-
Frontiers in Public Health 2023Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of diseases. Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) serves as a central rate-limiting enzyme in NAD synthesis, making it an indispensable health mediator. This meta-analysis examined the effect of exercise training on the expression of iNAMPT in humans.
METHODS
We searched PubMed, Scopus, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies published between the inception of the database and July 5, 2023. Using the common-effect model, evidence for the change in iNAMPT following exercise training was synthesized as Cohen's .
RESULTS
The search yielded five eligible studies. The overall effect size is 0.81, with a 95% confidence interval of 0.55 to 1.07. Therefore, a random adult will have a 71.7% probability that iNAMPT will be up-regulated following exercise training. In general, exercise training resulted in a 1.46-fold increase in iNAMPT. Our probability statistics indicate that subgroups of interest may differ practically. Specifically, there is a 79.3% probability of increased iNAMPT in men, compared to a 69.0% probability in the overall population; young adults have a 75.6% probability of having an increased iNAMPT, whereas aged adults have a 68.7% probability; and, iNAMPT has a 75.1% probability increase after aerobic exercise and a 66.4% probability increase after resistance exercise.
CONCLUSION
Exercise training is effective for increasing iNAMPT levels in skeletal muscles. This essential enzyme regulates not only cellular energetics but also healthspan. Therefore, exercise should be promoted as a natural slow-aging lifestyle.
Topics: Humans; Aging; Exercise; Muscle, Skeletal; NAD; Nicotinamide Phosphoribosyltransferase
PubMed: 37954044
DOI: 10.3389/fpubh.2023.1287421 -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Frontiers in Physiology 2023Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36...
Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36 (CD36) gene. This receptor has a high affinity for fatty acids and is involved in lipid metabolism. An abundance of FAT/CD36 during exercise occurs in mitochondria and solitary muscles. As such, we aimed to systematically review the evidence for the relationship FAT/CD36 and adipose tissue lipolysis during exercise training. Five electronic databases were selected for literature searches until June 2022: PubMed, Web of Science, Scopus, science direct, and Google Scholar. We combined the different synonyms and used the operators ("AND", "OR", "NOT"): (CD36 gene) OR (CD36 polymorphism) OR (cluster of differentiation 36) OR (FAT/CD36) OR (fatty acid translocase) OR (platelet glycoprotein IV) OR (platelet glycoprotein IIIb) AND (adipose tissue lipolysis) OR (fatty acids) OR (metabolism lipid) OR (adipocytes) AND (physical effort) OR (endurance exercise) OR (high-intensity training). All published cross-sectional, cohort, case-control, and randomized clinical trials investigating CD36 polymorphisms and adipose tissue lipolysis during exercise in subjects (elite and sub-elite athletes, non-athletes, sedentary individuals and diabetics), and using valid methods to measure FAT/CD36 expression and other biomarkers, were considered for inclusion in this review. We initially identified 476 publications according to the inclusion and exclusion criteria, and included 21 studies investigating FAT/CD36 and adipose tissue lipolysis during exercise in our systematic review after examination of titles, abstracts, full texts, and quality assessments using the PEDro scale. There were nine studies with male-only participants, three with female-only participants, and nine studies included both female and male participants. There were 859 participants in the 21 selected studies. Studies were classified as either low quality ( = 3), medium quality ( = 13), and high quality ( = 5). In general, the data suggests an association between FAT/CD36 and adipose tissue lipolysis during exercise training. Improvements in FAT/CD36 were reported during or after exercise in 6 studies, while there were no changes reported in FAT/CD36 in 4 studies. An association between fat oxidation and FAT/CD36 expression during exercise was reported in 7 studies. No agreement was reached in 5 studies on FAT/CD36 content after dietary changes and physical interventions. One study reported that FAT/CD36 protein expression in muscle was higher in women than in men, another reported that training decreased FAT/CD36 protein in insulin-resistant participants, while another study reported no differences in FAT/CD36 in young, trained individuals with type 2 diabetes. Our analysis shows an association between FAT/CD36 expression and exercise. Furthermore, an association between whole-body peak fat oxidation and FAT/CD36 expression during exercise training was demonstrated. Systematic Review Registration: [PROSPERO], identifier [CRD42022342455].
PubMed: 38074329
DOI: 10.3389/fphys.2023.1256440 -
Coenzyme Q10 as Adjunctive Therapy for Cardiovascular Disease and Hypertension: A Systematic Review.The Journal of Nutrition Jul 2022Mitochondrial ATP production requires a small electron carrier, coenzyme Q10 (CoQ10), which has been used as adjunctive therapy in patients with cardiovascular disease...
BACKGROUND
Mitochondrial ATP production requires a small electron carrier, coenzyme Q10 (CoQ10), which has been used as adjunctive therapy in patients with cardiovascular disease (CVD) and hypertension (HTN) because of its bioenergetics and antioxidant properties. Randomized controlled trials (RCTs) beyond the last 2 decades evaluating CoQ10 added to conventional therapy resulted in mixed results and were underpowered to address major clinical endpoints.
OBJECTIVES
The objective of this systematic review was to examine the impact of CoQ10 supplementation on older adults with CVD or HTN in the last 2 decades (2000-2020).
METHODS
PubMed/Medline, Cochrane Database, CINAHL, and Google Scholar databases were searched systematically, and references from selected studies were manually reviewed, to identify RCTs or crossover studies evaluating the efficacy of CoQ10 supplementation. Data extracted from selected studies included trial design and duration, treatment, dose, participant characteristics, study variables, and important findings.
RESULTS
A total of 14 studies (1067 participants) met the inclusion criteria. The effect of CoQ10 supplementation was examined among predominantly older adult males with heart failure (HF) (n = 6), HTN (n = 4), and ischemic heart disease (n = 3), and preoperatively in patients scheduled for cardiac surgery (n = 1). CoQ10 supplementation in patients with HF improved functional capacity, increased serum CoQ10 concentrations, and led to fewer major adverse cardiovascular events. CoQ10 had positive quantifiable effects on inflammatory markers in patients with ischemic heart disease. Myocardial hemodynamics improved in patients who received CoQ10 supplementation before cardiac surgery. Effects on HTN were inconclusive.
CONCLUSIONS
In predominantly older adult males with CVD or HTN, CoQ10 supplementation added to conventional therapy is safe and offers benefits clinically and at the cellular level. However, results of the trials need to be viewed with caution, and further studies are indicated before widespread usage of CoQ10 is recommended in all older adults.
Topics: Aged; Antioxidants; Cardiovascular Diseases; Heart Failure; Humans; Hypertension; Male; Myocardial Ischemia; Ubiquinone
PubMed: 35348726
DOI: 10.1093/jn/nxac079 -
Biomedicines Jan 2023Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated... (Review)
Review
Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries alongside propagating and amplifying the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (e.g., MPO (myeloperoxidase) and various proteinases) but can congregate other proteins found in blood (e.g., tissue factor procoagulant). This systematic review discusses the current hypothesis of neutrophil biology, focusing on the triggers and mechanisms of NET formation. Furthermore, the contribution of NETs to atherosclerosis and thrombosis is extensively addressed. Again, the use of NET markers in clinical trials was considered. Ultimately, given the vast body of the published literature, we aim to integrate the experimental evidence with the growing body of clinical information relating to NET critically.
PubMed: 36672621
DOI: 10.3390/biomedicines11010113 -
EBioMedicine Feb 2022Mitochondrial DNA (mtDNA) encodes 37 genes necessary for synthesizing 13 essential subunits of the oxidative phosphorylation system. mtDNA alterations are known to cause...
BACKGROUND
Mitochondrial DNA (mtDNA) encodes 37 genes necessary for synthesizing 13 essential subunits of the oxidative phosphorylation system. mtDNA alterations are known to cause mitochondrial disease (MitD), a clinically heterogeneous group of disorders that often present with neuropsychiatric symptoms. Understanding the nature and frequency of mtDNA alterations in health and disease could be a cornerstone in disentangling the relationship between biochemical findings and clinical symptoms of brain disorders. This systematic review aimed to summarize the mtDNA alterations in human brain tissue reported to date that have implications for further research on the pathophysiological significance of mtDNA alterations in brain functioning.
METHODS
We searched the PubMed and Embase databases using distinct terms related to postmortem human brain and mtDNA up to June 10, 2021. Reports were eligible if they were empirical studies analysing mtDNA in postmortem human brains.
FINDINGS
A total of 158 of 637 studies fulfilled the inclusion criteria and were clustered into the following groups: MitD (48 entries), neurological diseases (NeuD, 55 entries), psychiatric diseases (PsyD, 15 entries), a miscellaneous group with controls and other clinical diseases (5 entries), ageing (20 entries), and technical issues (5 entries). Ten entries were ascribed to more than one group. Pathogenic single nucleotide variants (pSNVs), both homo- or heteroplasmic variants, have been widely reported in MitD, with heteroplasmy levels varying among brain regions; however, pSNVs are rarer in NeuD, PsyD and ageing. A lower mtDNA copy number (CN) in disease was described in most, but not all, of the identified studies. mtDNA deletions were identified in individuals in the four clinical categories and ageing. Notably, brain samples showed significantly more mtDNA deletions and at higher heteroplasmy percentages than blood samples, and several of the deletions present in the brain were not detected in the blood. Finally, mtDNA heteroplasmy, mtDNA CN and the deletion levels varied depending on the brain region studied.
INTERPRETATION
mtDNA alterations are well known to affect human tissues, including the brain. In general, we found that studies of MitD, NeuD, PsyD, and ageing were highly variable in terms of the type of disease or ageing process investigated, number of screened individuals, studied brain regions and technology used. In NeuD and PsyD, no particular type of mtDNA alteration could be unequivocally assigned to any specific disease or diagnostic group. However, the presence of mtDNA deletions and mtDNA CN variation imply a role for mtDNA in NeuD and PsyD. Heteroplasmy levels and threshold effects, affected brain regions, and mitotic segregation patterns of mtDNA alterations may be involved in the complex inheritance of NeuD and PsyD and in the ageing process. Therefore, more information is needed regarding the type of mtDNA alteration, the affected brain regions, the heteroplasmy levels, and their relationship with clinical phenotypes and the ageing process.
FUNDING
Hospital Universitari Institut Pere Mata; Institut d'Investigació Sanitària Pere Virgili; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI18/00514).
Topics: Brain; DNA, Mitochondrial; Humans; Mitochondria; Mitochondrial Diseases; Mutation
PubMed: 35085849
DOI: 10.1016/j.ebiom.2022.103815 -
Biomedicines Aug 2021This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control... (Review)
Review
This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned the effects of treadmill exercise on neural mitochondria in Parkinson's disease were included. The CAMARADES checklist was used to assess the methodological quality of the studies. Ten controlled trials were included (median CAMARADES score = 5.7/10) with various treadmill exercise durations (1-18 weeks). Seven studies analyzed the neural mitochondrial respiration, showing that treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II-V abnormalities in Parkinson's disease. Nine studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson's disease. The review findings supported the hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease, suggesting that treadmill training might slow down the progression of Parkinson's disease.
PubMed: 34440215
DOI: 10.3390/biomedicines9081011 -
International Journal of Molecular... Nov 2022Thymoquinone (TQ), a plant-based bioactive constituent derived from the volatile oil of , has been shown to possess some anti-neoplastic activities. The present study...
Thymoquinone (TQ), a plant-based bioactive constituent derived from the volatile oil of , has been shown to possess some anti-neoplastic activities. The present study aimed to investigate the mitochondria and apoptosis observed when TQ is applied against hepatocellular carcinoma (HepG2) and cholangiocarcinoma (HuCCT1) cells, two of the most common primary tumors of the liver. All cell lines were treated with increasing concentrations of TQ for varying durations. The anti-proliferative effect of TQ was measured using the methoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and resulted in dose- and time-dependent growth inhibition in both cell lines. Cell cycle, apoptosis, and assessment of mitochondria viability by morphology assessment and evaluation of the mitochondrial membrane potential were investigated. The present study confirms that TQ caused cell cycle arrest at different phases and induced apoptosis in both cell lines. A systematic review of rodent animal models was also carried out. Overall, our data seem to represent the most robust results, suggesting that TQ possesses promising therapeutic potential as an anti-tumor agent for the treatment of hepatocellular carcinoma and cholangiocarcinoma.
Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Benzoquinones; Apoptosis; Cholangiocarcinoma; Mitochondria; Bile Ducts, Intrahepatic; Bile Duct Neoplasms
PubMed: 36498999
DOI: 10.3390/ijms232314669 -
Frontiers in Cardiovascular Medicine 2023Inflammation and dyslipidemia underlie the pathological basis of atherosclerosis (AS). Clinical studies have confirmed that there is still residual risk of... (Review)
Review
Aldehyde dehydrogenase 2 and NOD-like receptor thermal protein domain associated protein 3 inflammasome in atherosclerotic cardiovascular diseases: A systematic review of the current evidence.
Inflammation and dyslipidemia underlie the pathological basis of atherosclerosis (AS). Clinical studies have confirmed that there is still residual risk of atherosclerotic cardiovascular diseases (ASCVD) even after intense reduction of LDL. Some of this residual risk can be explained by inflammation as anti-inflammatory therapy is effective in improving outcomes in subjects treated with LDL-lowering agents. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation is closely related to early-stage inflammation in AS. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme of toxic aldehyde metabolism located in mitochondria and works in the metabolism of toxic aldehydes such as 4-HNE and MDA. Despite studies confirming that ALDH2 can negatively regulate NLRP3 inflammasome and delay the development of atherosclerosis, the mechanisms involved are still poorly understood. Reactive Oxygen Species (ROS) is a common downstream pathway activated for NLRP3 inflammasome. ALDH2 can reduce the multiple sources of ROS, such as oxidative stress, inflammation, and mitochondrial damage, thereby reducing the activation of NLRP3 inflammasome. Further, according to the downstream of ALDH2 and the upstream of NLRP3, the molecules and related mechanisms of ALDH2 on NLRP3 inflammasome are comprehensively expounded as possible. The potential mechanism may provide potential inroads for treating ASCVD.
PubMed: 36910525
DOI: 10.3389/fcvm.2023.1062502 -
Frontiers in Molecular Neuroscience 2021This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural... (Review)
Review
Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies.
This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for studies) and the TOXRTOOL checklist (for studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome , caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808). [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].
PubMed: 35002619
DOI: 10.3389/fnmol.2021.778569