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Molecular Metabolism Jun 2022With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is... (Review)
Review
BACKGROUND
With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications.
SCOPE OF REVIEW
we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects.
MAJOR CONCLUSIONS
In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.
Topics: Apoptosis; Autophagy; Diabetes Complications; Diabetes Mellitus; Ferritins; Ferroptosis; Humans
PubMed: 35304332
DOI: 10.1016/j.molmet.2022.101470 -
Journal of Cachexia, Sarcopenia and... Jun 2023Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta-analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non-hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty-eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28-42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23-41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49-72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2-85%) in patients with coronary artery disease, 30% (95% CI: 25-35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10-59%) in patients with congenital heart disease and 12% (95% CI: 7-17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9-17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high-risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.
Topics: Humans; Cardiovascular Diseases; Sarcopenia; Aging; Heart Failure
PubMed: 37002802
DOI: 10.1002/jcsm.13221 -
Theranostics 2021Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and...
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Topics: Autophagy; Humans; Macroautophagy; Mitophagy; Organelles
PubMed: 33391472
DOI: 10.7150/thno.49860 -
The Cochrane Database of Systematic... Feb 2021Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014.
OBJECTIVES
To review the safety and efficacy of coenzyme Q10 in heart failure.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection.
MAIN RESULTS
We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision.
AUTHORS' CONCLUSIONS
The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.
Topics: Ataxia; Heart Failure; Humans; Mitochondrial Diseases; Muscle Weakness; Myocardial Infarction; Quality of Life; Stroke; Stroke Volume; Ubiquinone; Ventricular Function, Left
PubMed: 35608922
DOI: 10.1002/14651858.CD008684.pub3 -
Biology of Reproduction Feb 2022The ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in...
The ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in oocyte quantity and quality, which is associated with an increase in infertility, spontaneous abortions, and birth defects. Reproductive aging also has implications for overall health due to decreased endocrinological output. Understanding the mechanisms underlying reproductive aging has significant societal implications as women globally are delaying childbearing and medical interventions have greatly increased the interval between menopause and total lifespan. Age-related changes inherent to the female gamete are well-characterized and include defects in chromosome and mitochondria structure, function, and regulation. More recently, it has been appreciated that the extra-follicular ovarian environment may have important direct or indirect impacts on the developing gamete, and age-dependent changes include increased fibrosis, inflammation, stiffness, and oxidative damage. The cumulus cells and follicular fluid that directly surround the oocyte during its final growth phase within the antral follicle represent additional critical local microenvironments. Here we systematically review the literature and evaluate the studies that investigated the age-related changes in cumulus cells and follicular fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, and proteomic changes with associated metabolomic alterations, redox status imbalance, and increased apoptosis in the local oocyte microenvironment. We propose a model of how these changes interact, which may explain the rapid decline in gamete quality with age. We also review the limitations of published studies and highlight future research frontiers.
Topics: Cumulus Cells; Female; Follicular Fluid; Humans; Oocytes; Ovarian Follicle; Pregnancy; Proteomics
PubMed: 34982142
DOI: 10.1093/biolre/ioab241 -
Nutrients Aug 2023Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this... (Review)
Review
The Role of Nutrition in the Treatment of Sarcopenia in Old Patients: From Restoration of Mitochondrial Activity to Improvement of Muscle Performance, a Systematic Review.
Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.
Topics: Humans; Aged; Sarcopenia; Muscles; Nutritional Status; Malnutrition; Vitamin D; Vitamins; Amino Acids, Branched-Chain; Mitochondria
PubMed: 37686735
DOI: 10.3390/nu15173703 -
Journal of Assisted Reproduction and... Jun 2023The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER... (Review)
Review
The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER is the largest organelle in the cell composed of rough ER, smooth ER, and nuclear envelope, and is the main site of protein synthesis, transport and folding, and lipid and steroid synthesis. An appropriate calcium signaling response can initiate oocyte development and embryogenesis, and the ER is the central link that initiates calcium signaling. The transition from immature oocytes to zygotes also requires many coordinated organelle reorganizations and changes. Therefore, the purpose of this review is to generalize information on the function, structure, interaction with other organelles, and spatiotemporal localization of the ER in mammalian oocytes. Mechanisms related to maintaining ER homeostasis have been extensively studied in recent years. Resolving ER stress through the unfolded protein response (UPR) is one of them. We combined the clinical problems caused by the ER in in vitro maturation (IVM), and the mechanisms of ER have been identified by single-cell RNA-seq. This article systematically reviews the functions of ER and provides a reference for assisted reproductive technology (ART) research.
Topics: Animals; Oocytes; Unfolded Protein Response; Endoplasmic Reticulum Stress; Oogenesis; Endoplasmic Reticulum; Mammals
PubMed: 37171741
DOI: 10.1007/s10815-023-02782-3 -
BMC Psychiatry Nov 2023Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have identified alterations in the content of mitochondrial DNA (mtDNA) in peripheral blood and cerebrospinal fluid of individuals with depression. Researchers have sought to establish a clear association between mtDNA and depression. Consequently, we conducted a comprehensive meta-analysis to assess the existing evidence regarding the impact of mtDNA on depression.
METHODS
This study conducted a thorough search of the following databases up to March 13, 2023: PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, the China Science and Technology Journal Database, and China National Knowledge Infrastructure. The meta-analysis was carried out using RevMan (version 5.4) and Stata (version 16.0) software. In addition, publication bias was assessed with funnel plots, Begg's test and Egger's test.
RESULTS
Our analysis included data from 10 articles, including 12 studies for further examination. A total of 1400 participants were included in this study, comprising 709 (including 300 males and 409 females) patients with depression and 691 (including 303 males and 388 females) healthy controls. The average age of depressed patients was (42.98 ± 2.55) years, and the average age of healthy people was (41.71 ± 2.6) years. The scales used to assess outcomes are Hamilton-rating scale for Depression(4 articles), Montgomery-Asberg Depression Rating Scale(3 articles), and Mini-Internatioal Neuropsychiatric Interview (1 articles). The meta-analysis revealed significantly higher levels of mtDNA in circulating blood samples and skin fibroblasts of individuals with depression in comparison to healthy controls [standardized mean difference(SMD) = 0.42, 95% confidence intervals(CI): 0.16, 0.67].
CONCLUSIONS
Our study concludes that there is a significant (p < 0.05) increase in mtDNA levels in serum, plasma, and cerebrospinal fluid in individuals with depression. These findings suggest that mtDNA could serve as a potential biomarker for diagnosing depression.
REGISTRATION NUMBER
PROSPERO CRD42023414285.
Topics: Male; Female; Humans; Adult; Middle Aged; Depression; DNA, Mitochondrial; Risk Factors; Health Status; Mitochondria
PubMed: 37993802
DOI: 10.1186/s12888-023-05358-8 -
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 -
Biomolecules Mar 2023Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical to optimize patient management and improve long-term prognosis. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are recently emerging non-coding RNAs, and are highly stable and easily detected in the circulation, representing a promising non-invasive approach for predicting NAFLD. A literature search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was performed and 36 eligible studies were retrieved, including 18 on NAFLD, 13 on nonalcoholic steatohepatitis (NASH), and 11 on fibrosis and/or cirrhosis. Dynamic changes in lncRNA expression were associated with the occurrence and progression of NAFLD, among which lncRNA NEAT1, MEG3, and MALAT1 exhibited great potential as biomarkers for NAFLD. Moreover, mitochondria-located circRNA SCAR can drive metaflammation and its inhibition might be a promising therapeutic target for NASH. In this systematic review, we highlight the great potential of lncRNA/circRNA for early diagnosis and progression assessment of NAFLD. To further verify their clinical value, large-cohort studies incorporating lncRNA and circRNA expression both in liver tissue and blood should be conducted. Additionally, detailed studies on the functional mechanisms of NEAT1, MEG3, and MALAT1 will be essential for elucidating their roles in diagnosing and treating NAFLD, NASH, and fibrosis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; RNA, Long Noncoding; RNA, Circular; Liver; Fibrosis
PubMed: 36979495
DOI: 10.3390/biom13030560