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Reproductive Sciences (Thousand Oaks,... Oct 2022Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha... (Review)
Review
Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha (HIF1-α) is associated with the incidence of hypoxia. In this study, we investigated the expression of HIF1-α in varicocele disease through a comprehensive systematic review. We searched PubMed, Scopus, Web of Science, and Embase databases to identify the related studies published up to February 2021. Human studies have demonstrated an increase in the HIF-1α protein expression in the internal spermatic vein (ISV) of the varicocele testicle. HIF-1α mRNA expression in the seminal plasma was significantly higher in infertile varicocele patient compared with fertile ones. Similarly, most animal studies demonstrated a significant increase in HIF-1α gene and protein expression in varicocele testicular tissue compared with control groups. The studies illustrated that hypoxia followed by increased expression of hypoxia-inducible factor 1-alpha (HIF1-α) mRNA and protein occurs in varicocele disease. Expression of HIF-1α regulates the expression of many genes, including VEGF, p53, GLUT, Bax, and Caspase-3, that could be involved in many of the varicocele pathophysiological effects such as DNA fragmentation and apoptosis of sperm cells. Further studies with a large number of patients are necessary and can provide more definitive evidence.
Topics: Animals; Caspase 3; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Male; RNA, Messenger; Semen; Tumor Suppressor Protein p53; Varicocele; Vascular Endothelial Growth Factor A; bcl-2-Associated X Protein
PubMed: 34313997
DOI: 10.1007/s43032-021-00696-y -
Expert Review of Clinical Immunology 2016Regulatory T-cells (Tregs) are key players in successful pregnancy and their deficiencies are implicated in pregnancy complications such as preeclampsia (PE), but the... (Review)
Review
Regulatory T-cells (Tregs) are key players in successful pregnancy and their deficiencies are implicated in pregnancy complications such as preeclampsia (PE), but the results are inconsistent among studies. This study aims to compile an overview of the studies about the associations of Tregs and PE risk and to provide recommendations for future research. A sensitive search of three databases including PubMed, Scopus and Google scholar (from 1995 to January 9, 2015) identified 636 unique titles. An accurate process of study selection, data extraction and method qualification were independently conducted by authors on retrieved papers. Seventeen papers met the inclusion criteria and were included in quality assessment. Regarding the source of Tregs, 14 studies assessed Tregs in peripheral blood, 2 studies in peripheral blood and decidua and one study in peripheral blood and umbilical cord blood. Despite variation in the combinations of markers and other aspects of the studies designs, remarkable constancy in the results of studies that measured Tregs as CD4+FoxP3+ or CD4+CD25+FoxP3+ cells (but not CD4+CD25(high/low)FoxP3+ markers) was found, which in broad terms showed a shift towards fewer Treg cells in PE. This review revealed an association between lower percentage of circulating CD4+FoxP3+ or CD4+CD25+FoxP3+ Tregs and the risk of PE. Given the above issue and regarding the high consistency of studies on reduction of suppressive activity of Tregs in PE, we have proposed a model in which the Tregs deficiency is a reflection of immune endocrine imbalance, which reverses maternal tolerance and results in development of preeclampsia.
Topics: Female; Forkhead Transcription Factors; Humans; Immune Tolerance; Interleukin-2 Receptor alpha Subunit; Lymphocyte Count; Pre-Eclampsia; Pregnancy; T-Lymphocytes, Regulatory
PubMed: 26580672
DOI: 10.1586/1744666X.2016.1105740 -
Annals of Allergy, Asthma & Immunology... Jun 2024Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in...
A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.
BACKGROUND
Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians.
OBJECTIVE
To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab.
METHODS
A systematic review of the literature was performed, and an expert Delphi Panel was assembled.
RESULTS
The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective.
CONCLUSION
Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.
PubMed: 38848870
DOI: 10.1016/j.anai.2024.05.014 -
PloS One 2016S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid... (Review)
Review
S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer's Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (padj = 3.1 x 10(-4)) and worse GOS outcome (padj = 5.5 x 10(-11)). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome.
Topics: Biomarkers; Humans; Prognosis; S100 Calcium Binding Protein beta Subunit; Subarachnoid Hemorrhage
PubMed: 27007976
DOI: 10.1371/journal.pone.0151853 -
Journal of Dermatological Science May 2018Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD).
OBJECTIVE
We aimed to assess the overall efficacy and safety of dupilumab treatment in AD.
METHODS
PubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively).
RESULTS
Six trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04).
CONCLUSIONS
Our analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Humans; Injections, Subcutaneous; Interleukin-4 Receptor alpha Subunit; Pruritus; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 29472119
DOI: 10.1016/j.jdermsci.2018.01.016 -
Pharmacology, Biochemistry, and Behavior Feb 2023Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are... (Review)
Review
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Topics: Humans; Ketamine; Depression; Depressive Disorder, Major; Systems Biology; Antidepressive Agents; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 36731751
DOI: 10.1016/j.pbb.2023.173523 -
Genetic Testing and Molecular Biomarkers Mar 2016Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study was to conduct a systematic review and meta-analysis investigating whether the polymorphism in the NFKB1 promoter region (NFKB1-94ins(I)/del(D)ATTG, rs28362491) is associated with CAD susceptibility.
METHODS
PubMed, Embase, Cochrane Library and CNKI databases were searched up to 30 July 2015. All observational case-control studies that investigated the association of NFKB1 I/D polymorphism and CAD risk were included. Two reviewers independently selected the studies and extracted the data.
RESULTS
A total of 7 studies were included in this meta-analysis. Comparison between alleles showed a 13% increased risk of CAD for D vs. I (OR = 1.13, 95% CI 1.06-1.19, PH = 0.318), and comparisons among genotypes showed a 26% increased risk of CAD for DD vs. II (OR = 1.26, 95% CI 1.12-1.43, PH = 0.125) and in the heterozygote model ID vs. II had an 11% increased risk (OR = 1.11, 95% CI 1.01-1.21, PH = 0.751). In the dominant model the risk of CAD risk was reduced by 13% (OR = 0.87, 95%CI 0.80-0.95, PH = 0.814) across the total population. Subgroup analysis by ethnicity indicated that the additive model was associated with a 21% increased risk for CAD in the Caucasian population (OR = 1.21, 95% CI 1.09-1.34, PH = 0.522), while the homozygote model gave a 47% increased risk for CAD in Asian population (OR = 1.47, 95% CI 1.21-1.78, PH = 0.314).
CONCLUSIONS
Our results indicated that the NFKB1-94ins/del ATTG polymorphism was associated with susceptibility to CAD in both Asian and Caucasian populations.
Topics: Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; INDEL Mutation; NF-kappa B p50 Subunit; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Factors
PubMed: 26799199
DOI: 10.1089/gtmb.2015.0242 -
International Journal of Surgery... May 2018The relationship between expression of runt related transcription factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric cancer (GC) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship between expression of runt related transcription factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric cancer (GC) is controversial.
METHODS
The studies were retrieved from those already published essay in PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar. All statistical tests in this meta-analysis were performed using Stata 10.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant.
RESULTS
A total of nine studies involving 796 patients were included in final meta-analysis. The pooled data showed that expression of RUNX3 was significant correlated with tumor's differentiation (OR = 0.387; 95%CI: 0.237-0.633; P = 0.000), depth of invasion (OR = 0.443; 95%CI: 0.273-0.717; P = 0.001), lymph node metastasis (OR = 0.394; 95%CI: 0.259-0.598; P = 0.000), distant metastasis (OR = 0.403; 95%CI: 0.213-0.764; P = 0.005) and TNM stage (OR = 0.461; 95%CI, 0.322-0.659; P = 0.000) in GC. Expression of RUNX3 was significant correlated with good overall survival (OS) [1-year OS (OR = 2.735; 95%CI: 1.966-3.806; P = 0.000), 3-year OS (OR = 4.782; 95%CI: 3.634-6.292; P = 0.000), 5-year OS (OR = 5.191; 95%CI: 3.775-7.138; P = 0.000]. However, RUNX3 was not correlated with gender (OR = 1.409; 95%CI: 0.986-2.014; P = 0.060).
CONCLUSION
RUNX3 expression correlates with tumor's differentiation, depth of invasion, lymph node metastasis, distant metastasis, TNM stage and OS of GC patients.
Topics: Core Binding Factor Alpha 3 Subunit; Humans; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Staging; Prognosis; Stomach Neoplasms
PubMed: 29578091
DOI: 10.1016/j.ijsu.2018.03.041 -
Pathogens (Basel, Switzerland) Nov 2023Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants... (Review)
Review
Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). and genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe and variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on and studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in and could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.
PubMed: 38003785
DOI: 10.3390/pathogens12111320 -
Gastrointestinal Endoscopy May 2021Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a... (Meta-Analysis)
Meta-Analysis
Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs).
METHODS
Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI).
RESULTS
Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I = 86.74%), 91% (95% CI, 72-98; I = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001).
CONCLUSIONS
Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.
Topics: Biomarkers, Tumor; Chromogranins; Cyst Fluid; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Pancreatic Cyst; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras)
PubMed: 33359054
DOI: 10.1016/j.gie.2020.12.014