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PloS One 2018Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first... (Meta-Analysis)
Meta-Analysis
Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first trimester measurements of prenatal screening biomarkers are associated with subsequent risk of gestational diabetes mellitus (GDM). We aimed to systematically review and statistically summarize studies assessing the relationship between first trimester prenatal screening biomarker levels and GDM development. We comprehensively searched PubMed/MEDLINE, EMBASE, CINAHL, and Scopus (from inception through January 2018) and manually searched the reference lists of all relevant articles. We included original, published, observational studies examining the association of first trimester pregnancy associated plasma protein-A (PAPP-A) and/or free β-human chorionic gonadotropin (free β-hCG) levels with GDM diagnosis. Mean differences were calculated comparing PAPP-A and free β-hCG multiples of median (MoM) levels between women who developed GDM and those who did not and were subsequently pooled using two-sided random-effects models. Our meta-analysis of 13 studies on PAPP-A and nine studies on free β-hCG indicated that first trimester MoM levels for both biomarkers were lower in women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (MD -0.17; 95% CI -0.24, -0.10; MD -0.04; 95% CI -0.07-0.01). There was no evidence for between-study heterogeneity among studies on free β-hCG (I2 = 0%). A high level of between-study heterogeneity was detected among the studies reporting on PAPP-A (I2 = 90%), but was reduced after stratifying by geographic location, biomarker assay method, and timing of GDM diagnosis. Our meta-analysis indicates that women who are diagnosed with GDM have lower first trimester levels of both PAPP-A and free β-hCG than women who remain normoglycemic throughout pregnancy. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed.
Topics: Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Diabetes, Gestational; Female; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis
PubMed: 30048548
DOI: 10.1371/journal.pone.0201319 -
European Journal of Endocrinology Nov 2023Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding...
BACKGROUND
Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding protein (Gsα) resulting from maternal GNAS gene variation. The clinical manifestations are related to PTH resistance (hypocalcemia, hyperphosphatemia, and elevated serum intact PTH) in the presence or absence of multihormone resistance, and Albright's hereditary osteodystrophy (AHO).
OBJECTIVES
To summarize the molecular genetics results and clinical characteristics as well as to explore the correlations between them.
METHODS
Articles pertaining to PHP1a until May, 31, 2021 were reviewed and 527 patients with genetic diagnosis were included in the data analysis. The clinical characteristics and molecular genetics results of these patients were analyzed and compared to explore the correlations between them.
RESULTS
A total of 258 GNAS rare variants (RVs) were identified in 527 patients. The RVs were most commonly found in exons 1 and 7 (17.6% each), with frameshift (36.8%), and missense (31.3%) being the main types of RVs. The median age of onset was 5.0 years old. The most common clinical manifestations were elevation of PTH (86.7%) and AHO (87.5%). Thyroid stimulating hormone resistance was the most common hormone resistance (75.5%) other than PTH resistance. Patients with missense and in-frame RVs had lower incidence rates of the round face (P = .001) and subcutaneous ossifications (P < .001) than those with loss-of-function (non-sense, frameshift, splicing site variants, and large deletions) variants.
CONCLUSIONS
This study revealed the correlation between loss-of-function RVs with round faces and subcutaneous ossifications in PHP 1a patients. Further exploration of genotype-phenotype correlations through more standardized and prospective studies with long-term follow-up is necessary.
Topics: Humans; Child, Preschool; Prospective Studies; Chromogranins; Pseudohypoparathyroidism; GTP-Binding Protein alpha Subunits, Gs; Genetic Association Studies
PubMed: 37837607
DOI: 10.1093/ejendo/lvad142 -
PloS One 2024Colibacillosis, a disease caused by Escherichia coli in broiler chickens has serious implications on food safety, security, and economic sustainability. Antibiotics are... (Meta-Analysis)
Meta-Analysis
Colibacillosis, a disease caused by Escherichia coli in broiler chickens has serious implications on food safety, security, and economic sustainability. Antibiotics are required for treating the disease, while vaccination and biosecurity are used for its prevention. This systematic review and meta-analysis, conducted under the COST Action CA18217-European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT), aimed to assess the efficacy of E. coli vaccination in broiler production and provide evidence-based recommendations. A comprehensive search of bibliographic databases, including, PubMed, CAB Abstracts, Web of Science and Agricola, yielded 2,722 articles. Following a defined protocol, 39 studies were selected for data extraction. Most of the studies were experimental infection trials, with only three field studies identified, underscoring the need for more field-based research. The selected studies reported various types of vaccines, including killed (n = 5), subunit (n = 8), outer membrane vesicles/protein-based (n = 4), live/live-attenuated (n = 16), and CpG oligodeoxynucleotides (ODN) (n = 6) vaccines. The risk of bias assessment revealed that a significant proportion of studies reporting mortality (92.3%) or feed conversion ratio (94.8%) as outcomes, had "unclear" regarding bias. The meta-analysis, focused on live-attenuated and CpG ODN vaccines, demonstrated a significant trend favoring both vaccination types in reducing mortality. However, the review also highlighted the challenges in reproducing colibacillosis in experimental setups, due to considerable variation in challenge models involving different routes of infection, predisposing factors, and challenge doses. This highlights the need for standardizing the challenge model to facilitate comparisons between studies and ensure consistent evaluation of vaccine candidates. While progress has been made in the development of E. coli vaccines for broilers, further research is needed to address concerns such as limited heterologous protection, practicability for application, evaluation of efficacy in field conditions and adoption of novel approaches.
Topics: Animals; Escherichia coli; Chickens; Poultry Diseases; Escherichia coli Infections; Escherichia coli Vaccines; Vaccination
PubMed: 38517875
DOI: 10.1371/journal.pone.0301029 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
International Journal of Environmental... Dec 2019Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor...
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.
Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like () , adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) , ADD1, , MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Topics: DNA Methylation; Essential Hypertension; Female; Genotype; Humans
PubMed: 31805646
DOI: 10.3390/ijerph16234829 -
Resuscitation Mar 2020To summarise and compare the prognostic accuracy of the blood biomarkers of brain injury, including NSE and S-100B, for neurological outcomes in adult post-cardiac... (Meta-Analysis)
Meta-Analysis Review
AIM
To summarise and compare the prognostic accuracy of the blood biomarkers of brain injury, including NSE and S-100B, for neurological outcomes in adult post-cardiac arrest patients.
METHODS
We systematically searched PubMed and Embase databases from their inception to March 2019. We selected studies providing sufficient data of prognostic values of NSE or S-100B to predict neurological outcomes in adult post-cardiac arrest patients. We adopted QUADAS-2 to assess risk of bias and a Bayesian bivariate random-effects meta-analysis model to synthesise the prognostic data. The study protocol was registered with PROSPERO (CRD42018084933).
RESULTS
We included 42 studies involving 4806 patients in the meta-analysis. The NSE was associated with a pooled sensitivity of 0.56 (95% credible interval [CrI], 0.47-0.65) and pooled specificity of 0.99 (95% CrI, 0.98-1.00). The S-100B was associated with a pooled sensitivity of 0.63 (95% CrI, 0.46-0.78) and pooled specificity of 0.97 (95% CrI, 0.92-1.00). The heterogeneity for NSE (I, 22.4%) and S-100B (I, 16.1%) was low and publication bias was not significant. In subgroup analyses, both biomarkers were associated with high specificity across all subgroups with regard to different populations (i.e. whether patients were out-of-hospital cardiac arrest or whether patients received targeted temperature management), different timings of measurement, and different timings of outcome assessment.
CONCLUSIONS
The prognostic performance was comparable between NSE and S-100B. Both biomarkers may be integrated into a multimodal neuroprognostication algorithm for post-cardiac arrest patients and institution-specific cut-off points for both biomarkers should be established.
Topics: Adult; Bayes Theorem; Biomarkers; Humans; Hypothermia, Induced; Phosphopyruvate Hydratase; Prognosis; S100 Calcium Binding Protein beta Subunit
PubMed: 31978453
DOI: 10.1016/j.resuscitation.2020.01.006 -
Journal of Cellular Physiology Apr 2021Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments....
Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments. Pathways of the viral entry into cells are interesting subjects for targeted therapy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aims to provide a systematic evaluation of the most recent in vitro and in vivo investigations targeting SARS-CoV-2 cell entry. A systematic search was carried out in major medical sources, including MEDLINE (through PubMed), Web of Science, Scopus, and EMBASE. Combinations of the following search terms were used: SARS-CoV-2, in vitro, in vivo, preclinical, targeted therapy, and cell entry. A modified version of the Consolidated Standards of Reporting Trials and Systematic Review Centre for Laboratory Animal Experimentation assessment tools were applied for evaluating the risk of bias of in vitro and in vivo studies, respectively. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. A total of 2,649 articles were identified through searching PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and Biorxiv. Finally, 22 studies (one in vivo study and 21 in vitro studies) were included. The spike (S) glycoprotein of the SARS-CoV-2 was the main target of investigation in 19 studies. SARS-CoV-2 can enter into the host cells through endocytosis or independently. SARS-CoV-2 S protein utilizes angiotensin-converting enzyme 2 or CD147 as its cell-surface receptor to attach host cells. It consists of S1 and S2 subunits. The S1 subunit mediates viral attachment to the host cells, while the S2 subunit facilitates virus-host membrane fusion. The cleavage of the S1-S2 protein, which is required for the conformational changes of the S2 subunit and processing of viral fusion, is regulated by the host proteases, including cathepsin L (during endocytosis) and type II membrane serine protease (independently). Targeted therapy strategies against SARS-CoV-2 cell entry mechanisms fall into four main categories: strategies targeting virus receptors on the host, strategies neutralizing SARS-CoV-2 spike protein, strategies targeting virus fusion to host cells, and strategies targeting endosomal and non-endosomal dependent pathways of virus entry. Inhibition of the viral entry by targeting host or virus-related components remains the most potent strategy to prevent and treat COVID-19. Further high-quality investigations are needed to assess the efficacy of the proposed targets and develop specific antivirals against SARS-CoV-2.
Topics: Animals; Antiviral Agents; COVID-19; Humans; SARS-CoV-2; Virus Internalization; COVID-19 Drug Treatment
PubMed: 32901936
DOI: 10.1002/jcp.30032 -
Medicine Sep 2015The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent... (Meta-Analysis)
Meta-Analysis Review
The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis. PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed. A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898-2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595-2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675-1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667-3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566-1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206-3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629-3.407, P = 0.000). The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.
Topics: Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Neoplasms; Prognosis; Protein Isoforms
PubMed: 26402839
DOI: 10.1097/MD.0000000000001646 -
Journal of Medical Genetics Apr 2020Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.
METHODS
We searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.
RESULTS
The highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%-41%) and the lowest risk by SDHD mutation (~4%).
CONCLUSION
There was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.
Topics: Adrenal Gland Neoplasms; Electron Transport Complex II; Germ-Line Mutation; Heterozygote; Humans; Membrane Proteins; Mitochondrial Proteins; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31649053
DOI: 10.1136/jmedgenet-2019-106324 -
The Journal of International Medical... Aug 2020Interleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the impacts of the IL-12 rs3212227 and rs568408 gene polymorphisms on HCC.
METHODS
We searched PubMed, Embase, Web of Science, and Chinese Knowledge Infrastructure databases for studies on the associations between HCC and IL-12 rs568408 and rs3212227 polymorphisms published prior to 1 May 2020. The effects of the polymorphisms on HCC susceptibility were presented as odds ratios (ORs) and associated 95% confidence intervals.
RESULTS
Seven studies were ultimately included, including 2375 cases and 3445 controls. The rs3212227 polymorphism was significantly associated with the risk of HCC in both the dominant model (CC+AC vs. AA, OR=1.22) and the allele model (C vs. A, OR=1.12). Combined analysis of rs568408 yielded a significant relative risk for HCC in the dominant (AA+AG vs. GG, OR=1.13), recessive (AA vs. AG+GG, OR=1.72), allele (A vs. G, OR=1.29), heterozygote (AG vs. GG, OR=1.27), and homozygote models (AA vs. GG, OR 1.17).
CONCLUSION
The IL-12 rs3212227 and rs568408 gene polymorphisms are associated with an increased risk of HCC.
Topics: Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Interleukin-12; Interleukin-12 Subunit p35; Liver Neoplasms; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 32809897
DOI: 10.1177/0300060520943420