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Frontiers in Immunology 2022As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several...
As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several cytoplasm pattern recognition receptors exist to sense the attacks from either foreign or host origins, triggering the immune response to battle with the infections. Among them, cGAS-STING is the major pathway that mainly responds to microbial DNA, DNA virus infections, or self-DNA, which mainly comes from genome instability by-product or released DNA from the mitochondria. cGAS was initially found functional in the cytoplasm, although intriguing evidence indicates that cGAS exists in the nucleus where it is involved in the DNA damage repair process. Because the close connection between DNA damage response and immune response and cGAS recognizes DNA in length-dependent but DNA sequence-independent manners, it is urgent to clear the function balance of cGAS in the nucleus versus cytoplasm and how it is shielded from recognizing the host origin DNA. Here, we outline the current conception of immune response and the regulation mechanism of cGAS in the nucleus. Furthermore, we will shed light on the potential mechanisms that are restricted to be taken away from self-DNA recognition, especially how post-translational modification regulates cGAS functions.
Topics: Signal Transduction; Immunity, Innate; Nucleotidyltransferases; DNA; DNA Damage
PubMed: 36591232
DOI: 10.3389/fimmu.2022.1076784 -
International Journal of Molecular... Nov 2022Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased... (Review)
Review
Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. One of the key mechanisms determining myocardial dysfunction in heart failure is oxidative stress. MicroRNAs (miRNAs, miRs) are short, endogenous, conserved, single-stranded non-coding RNAs of around 21-25 nucleotides in length that act as regulators of multiple processes. A systematic review following the PRISMA guidelines was performed on the evidence on the interplay between microRNA and oxidative stress in heart failure. A search of Pubmed, Embase, Scopus, and Scopus direct databases using the following search terms: 'heart failure' AND 'oxidative stress' AND 'microRNA' or 'heart failure' AND 'oxidative stress' AND 'miRNA' was conducted and resulted in 464 articles. Out of them, 15 full text articles were eligible for inclusion in the qualitative analysis. Multiple microRNAs are involved in the processes associated with oxidative stress leading to heart failure development including mitochondrial integrity and function, antioxidant defense, iron overload, ferroptosis, and survival pathways.
Topics: Humans; MicroRNAs; Heart Failure; Oxidative Stress; Antioxidants; Cardiomyopathies
PubMed: 36499336
DOI: 10.3390/ijms232315013 -
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 2022Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial...
OBJECTIVE
Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial respiration and cardiac mitochondrial quality control in IHD.
METHODS
A narrative synthesis was conducted after searching animal studies written in English in three databases (PubMed, Web of Science, and EMBASE) until December 2020. Studies that used aerobic exercise as an intervention for at least 3 weeks and had at least normal, negative (sedentary IHD), and positive (exercise-trained IHD) groups were included. The CAMARADES checklist was used to check the quality of the included studies.
RESULTS
The 10 included studies (CAMARADES score: 6-7/10) used swimming or treadmill exercise for 3-8 weeks. Seven studies showed that ET ameliorated cardiac mitochondrial respiratory function as manifested by decreased reactive oxygen species (ROS) production and increased complexes I-V activity, superoxide dismutase 2 (SOD2), respiratory control ratio (RCR), NADH dehydrogenase subunits 1 and 6 (ND1/6), Cytochrome B (CytB), and adenosine triphosphate (ATP) production. Ten studies showed that ET improved cardiac mitochondrial quality control in IHD as manifested by enhanced and/or controlled mitochondrial biogenesis, dynamics, and mitophagy. Four other studies showed that ET resulted in better cardiac mitochondrial physiological characteristics.
CONCLUSION
Exercise training could improve cardiac mitochondrial functions, including respiration, biogenesis, dynamics, and mitophagy in IHD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID=226817, identifier: CRD42021226817.
PubMed: 36304547
DOI: 10.3389/fcvm.2022.949744 -
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 -
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 -
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 -
Journal of Clinical Pathology Dec 2022Polycystic ovary syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, while the contribution of mitochondrial genetics in PCOS remains largely unknown.
AIM
This study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS.
METHODS
A literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE, (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) were extracted. Quantitative data were presented in forest plots, and where this was not possible, data were analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool.
RESULTS
Of the 13 812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9 bp deletion, and aberrant single nucleotide polymorphisms (SNPs) in the ND5, A6 and 7 transfer RNA-encoding genes. They also showed lower frequencies of two SNPs in the D-loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number.
CONCLUSION
Women with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations.
PROSPERO REGISTRATION NUMBER
CRD42021267991.
Topics: Female; Humans; Polycystic Ovary Syndrome; Genome, Mitochondrial; DNA, Mitochondrial; Polymorphism, Single Nucleotide; Mitochondria
PubMed: 36113966
DOI: 10.1136/jcp-2021-208028 -
Journal of Orthopaedic Translation Jul 2022Sarcopenia is a hallmark of the ageing process, which is characterized by the decline in muscle mass and strength. Growing evidence indicates that mitochondria... (Review)
Review
BACKGROUND
Sarcopenia is a hallmark of the ageing process, which is characterized by the decline in muscle mass and strength. Growing evidence indicates that mitochondria dysfunction play core roles in this process. Meanwhile, physical exercise is regarded as one of the efficiency therapies to attenuate sarcopenia via regulating mitochondrial function during ageing. However, the specific mechanisms among exercise, mitochondrial function and sarcopenia are still unclear. The aim of this systematic review is to delineate the effects of physical exercise on mitochondria during ageing in order to explore potential target for rescuing sarcopenia.
METHODS
A systematic literature search was performed in PubMed, Embase and Web of Science. Information was extracted from the included studies for review.
RESULTS
In this review, 16 pre-clinical studies were included and 105 clinical studies that were not mechanistic research were excluded. 16 pre-clinical studies provided evidence that physical exercise could affect mitochondrial quality control to attenuate sarcopenia. Most of the included studies described the important role of mitochondrial dynamic equilibrium in sarcopenia and showed that effective physical exercise could influence mitochondrial biogenesis, fusion, fission and mitophagy to attenuate sarcopenia in aged animal.
CONCLUSIONS
This systematic review provides an up-to-date sequential overview and highlights the link in the potential mitochondria-related target and physical exercise in aged animal.
TRANSLATION OF THIS ARTICLE
Currently, there is no standard treatment method for sarcopenia. This systematic review revealed the underlying mechanisms for how physical exercise improved muscle performance via regulating mitochondrial dynamic equilibrium, which could provide scientific support for using exercise as a timely intervention for sarcopenia. Additionally, this systematic review allows a better understanding of mitochondrial dynamic equilibrium and exercise for future development of new therapeutic interventions to attenuate sarcopenia.
PubMed: 36090001
DOI: 10.1016/j.jot.2022.06.003 -
Cells Aug 2022Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease (DKD). Compared to the vast body of evidence from preclinical in vitro and in vivo... (Review)
Review
Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease (DKD). Compared to the vast body of evidence from preclinical in vitro and in vivo studies, evidence from human studies is limited. In a comprehensive search of the published literature, findings from studies that reported evidence of mitochondrial dysfunction in individuals with DKD were examined. Three electronic databases (PubMed, Embase, and Scopus) were searched in March 2022. A total of 1339 articles were identified, and 22 articles met the inclusion criteria. Compared to non-diabetic controls (NDC) and/or individuals with diabetes but without kidney disease (DC), individuals with DKD (age ~55 years; diabetes duration ~15 years) had evidence of mitochondrial dysfunction. Individuals with DKD had evidence of disrupted mitochondrial dynamics (11 of 11 articles) uncoupling (2 of 2 articles), oxidative damage (8 of 8 articles), decreased mitochondrial respiratory capacity (1 of 1 article), decreased mtDNA content (5 of 6 articles), and decreased antioxidant capacity (3 of 4 articles) compared to ND and/or DC. Neither diabetes nor glycemic control explained these findings, but rather presence and severity of DKD may better reflect degree of mitochondrial dysfunction in this population. Future clinical studies should include individuals closer to diagnosis of diabetes to ascertain whether mitochondrial dysfunction is implicated in the development of, or is a consequence of, DKD.
Topics: Antioxidants; Diabetes Mellitus; Diabetic Nephropathies; Humans; Middle Aged; Mitochondria; Mitochondrial Dynamics; Oxidative Stress
PubMed: 36010558
DOI: 10.3390/cells11162481