Bart Syndrome with Ear Malformation

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MicroRNAs: a new piece in the paediatric cardiovascular disease puzzle

Cardiovascular diseases in children comprise a large public health problem. The major goals of paediatric cardiologists and paediatric cardiovascular researchers are to identify the cause(s) of these diseases to improve treatment and preventive protocols. Recent studies show the involvement of microRNAs (miRs) in different aspects of heart development, function, and disease. Therefore, miR-based research in paediatric cardiovascular disorders is crucial for a better understanding of the underlying pathogenesis of the disease, and unravelling novel, efficient, preventive, and therapeutic means. The ultimate goal of such research is to secure normal cardiac development and hence decrease disabilities, improve clinical outcomes, and decrease the morbidity and mortality among children. This review focuses on the role of miRs in different paediatric cardiovascular conditions in an effort to encourage miR-based research in paediatric cardiovascular disorders

Evaluation of Serum and Gene Expression of Galectin-4, Interleukin-27, and Complement-7 in Hepatitis C Virus-Infected Egyptian Patients

Background. Hepatitis C virus (HCV) is considered a major global public health problem. Recently, there are great advances in HCV therapy, but there are some limitations that are creating an urgent need for assessment of some cytokines that have a potent antiviral effect in the immune system and anti-inflammatory effects to provide a potential novel immunotherapeutic target in HCV infection. Objective. This study was directed to assess the serum levels and gene expression levels of Galectin-4 (LEG4), Interleukin-27 (IL-27), and Complement-7 (C-7) and their correlation with the viral load in HCV infection. Subjects and Methods. This work was conducted on 80 subjects, Group 1 (n=40) early detected HCV patients and Group 2 (n=40) healthy controls. LEG4, IL-27, and C-7 were assessed at the protein levels by ELISA, and their gene expression was assessed by RT-qPCR. The viral load was measured by PCR. Results. There were significant elevations in the mean levels of gene expression and serum levels of all studied parameters LEG4, IL-27, and C-7 in the HCV group compared to the control group. Significant negative correlations between the viral load and each of the serum proteins and gene expressions of both LEG4 and IL-27 in HCV patients were found. The gene expression levels of LEG4, IL-27, and C-7 were positively correlated with their corresponding serum proteins in HCV patients.Conclusion. LEG4 and IL-27 showed significant negative correlations with the viral load, which could be an immune response to the control of the extent of hepatic inflammation, thus creating a potential novel immunotherapeutic approach in HCV infection for further studies or therapeutic clinical trials

Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors

Abstract Background Single-cell gene expression profiling provides unique opportunities to understand tumor heterogeneity and the tumor microenvironment. Because of cost and feasibility, profiling bulk tumors remains the primary population-scale analytical strategy. Many algorithms can deconvolve these tumors using single-cell profiles to infer their composition. While experimental choices do not change the true underlying composition of the tumor, they can affect the measurements produced by the assay. Results We generated a dataset of high-grade serous ovarian tumors with paired expression profiles from using multiple strategies to examine the extent to which experimental factors impact the results of downstream tumor deconvolution methods. We find that pooling samples for single-cell sequencing and subsequent demultiplexing has a minimal effect. We identify dissociation-induced differences that affect cell composition, leading to changes that may compromise the assumptions underlying some deconvolution algorithms. We also observe differences across mRNA enrichment methods that introduce additional discrepancies between the two data types. We also find that experimental factors change cell composition estimates and that the impact differs by method. Conclusions Previous benchmarks of deconvolution methods have largely ignored experimental factors. We find that methods vary in their robustness to experimental factors. We provide recommendations for methods developers seeking to produce the next generation of deconvolution approaches and for scientists designing experiments using deconvolution to study tumor heterogeneity

Aberrant p16INK4A methylation: Relation to viral related chronic liver disease and hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5′-cytosine-phosphoguanine island within the promoter region. Aim: To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis. Patients and Methods: This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ2 ) test was performed. Exact test was used instead when the expected frequency was less than 5. Results: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 μg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size. Conclusion: Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC

Cairo University fibrosis index (CUFI): A score based on microRNA for diagnosis of significant hepatic fibrosis: A biopsy based study

Introduction: Identification of HCV- induced liver fibrosis is mandatory for tailoring therapy, and management of complications. The current study evaluated the accuracy of circulating miRNAs; in diagnosis of hepatic fibrosis. Patients  and methods: Seventy HCV patients were subjected to routine laboratory investigations, HCV-RNA, serum miRNA-122, 221, 192, 224 , 375, and 885  by PCR, liver biopsy and calculation of the following scores:  aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), aspartate to platelet ratio index (APRI), FIB-4 score,  Hui index,  Fibrosis Index (FI), Fibro-Q ,  Fibro-Alfa Biotechnology Research Center (BRC) score and  Gotebörg University Cirrhosis Index (GUCI). Results: Patients with significant and advanced fibrosis have significantly lower miR-122 (P < 0.0001 and P= 0.007, respectively).  miR-122, bilirubin and miR-855 were found to be  independent predictors of significant fibrosis in univariate analysis. A novel score; Cairo University Fibrosis Index (CUFI) based on microRNA 122, bilirubin and microRNA 855 were formulated for predicting significant liver fibrosis. The AUC of this score, for predicting significant and advanced hepatic fibrosis was 0.83 and 0.80 respectively.  This AUC was higher than those of other fibrosis scores. Conclusion: Cairo University Fibrosis Index is better than the existing scores in assessing fibrosis in chronic HCV patients