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Journal of Translational Medicine Jul 2020Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms... (Review)
Review
BACKGROUND
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.
METHODS
Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.
RESULTS
Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.
CONCLUSION
Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.
Topics: Biomarkers; Case-Control Studies; Fatigue Syndrome, Chronic; Humans
PubMed: 32727475
DOI: 10.1186/s12967-020-02452-3 -
Frontiers in Endocrinology 2023A systematic review analysis was used to assess the profile of mitochondrial involvement in adipose tissue regulation and potential reagents to intervene in obesity...
INTRODUCTION
A systematic review analysis was used to assess the profile of mitochondrial involvement in adipose tissue regulation and potential reagents to intervene in obesity through the mitochondrial pathway.
METHODS
Three databases, PubMed, Web of Science, and Embase, were searched online for literature associated with mitochondria, obesity, white adipose tissue, and brown adipose tissue published from the time of their creation until June 22, 2022, and each paper was screened.
RESULTS
568 papers were identified, of which 134 papers met the initial selection criteria, 76 were selected after full-text review, and 6 were identified after additional searches. A full-text review of the included 82 papers was performed.
CONCLUSION
Mitochondria play a key role in adipose tissue metabolism and energy homeostasis, including as potential therapeutic agents for obesity.
Topics: Humans; Obesity; Adipose Tissue, Brown; Adipose Tissue, White; Energy Metabolism; Mitochondria
PubMed: 37396170
DOI: 10.3389/fendo.2023.1132342 -
Frontiers in Pharmacology 2024Matrine, an alkaloid derived from the dried roots of Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns....
Matrine, an alkaloid derived from the dried roots of Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns. However, the precise condition and mechanism of action of matrine on the liver remain inconclusive. Therefore, the objective of this systematic review and meta-analysis is to comprehensively evaluate both the hepatoprotective and hepatotoxic effects of matrine and provide therapeutic guidance based on the findings. The meta-analysis systematically searched relevant preclinical literature up to May 2023 from eight databases, including PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang Med Online, China Science and Technology Journal Database, and China Biomedical Literature Service System. The CAMARADES system assessed the quality and bias of the evidence. Statistical analysis was conducted using STATA, which included the use of 3D maps and radar charts to display the effects of matrine dosage and frequency on hepatoprotection and hepatotoxicity. After a thorough screening, 24 studies involving 657 rodents were selected for inclusion. The results demonstrate that matrine has bidirectional effects on ALT and AST levels, and it also regulates SOD, MDA, serum TG, serum TC, IL-6, TNF-α, and CAT levels. Based on our comprehensive three-dimensional analysis, the optimal bidirectional effective dosage of matrine ranges from 10 to 69.1 mg/kg. However, at a dose of 20-30 mg/kg/d for 0.02-0.86 weeks, it demonstrated high liver protection and low toxicity. The molecular docking analysis revealed the interaction between MT and SERCA as well as SREBP-SCAP complexes. Matrine could alter Ca homeostasis in liver injury via multiple pathways, including the SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, and Cul3/Rbx1/Keap1/Nrf2. Matrine has bidirectional effects on the liver at doses ranging from 10 to 69.1 mg/kg by influencing Ca homeostasis in the cytoplasm, endoplasmic reticulum, Golgi apparatus, and mitochondria. https://inplasy.com/, identifier INPLASY202340114.
PubMed: 38348397
DOI: 10.3389/fphar.2024.1315584 -
Journal of Translational Medicine Feb 2021Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination... (Review)
Review
BACKGROUND
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS.
METHODS
A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale.
RESULTS
Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters.
CONCLUSION
There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.
Topics: Dietary Supplements; Fatigue Syndrome, Chronic; Humans; Mitochondria; Quality of Life; Severity of Illness Index
PubMed: 33596913
DOI: 10.1186/s12967-021-02742-4 -
International Journal of Molecular... Oct 2022Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy... (Meta-Analysis)
Meta-Analysis Review
Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.
Topics: Humans; Antioxidants; Exercise; Cardiovascular Diseases; Mitochondria; Succinates
PubMed: 36293409
DOI: 10.3390/ijms232012559 -
PloS One 2024Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually... (Meta-Analysis)
Meta-Analysis
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.
Topics: Humans; Amyotrophic Lateral Sclerosis; Quality of Life; Neurodegenerative Diseases; Exercise Therapy; Muscle Spasticity
PubMed: 38551974
DOI: 10.1371/journal.pone.0300671 -
PloS One 2024This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data from eligible studies.
MATERIALS AND METHODS
Through a comprehensive searching of pubmed, embase, web of science, cochrane from establishment of the database to October 31, 2022, studies were selected that investigated the association of circulating cell free mitochondria DNA with inflammatory factors in non-infectious diseases. Studies that met the inclusion criteria and were published in English or Chinese were included. Data of each correlation coefficients were extracted from the paper and 95% confidence intervals were calculated. Sensitivity and heterogeneity tests were carried out for each data.
RESULTS
A total of 660 articles were retrieved and 22 were included in this meta-analysis, including 2600 patients. A fixed effects model was employed to examine ISS and IL-8, others were analyzed using random effects models. The correlation coefficient between mtDNA and ISS score was 0.37 (95%CI = [0.232;0.494]), p<0.0001, heterogeneity I2 = 46%, p = 0.11). The correlation coefficients between mtDNA and inflammatory factors are as follows: TNFα, 0.405 [(95%CI = [0.253;0.538], p<0.0001, heterogeneity I2 = 77%, p = 0.0001]. IL-6, 0.469 [(95%CI = [0.296;0.612]), p = 0.0001, heterogeneity I2 = 93%, p<0.0001]. CRP, 0.333[(95%CI = [0.149;0.494]), p = 0.005, heterogeneity I2 = 85%, p<0.0001]. IL-8, 0.343[(95%CI = [0.233;0.524]), p = 0.001, heterogeneity I2 = 50%, p = 0.09]. PCT, 0.333 [(95%CI = [0.06;0.64]), p = 0.09,heterogeneity I2 = 64%,p = 0.06]. There were no significant publication bias for TNFα, IL-6 and CRP.
CONSLUSION
Circulating cell free mtDNA was moderate positively correlated with the expression of inflammatory factors and the degree of trauma.
Topics: Humans; Noncommunicable Diseases; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-8; Inflammation; DNA, Mitochondrial; Mitochondria
PubMed: 38241222
DOI: 10.1371/journal.pone.0289338 -
Journal of the American Heart... Nov 2019Background Right ventricular (RV) failure because of chronic pressure load is an important determinant of outcome in pulmonary hypertension. Progression towards RV... (Meta-Analysis)
Meta-Analysis
Background Right ventricular (RV) failure because of chronic pressure load is an important determinant of outcome in pulmonary hypertension. Progression towards RV failure is characterized by diastolic dysfunction, fibrosis and metabolic dysregulation. Metabolic modulation has been suggested as therapeutic option, yet, metabolic dysregulation may have various faces in different experimental models and disease severity. In this systematic review and meta-analysis, we aimed to identify metabolic changes in the pressure loaded RV and formulate recommendations required to optimize translation between animal models and human disease. Methods and Results Medline and EMBASE were searched to identify original studies describing cardiac metabolic variables in the pressure loaded RV. We identified mostly rat-models, inducing pressure load by hypoxia, Sugen-hypoxia, monocrotaline (MCT), pulmonary artery banding (PAB) or strain (fawn hooded rats, FHR), and human studies. Meta-analysis revealed increased Hedges' g (effect size) of the gene expression of GLUT1 and HK1 and glycolytic flux. The expression of MCAD was uniformly decreased. Mitochondrial respiratory capacity and fatty acid uptake varied considerably between studies, yet there was a model effect in carbohydrate respiratory capacity in MCT-rats. Conclusions This systematic review and meta-analysis on metabolic remodeling in the pressure-loaded RV showed a consistent increase in glucose uptake and glycolysis, strongly suggest a downregulation of beta-oxidation, and showed divergent and model-specific changes regarding fatty acid uptake and oxidative metabolism. To translate metabolic results from animal models to human disease, more extensive characterization, including function, and uniformity in methodology and studied variables, will be required.
Topics: Animals; Fatty Acids; Glucose; Heart Ventricles; Humans; Hypertension, Pulmonary; Mitochondria; Ventricular Remodeling
PubMed: 31657265
DOI: 10.1161/JAHA.119.012086 -
Cellular and Molecular Neurobiology May 2022Neurodegenerative diseases might be slow but relentless, as we continue to fail in treating or delaying their progression. Given the complexity in the pathogenesis of... (Review)
Review
Neurodegenerative diseases might be slow but relentless, as we continue to fail in treating or delaying their progression. Given the complexity in the pathogenesis of these diseases, a broad-acting approach like photobiomodulation can prove promising. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits, working by stimulating growth and proliferation. The implications of photobiomodulation have been studied in several neurodegenerative disease models. It has been shown to improve cell survival, decrease apoptosis, alleviate oxidative stress, suppress inflammation, and rescue mitochondrial function. In in vivo models, it has reportedly preserved motor and cognitive skills. Beyond mitochondrial stimulation, the molecular mechanisms by which photobiomodulation protects against neurodegeneration have not been very well studied. This review has systematically been undertaken to study the effects of photobiomodulation at a molecular level and identify the different biochemical pathways and molecular changes in the process. The data showed the involvement of pathways like extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), and protein kinase B (Akt). In addition, the expression of several genes and proteins playing different roles in the disease mechanisms was found to be influenced by PBM, such as neurotrophic factors and secretases. Studying the literature indicated that PBM can be translated to a potential therapeutic tool, acting through a spectrum of mechanisms that work together to decelerate disease progression in the organism, which is difficult to achieve through pharmacological interventions.
Topics: Cell Survival; Humans; Low-Level Light Therapy; Mitochondria; Mitogen-Activated Protein Kinases; Neurodegenerative Diseases
PubMed: 33301129
DOI: 10.1007/s10571-020-01016-9 -
Annals of Translational Medicine Sep 2022Though best known for its immunosuppressant effects, cyclosporine A (CsA) has also been studied as a treatment to mitigate ischemia-reperfusion injury (IRI) by its...
BACKGROUND
Though best known for its immunosuppressant effects, cyclosporine A (CsA) has also been studied as a treatment to mitigate ischemia-reperfusion injury (IRI) by its inhibition of the mitochondria permeability transition pore (mPTP). Despite numerous preclinical studies supporting its benefit in reducing infarct size following myocardial IRI, large randomized controlled clinical trials have been unable to show a beneficial effect. Exploring existing preclinical data can give us the opportunity to revisit some the assumptions that may have led to the failure of these studies to translate clinically. Herein, we present a systematic review of preclinical studies testing CsA to attenuate myocardial IRI (PROSPERO CRD42020159620).
METHODS
We conducted a systematic search of health research databases Ovid MEDLINE, Ovid EMBASE, Web of Science BIOSIS, and Scopus, as well as Cochrane and PROSPERO systematic review databases, on March 9, 2022 for non-human animal studies of myocardial IRI, using CsA as a treatment that reported clinically relevant outcomes. Bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool and a modified Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies checklist. Sub-group meta-analyses were conducted to identify potential factors influencing outcomes.
RESULTS
We identified 71 studies, 59 of which were studies of coronary occlusion. Overall, 75% of studies reported a clear positive effect of CsA in mitigating myocardial IRI by some clinically relevant parameter (e.g., infarct size). A meta-analysis including 43 coronary occlusion studies showed an overall reduction in infarct size with CsA treatment (16.09%; 95% CI: -18.50% to -13.67%). Subgroup meta-analyses identified species, age, timing of administration, and duration of ischemia as factors potentially affecting the efficacy of CsA in the setting of myocardial IRI.
CONCLUSIONS
Our systematic review and meta-analysis identifies questions that have yet to be answered by preclinical studies, highlighting important differences between these and clinical studies that should be addressed prior to proceeding with any further clinical studies using CsA to treat IRI in the heart or other organs. We also use the example of CsA to highlight general considerations for researchers attempting to translate animal studies into the clinical setting.
PubMed: 36267756
DOI: 10.21037/atm-22-618