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Annals of Medicine Dec 2023To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of... (Meta-Analysis)
Meta-Analysis
Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis.
OBJECTIVE
To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of developing diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to identify possible clinical biomarkers for early screening of DR.
MATERIALS AND METHODS
A meta-analysis based on case-control or cross-sectional studies was conducted to examine the correlation between eNOS 4a/b polymorphism and DR. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association strength.
RESULTS
We included 19 studies, covering 7838 subjects. An association was observed in Caucasians (allelic model: OR = 1.273, 95% CI: 1.006-1.610, = .045; recessive model: OR = 0.575, 95% CI: 0.371-0.892, = .014; dominant model: OR = 1.268, 95% CI: 1.052-1.528, = .013; homozygote model: OR = 1.833, 95% CI: 1.176-2.856, = .007). Moreover, population-based studies have indicated an association between eNOS 4a/b polymorphism and DR susceptibility.
CONCLUSIONS
The present study showed that intron 4a allele of eNOS 4a/b is a risk factor for DR in Caucasians with T2DM. Thus, eNOS 4a/b may be used as a biomarker for the early screening and diagnosis of DR in Caucasian T2DM patients.Key messagesEndothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the risk of developing diabetic retinopathy in the overall population, Asians, or Chinese Han patients with type 2 diabetes. However, 4a is a risk factor for the development of diabetic retinopathy in Caucasians.Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with the type of diabetic retinopathy.
Topics: Humans; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Genetic Predisposition to Disease; Genotype; Nitric Oxide Synthase Type III; Polymorphism, Genetic
PubMed: 37353997
DOI: 10.1080/07853890.2023.2226908 -
Medicine May 2023Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT.
METHODS
A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs).
RESULTS
After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment.
CONCLUSIONS
Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.
Topics: Humans; Selenium; Dietary Supplements; Hashimoto Disease; Iodide Peroxidase; Thyroglobulin
PubMed: 37335715
DOI: 10.1097/MD.0000000000033791 -
Medicine Jun 2023Vascular dementia is a cognitive dysfunction syndrome caused by cerebral vascular factors such as ischemic stroke and hemorrhagic stroke. The effect of acupuncture on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular dementia is a cognitive dysfunction syndrome caused by cerebral vascular factors such as ischemic stroke and hemorrhagic stroke. The effect of acupuncture on vascular dementia models is ambiguous, and there is controversy about whether acupuncture has a placebo effect. Oxidative stress and inflammation are the most essential mechanisms in preclinical studies of vascular dementia. However, there is no meta-analysis on the mechanism of vascular dementia in animal models. It is necessary to explore the efficacy of acupuncture through Meta-analysis of preclinical studies.
METHODS
Three major databases, PubMed, Embase and Web of Science (including medline), were searched in English until December 2022.The quality of the including literature was assessed using SYRCLE's risk of bias tool. Review Manager 5.3 was used to statistically summarize the included studies and the statistical effect values were expressed by SMD. The outcomes included: behavioral tests (escape latency, number of crossings), pathological sections (Nissl and TUNEL staining), oxidative stress markers (ROS, MDA, SOD, GSH-PX) and neuroinflammatory factors (TNF-α, IL-1β, IL-6).
RESULTS
A total of 31 articles were included in this meta-analysis. The results showed that the escape latency, the contents of ROS, MDA, IL-1β, and IL-6 were decreased, and the contents of SOD and Nissl-positive neurons were increased in the acupuncture group as compared with the non-group (P < .05). Compared with the impaired group, the acupuncture group also had the above advantages (P < .05). In addition, the acupuncture group also increased the number of crossings and GSH-PX content, and decreased the expression of TUNEL-positive neurons and TNF-α (P < .05).
CONCLUSIONS
From behavioral tests to slices and pathological markers in animal models of vascular dementia, it can be proved that acupuncture is effective in targeting oxidative stress and neuroinflammatory damage, and acupuncture is not a placebo effect. Nevertheless, attention needs to be paid to the gap between animal experiments and clinical applications.
Topics: Animals; Dementia, Vascular; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Interleukin-6; Acupuncture Therapy; Oxidative Stress; Disease Models, Animal; Superoxide Dismutase
PubMed: 37335660
DOI: 10.1097/MD.0000000000033989 -
Medicine Jun 2023This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility.
METHODS
The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx.
RESULTS
Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]).
CONCLUSION
The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.
Topics: Humans; Male; Case-Control Studies; Genetic Predisposition to Disease; Genotype; Infertility, Male; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide
PubMed: 37327284
DOI: 10.1097/MD.0000000000033993 -
Cancer Reports (Hoboken, N.J.) Aug 2023Oxidative stress induced by free radical accumulation contributes to many pathologies, including cancer. Antioxidant defense system fails to scavenge free radicals when... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oxidative stress induced by free radical accumulation contributes to many pathologies, including cancer. Antioxidant defense system fails to scavenge free radicals when it is excessively accumulated. Assessing individual antioxidant enzymes and total antioxidant capacity could direct the customized therapeutic strategies.
OBJECTIVE
Evaluation of total antioxidant status and enzyme glutathione peroxidase activity in the oral cancer group compared to the healthy control group.
METHOD
The literature search included databases PubMed, Science Direct, Wiley Online Library, Cochrane and Cross Reference between 1999 and 2021. The database search was completed in the month of August 2022. The extracted data were analyzed by Comprehensive Meta-Analysis (CMA) version 3 software (Biostat Inc. Englewood, NJ). Based on search strategies, 1435 articles have been retrieved from the database. In the segregated articles, 1365 were excluded due to duplicated articles, animal studies, low-quality studies, articles unrelated to the research question, and with unmatched objectives. Based on inclusion criteria, 70 articles were selected for full-text valuation. However, 33 articles were found highly suitable for inclusion and data extraction. Finally, 11 articles were selected for meta-analysis.
RESULTS
The meta-analysis of four included studies of tissue samples showed a significantly (p < .001) increased GPx activity in the oral cancer group, when compared to the control group, whereas three included studies of erythrocyte samples displayed a significantly (p < .001) decreased GPx activity in the oral cancer group than the control group with the pooled standardized mean difference value of -2.766 moles/min/g Hb at 95% CI (-3.297 to -2.234). The meta-analysis of the included studies depicted an insignificant (p = .947) reduction of salivary TAS levels in the oral cancer group when compared to the control group.
CONCLUSION
Our systematic review and meta-analysis depict antioxidant GPx enzyme activity in the regional tissue samples of the oral cancer group differs from other systemic biological fluid samples compared to the healthy control group.
Topics: Humans; Antioxidants; Glutathione Peroxidase; Mouth Neoplasms
PubMed: 37265029
DOI: 10.1002/cnr2.1842 -
Journal of Assisted Reproduction and... Jul 2023Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis.
METHODS
Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale.
RESULTS
A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and β-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL.
CONCLUSION
This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.
Topics: Pregnancy; Humans; Female; Genetic Predisposition to Disease; Polymorphism, Genetic; Thrombophilia; Plasminogen Activator Inhibitor 1; Abortion, Habitual; Methylenetetrahydrofolate Reductase (NADPH2); Observational Studies as Topic
PubMed: 37248348
DOI: 10.1007/s10815-023-02823-x -
Cells Apr 2023Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline -oxide (ANO) is...
Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline -oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with -acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial-mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis.
Topics: Arecoline; Cyclic N-Oxides; Mouth Neoplasms; Carcinogenesis; Humans; Animals; Mice; Areca; Oxygenases; Oxidation-Reduction; Acetylcysteine; Epigenesis, Genetic; Carcinogens
PubMed: 37190117
DOI: 10.3390/cells12081208 -
Drug Design, Development and Therapy 2023Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain,... (Review)
Review
Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950-2022), Google Scholar (2004-2022), Cochrane Library (2010-2022) and Researchgate (2010-2022). The search included the following medical subject headings (MeSH) or keywords: "Aromatase Inhibitors" AND "Endometriosis" AND "Systematic reviews" OR "Systematic review" AND "Reviews" OR "Reviews" AND "Endometriosis". The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy.
Topics: Female; Humans; Aromatase; Aromatase Inhibitors; Endometriosis; Estrogens; Systematic Reviews as Topic
PubMed: 37168488
DOI: 10.2147/DDDT.S315726 -
JAMA Oncology Jun 2023Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.
OBJECTIVE
To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.
DATA SOURCES
A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.
STUDY SELECTION
Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.
DATA EXTRACTION AND SYNTHESIS
This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.
MAIN OUTCOMES AND MEASURES
The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.
RESULTS
Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.
Topics: Humans; Male; Prostate-Specific Antigen; Prospective Studies; 5-alpha Reductase Inhibitors; Retrospective Studies; Prostatic Neoplasms; Oxidoreductases
PubMed: 37079318
DOI: 10.1001/jamaoncol.2023.0260 -
The Clinical Respiratory Journal Jun 2023This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms.
METHODS
After a systematic literature search in electronic databases, studies were selected based on eligibility criteria. Data were extracted from research articles and were synthesized and tabulated. Where a particular polymorphism data were reported by multiple studies, meta-analyses of odds ratios were performed, or odds ratios reported by individual studies were pooled.
RESULTS
Twenty studies (4450 asthma patients and 5306 non-asthmatic individuals) were identified. Many studies did not find any association between CCTTT repeat polymorphism in NOS2 gene and asthma. However, a study reported that pretreatment mean exhaled NO levels in asthmatics were found to be significantly higher in genotypes with higher number of CCTTT repeats. Also, alleles with <11 CCTTT repeats were associated with poor asthma treatment outcomes. A single nucleotide polymorphism, G894T, in NOS3 gene was not found to be significantly associated with asthma by at least four studies. However, a T allele at this locus was associated with lower NO levels. Also, G894T frequency was significantly higher in asthmatic children who responded to inhaled corticosteroids along with long-lasting beta2-agonists. A T allele of NOS3 786C/T polymorphism increased the probability of bronchial asthma with comorbid essential hypertension in asthma patients. Asthma severity also differed for different Ser608Leu exon 16 variants of NOS2 gene.
CONCLUSIONS
Several polymorph NOS gene variants are identified, some of which appear to have influence on asthma prevalence or outcomes. However, data are varying depending on the nature of variant, ethnicity, study design, and disease parameters.
Topics: Child; Humans; Gene Frequency; Nitric Oxide Synthase Type III; Nitric Oxide Synthase; Polymorphism, Single Nucleotide; Genotype; Asthma; Nitric Oxide
PubMed: 37076778
DOI: 10.1111/crj.13617