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Frontiers in Endocrinology 2023The relationship of the methylenetetrahydrofolate reductase () gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The relationship of the methylenetetrahydrofolate reductase () gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.
METHODS
Several databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.
RESULTS
A total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.
CONCLUSION
The gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Genetic Predisposition to Disease; East Asian People; Polymorphism, Genetic; Risk Factors; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 37964957
DOI: 10.3389/fendo.2023.1273218 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436 -
Cytokine Jan 2024Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for angiogenesis. However, the relationship between NOS3 gene polymorphisms and genetic susceptibility to congenital heart disease (CHD) was still unclear.
METHODS
We searched five databases including Pubmed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang, to find all studies on NOS3 gene polymorphisms and CHD. Rstudio was used to merge the data included in the study to obtain OR, 95%CI, and forest plots.
RESULTS
Five relevant literatures were included, including three sites of NOS3 gene, rs1799983 (G894T), rs2070744 (T-786C), and rs7830 (G10T). Several models including the homozygous model of rs1799983 (G894T) gene polymorphism (TT VS GG: OR = 1.602, 95%CI: 1.098 ∼ 2.337, P = 0.027), rs7830 (G10T) gene polymorphism allele model (A VS C: OR = 1.171, 95%CI: 1.029 ∼ 1.333, P = 0.017), homozygous model (AA VS CC: OR = 1.474, 95%CI: 1.122 ∼ 1.936, P = 0.005) and implicit model (AA VS CC + AC: OR = 1.451, 95%CI: 1.133 ∼ 1.859, P = 0.003) indicated that there was a correlation. The results of the combined analysis of each gene model of rs2070744 (T-786C) gene polymorphism sites were not statistically significant, and their P values were all>0.05.
CONCLUSION
rs1799983 (G894T) and rs7830 (G10T) polymorphic sites might play a role in the susceptibility of sporadic congenital heart disease and increase the risk of CHD. Yet, it is still necessary to expand the sample size and conduct more prospective/retrospective studies to confirm whether the rs2070744 (T-786C) polymorphism tended to increase the incidence of CHD.
Topics: Humans; Nitric Oxide Synthase Type III; Retrospective Studies; Prospective Studies; Polymorphism, Genetic; Genetic Predisposition to Disease; Case-Control Studies; Heart Defects, Congenital; Polymorphism, Single Nucleotide; Genotype
PubMed: 37952311
DOI: 10.1016/j.cyto.2023.156415 -
Amino Acids Dec 2023Bioactive peptides consist of small protein fragments, which are inactive in their original conformation, and they become active when released from these through... (Review)
Review
Bioactive peptides consist of small protein fragments, which are inactive in their original conformation, and they become active when released from these through enzymatic hydrolysis or fermentation processes. The bioactivity of such peptides has been extensively reported in the literature as contributors to organic homeostasis processes, as well as in immunomodulation, organism defense against oxidative processes, among others. In this study, reports of the activity of BPs isolated from milk with the potential glycemic control, antihypertensive activity, and inhibitors of uric acid formation were compiled. A systematic literature review and bibliometric analysis were conducted, using the PICO strategy for the research. The temporal analysis of publications revealed a growing interest in the investigation of bioactive peptides with potential antidiabetic, antihypertensive, and xanthine oxidase inhibitory activities, using dairy sources as products for their extraction. The literature analysis also revealed an increase in research involving non-bovine dairy products for bioactive peptide extraction. The collaboration network among authors exhibited weaknesses in scientific cooperation. Regarding the analysis of keywords, the usage of terms such as "bioactive peptides", "antioxidant", "antihypertensive", and "diabetes" was evident, constituting the main research clusters. Peptides with low molecular weight, typically < 10 kDa, of hydrophobic nature with aliphatic and aromatic chains, have significant implications in molecular interactions for the required activities. Although there is a growing interest in the industry regarding the utilization of bioactive peptides as potential drugs, there is a need to address gaps related to elucidating their interactions with cellular targets and their use in human therapy.
Topics: Humans; Animals; Antihypertensive Agents; Milk; Xanthine Oxidase; Hypoglycemic Agents; Peptides; Enzyme Inhibitors
PubMed: 37938416
DOI: 10.1007/s00726-023-03351-9 -
CNS Neuroscience & Therapeutics Mar 2024Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia....
BACKGROUND
Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype.
METHODS
We screened a Chinese boy with weakness of limbs and his non-consanguineous parents by whole exome sequencing and targeted sequencing.
RESULTS
We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719-732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation.
CONCLUSIONS
A new type of TTC19 mutation (c.719-732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII-deficient diseases.
Topics: Male; Humans; Electron Transport Complex III; Membrane Proteins; Mutation; Peripheral Nervous System Diseases; Movement Disorders; Pedigree; Mitochondrial Diseases
PubMed: 37927170
DOI: 10.1111/cns.14425 -
Critical Reviews in Food Science and... Oct 2023Lactobionic acid is a comparatively less explored lactose derivative with impressive biofunctional qualities, and is currently being used by the advanced chemical and... (Review)
Review
Lactobionic acid is a comparatively less explored lactose derivative with impressive biofunctional qualities, and is currently being used by the advanced chemical and pharmaceutical research industries. It is an aldonic acid with probiotics, antimicrobial, antioxidant, calcium chelating activity. In dairy and food products, it can be used to improve flavor, texture, yield and shelf life with additional health benefits. The biochemical method for producing lactobionic acid makes it safe for humans to consume as food or medicine. This systematic review describes the various bioproduction methods of lactobionic acid. This study emphasizes the production method, conversion rate, and specific yield of various microorganisms and enzymes employed in biosynthesis of lactobionic acid. Scopus advanced search is used for database mining. Original, traceable peer-reviewed research articles directly related to lactobionic acid are selected for this systematic review. The selected articles are grouped for ease of discussion and understanding. In the last 75 years, several bioproduction methods of lactobionic acid have been developed. By fine-tuning the microbial incubation conditions, the productivity of lactobionic acid can be significantly improved. The oxidoreductase enzymes responsible for the conversion of lactose can be purified from the system by advanced membrane technology. In the presence of a suitable redox mediator and regenerative enzyme, an efficient continuous lactobionic acid production system can be developed. To date, several methods are available for the complete conversion of lactose to lactobionic acid with an impressive specific production rate. This review will help researchers and industries to have better insights and understanding of the bioproduction of lactobionic acid.
PubMed: 37874029
DOI: 10.1080/10408398.2023.2273450 -
Medicine and Science in Sports and... Feb 2024This study aimed to summarize and meta-analyze existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to summarize and meta-analyze existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance and to investigate the interaction between genotype, dosage, and timing of caffeine supplementation.
METHODS
Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise performance between CYP1A2 genotypes. Three-level meta-analyses were performed using standardized mean differences (SMD; Hedge's g ) to determine the effect of caffeine on exercise outcomes within and between CYP1A2 genotypes (AA, AC, and CC). Meta-regressions were performed for dose, timing, and presence of reported conflict of interests (RCOI). A meta-analysis was also performed with placebo values to assess for imbalances between genotypes.
RESULTS
Thirteen studies, totaling 119 outcomes and 440 participants, were included (233 AA, 175 AC, ad 34 CC). Caffeine improved performance for AA (SMD = 0.30, 95% confidence interval [CI] = 0.21-0.39, P < 0.0001) and AC (SMD = 0.16, 95% CI = 0.06-0.25, P = 0.022) but worsened performance for CC (SMD = -0.22, 95% CI = -0.44 to -0.01, P < 0.0001). Dose affected only CC, with greater doses generating more positive SMD (CC-dose estimate: +0.19/1 mg·kg -1 body mass, 95% CI = 0.04-0.33, P = 0.01). Timing influenced only CC, with better performance with later onset of exercise after supplementation (CC-timing estimate: +0.01/min, 95% CI = 0.00-0.02, P = 0.02). RCOI only affected SMD of CC (CC-RCOI estimate: -0.57, 95% CI = -1.02 to -0.12, P = 0.01). After excluding studies with RCOI, no influence of genotype was seen (all P ≥ 0.19). Small, nonsignificant differences were seen in placebo between genotypes (SMD AA vs CC: -0.13; AA vs AC: -0.12; AC vs CC: -0.05; all P ≥ 0.26).
CONCLUSIONS
Caffeine improved performance for AA and AC but worsened performance for CC. Dose and timing moderated the efficacy of caffeine for CC only. Caution is advised because baseline differences and studies with RCOI could have influenced these results.
Topics: Humans; Caffeine; Cytochrome P-450 CYP1A2; Genotype; Exercise; Performance-Enhancing Substances
PubMed: 37844569
DOI: 10.1249/MSS.0000000000003313 -
The Cochrane Database of Systematic... Oct 2023Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring... (Review)
Review
BACKGROUND
Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring enzyme which provides a defense against such oxidant injury. Providing supplementary SOD has been tested in clinical trials to prevent BPD in preterm infants.
OBJECTIVES
To determine the efficacy and safety of SOD in the prevention and treatment of BPD on mortality and other complications of prematurity in infants at risk for, or having BPD.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three trials registers on 22 September 2022 together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
Randomized, quasi-randomized and cluster-randomized controlled trials (RCTs) where the participants were preterm infants who had developed, or were at risk of developing BPD, and who were randomly allocated to receive either SOD (in any form, by any route, any dose, anytime) or placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality, mortality prior to discharge, and BPD or death at 36 weeks' postmenstrual age. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs) for the dichotomous outcomes. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included three RCTs (380 infants) on SOD administration in preterm infants at risk for BPD, and no studies in preterm infants with evolving BPD / early respiratory insufficiency. The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days (RR 1.09, 95% CI 0.94 to 1.26; RD 0.06, 95% CI -0.05 to 0.16, 1 study, 302 infants; I for RR and RD not applicable), BPD defined as oxygen at 36 weeks' postmenstrual age (RR 0.96, 95% CI 0.72 to 1.29; RD -0.01, 95% CI -0.11 to 0.09, 2 studies, 335 infants; I for RR and RD = 0%), neonatal mortality (RR 0.98, 95% CI 0.57 to 1.68; RD -0.00, 95% CI -0.08 to 0.07, 2 studies, 335 infants; I for RR and RD = 0%), and mortality prior to discharge (RR 1.20, 95% CI 0.53 to 2.71; RD 0.04, 95% CI -0.14 to 0.23, 2 studies, 78 infants; I for RR and RD = 0%). No studies reported BPD or death at 36 weeks' postmenstrual age. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage (RR 0.95, 95% CI 0.78 to 1.15; RD -0.03, 95% CI -0.15 to 0.08, 2 studies, 335 infants; Ifor RR = 0%, I for RD = 8%), and severe retinopathy of prematurity (ROP) (RR 0.97, 95% CI 0.57 to 1.65; RD -0.01, 95% CI -0.10 to 0.09, 1 study, 244 infants; I for RR and RD not applicable). No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. Certainty of evidence was very low for all outcomes. We identified no ongoing trials.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality and mortality prior to discharge compared to placebo. No studies reported BPD or death at 36 weeks' postmenstrual age and need for supplemental oxygen. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage and severe retinopathy of prematurity. No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. The effects of SOD in preterm infants has not been reported in any trial in the last few decades, considering that the most recent trial on SOD in preterm infants was conducted in 1997/1998, and no new studies are ongoing. In the light of the limited available evidence, new data from preclinical and observational studies are needed to justify the conduction of new RCTs. Observational studies might report how SOD is administered, including indication, dose and association with relevant outcomes such as mortality, BPD and long-term neurodevelopment.
Topics: Infant, Newborn; Infant; Humans; Retinopathy of Prematurity; Bronchopulmonary Dysplasia; Infant, Premature; Oxygen; Superoxide Dismutase; Randomized Controlled Trials as Topic
PubMed: 37811631
DOI: 10.1002/14651858.CD013232.pub2 -
Pain Physician Sep 2023Responsiveness to opioid analgesics differs among patients with acute postoperative pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Responsiveness to opioid analgesics differs among patients with acute postoperative pain.
OBJECTIVE
Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids.
STUDY DESIGN
An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain.
METHODS
PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021.
RESULTS
Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human μ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms.
LIMITATIONS
Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis.
CONCLUSIONS
In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia.
KEY WORDS
Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Topics: Humans; Analgesics, Opioid; Catechol O-Methyltransferase; Cytochrome P-450 CYP3A; Pain, Postoperative; Polymorphism, Single Nucleotide
PubMed: 37774182
DOI: No ID Found -
Renal Failure 2023The purpose of this study was to investigate how aerobic exercise affects oxidative stress (OS) in patients with chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The purpose of this study was to investigate how aerobic exercise affects oxidative stress (OS) in patients with chronic kidney disease (CKD).
METHODS
Retrieval dates range from the date the database was established to 19 July 2023, without languages being restricted. A meta-analysis and sensitivity analysis were conducted using RevMan 5.3 and Stata 16.0.
RESULTS
The meta-analysis showed that, compared to usual activity or no exercise, aerobic exercise significantly reduced the oxidative markers malondialdehyde (MDA) (mean differences (MD) - 0.96 (95% CI -1.33, - 0.59); < 0.00001), advanced oxidation protein product (AOPP) (MD - 3.49 (95% CI - 5.05, - 1.93); < 0.00001), F2-isoprostanes (F2-iso) (MD - 11.02 (95% CI - 17.79, - 4.25); = 0.001). Aerobic exercise also increased the antioxidant marker superoxide dismutase (SOD) in CKD patients (standardized mean differences (SMD) 1.30 (95% CI 0.56, 2.04); = 0.0005). Subgroup analysis showed a significant increase in glutathione peroxidase (GPX) in patients aged ≥60 years (SMD 2.11 (95% CI 1.69, 2.54); < 0.00001). The change in total antioxidant capacity (TAC) after aerobic exercise was insignificant in patients with CKD. The trial sequential analysis supported aerobic exercise's effectiveness in improving MDA, SOD, AOPP, and F2-iso in patients with CKD.
CONCLUSION
The results of this review suggest that aerobic exercise improves OS indicators (MDA, SOD, AOPP, and F2-iso) in CKD patients compared to conventional treatment or no exercise and that the effects on GPX and TAC indicators need further confirmation. For better validation of benefits and exploration of the best aerobic exercise regimen to improve OS status with CKD, further studies with high methodological quality and large sample sizes are needed.
Topics: Humans; Antioxidants; Advanced Oxidation Protein Products; Exercise; Oxidative Stress; Renal Insufficiency, Chronic; Glutathione Peroxidase; Superoxide Dismutase
PubMed: 37753870
DOI: 10.1080/0886022X.2023.2252093