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Nutrition, Metabolism, and... Jul 2016New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition... (Review)
Review
BACKGROUND
New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences.
AIM
To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR).
METHOD AND RESULTS
Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies.
CONCLUSIONS AND RELEVANCE
Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.
Topics: Acetylation; Biomarkers; Blood Glucose; Chromatin Assembly and Disassembly; DNA Methylation; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Female; Gene Expression Regulation; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Histones; Humans; Insulin; Insulin Resistance; Male; Phenotype; Risk Factors
PubMed: 27146363
DOI: 10.1016/j.numecd.2016.04.002 -
Journal of Basic and Clinical... Nov 2020The objective of this study is to explore the efficacy and safety of -acetyl-cysteine (NAC) as adjuvant therapy in female infertility. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The objective of this study is to explore the efficacy and safety of -acetyl-cysteine (NAC) as adjuvant therapy in female infertility.
CONTENT
We performed a systematic literature search of PubMed, Cochrane Library, Embase, and Ovid databases through April 2019 for Randomized Controlled Trials (RCTs) evaluating the effectiveness and safety of NAC as adjuvant therapy in female infertility. The outcomes assessed were rates of ovulation, pregnancy, miscarriage and multiple pregnancy, presented as pooled odds ratio with 95% confidence interval (CI) using the random-effects model. Heterogeneity and inconsistency of the measurements were identified through Cochrane's Q statistic and I2 statistic. We also performed a sensitivity analysis, publication bias (using funnel plot and Begg's test), and subgroup analysis.
SUMMARY
Fifteen RCTs recruiting 2330 female receiving NAC were included. The pooled estimate showed the statistically insignificant improvement in outcomes; clinical pregnancy rate 1.55 (95% CI 0.98-2.47; I2=68%; p<0.01), ovulation rate 1.77 (95% CI 0.76-4.14; I2=90%; p<0.01), multiple pregnancy rate 0.83 (95% CI 0.34-1.99; I2=10%; p=0.31) and miscarriage rate 0.76 (95% CI= 0.37, 1.53; I2=0%; p=0.69) . NAC was found less efficacious and safe than metformin in all outcomes. Overall, NAC showed statistically insignificant (OR=0.98-2.47).
OUTLOOK
NAC can be an effective adjuvant in PCOS related and unexplained female infertility. The effect could be more profound in women with high BMI, insulin resistance, and oxidative stress. However, the findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in more extended follow-up periods.
Topics: Abortion, Spontaneous; Acetylcysteine; Female; Humans; Infertility, Female; Live Birth; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate
PubMed: 34592079
DOI: 10.1515/jbcpp-2020-0107 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
Critical Reviews in Oncology/hematology Feb 2016Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-L-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. L-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-L-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions.
Topics: Acupuncture Therapy; Antineoplastic Agents; Biological Products; Complementary Therapies; Dietary Supplements; Exercise; Fatty Acids, Omega-3; Glutamine; Humans; Peripheral Nervous System Diseases; Vitamin E
PubMed: 26652982
DOI: 10.1016/j.critrevonc.2015.11.014 -
PloS One 2013Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs,... (Review)
Review
BACKGROUND
Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression.
METHODS
A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed.
RESULTS
Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1).
CONCLUSIONS
Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.
Topics: Apoptosis Regulatory Proteins; Caspase 8; Cyclin-Dependent Kinase Inhibitor p16; DNA Methylation; Epigenesis, Genetic; Humans; Pituitary Neoplasms; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 24367530
DOI: 10.1371/journal.pone.0082619 -
Journal of Alzheimer's Disease : JAD 2015The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer's disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear.
OBJECTIVE
Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients.
METHODS
Using Hedges' g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis.
RESULTS
According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =-0.924, p < 0.005) and bilateral hippocampus (left hippocampus: ES =-1.329, p < 0.005; right hippocampus: ES =-1.287, p < 0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =-1.052, p < 0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes.
CONCLUSION
The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.
Topics: Alzheimer Disease; Aspartic Acid; Brain; Creatine; Databases, Bibliographic; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Protons
PubMed: 26402632
DOI: 10.3233/JAD-143225 -
Iranian Journal of Reproductive Medicine Jan 2015Recently there is a focus on the antioxidants as adjuvant treatment of polycystic ovary syndrome (PCOS), the most endocrinopathy in reproductive age women. (Review)
Review
BACKGROUND
Recently there is a focus on the antioxidants as adjuvant treatment of polycystic ovary syndrome (PCOS), the most endocrinopathy in reproductive age women.
OBJECTIVE
The aim of this review is answer to the question whether antioxidants are effective for managing of hormonal and metabolic problems in women with PCOS based on first degree evidences from Iran.
MATERIALS AND METHODS
A systematic review of clinical trials was done in Persian and international databases including PubMed, Scientific Information Database, Google Scholar, Iran Medex, and Magiran up to 2013. Keywords were including polycystic ovary syndrome, Iran, vitamin, antioxidant. From 440 potential studies found electronically, 11 studies; including 444 women in intervention and 390 women in control groups. Intervention in three studies was Calcium-vitamin D or calcitriol; in three studies was ω-3 fatty acids; in two studies was N-acetyl cysteine; in one study was folic acid; in one study was Zinc; and in one study was Soy.
RESULTS
Finally, 11 studies that were relevant and met the inclusion criteria reviewed. There were 7 studies in English and 4 studies in Persian. We couldn't include all studies because all full texts were not accessible.
CONCLUSION
The results showed that antioxidants and vitamins have positive effects on management of PCOS women. Although it seems more studies is necessary in this field.
PubMed: 25653669
DOI: No ID Found -
Breast Cancer Research and Treatment Oct 2018Cancer-related fatigue (CRF) is defined as a distressing, persistent, and subjective sense of physical or emotional and/or cognitive exhaustion. The treatment of CRF...
PURPOSE
Cancer-related fatigue (CRF) is defined as a distressing, persistent, and subjective sense of physical or emotional and/or cognitive exhaustion. The treatment of CRF includes pharmacological and non-pharmacological therapies; dietary strategies with promising results have also been used. This study aimed to identify dietary supplements that improve fatigue in patients with breast cancer.
METHODS
A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained from PubMed, Scopus, MEDLINE, CENTRAL, and CINAHL databases using the following MeSH terms: breast neoplasms, dietary supplements, diet, and fatigue. In addition, the Google and Google Scholar search engines were used to find grey literature. Methodological quality was evaluated using the risk of bias in randomised clinical trials in the systematic Cochrane reviews, and the quality of the evidence was also analysed using the GRADE system.
RESULTS
A total of 893 studies were assessed, of which eight were included in the review, with 932 women diagnosed with breast cancer. The most commonly used supplements that improve fatigue were guarana, acetyl-L-carnitine, and co-enzyme Q10. Two studies had a low risk of bias in all categories and three had high-quality evidence.
CONCLUSIONS
Dietary supplements or diet patterns are seldom used to treat fatigue in patients with breast cancer. The results of this review showed that guarana extract and a diet rich in whole foods, omega-3 fatty acids, fruits, and vegetables could be used to treat CRF in patients with breast cancer. The studies had a low risk of bias with high-quality evidence on the efficacy of the interventions in treating fatigue in the study population.
Topics: Breast Neoplasms; Dietary Supplements; Fatigue; Female; Humans; Quality of Life
PubMed: 29915949
DOI: 10.1007/s10549-018-4857-0 -
Biological Psychiatry Mar 2011It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to determine which brain regions show the most robust reductions in NAA first episode and chronic schizophrenia as measured by proton magnetic resonance spectroscopy and to determine whether these changes are present in individuals at high risk of developing schizophrenia.
METHODS
We identified 131 articles, of which 97 met inclusion criteria. Data were separated by stage of illness (at risk, first episode schizophrenia, chronic schizophrenia) and by brain region. For each region, mean and SD of the NAA measure was extracted.
RESULTS
Significant reductions in NAA levels were found in frontal lobe, temporal lobe, and thalamus in both patient groups (effect size > .3; p < .01). In individuals at high risk of schizophrenia (of whom approximately 20% would be expected to undergo transition to psychosis), significant NAA reductions were present in thalamus (effect size = .78; p < .05), with reductions at trend level only in temporal lobe (effect size = .32; p < .1), and no reductions in frontal lobe (effect size = .05; p = .5).
CONCLUSIONS
These data suggest that schizophrenia is associated with loss of neuronal integrity in frontal and temporal cortices and in the thalamus and suggest that these changes in the frontal and temporal lobe might occur in the transition between the at-risk phase and the first episode.
Topics: Aspartic Acid; Data Interpretation, Statistical; Disease Progression; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Publication Bias; Regression Analysis; Risk; Schizophrenia; Schizophrenic Psychology; Temporal Lobe; Thalamus
PubMed: 21145039
DOI: 10.1016/j.biopsych.2010.10.004 -
Reproductive Biomedicine Online Aug 2019This meta-analysis and systematic review investigated evidence of the effect of oral micronutrient supplementation on male fertility. Following searches of PubMed,... (Meta-Analysis)
Meta-Analysis
This meta-analysis and systematic review investigated evidence of the effect of oral micronutrient supplementation on male fertility. Following searches of PubMed, Ovid/Ovid Medline(r) and Embase, 18 randomized, double-blind, placebo-controlled trials were included in the meta-analysis (seven studies) and/or the systematic review (12 studies). The meta-analysis showed significant improvement in semen parameters for selenium (200µg/day and 100µg/day) (standard mean difference [SMD] 0.64 for oligozoospermia, 1.39 for asthenozoospermia), L-carnitine (2 g/day) and acetyl-L-carnitine (LAC; 1 g/day) combined (SMD 0.57 for asthenozoospermia), and co-enzyme Q10 (200 and 300 mg/day) (SMD 0.95 for oligozoospermia, 1.48 for asthenozoospermia, 0.63 for teratozoospermia). The systematic review identified promising data for supplementation with 66 mg/day zinc combined with folic acid (5 mg/day), and the polyunsaturated fatty acids eicosapentaenoic acid (EPA; 1.12 g/day) and docosahexaenoic acid (DHA; 0.72 g/day). Pregnancy rate was evaluated in a limited number of trials (four in the meta-analysis, three in the systematic review). This analysis suggests supplementation with selenium (alone or combined with N-acetylcysteine), co-enzyme Q10 and the combinations L-carnitine + acetyl-L-carnitine, folic acid + zinc and EPA + DHA is beneficial in the treatment of male infertility. Because of the small number of available studies and low number of participants, further well-designed clinical studies are needed to obtain a better overview of efficient methods of treating male infertility.
Topics: Acetylcysteine; Administration, Oral; Ascorbic Acid; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Folic Acid; Humans; Infertility, Male; Male; Minerals; Randomized Controlled Trials as Topic; Selenium; Spermatozoa; Ubiquinone; Vitamin E; Vitamins
PubMed: 31160241
DOI: 10.1016/j.rbmo.2019.03.099