-
Journal of Alzheimer's Disease Reports Apr 2020Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is... (Review)
Review
Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Sildenafil inhibits PDE5 and increases cGMP levels. Integrating previous findings, we determine that most doses of sildenafil (especially low doses) likely activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) via protein kinase G-mediated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) phosphorylation and/or Sirtuin-1 activation and PGC1α deacetylation. Via PGC1α signaling, low-dose sildenafil likely suppresses β-secretase 1 expression and amyloid-β (Aβ) generation, upregulates antioxidant enzymes, and induces mitochondrial biogenesis. Plus, sildenafil should increase brain perfusion, insulin sensitivity, long-term potentiation, and neurogenesis while suppressing neural apoptosis and inflammation. A systematic review of sildenafil in AD was undertaken. sildenafil protected neural mitochondria from Aβ and advanced glycation end products. In transgenic AD mice, sildenafil was found to rescue deficits in CREB phosphorylation and memory, upregulate brain-derived neurotrophic factor, reduce reactive astrocytes and microglia, decrease interleukin-1β, interleukin-6, and tumor necrosis factor-α, decrease neural apoptosis, increase neurogenesis, and reduce tau hyperphosphorylation. All studies that tested Aβ levels reported significant improvements except the two that used the highest dosage, consistent with the dose-limiting effect of cGMP-induced phosphodiesterase 2 (PDE2) activation and cAMP depletion on PGC1α signaling. In AD patients, a single dose of sildenafil decreased spontaneous neural activity, increased cerebral blood flow, and increased the cerebral metabolic rate of oxygen. A randomized control trial of sildenafil (ideally with a PDE2 inhibitor) in AD patients is warranted.
PubMed: 32467879
DOI: 10.3233/ADR-200166 -
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 -
Psychosomatic Medicine 2018Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress...
OBJECTIVE
Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function.
METHODS
A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria.
RESULTS
A total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number.
CONCLUSONS
Overall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.
Topics: Animals; Humans; Mitochondria; Stress, Psychological
PubMed: 29389736
DOI: 10.1097/PSY.0000000000000545 -
World Journal of Surgical Oncology Oct 2022Mitochondria play critical roles in cellular physiological activity as cellular organelles. Under extracellular stimulation, mitochondria undergo constant fusion and... (Review)
Review
BACKGROUND
Mitochondria play critical roles in cellular physiological activity as cellular organelles. Under extracellular stimulation, mitochondria undergo constant fusion and fission to meet different cellular demands. Mitochondrial dynamics, which are involved in mitochondrial fusion and fission, are regulated by specialized proteins and lipids, and their dysregulation causes human diseases, such as cancer. The advanced literature about the crucial role of mitochondrial dynamics in breast cancer is performed.
METHODS
All related studies were systematically searched through online databases (PubMed, Web of Science, and EMBASE) using keywords (e.g., breast cancer, mitochondrial, fission, and fusion), and these studies were then screened through the preset inclusion and exclusion criteria.
RESULTS
Eligible studies (n = 19) were evaluated and discussed in the systematic review. These advanced studies established the roles of mitochondrial fission and fusion of breast cancer in the metabolism, proliferation, survival, and metastasis. Importantly, the manipulating of mitochondrial dynamic is significant for the progresses of breast cancer.
CONCLUSION
Understanding the mechanisms underlying mitochondrial fission and fusion during tumorigenesis is important for improving breast cancer treatments.
Topics: Breast Neoplasms; Cell Transformation, Neoplastic; Female; Humans; Lipids; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins
PubMed: 36192752
DOI: 10.1186/s12957-022-02799-5 -
Oxidative Medicine and Cellular... 2018Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years,... (Meta-Analysis)
Meta-Analysis Review
Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years, particular focus has been put on mitochondria-targeted antioxidants, to decrease the concentration of reactive oxygen species and help alleviate the accumulation of oxidative damage and associated aging. MitoQ is a mitochondria-targeted antioxidant of which is reported to support healthy aging. The aim of this systematic review is to investigate the effects of MitoQ on oxidative outcomes related to the aging process. A predeveloped search strategy was run against MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, which identified 10,255 articles of interest, with 27 of these finalised for use after screening. Three outcomes had sufficient data to meta-analyse nitrotyrosine concentration (190 animals, SMD -0.67, 95% CI (-1.30, -0.05), = 0.04), membrane potential (63 animals, MD 11.44, 95% CI (1.28-21.60), = 0.03), and protein carbonyl concentration (182 animals, SMD -0.13, 95% CI (-0.44, 0.18), = 0.41). MitoQ intervention produced a statistically significant reduction in nitrotyrosine concentration and increased membrane potential. MitoQ may be of some benefit in alleviating oxidative stress related to aging.
Topics: Aging; Biomarkers; Humans; Mitochondria; Organophosphorus Compounds; Ubiquinone
PubMed: 30116495
DOI: 10.1155/2018/8575263 -
Molecular Neurodegeneration Nov 2017Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain.... (Review)
Review
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients. Furthermore, knockout or genetic inactivation of NADPH oxidases exert a neuroprotective effect and reduce detrimental aspects of pathology in experimental models of the disease. However, the connections between NADPH oxidases and the biological processes believed to contribute to neuronal death are not well known. This review provides a comprehensive summary of our current understanding about expression and physiological function of NADPH oxidases in neurons, microglia and astrocytes and their pathophysiological roles in PD. It summarizes the findings supporting the role of both microglial and neuronal NADPH oxidases in cellular disturbances associated with PD such as neuroinflammation, alpha-synuclein accumulation, mitochondrial and synaptic dysfunction or disruption of the autophagy-lysosome system. Furthermore, this review highlights different steps that are essential for NADPH oxidases enzymatic activity and pinpoints major obstacles to overcome for the development of effective NADPH oxidases inhibitors for PD.
Topics: Animals; Humans; NADPH Oxidases; Parkinson Disease
PubMed: 29132391
DOI: 10.1186/s13024-017-0225-5 -
Mitochondrion Jul 2021Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established... (Review)
Review
Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from oxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research. In this systematic review we aim to provide a comprehensive overview and critical appraisal of strategies reported to circumvent the Crabtree effect.
Topics: Cell Culture Techniques; Culture Media; Glucose; Glycolysis; Humans; Mitochondria; Mitochondrial Dynamics; Oxidative Phosphorylation
PubMed: 33812964
DOI: 10.1016/j.mito.2021.03.014 -
The World Journal of Men's Health Dec 2016Male factors account for 20% to 50% of infertility cases, and infection in the genitourinary tract may play a contributing role in up to 15% of male infertility.... (Review)
Review
Male factors account for 20% to 50% of infertility cases, and infection in the genitourinary tract may play a contributing role in up to 15% of male infertility. Leukocytospermia is a well-known indicator of infection or inflammation in the male sex glands and the urogenital tract. Although great deal of effort has been expended to elucidate definite management strategies in infertile men with leukocytospermia, the gold standard of treatment remains unclear. Until recently, broad spectrum antibiotics and antioxidants have been used in the treatment of leukocytospermia for male infertility to eliminate infection and reduce reactive oxygen free radicals produced inside cellular mitochondria as a result of inflammation. The present review reveals that antibiotics might improve sperm parameters, the rate of resolution of leukocytospermia, the bacteriologic cure rate, and even the pregnancy rate, although some reports conflict. Antioxidants might also have clinical benefits for sperm function as shown by studies. However, the data are insufficient to conclude whether antibiotics and antioxidants for the treatment of infertile men with leukocytospermia are effective or not. Better designed investigations into leukocytospermia are needed.
PubMed: 28053945
DOI: 10.5534/wjmh.2016.34.3.165 -
Frontiers in Genetics 2021Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional... (Review)
Review
Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional dysregulation accompanied by epigenetic alterations is an early and central disease mechanism in HD yet, the exact mechanisms and regulators, and their associated gene expression programs remain incompletely understood. This systematic review investigates genome-wide transcriptional studies that were conducted using RNA sequencing (RNA-seq) technology in HD patients and models. The review protocol was registered at the Open Science Framework (OSF). The biomedical literature and gene expression databases, PubMed and NCBI BioProject, Array Express, European Nucleotide Archive (ENA), European Genome-Phenome Archive (EGA), respectively, were searched using the defined terms specified in the protocol following the PRISMA guidelines. We conducted a complete literature and database search to retrieve all RNA-seq-based gene expression studies in HD published until August 2020, retrieving 288 articles and 237 datasets from PubMed and the databases, respectively. A total of 27 studies meeting the eligibility criteria were included in this review. Collectively, comparative analysis of the datasets revealed frequent genes that are consistently dysregulated in HD. In postmortem brains from HD patients, and genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage, and and genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins. Specifically in indirect pathway medium spiny neurons (iMSNs), mitochondria related genes were among the top uniquely dysregulated genes. Interestingly, blood from HD patients showed commonly differentially expressed genes with a number of brain regions and cells, with the highest number of overlapping genes with MSNs and BA9 region at symptomatic stage. We also found the differential expression and predicted altered activity of a set of transcription factors and epigenetic regulators, including and , respectively, which may underlie the observed transcriptional changes in HD. Altogether, our work provides a complete overview of the transcriptional studies in HD, and by data synthesis, reveals a number of common and unique gene expression and regulatory changes across different cell and tissue types in HD. These changes could elucidate new insights into molecular mechanisms of differential vulnerability in HD. https://osf.io/pm3wq.
PubMed: 34721539
DOI: 10.3389/fgene.2021.751033 -
International Journal of Environmental... Feb 2023An understanding of physical demands during official competitions is essential to achieving the highest performance in handball. The aim of this systematic review was to... (Review)
Review
An understanding of physical demands during official competitions is essential to achieving the highest performance in handball. The aim of this systematic review was to summarise the available scientific evidence associated with physical demands during official competitions in elite handball according to playing positions, competition level and gender. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 17 studies were selected after a systematic search and selection process of three digital databases: PubMed, Web of Science and Sport Discus. The quality of the selected studies was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology checklist; the average score was 18.47 points. The sample consisted of 1175 handball players, of whom 1042 were men (88.68%) and 133 were women (11.32%). The results show that an elite handball player covered on average 3664.4 ± 1121.6 m during a match. The average running pace was 84.8 ± 17.2 m∙min. The total distance covered was largely greater in national competitions (4506.7 ± 647.9 m) compared with international competitions (2190.3 ± 1950.5 m) (effect size (ES) = 1.2); however, the running pace did not present any significant difference between the international or national level (ES = 0.06). In regard to gender, the total distance covered was moderately greater in female competitions (4549.1 ± 758.6 m) compared with male competitions (3332.6 ± 1257.7 m) (ES = 0.9), and the running pace was largely greater in female competitions (110.5 ± 7.2 m∙min) compared with male competitions (78.4 ± 19.7 m∙min) (ES = 1.6). In relation to playing position, backs and wings covered a moderately greater total distance (ES = 0.7 and 0.6) and slightly more meters per minute (ES = 0.4 and 0.2) than pivots. Moreover, the technical activity profile differed between playing positions. Backs performed moderately more throws than pivots and wings (ES = 1.2 and 0.9), pivots exhibited largely more body contact than backs and wings, and wings performed moderately more fast breaks (6.7 ± 3.0) than backs (2.2 ± 2.3) (ES = 1.8). Therefore, this research study provides practical applications for handball coaches and strength and conditioning professionals with respect to designing and implementing more individualised training programmes to maximise performance and reduce injury risk.
Topics: Humans; Male; Female; Athletic Performance; Anthropometry
PubMed: 36834047
DOI: 10.3390/ijerph20043353