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Frontiers in Endocrinology 2021The CDK5 regulatory subunit-associated protein 1-like 1 () contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The CDK5 regulatory subunit-associated protein 1-like 1 () contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.
MATERIALS AND METHODS
A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.
RESULTS
A total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG AA: OR = 1.23, 95% CI = 1.08, 1.41, = 0.002; GG AA: OR = 1.47, 95% CI = 1.05, 2.05, = 0.024 for rs7756992; and CG GG: OR = 1.36, 95% CI = 1.13, 1.65, = 0.002; CC GG: OR = 1.76, 95% CI = 1.37, 2.26, < 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.
CONCLUSIONS
This study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.
Topics: Case-Control Studies; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors; tRNA Methyltransferases
PubMed: 34721291
DOI: 10.3389/fendo.2021.722674 -
Frontiers in Immunology 2023In sepsis, brain dysfunction is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In sepsis, brain dysfunction is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Our systematic review and meta-analysis aimed to explore the diagnostic and prognostic value of serum S100 calcium-binding protein B (S100B) in SAE patients.
METHODS
We conducted a systematic search of the databases PubMed, Web of Science, Embase, Cochrane databases, CNKI, VIP, and WFSD from their inception dates until August 20, 2022. A Meta-analysis of the included studies was also performed using Review Manager version 5.4 and Stata16.0.
RESULTS
This meta-analysis included 28 studies with 1401 serum samples from SAE patients and 1591 serum samples from no-encephalopathy septic (NE) patients. The Meta-Analysis showed that individuals with SAE had higher serum S100B level than NE controls (MD, 0.49 [95% CI (0.37)-(0.60), Z =8.29, < 0.00001]), and the baseline level of serum S100B in septic patients with burn was significantly higher than average (1.96 [95% CI (0.92)-(2.99), Z =3.71, P < 0.0002]) In addition, septic patients with favorable outcomes had lower serum S100B levels than those with unfavorable outcomes (MD, -0.35 [95% CI (-0.50)-(-0.20), Z =4.60, < 0.00001]).
CONCLUSION
Our Meta-Analysis indicates that higher serum S100B level in septic patients are moderately associated with SAE and unfavorable outcomes (The outcomes here mainly refer to the mortality). The serum S100B level may be a useful diagnostic and prognostic biomarker of SAE.
Topics: Humans; Sepsis-Associated Encephalopathy; Prognosis; Biomarkers; S100 Calcium Binding Protein beta Subunit; Brain Diseases; Sepsis
PubMed: 36776893
DOI: 10.3389/fimmu.2023.1102126 -
Vaccine Jan 2024To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023. (Review)
Review
PURPOSE
To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023.
METHODS
EMBASE, MEDLINE, Cochrane Library and clinicaltrial.gov. databases were searched for clinical studies that reported immunogenicity and/or safety of GBS vaccine in non-pregnant adults, pregnant women and infants between 1st of January 1996 to 31st of July 2023. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42020185213).
RESULTS
We retrieved 1472 records from the literature search; 20 studies and 6 sub-studies were included, involving 4440 non-pregnant participants and 1325 pregnant women with their newborns. There was a significantly higher IgG Geometric Mean Concentration (GMC) and IgG placental transfer ratios in vaccinated compared to placebo groups, with peak response 4-8 weeks after vaccination. Placental transfer ratio varied from 0.4 to 1.4 across five studies. The different clinical trials used different assays that limited direct comparison. There were no significant differences in the risk of serious adverse events (adjusted OR 0.73; 95 % CI 0.49-1.07), serious adverse events leading to withdrawal (adjusted OR 0.44; 95 % CI 0.13-1.51), and systemic illness or fever (adjusted OR 1.05; 95 % CI 0.26-4.19) between the vaccine and placebo groups.
CONCLUSIONS
The published clinical trials show significant IgG GMC response in subjects receiving the conjugated capsular polysaccharide and surface subunit protein vaccines compared to placebo. In current clinical trials of experimental GBS maternal vaccines, there have been no observed serious adverse events of special interest directly linked to vaccination.
Topics: Infant; Adult; Humans; Infant, Newborn; Female; Pregnancy; Placenta; Vaccines; Vaccination; Streptococcus agalactiae; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 38072754
DOI: 10.1016/j.vaccine.2023.11.056 -
Tumour Biology : the Journal of the... Oct 2014Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including hepatocellular carcinoma (HCC). However, the... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including hepatocellular carcinoma (HCC). However, the correlation between RUNX3 hypermethylation and incidence of HCC remains unclear. Here, we conducted a systematic review and meta-analysis aiming to comprehensively assess the potential role of RUNX3 hypermethylation in the pathogenesis of HCC. A detailed literature search was made from PubMed, EMBASE, and ISI web of knowledge to identify studies for related research publications. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed. Odds ratio (OR) was calculated and summarized, respectively. Final analysis of 821 HCC patients from 14 eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in HCC than in normal liver tissue, the pooled OR from eight studies including 382 HCC and 161 normal liver tissue (OR = 39.32, 95 % confidence interval (CI) = 13.72-112.7, p < 0.00001). The pooled analysis showed significantly increased OR of RUNX3 hypermethylation (OR = 5.4, 95 % CI = 2.06-14.17, p < 0.00001) in HCC tissues and non-tumor liver tissues. In addition, statistically significant OR of RUNX3 hypermethylation was obtained from non-tumorous liver tissue of HCC patients and normal liver tissue (OR = 12.57, 95 % CI = 3.56-44.35, p < 0.0001). The results of this meta-analysis suggest that RUNX3 hypermethylation may be implicated in the pathogenesis of HCC. Thus, detection of RUNX3 hypermethylation may be a helpful and valuable biomarker for diagnosis of HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Core Binding Factor Alpha 3 Subunit; DNA Methylation; Humans; Liver Neoplasms; Odds Ratio
PubMed: 25037468
DOI: 10.1007/s13277-014-2329-7 -
The Malaysian Journal of Medical... Jun 2022The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through... (Review)
Review
The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through insulin resistance. Glucose levels are related to AMPK subunit α2 encoded by . This systematic review and meta-analysis aimed to analyse the association between variation and T2DM risk. Publication search related to and T2DM used PubMed, ProQuest, and ScienceDirect databases. Article selection based on inclusion and exclusion criteria only included Japanese and Chinese populations. This meta-analysis used five genotype models to estimate the effect of variation and T2DM risk. Additionally, a fixed-effect model was selected to measure the pooled size effect if > 0.05 or I < 50%. Qualitative analysis included four eligible studies, and meta-analysis included only two studies because both showed data concerning rs2746342 variation. Patients with G allele are 1.45 times more likely to have T2DM than patients with T allele (95% confidence interval [CI]: 1.20, 1.76; : 0.0001). Notably, patients who had GG genotype have 1.96 times higher risk of T2DM compared with those with TT genotype (95% CI: 1.34, 2.87; : 0.0005), dominant model (odds ratio [OR]: 1.75; 95% CI: 1.32, 2.31; : 0.001), and recessive model (OR: 1.43; 95% CI: 1.01, 2.01; : 0.04). variation, especially in rs2746342, has an association with T2DM risk in the G allele, additive, dominant, and recessive models. G allele might be the most contributable factor in increasing T2DM susceptibility.
PubMed: 35846493
DOI: 10.21315/mjms2022.29.3.2 -
Experimental Cell Research Aug 2016In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on... (Meta-Analysis)
Meta-Analysis Review
In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on the malignant thyroid. The PKA signaling pathway is differentially activated by the expression of regulatory subunits 1 (R1) and 2 (R2), whose levels change during development, differentiation, and neoplastic transformation. Following the identification of gene mutations within the PKA regulatory subunit R1A (PRKAR1A) that cause Carney complex-associated neoplasms, several investigators have studied PRKAR1A expression in sporadic thyroid tumors. The PKA regulatory subunit R2B (PRKAR2B) is highly expressed in benign, as well as in malignant differentiated and undifferentiated lesions. PRKAR1A is highly expressed in follicular adenomas and malignant lesions with a statistically significant gradient between benign and malignant tumors; however, it is not expressed in hyperplastic nodules. Although the importance of PKA in human malignancy outcomes is not completely understood, PRKAR1A expression correlates with tumor dimension in malignant lesions. Additional studies are needed to determine whether a relationship exists between PKA subunit expression and clinical outcomes, particularly in undifferentiated tumors. In conclusion, the R1A subunit might be a good molecular candidate for the targeted treatment of malignant thyroid tumors.
Topics: Adult; Aged; Aged, 80 and over; Cell Differentiation; Cyclic AMP-Dependent Protein Kinases; Female; Humans; Hyperplasia; Male; Middle Aged; Prognosis; Protein Subunits; Thyroid Gland; Thyroid Neoplasms
PubMed: 27321957
DOI: 10.1016/j.yexcr.2016.06.004 -
Seizure Nov 2023Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults,... (Meta-Analysis)
Meta-Analysis
Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults, but their role in epilepsy in children has just gained traction and results have remained inconsistent. In this work, we performed a systematic review and meta-analysis to assess the association between SCN1A polymorphisms and risk for epilepsy in children. A systematic literature search was performed in PubMed, Scopus, Web of Science, China National Knowledge Internet, Wanfang and VIP databases to identify eligible studies up to June 2023. Quantitative data synthesis was then performed under five genetic models: dominant, recessive, homozygous, heterozygous, and allele. Five studies involving 1380 subjects were included in the meta-analysis. Among many SCN1A polymorphisms reported, only rs2298771 was repeatedly studied in these reports. Pooled analysis demonstrated that there was no significant association between the polymorphism and risk of epilepsy in children (P>0.05). In conclusion, SCN1A rs2298771 polymorphism was not significantly associated with the risk of epilepsy in children.
Topics: Adult; Humans; Child; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; NAV1.1 Voltage-Gated Sodium Channel; Epilepsy; China
PubMed: 37741152
DOI: 10.1016/j.seizure.2023.09.012 -
Hypoxia and hypoxia response-associated molecular markers in esophageal cancer: A systematic review.Methods (San Diego, Calif.) Nov 2017In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set... (Review)
Review
PURPOSE
In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set into the context of the role of hypoxia in the prediction of esophageal cancer, treatment response and treatment outcome.
METHODS
A systematic literature search was performed in Web of Science, MEDLINE, and PubMed databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and treatment response. Eligible publications were independently evaluated by two reviewers. In total, 22 out of 419 records were included for systematic review. The described search strategy was applied weekly, with the last update being performed on April 3rd, 2017.
RESULTS
In esophageal cancer, several (non-)invasive biomarkers for hypoxia could be identified. Independent prognostic factors for treatment response include HIF-1α, CA IX, GLUT-1 overexpression and elevated uptake of the PET-tracer F-fluoroerythronitroimidazole (F-FETNIM). Hypoxia-associated molecular responses represents a clinically relevant phenomenon in esophageal cancer and detection of elevated levels of hypoxia-associated biomarkers and tends to be associated with poor treatment outcome (i.e., overall survival, disease-free survival, complete response and local control).
CONCLUSION
Evaluation of tumor micro-environmental conditions, such as intratumoral hypoxia, is important to predict treatment outcome and efficacy. Promising non-invasive imaging-techniques have been suggested to assess tumor hypoxia and hypoxia-associated molecular responses. However, extensive validation in EC is lacking. Hypoxia-associated markers that are independent prognostic factors could potentially provide targets for novel treatment strategies to improve treatment outcome. For personalized hypoxia-guided treatment, safe and reliable makers for tumor hypoxia are needed to select suitable patients.
Topics: Animals; Biomarkers, Tumor; Carbonic Anhydrase IX; Esophageal Neoplasms; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 28705470
DOI: 10.1016/j.ymeth.2017.07.002 -
Expert Review of Vaccines Sep 2022A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are becoming apparent from clinical trials.
METHODS
Five databases (Medline, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, London School of Hygiene and Tropical Medicine COVID-19 vaccine tracker) were searched for relevant randomized controlled trials between 1 January 2020 and 12 January 2022 according to predetermined criteria with no language limitations.
RESULTS
Forty-two datasets were identified, with 20 vaccines using four different technologies (viral vector, inactivated, mRNA and protein sub-unit). Adults and adolescents over 12 years were included. Control groups used saline placebos, adjuvants, and comparator vaccines. The most consistently reported solicited adverse events were fever, fatigue, headache, pain at injection site, redness, and swelling. Both doses of mRNA vaccines, the second dose of protein subunit and the first dose of adenovirus vectored vaccines were the most reactogenic, while the inactivated vaccines were the least reactogenic.
CONCLUSIONS
The different COVID-19 vaccines currently available appear to have distinct reactogenicity profiles, dependent on the vaccine technology employed. Awareness of these differences may allow targeted recommendations for specific populations. Greater standardization of methods for adverse event reporting will aid future research in this field.
Topics: Adjuvants, Immunologic; Adolescent; Adult; COVID-19; COVID-19 Vaccines; Humans; Vaccines, Inactivated
PubMed: 35796029
DOI: 10.1080/14760584.2022.2098719 -
The Indian Journal of Medical ResearchThe COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission,... (Review)
Review
BACKGROUND & OBJECTIVES
The COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission, with a few vaccines having progressed to advanced stages of clinical trials. The aim of this systematic review was to compare immunogenicity and protective efficacy of various SARS-CoV-2 vaccine candidates tested in non-human primate (NHP) models.
METHODS
Literature on effect of SARS-CoV-2 vaccines in NHP models reported on PubMed and preprint platforms (medRxiv and bioRxiv) till October 22, 2020, was searched with the following terms: coronavirus vaccine, COVID-19 vaccine, SARS-CoV-2 vaccine, nonhuman primate, and rhesus macaque.
RESULTS
Our search yielded 19 studies, which reported immune response elicited by 18 vaccine candidates in NHP. All the vaccines induced detectable neutralizing antibody (NAb) titres in the serum of vaccinated animals, with some showing effective viral clearance from various organs. The vaccinated animals also showed nil to mild histopathological changes in their lungs compared to placebo groups in the trials that performed necropsy.
INTERPRETATION & CONCLUSIONS
Our findings highlighted onset of quick immunogenicity and protective efficacy of mRNA-1273, followed by Ad26.CoV2.S, NVX-CoV2373, BNT162b2, RBD and BBV152 vaccine candidates in preclinical trials as compared to the others. NHP data also showed correlation with clinical trial data available for a few vaccines. Preclinical trials of COVID-19 vaccine candidates in NHPs yielded promising results, with some candidates faring better than others.
Topics: 2019-nCoV Vaccine mRNA-1273; Ad26COVS1; Animals; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Disease Models, Animal; Immunogenicity, Vaccine; Macaca mulatta; Primates
PubMed: 33361645
DOI: 10.4103/ijmr.IJMR_4431_20