Association of group‐specific component exon 11 polymorphisms with bronchial asthma in children and adolescents

Several studies have investigated the association of Group‐specific Component (GC) gene, also known as vitamin D‐binding protein (VDBP), and various respiratory disorder susceptibility with conflicting results. In this sense, we aimed to investigate whether rs7041 and rs4588 variants confer susceptibility to bronchial asthma in a sample of an Egyptian population and to elucidate by in silico analysis the structural and functional impact of these variants. Group‐specific Component polymorphisms rs7041 and rs4588 were genotyped in 192 Egyptian children and adolescents (96 with asthma and 96 healthy controls) by TaqMan single nucleotide polymorphism genotyping assay. The rs7041 GG genotype showed a significantly elevated frequency among patients under codominant, dominant, recessive and allelic models where the patient group had greater carriage rate of G allele [OR 2.15, CI 95% (1.32‐3.50; P = 0.002)], while rs4588 CA and AA genotypes were found to be protective genotypes with controls showing a greater carriage rate of A allele [OR 0.52, CI 95% (0.30 ‐ 0.90; P = 0.02)]. Three haplotype allele combinations were identified with frequencies of GC (44.3%), TC (31.3%) and TA (24.5%) in the total study population. GC haplotype was shown to be more frequent in controls, while TC and TA haplotypes were more predominant in the patient group. Only rs7041 variant showed a significant association with family history and pubertal status. In conclusion, both study GC variants could be implicated in childhood bronchial asthma pathogenesis; rs7041 GG genotype and G allele increased asthma risk while rs4588 AA genotype and A allele conferred protection in the study population.     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Prognostic value of BRAF/MIR‐17 signature and B‐Raf protein expression in patients with colorectal cancer: A pilot study

BackgroundDespite the recent improvement in colorectal cancer (CRC) treatment, it still has a poor prognosis with a low survival rate. Genetic and epigenetic mechanisms have proved to play a substantial role in CRC tumorigenesis and progression. According to Gene Ontology and TargetScan analyses, the B‐Raf proto‐oncogene (BRAF) gene is one of the microRNA‐17 (miR‐17) targets. We aimed to explore the prognostic value of B‐Raf protein and BRAF/microRNA‐17 (MIR‐17) gene expression signature in CRC archived samples.MethodsB‐Raf protein expression was identified by immunohistochemistry, while gene expression studies were quantified by real‐time qPCR in 53 paired archived CRC specimens.ResultsThe BRAF showed higher expressions in CRC specimens relative to non‐cancer tissues (p = 0.006). MIR17 expression was inversely and significantly correlated with both B‐Raf protein (r = −0.79, p < 0.001) and gene expression (r = −0.35, p = 0.010) and showed a significant direct correlation with a high rate of relapse (p = 0.020). BRAF/miR‐17 expression in CRC was associated inversely with tumor size, high grade of colonic carcinoma, lymph node metastasis, and carcinoma subtype. Spearman correlation and Kaplan‐Meier survival curve analyses revealed that disease‐free survival and overall survival were inversely and significantly correlated with positive B‐Raf protein expression (r = −0.31 and −0.35, p = 0.023 and 0.011, respectively) and directly correlated with log BRAF/MIR17 ratio (r = 0.50 and 0.41, p < 0.001 and = 0.003, respectively). Cox hazard regression analysis revealed the BRAF/MIR17 ratio could predict both types of patients'' survival, among other variables.Conclusion BRAF/MIR17 ratio could have prognostic utility in patients with CRC. Further larger‐scale studies are warranted to confirm this utility.     

Glutamine up-regulates pancreatic sodium-dependent neutral aminoacid transporter-2 and mitigates islets apoptosis in diabetic rats

Background

Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabetic rats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2).

Multisystem inflammatory syndrome in pediatric COVID-19 patients:a meta-analysis

Background We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflam-matory syndrome in pediatrics diagnose...     

Impact of psychiatric comorbidities on outcomes related to thyroid and parathyroid operations

BackgroundWe examined the effect of psychiatric comorbidities on perioperative surgical outcomes and the leading causes of readmissions in patients who underwent thyroid and parathyroid operations.MethodPatient information was retrieved from the Nationwide Readmission Database (2010–2017). Multivariate analysis was used to identify predictors for hospital readmissions.ResultsA total of 181,007 and 53,808 patients underwent thyroid and parathyroid operations, respectively. Of those, 8,468 (4.7%) and 6,112 (11.4%) patients were readmitted within 30 days. Psychiatric comorbidities were more frequent in readmitted cohorts after thyroidectomies (14.9% vs 10.4%; P < .001) and parathyroidectomies (16.8% vs 11.5%; P < .001), with anxiety being the most frequent cause (thyroid: 7.87%, parathyroid: 6.8%). Psychiatric comorbidities were associated with greater risk of in-hospital mortality (thyroid: odds ratio = 2.07, 95% confidence interval = 1.13–3.53; P = .015 and parathyroid: odds ratio = 1.67, 95% confidence interval = 1.04–2.70; P = .005), postoperative complications (thyroid: odds ratio = 1.528, 95% confidence interval = 1.473–1.585; P < .001 and parathyroid: odds ratio = 3.26, 95% confidence interval = 2.84–3.73; P < .001), prolonged duration of stay (thyroid: beta coefficient = 1.142, 95% confidence interval = 1.076–1.207; P < .001 and parathyroid: beta coefficient = 2.15, 95% confidence interval = 1.976–2.32; P < .001), and 30-day readmissions (thyroid: hazard ratio = 1.18, 95% confidence interval = 1.03–1.18; P = .047 and parathyroid: hazard ratio = 1.23, 95% confidence interval = 1.11–1.36; P < .001). Psychosis had the greatest risk of readmission (thyroid: hazard ratio = 1.51 and parathyroid: hazard ratio = 1.42), and dementia (odds ratio = 2.58) had the greatest risk of postoperative complications.ConclusionConcomitant psychiatric conditions after thyroid and parathyroid operations were associated with increased risk of postoperative complications, prolonged hospital stays, and greater rates of readmissions.     

COVID-19 and liver dysfunction: A systematic review and meta-analysis of retrospective studies

Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.     

Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.MethodsThe CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.ResultsA higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed.ConclusionThe CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.