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Medicine Dec 2014The connection between Helicobacter pylori (Hp) infection and eye diseases has been increasingly reported in the literature and in active research. The implication of... (Review)
Review
The connection between Helicobacter pylori (Hp) infection and eye diseases has been increasingly reported in the literature and in active research. The implication of this bacterium in chronic eye diseases, such as blepharitis, glaucoma, central serous chorioretinopathy and others, has been hypothesized. Although the mechanisms by which this association occurs are currently unknown, this review describes shared pathogenetic mechanisms in an attempt to identify a lowest common denominator between eye diseases and Hp infection. The aim of this review is to assess whether different studies could be compared and to establish whether or not Hp infection and Eye diseases share common pathogenetic aspects. In particular, it has been focused on oxidative damage as a possible link between these pathologies. Text word search in Medline from 1998 to July 2014. 152 studies were included in our review. Were taken into considerations only studies that related eye diseases more frequent and/or known. Likely oxidative stress plays a key role. All of the diseases studied seem to follow a common pattern that implicates a cellular response correlated with a sublethal dose of oxidative stress. These alterations seem to be shared by both Hp infections and ocular diseases and include the following: decline in mitochondrial function, increases in the rate of reactive oxygen species production, accumulation of mitochondrial DNA mutations, increases in the levels of oxidative damage to DNA, proteins and lipids, and decreases in the capacity to degrade oxidatively damaged proteins and other macromolecules. This cascade of events appears to repeat itself in different diseases, regardless of the identity of the affected tissue. The trabecular meshwork, conjunctiva, and retina can each show how oxidative stress may acts as a common disease effector as the Helicobacter infection spreads, supported by the increased oxidative damage and other inflammation.
Topics: Eye Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Oxidative Stress
PubMed: 25526440
DOI: 10.1097/MD.0000000000000216 -
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 -
Medical Hypothesis, Discovery &... 2017Diabetic Retinopathy (DR) is the most prevalent health problem, which is influenced by environmental and genetic factors with an increasing prevalence. The current... (Review)
Review
Diabetic Retinopathy (DR) is the most prevalent health problem, which is influenced by environmental and genetic factors with an increasing prevalence. The current systematic review is focused on mtDNA modification, including polymorphism and mutation/deletion, with a direct effect on DR.This systematic search was initially done through PubMed, Cochrane, EMBASE, SCOPUS, and Web of Science without a restriction on the years of publication. The terms searched included ''mtDNA'', ''mitochondrial DNA'', ''diabetes'', ''diabetic'', ''retina'', and ''diabetic retinopathy''. Animal, cohort, cross-sectional, and in vitro studies, as well as case series, case reports, review articles, and Letters to Editor were excluded from this research.From 1528 resulting searched articles, only 12papers were finally chosen as the case-control studies considering mtDNA gene and DR. Actually, of these 12 articles, 8 studies were concerned with mtDNA polymorphisms (UCP1, UCP2, ROMO-1, and Mn-SOD) and 4 articles were related to mtDNA mutation (A3243G mutation in tRNA gene and mtDNA deletion (ΔmtDNA 4977)).Some conflicting results were found between the selected genetic modifications of mtDNA, such as Mn-SOD, UCP1, ΔmtDNA 4977, tRNALeu (UUR), and ROMO-1.Finally, A3243G mutation in the tRNA gene and rs660339 and V16A polymorphisms of UCP2 and Mn-SOD genes were respectively considered as the most important factors in the pathogenesis of DR.
PubMed: 29367932
DOI: No ID Found -
Frontiers in Medicine 2022Acute respiratory distress syndrome (ARDS) is one of the main causes of Intensive Care Unit morbidity and mortality. Metabolic biomarkers of mitochondrial dysfunction...
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is one of the main causes of Intensive Care Unit morbidity and mortality. Metabolic biomarkers of mitochondrial dysfunction are correlated with disease development and high mortality in many respiratory conditions, however it is not known if they can be used to assess risk of mortality in patients with ARDS.
OBJECTIVES
The aim of this systematic review was to examine the link between recorded biomarkers of mitochondrial dysfunction in ARDS and mortality.
METHODS
A systematic review of CINAHL, EMBASE, MEDLINE, and Cochrane databases was performed. Studies had to include critically ill ARDS patients with reported biomarkers of mitochondrial dysfunction and mortality. Information on the levels of biomarkers reflective of energy metabolism and mitochondrial respiratory function, mitochondrial metabolites, coenzymes, and mitochondrial deoxyribonucleic acid (mtDNA) copy number was recorded. RevMan5.4 was used for meta-analysis. Biomarkers measured in the samples representative of systemic circulation were analyzed separately from the biomarkers measured in the samples representative of lung compartment. Cochrane risk of bias tool and Newcastle-Ottawa scale were used to evaluate publication bias (Prospero protocol: CRD42022288262).
RESULTS
Twenty-five studies were included in the systematic review and nine had raw data available for follow up meta-analysis. Biomarkers of mitochondrial dysfunction included mtDNA, glutathione coupled mediators, lactate, malondialdehyde, mitochondrial genetic defects, oxidative stress associated markers. Biomarkers that were eligible for meta-analysis inclusion were: xanthine, hypoxanthine, acetone, -pentane, isoprene and mtDNA. Levels of mitochondrial biomarkers were significantly higher in ARDS than in non-ARDS controls ( = 0.0008) in the blood-based samples, whereas in the BAL the difference did not reach statistical significance ( = 0.14). mtDNA was the most frequently measured biomarker, its levels in the blood-based samples were significantly higher in ARDS compared to non-ARDS controls ( = 0.04). Difference between mtDNA levels in ARDS non-survivors compared to ARDS survivors did not reach statistical significance ( = 0.05).
CONCLUSION
Increased levels of biomarkers of mitochondrial dysfunction in the blood-based samples are positively associated with ARDS. Circulating mtDNA is the most frequently measured biomarker of mitochondrial dysfunction, with significantly elevated levels in ARDS patients compared to non-ARDS controls. Its potential to predict risk of ARDS mortality requires further investigation.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero], identifier [CRD42022288262].
PubMed: 36590959
DOI: 10.3389/fmed.2022.1011819 -
Medicina (Kaunas, Lithuania) Mar 2023. Defects of mitochondrial DNA (mtDNA) involved in the function of the mitochondrial electron transport chain can result in primary mitochondrial diseases (PMDs).... (Review)
Review
. Defects of mitochondrial DNA (mtDNA) involved in the function of the mitochondrial electron transport chain can result in primary mitochondrial diseases (PMDs). Various features can influence the phenotypes of different PMDs, with relevant consequences on clinical presentation, including the presence of hearing impairment. This paper aims to describe the hearing loss related to different PMDs, and when possible, their phenotype. A systematic review was performed according to PRISMA guidelines, searching Medline until December 2022. A total of 485 papers were identified, and based on specified criteria, 7 were included in this study. A total of 759 patients affected by PMDs and hearing loss were included. The age of patients ranged from 2 days to 78 years old, and the male-to-female ratio was 1.3:1. The percentage of subjects affected by hearing loss was 40.8%, (310/759), and in most cases, hearing impairment was described as sensorineural, bilateral, symmetrical, and progressive, with different presentations depending on age and syndrome severity. . PMDs are challenging conditions with different clinical phenotypes. Hearing loss, especially when bilateral and progressive, may represent a red flag; its association with other systemic disorders (particularly neuromuscular, ocular, and endocrine) should alert clinicians, and confirmation via genetic testing is mandatory nowadays.
Topics: Male; Female; Humans; Hearing Loss, Sensorineural; Mitochondrial Diseases; Mitochondria; Hearing Loss; DNA, Mitochondrial; Deafness
PubMed: 36984609
DOI: 10.3390/medicina59030608 -
Medicine Jul 2019Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA 4977 bp deletion between presbycusis patients and controls by conducting a meta-analysis of published studies.
METHODS
Databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to collect case-control studies on the correlation between mitochondrial DNA 4977 bp deletion and presbycusis. The research findings of related articles were collected according to the inclusion criteria. Pooled odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated. Meanwhile, subgroup analysis was performed to examine the source of heterogeneity. Revman 5.3 and Stata 12.0 software were used for data synthesis.
RESULTS
Eight English and Chinese studies were included in the meta-analysis, the results of which showed that mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis (OR = 8.16, 95% CI: 3.51-18.99), and the difference was statistically significant (P <. 01). Analysis of the polled OR showed the incidence of mtDNA 4977 bp deletion was 8.50 times higher in Asians with presbycusis than in the control group. And the OR in the studies of occidentals was 7.24. Sample source analysis was also performed with the sample source divided by temporal bone source and other sources (hair and blood). The OR was 4.18 and 22.36 for the temporal bone and other sources, respectively.
CONCLUSION
Mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis.
Topics: Case-Control Studies; DNA, Mitochondrial; Humans; Presbycusis; Sequence Deletion
PubMed: 31277167
DOI: 10.1097/MD.0000000000016302 -
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 -
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 -
Human Reproduction Update Jan 2018Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance... (Review)
Review
BACKGROUND
Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence.
OBJECTIVE AND RATIONALE
This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract.
SEARCH METHODS
A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects.
OUTCOMES
A total of 890 articles were identified of which 197 (32 clinical, 165 animal studies) were selected for qualitative analysis. While the clinical data from men with hyperglycemia-induced reproductive dysfunction were reported in most studies on T1D, the study designs were variable and lacked complete information on patients. Moreover, only a few studies (and mostly animal studies) addressed the underlying mechanisms of how hyperglycemia induces infertility. Potential causes included impaired function of the hypothalamic-pituitary-gonadal axis, increased DNA damage, perturbations in the system of advanced glycation endproducts and their receptor, oxidative stress, increased endoplasmatic reticulum stress, modulation of cellular pathways, impaired mitochondrial function and disrupted sympathetic innervation. However, intervention studies to identify and confirm the pathological mechanisms were missing: data that are essential in understanding these interactions.
WIDER IMPLICATIONS
While the effects of regulating the hyperglycemia by the use of insulin and other modulators of glucose metabolism have been reported, more clinical trials providing high quality evidence and specifically addressing the beneficial effects on male reproduction are required. We conclude that interventions using insulin to restore normoglycemia should be a feasible approach to assess the proposed underlying mechanisms of infertility.
Topics: Animals; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Infertility, Male; Insulin; Male; Mitochondrial Diseases; Reproduction
PubMed: 29136166
DOI: 10.1093/humupd/dmx033 -
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