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The Cochrane Database of Systematic... Dec 2017Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in October 2015.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (16 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE (1949 to 16 May 2017), Embase (1980 to 16 May 2017), CINAHL (1982 to 16 May 2017), AMED (1985 to 16 May 2017), and 11 Chinese databases (16 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the quality of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous.Recurrent strokeThree studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence interval and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-quality evidence).Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-quality evidence that PPAR-γ agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-quality evidence).Other outcomesOne study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
Topics: Cardiovascular Diseases; Carotid Artery Diseases; Humans; Hypoglycemic Agents; Insulin Resistance; Ischemic Attack, Transient; Myocardial Infarction; PPAR gamma; Pioglitazone; Proteasome Endopeptidase Complex; Randomized Controlled Trials as Topic; Recurrence; Rosiglitazone; Secondary Prevention; Stroke; Thiazolidinediones; Ubiquitin
PubMed: 29197071
DOI: 10.1002/14651858.CD010693.pub4 -
Cureus Dec 2020Lichen planus (L.P.) is a long-standing mucocutaneous inflammatory condition. A less familiar but essential illness association is increased arterial stiffness,... (Review)
Review
Can Pioglitazone Safeguard Patients of Lichen Planus Against Homocysteine Induced Accelerated Cardiovascular Aging and Reduced Myocardial Performance: A Systematic Review.
Lichen planus (L.P.) is a long-standing mucocutaneous inflammatory condition. A less familiar but essential illness association is increased arterial stiffness, endothelial dysfunction, and advanced atherosclerosis. Enhanced cardiac reconditioning and reduced performance of the heart have been suggested. Thiazolidinediones were commenced to manage hyperglycemia in diabetes mellitus. Recently, the class attained popularity after its action on vascular physiology was discovered. With this review, we attempted to explore whether an antidiabetic drug, pioglitazone (PIO), a peroxisome proliferator‑activated receptor γ (PPAR gamma) agonist, can defend patients of lichen planus against increased arterial stiffness and cardiac changes. We methodically screened numerous databases using focused words and phrases for relevant articles. After a comprehensive exploration, we applied the inclusion and exclusion criteria and performed a quality appraisal. Items retained were exhaustively studied. High homocysteine (HHcy) levels in lichen planus play a significant role in modifying the arteries and leading to their dysfunction. Not only does homocysteine affect the precursor cells, but it also increases the free radical damage. Arterial damage and upraised resistance encountered by the heart reduce its performance. After an exhaustive analysis, in our opinion, pioglitazone works in various miscellaneous ways to mitigate the homocysteine mediated changes. Early inclusion of the drug in managing patients with lichen planus seems promising in minimizing the harmful effects of high homocysteine. Evaluating the risk-benefit ratio, we believe that a trial of pioglitazone could be given to patients without underlying cardiac conditions.
PubMed: 33527053
DOI: 10.7759/cureus.12372 -
Archives of Iranian Medicine Oct 2023Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However,...
Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However, pesticide exposure is also associated with cardiovascular disease (CVD) as the leading cause of death worldwide. In this systematic review, results on the link between organochlorine pesticide pollution and CVD were collected from databases (Medline (PubMed), Scopus and Science Direct) in May 2022 from studies published between 2010 and 2022. A total of 24 articles were selected for this systematic review. Sixteen articles were extracted by reviewers using a standardized form that included cross-sectional, cohort, and ecological studies that reported exposure to organochlorine pesticides in association with increased CVD risk. In addition, eight articles covering molecular mechanisms organochlorine pesticides and polychlorinated biphenyls (PCBs) on cardiovascular effects were retrieved for detailed evaluation. Based on the findings of the study, it seems elevated circulating levels of organochlorine pesticides and PCBs increase the risk of coronary heart disease, especially in early life exposure to these pesticides and especially in men. Changes in the regulatory function of peroxisome proliferator-activated γ receptor (PPARγ), reduction of paroxonase activity (PON1), epigenetic changes of histone through induction of reactive oxygen species, vascular endothelial inflammation with miR-expression 126 and miR-31, increased collagen synthesis enzymes in the extracellular matrix and left ventricular hypertrophy (LVH) and fibrosis are mechanisms by which PCBs increase the risk of CVD. According to this systematic review, organochlorine pesticide exposure is associated with increased risk of CVD and CVD mortality through the atherogenic and inflammatory molecular mechanism involving fatty acid and glucose metabolism.
Topics: Male; Humans; Polychlorinated Biphenyls; Environmental Pollutants; Cardiovascular Diseases; Cross-Sectional Studies; Hydrocarbons, Chlorinated; Pesticides; MicroRNAs; Aryldialkylphosphatase
PubMed: 38310416
DOI: 10.34172/aim.2023.86 -
F1000Research 2017Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the...
Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews.
PubMed: 28620456
DOI: 10.12688/f1000research.11107.2 -
Nutrients Jan 2021Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism ( Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We...
Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism ( Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.
Topics: Adult; Aged; Alcohol Drinking; Alleles; Breast Neoplasms; Colonic Neoplasms; Diet; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Neoplasms; PPAR gamma; Polymorphism, Genetic; Prostatic Neoplasms; Rectal Neoplasms; Risk Factors
PubMed: 33477496
DOI: 10.3390/nu13010261 -
Disease Markers 2019Genome-wide association study (GWAS) provides an unprecedented opportunity to reveal substantial genetic contribution to type 2 diabetes mellitus (T2DM) and glycemic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Genome-wide association study (GWAS) provides an unprecedented opportunity to reveal substantial genetic contribution to type 2 diabetes mellitus (T2DM) and glycemic identification of allelic heterogeneity and population-specific genetic variants, yet it also faces difficulty due to the vast amount of potential confounding factors and limited availability of clinical data. To identify responsible susceptibility loci and genomic polymorphism for T2DM and glycemic traits, we have systematically investigated a genome-wide association study related to T2DM. Although GWAS has captured many common genetic variations, which are related to T2DM, each risk allele (RA) of single-nucleotide polymorphisms (SNPs) at these loci is not conclusive. Therefore, it is common to present a combination of several SNPs to infer T2DM risk, yet it is still insufficient to be deterministic. To streamline the identification of a deterministic genetic variation in T2DM, we developed this meta-analysis as a showcase to comprehensively identify the association between cumulative RAs and T2DM risk by combining different studies in reported literature and databases. After all, we identified that PGC-1 rs8192678 polymorphism can be considered as a potentially deterministic biomarker in T2DM risk. Previous studies have potentially linked PGC-1 rs8192678 polymorphism to type 2 diabetes mellitus (T2DM) risk, but the results remain inconsistent in different populations and are not conclusive. We developed a new meta-analysis approach to systematically identify the association between PGC-1 rs8192678 polymorphism and T2DM, and we have comprehensively assessed different ethnic groups to validate our findings.
METHODS
We performed comprehensive information retrieval and knowledge discovery meta-analysis by searching extensively published literature and different electronic databases to acquire eligible studies for the above association study. We developed a method to use pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) in five genetic models (allelic, dominant, recessive, homozygous, and heterozygous genetic models) to identify the relationship among ethnicity subgroup analyses comprehensively.
RESULTS
We identified 20 eligible studies consisting of 16,182 subjects (8,038 cases and 8,144 controls) in our meta-analysis. PGC-1 rs8192678 polymorphisms of all subjects showed a significant association with T2DM susceptibility under all genetic models: allelic (OR: 1.24, 95% CI: 1.13-1.35), dominant (OR: 1.27, 95% CI: 1.14-1.42), recessive (OR: 1.24, 95% CI: 1.14-1.36), homozygous (OR: 1.40, 95% CI: 1.20-1.64), and heterozygous (OR: 1.20, 95% CI: 1.06-1.35). In the subgroup analysis, we identified a significant association between PGC-1 rs8192678 polymorphism and T2DM in the Caucasian and Indian populations under all genetic models we investigated. This is the most comprehensive study of the subject to date.
CONCLUSION
Our development of meta-analysis revealed that the minor allele (A) carriers, especially AA genotype carriers, can lead to risk of T2DM in the Caucasian and Indian populations. This is the first report that such risk has been confirmed. Our finding shed new light into the genetic alteration in T2DM.
Topics: Diabetes Mellitus, Type 2; Humans; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polymorphism, Single Nucleotide
PubMed: 30944665
DOI: 10.1155/2019/2970401 -
Frontiers in Physiology 2022Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without...
BACKGROUND
Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without BFR on angiogenesis-related factors in skeletal muscle among healthy adults.
METHODOLOGY
Searches were made in Web of Science, Scopus, PubMed, and EBSCO databases from January 2001 to June 2021. Studies were screened, quality was evaluated, and data were extracted. The review protocol was registered at PROSPERO (PROSPERO registration number: CRD42021261367). Standardized mean differences (SMD) of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) and endothelial nitric oxide synthase (eNOS) were analyzed using Revman 5.4 software with a 95% confidence interval (95% CI).
RESULTS
Ten studies fulfilled the inclusion criteria with a total of 75 participants for BFR group and 77 for CON group. BFR exercise elicits greater expression of VEGF (heterogeneity test, = 0.09, I = 44%; SMD, 0.93 [0.38, 1.48], < 0.05), VEGFR-2 (heterogeneity test, = 0.81, I = 0%; SMD, 0.64 [0.08, 1.21], < 0.05), HIF-1α (heterogeneity test, = 0.67, I = 0%; SMD, 0.43 [0.03, 0.82], < 0.05), PGC-1α (heterogeneity test, = 0.02, I = 54%; SMD, 0.74 [0.21, 1.28], < 0.05) and eNOS (heterogeneity test, = 0.88, I = 0%; SMD, 0.60 [0.04, 1.17], < 0.05) mRNA than non-BFR exercise. In the sub-group analysis, resistance exercise with BFR elicits greater expression of VEGF (heterogeneity test, = 0.36, I = 6%; SMD, 1.66 [0.97, 2.35], < 0.05) and HIF-1α (heterogeneity test, = 0.56, I = 0%; SMD, 0.51 [0.01, 1.02], < 0.05) mRNA than aerobic exercise with BFR.
CONCLUSION
Exercise with BFR elicited more angiogenesis-related factors mRNA expression than exercise without BFR, but not VEGF and PGC-1α protein expression. Therefore, BFR training may be a potential training program to improve vascular function.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021261367].
PubMed: 35250618
DOI: 10.3389/fphys.2022.814965 -
Clinical Journal of the American... Oct 2018Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact...
BACKGROUND AND OBJECTIVES
Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
RESULTS
We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
CONCLUSIONS
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.
Topics: Environmental Exposure; Environmental Pollutants; Fluorocarbon Polymers; Humans; Kidney Diseases
PubMed: 30213782
DOI: 10.2215/CJN.04670418 -
PloS One 2019Genetics plays a role in determining potential for athletic ability (AA) and sports performance (SP). In this study, AA involves comparing sedentary controls with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Genetics plays a role in determining potential for athletic ability (AA) and sports performance (SP). In this study, AA involves comparing sedentary controls with competitive athletes in power and endurance activities as well as a mix between the two (SP). However, variable results from genetic association studies warrant a meta-analysis to obtain more precise estimates of the association between PPARGC1A Gly482Ser polymorphism and AA/SP.
METHODS
Multi-database literature search yielded 14 articles (16 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate associations. Summary effects were modified based on statistical power. Subgroup analysis was based on SP (power, endurance and mixed) and race (Caucasians and Asians). Heterogeneity was assessed with the I2 metric and its sources examined with outlier analysis which dichotomized our findings into pre- (PRO) and post-outlier (PSO).
RESULTS
Gly allele effects significantly favoring AA/SP (OR > 1.0, P < 0.05) form the core of our findings in: (i) homogeneous overall effect at the post-modified, PSO level (OR 1.13, 95% CI 1.03-1.25, P = 0.01, I2 = 0%); (ii) initially homogeneous power SP (ORs 1.22-1.25, 95% CI 1.05-1.44, P = 0.003-0.008, I2 = 0%) which precluded outlier treatment; (iii) PRO Caucasian outcomes (ORs 1.29-1.32, 95% CI 1.12-1.54, P = 0.0005) over that of Asians with a pooled null effect (OR 0.99, 95% CI 0.72-1.99, P = 0.53-0.92) and (iv) homogeneous all > 80% (ORs 1.19-1.38, 95% CI 1.05-1.66, P = 0.0007-0.007, I2 = 0%) on account of high statistical power (both study-specific and combined). In contrast, none of the Ser allele effects significantly favored AA/SP and no Ser-Gly genotype outcome favored AA/SP. The core significant outcomes were robust and showed no evidence of publication bias.
CONCLUSION
Meta-analytical applications in this study generated evidence that show association between the Gly allele and AA/SP. These were observed in the overall, Caucasians and statistically powered comparisons which exhibited consistent significance, stability, robustness, precision and lack of bias. Our central findings rest on association of the Gly allele with endurance and power, differentially favoring the latter over the former.
Topics: Athletic Performance; Female; Genetic Association Studies; Genotype; Humans; Male; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polymorphism, Genetic; White People
PubMed: 30625151
DOI: 10.1371/journal.pone.0200967 -
Biology of Sport Mar 2016A meta-analysis was performed with the aim of re-evaluating the role of the peroxisome proliferator activated receptor alpha (PPARA) gene intron 7 G/C polymorphism...
UNLABELLED
A meta-analysis was performed with the aim of re-evaluating the role of the peroxisome proliferator activated receptor alpha (PPARA) gene intron 7 G/C polymorphism (rs4253778) in athletes' high ability in endurance sports.
DESIGN
A meta-analysis of case control studies assessing the association between the G/C polymorphisms of the PPARA gene and endurance sports was conducted. The Cochrane Review Manager software was used to compare the genotype and allele frequencies between endurance athletes and controls to determine whether a genetic variant is more common in athletes than in the general population. Five studies, encompassing 760 endurance athletes and 1792 controls, fulfilled our inclusion criteria. The pooled odds ratio (and confidence intervals, CIs) for the G allele compared to the C allele was 1.65 (95% CI 1.39-1.96). The pooled OR for the GG genotype compared to the GC genotype was 1.79 (95% CI 1.44-2.22), and for the GG genotype compared to the CC genotype 2.37 (95% CI 1.40-3.99). There was no evidence of heterogeneity (I(2) =0%) or of publication bias. Athletes with high ability in endurance sports had a higher frequency of the GG genotype and G allele.
PubMed: 26985127
DOI: 10.5604/20831862.1180170