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Cell Journal May 2024The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some...
OBJECTIVE
The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) genes have been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to the oocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs of PCOS, with or without insulin resistance.
MATERIALS AND METHODS
In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive (IS), and control (fertile women with male infertility history) groups. The expression of and was studied by real-time polymerase chain reaction (PCR), and normalization was performed considering and as reference genes. One-way ANOVA and Tukey test were used for data analysis.
RESULTS
The results showed that the expression of and was significantly higher in the IR group than IS and control groups (P<0.01). showed the highest expression in the IS group, which was significantly different from other groups (P<0.01). The other genes of interest, except , were observed with the most transcriptional levels in the IS group, although there was no significant difference for those genes.
CONCLUSION
Altered expression of genes involved in mitochondrial function compared to the control group in CCs of both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to the pathophysiology of PCOS.
PubMed: 38736407
DOI: 10.22074/cellj.2024.2006763.1357 -
Antioxidants (Basel, Switzerland) Mar 2024The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B,... (Review)
Review
Investigating the Neuroprotective and Cognitive-Enhancing Effects of : A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.
The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
PubMed: 38671841
DOI: 10.3390/antiox13040393 -
Genome Research Apr 2024Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a...
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, = 0.01, n = 13); however, no correlation was observed in fibroblasts ( = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.
Topics: Humans; DNA, Mitochondrial; Gene Frequency; Genetic Variation; Mitochondria; Mitochondrial Diseases; Oxidative Phosphorylation
PubMed: 38627095
DOI: 10.1101/gr.278200.123 -
Marine Environmental Research Apr 2024Microplastics (5 mm - 1 μm) have become one of the major pollutants in the environment. Numerous studies have shown that microplastics can have negative impacts on... (Meta-Analysis)
Meta-Analysis Review
Microplastics (5 mm - 1 μm) have become one of the major pollutants in the environment. Numerous studies have shown that microplastics can have negative impacts on aquatic organisms, affecting their liver function levels. However, the extent of these effects and their potential toxicological mechanisms are largely unknown. In this study, a meta-analysis and systematic review were conducted to assess the effects of microplastics on fish liver function and summarize the potential toxicological mechanisms of microplastic-induced liver toxicity. The meta-analysis results indicate that compared to the control group, exposure to microplastics significantly affects fish liver indicators: aspartate aminotransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), alkaline phosphatase (ALP) (p < 0.001), total protein (TP) (p < 0.001), and lactate dehydrogenase (LDH) (p < 0.001), including oxidative stress indicators: superoxide dismutase (SOD) (p < 0.001), glutathione S-transferase (GST) (p < 0.001), glutathione (GSH) (p < 0.001), and malondialdehyde (MDA) (p < 0.001) in fish liver. For fish living in different environments, the potential toxicological mechanisms of microplastics exposure on fish liver may exhibit some differences. For freshwater fish, the mechanism may be that microplastics exposure causes overproduction of reactive oxygen species (ROS) in fish hepatocyte mitochondria. ROS promotes the expression of toll-like receptor 2 (TLR2) and activates downstream molecules myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) of the TLR2 signaling pathway, leading to phosphorylation of NF-κB p65. This leads to the release of inflammatory factors and oxidative stress and inflammation in fish liver. In addition, for seawater fish, the mechanism may be that microplastics exposure can cause damage or death of fish hepatocytes, leading to continuous pathological changes, inflammation, lipid and energy metabolism disorders, thereby causing significant changes in liver function indexes.
Topics: Animals; Microplastics; Plastics; Toll-Like Receptor 2; Reactive Oxygen Species; Liver; Oxidative Stress; Glutathione; Inflammation; Fishes
PubMed: 38442589
DOI: 10.1016/j.marenvres.2024.106423 -
Journal of Animal Science Jan 2024Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in... (Meta-Analysis)
Meta-Analysis
Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in genomic methods and omics techniques have made it possible to breed more efficient dairy cows through genomic selection. The aim of this review is to obtain a comprehensive understanding of the biological background of feed efficiency (FE) complex traits in purebred Holstein dairy cows including heritability estimate, and genetic markers, genes, and pathways participating in FE regulation mechanism. Through a literature search, we systematically reviewed the heritability estimation, molecular genetic markers, genes, biomarkers, and pathways of traits related to feeding efficiency in Holstein dairy cows. A meta-analysis based on a random-effects model was performed to combine reported heritability estimates of FE complex. The heritability of residual feed intake, dry matter intake, and energy balance was 0.20, 0.34, and 0.22, respectively, which proved that it was reasonable to include the related traits in the selection breeding program. For molecular genetic markers, a total of 13 single-nucleotide polymorphisms and copy number variance loci, associated genes, and functions were reported to be significant across populations. A total of 169 reported candidate genes were summarized on a large scale, using a higher threshold (adjusted P value < 0.05). Then, the subsequent pathway enrichment of these genes was performed. The important genes reported in the articles were included in a gene list and the gene list was enriched by gene ontology (GO):biological process (BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Three GO:BP terms and four KEGG terms were statistically significant, which mainly focused on adenosine triphosphate (ATP) synthesis, electron transport chain, and OXPHOS pathway. Among these pathways, involved genes such as ATP5MC2, NDUFA, COX7A2, UQCR, and MMP are particularly important as they were previously reported. Twenty-nine reported biological mechanisms along with involved genes were explained mainly by four biological pathways (insulin-like growth factor axis, lipid metabolism, oxidative phosphorylation pathways, tryptophan metabolism). The information from this study will be useful for future studies of genomic selection breeding and genetic structures influencing animal FE. A better understanding of the underlying biological mechanisms would be beneficial, particularly as it might address genetic antagonism.
Topics: Female; Cattle; Animals; Lactation; Genetic Markers; Phenotype; Genome; Eating; Animal Feed; Milk
PubMed: 38354297
DOI: 10.1093/jas/skae040 -
International Journal of Molecular... Dec 2023Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria... (Review)
Review
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from HS and NH. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestinal Mucosa; Mitochondria
PubMed: 38069446
DOI: 10.3390/ijms242317124 -
Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.American Journal of Physiology.... Apr 2024Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS), older adults, Parkinson's disease, overweight, postmenopausal prediabetes, and Alzheimer's disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity, and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NADs use are muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters (e.g., a decrease in anxiety, maximum heart rate, inflammatory cytokines in serum, and cerebrospinal fluid). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.
Topics: Humans; Aged; Quality of Life; Fatigue Syndrome, Chronic; NAD; Dietary Supplements
PubMed: 37971292
DOI: 10.1152/ajpendo.00242.2023 -
Molecular Nutrition & Food Research Dec 2023Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral...
Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.
SCOPE
Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells.
METHOD AND RESULTS
The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed.
CONCLUSION
Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.
Topics: Dietary Fats; Transcriptome; Leukocytes, Mononuclear; Consensus; Proteomics; Meals; Postprandial Period; Cross-Over Studies; Triglycerides
PubMed: 37817369
DOI: 10.1002/mnfr.202300512 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
Frontiers in Aging Neuroscience 2023Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial...
Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aβ) plaques. probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in the human brain. Phosphorus-magnetic resonance spectroscopy (P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of P-MRS measures as biomarkers for the early detection of AD.
PubMed: 37273652
DOI: 10.3389/fnagi.2023.1183228