models, additional clinical trials are necessary to assess their effectiveness, safety, and potential translational therapeutic potential uses in NAFLD and NASH human cases.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Receptors, Adiponectin; Adiponectin
PubMed: 37866803
DOI: 10.1016/j.bcp.2023.115871 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging.... (Review)
Review
Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies.
Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.
Topics: Humans; Prospective Studies; Selenium; Lycopene; Cross-Sectional Studies; Curcumin; Proanthocyanidins; Randomized Controlled Trials as Topic; Vitamins; Vitamin A; Micronutrients; Folic Acid; Zinc; Beverages; Phytochemicals; DNA; DNA Damage; Biomarkers; Dietary Supplements
PubMed: 37573943
DOI: 10.1016/j.advnut.2023.08.004 -
Neurobiology of Disease Jul 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Meta-Analysis)
Meta-Analysis
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; DNA, Mitochondrial; Mitochondria; Mitochondrial Diseases
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520 -
Parkinsonism & Related Disorders Jun 2024Growing evidence has shown that mitochondrial dysfunction is part of the pathogenesis of Parkinson's disease (PD). However, the role of mitochondrial DNA (mtDNA)... (Review)
Review
BACKGROUND
Growing evidence has shown that mitochondrial dysfunction is part of the pathogenesis of Parkinson's disease (PD). However, the role of mitochondrial DNA (mtDNA) variants on PD onset is unclear.
OBJECTIVES
The present study aims to evaluate the effect of mtDNA variants and haplogroups on risk of developing PD.
METHODS
Systematic review and meta-analysis of studies investigating associations between PD and mtDNA variants and haplogroups.
RESULTS
A total of 33 studies were eligible from 957 screened studies. Among 13,640 people with PD and 22,588 control individuals, the association with PD was consistently explored in 13 mtDNA variants in 10 genes and 19 macrohaplogroups. Four mtDNA variants were associated with PD: m.4336C (odds ratio [OR] = 2.99; 95 % confidence interval [CI] = 1.79-5.02), m.7028T (OR = 0.80; 95 % CI = 0.70-0.91), m.10398G (OR = 0.92; 95 % CI = 0.85-0.98), and m.13368A (OR = 0.74; 95 % CI = 0.56-0.98). Four mtDNA macrohaplogroups were associated with PD: R (OR = 2.25; 95 % CI = 1.92-2.65), F (OR = 1.18; 95 % CI = 1.01-1.38), H (OR = 1.12; 95 % CI = 1.06-1.18), and B (OR = 0.77; 95 % CI = 0.65-0.92).
CONCLUSIONS
Despite most studies may be underpowered by the underrepresentation of people without dominant European- and Asian-ancestry, low use of next-generation sequencing for genotyping and small sample sizes, the identification of mtDNA variants and macrohaplogroups associated with PD strengthens the link between the disease and mitochondrial dysfunction and mtDNA genomic instability.
PubMed: 38917640
DOI: 10.1016/j.parkreldis.2024.107044 -
Frontiers in Bioscience (Landmark... Nov 2023Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases. Moreover, obesity has been shown to cause mitochondrial dysfunction through oxidative stress and inflammation, eventually affecting energy metabolism. However, high-intensity interval training (HIIT) can improve mitochondrial efficiency through exercise-induced mitochondrial adaptations. This systematic review and meta-analysis aims to examine the potential effects of HIIT on mitochondrial-associated indices in obese and overweight adults.
METHODS
PubMed, Scopus, and Web of Science databases were searched.
RESULTS
Twenty-eight eligible studies were included, involving 530 participants. HIIT was found to significantly improve the activity of citrate synthase (CS), cytochrome C (COX-IV), beta-hydroxyacyl CoA-dehydrogenase (β-HAD), Complexes I-V as well as VO2max in overweight and obese individuals, whereas no significant changes were shown in PGC-1α and SIRT1. Interestingly, subgroup analyses revealed that CS, COX-IV, β-HAD, and Complexes I-V activity exhibited a significant improvement only in the healthy subgroup.
CONCLUSIONS
Overall, HIIT can be utilized to enhance mitochondrial-associated indices in overweight and obese individuals. However, this improvement may be health status dependent.
Topics: Adult; Humans; Overweight; High-Intensity Interval Training; Oxygen Consumption; Obesity; Mitochondria
PubMed: 38062841
DOI: 10.31083/j.fbl2811281 -
Progress in Neuro-psychopharmacology &... Jul 2023Common mental disorders (CMDs) such as depression, anxiety and post-traumatic stress disorders account for 40% of the global burden of disease. In most psychiatric... (Meta-Analysis)
Meta-Analysis Review
Common mental disorders (CMDs) such as depression, anxiety and post-traumatic stress disorders account for 40% of the global burden of disease. In most psychiatric disorders, both diagnosis and monitoring can be challenging, frequently requiring long-term investigation and follow-up. The discovery of better methods to facilitate accurate and fast diagnosis and monitoring of psychiatric disorders is therefore crucial. Circulating nucleic acids (CNAs) are among these new tools. CNAs (DNA or RNA) can be found circulating in body biofluids, and can be isolated from biological samples such as plasma. They can serve as biomarkers for diagnosis and prognoses. They appear to be promising for disorders (such as psychiatric disorders) that involve organs or structures that are difficult to assess. This review presents an accurate assessment of the current literature about the use of plasma and serum cell-free DNA (cfDNA) as biomarkers for several aspects of psychiatric disorders: diagnosis, prognosis, treatment response, and monitor disease progression. For each psychiatric disorder, we examine the effect sizes to give insights on the efficacy of CNAs as biomarkers. The global effect size for plasma nuclear and mitochondrial cfDNA studies was generally moderate for psychiatric disorders. In addition, we discuss future applications of CNAs and particularly cfDNA as non-invasive biomarkers for these diseases.
Topics: Humans; Cell-Free Nucleic Acids; Biomarkers; Prognosis; DNA; Psychiatry
PubMed: 37068545
DOI: 10.1016/j.pnpbp.2023.110770 -
International Journal of Molecular... Dec 2023Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and... (Review)
Review
Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.
Topics: Humans; Atrial Fibrillation; Cardiac Conduction System Disease; Heart Diseases; Mitochondrial Diseases; Oxidative Stress
PubMed: 38203704
DOI: 10.3390/ijms25010535 -
Behavioural Brain Research Aug 2023Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research... (Review)
Review
BACKGROUND AND AIM
Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC- conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio- and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to systematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management.
MATERIAL AND METHODS
The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted.
RESULTS
The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and Aβ formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro-inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels.
CONCLUSION
While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.
Topics: Humans; Alzheimer Disease; Culture Media, Conditioned; Neurodegenerative Diseases; Stem Cells; Mesenchymal Stem Cells
PubMed: 37311523
DOI: 10.1016/j.bbr.2023.114543 -
Journal of Clinical Medicine Oct 2023Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an... (Review)
Review
Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training. We identified a wide variety of biomarkers, including imaging techniques, i.e., magnetic resonance imaging (MRI) and ultrasound, surface electromyography (sEMG), magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS). Imaging biomarkers, such as muscle maximum area and muscle thickness, and EMG biomarkers, such as compound muscle action potential (CMAP) amplitude, detected significant changes in muscle morphology and neural adaptations following resistance training. MRS and NIRS biomarkers, such as initial phosphocreatine recovery rate (V), mitochondrial capacity (Q), adenosine phosphate recovery half-time (ADP t), and micromolar changes in deoxygenated hemoglobin and myoglobin concentrations (Δ[deoxy(Hb + Mb)]), detected significant adaptations in oxidative metabolism after endurance training. We also identified biomarkers whose clinical relevance has not yet been assessed due to lack of sufficient study.
PubMed: 37959299
DOI: 10.3390/jcm12216834 -
Journal of Neurochemistry Jun 2024Parkinson's disease (PD) is the second most common neurodegenerative disorder. The primary pathological features of PD include the presence of α-synuclein aggregates... (Review)
Review
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The primary pathological features of PD include the presence of α-synuclein aggregates and Lewy bodies, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Recently, omega-3 fatty acids (ω-3 PUFAs) have been under investigation as a preventive and/or therapeutic strategy for PD, primarily owing to their antioxidant and anti-inflammatory properties. Therefore, the objective of this study was to conduct a systematic review of the literature, focusing on studies that assessed the effects of ω-3 PUFAs in rodent models mimicking human PD. The search was performed using the terms "Parkinson's disease," "fish oil," "omega 3," "docosahexaenoic acid," and "eicosapentaenoic acid" across databases PUBMED, Web of Science, Science Direct, Scielo, and Google Scholar. Following analysis based on predefined inclusion and exclusion criteria, 39 studies were included. Considering behavioral parameters, pathological markers of the disease, quantification of ω-3 PUFAs in the brain, as well as anti-inflammatory, antioxidant, and anti-apoptotic effects, it can be observed that ω-3 PUFAs exhibit a potential neuroprotective effect in PD. In summary, this systematic review presents significant scientific evidence regarding the effects and mechanisms underlying the neuroprotective properties of ω-3 PUFAs, offering valuable insights for the development of future clinical investigations.
PubMed: 38923542
DOI: 10.1111/jnc.16154