Exploring the Impact of Different Inflammatory Cytokines on Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is a global health concern affecting millions worldwide. Chronic HCV infection often leads to liver inflammation and can progress to cirrhosis and hepatocellular carcinoma. Inflammatory cytokines are crucial in modulating the immune response during HCV infection.

Overexpression of miRNA 26a and 26b with MMP-9 are valuable diagnostic biomarkers for colorectal cancer patients.

The key role of miRNA expression in incidence and progression of colorectal cancer (CLC) have been developed over the last decade. A total of 153 subjects were enrolled into two phases: 14 selected miRNAs were first evaluated in 50 subjects, then miR-26a and miR-26b relative expression were further evaluated in 103 subjects and their target protein MMP-9 was measured. miR-26a and -26b showed highly significant overexpression.

The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.

Objectives: In this study, we investigated the association between the IFN-λ3 rs12979860 single nucleotide polymorphism (SNP) and the transition from late fibrosis to HCC in Egyptian HCV-chronically infected patients.

Methods: The rs12979860 SNP was genotyped using real-time PCR in DNA from the whole blood of healthy subjects (n=60) and HCV patient   s (n=342). We stratified the patients into (1) treatment-naïve patients (n=218) with advanced fibrosis (F2-F4, n=123) and HCC (n=95 Treatment-experienced patients (n=124)  who received SOF-based therapy for 12 weeks and achieved SVR (SVR12).

Highly Sensitive Serum miRNA Panel for the Diagnosis of Hepatocellular Carcinoma in Egyptian Patients with HCV-Related HCC.

Objective: This study aimed at exploring the potential role of a panel of serum micro-RNA (miRNA) markers in liver fibrosis and hepatocellular carcinoma (HCC) diagnosis in patients with chronic hepatitis C virus (HCV) infection.

Methods: The study included 157 chronic HCV patients and 62 HCC patients who presented to the Cairo University Center for Hepatic Fibrosis, Endemic Medicine Department, from 2015 to 2017. Relevant clinical and laboratory data were collected and sera were subjected to miRNA expression profiling.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients.

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol.

Differential Expression of miR-21, miR-23a, and miR-27a, and Their Diagnostic Significance in Egyptian Colorectal Cancer Patients.

Colorectal cancer (CRC) rates are affected by genetics, ethnicity, and environmental factors; it is considered one of the most aggressive human malignancies with high mortality and morbidity rates worldwide due, in part, to its asymptomatic nature during the early stages of disease. Owing to the impact of microRNA (miRNA) dysregulation on CRC development and progression, this study was conducted to explore the expression levels of mir-21, -23a, and -27a in the sera and tissues of Egyptian CRC patients and to evaluate their diagnostic efficacy based on circulating levels. In the test phase, the relative expression levels of the studied miRNAs were evaluated in the sera of 70 participants (35 CRC patients and 35 healthy controls) using quantitative real-time-polymerase chain reaction and to verify their diagnostic value.

The potential value of miRNA-223 as a diagnostic biomarker for Egyptian colorectal patients.

Objectives: Colorectal cancer (CRC) is the third lethal malignancy worldwide. Dysregulation of microRNAs (miRNAs) mediates several growth factors signaling pathways and induces abnormal genes expression, which leads to colorectal carcinogenesis. We aimed to comprehensively assess the expression of miRNA-200c, miRNA-203a, miRNA-223 in Egyptian CRC tissue and their corresponding serum samples and to explore if they have any potential prognostic or diagnostic value for CRC patients.

A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice.

Background: Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice.

MicroRNAs expression profiling in Egyptian colorectal cancer patients.

Egypt has increased incidence and high rate of early onset colorectal cancer (CRC). This study aimed to profile the expression levels of 84 circulating microRNAs (miRNAs) in Egyptian CRC patients and to evaluate the diagnostic accuracy of some selected miRNAs as diagnostic biomarkers for CRC patients. A total of 129 subjects (84 CRC patients and 45 healthy controls) were enrolled in two independent sample sets: the screening set (39 subjects) and the validation set (90 subjects).

Dysregulation of fibrosis related genes in HCV induced liver disease.

Background: Liver fibrosis results from a wound healing response to chronic injury, which leads to excessive matrix deposition. Genome wide association studies have showen transcriptional dysregulation in mild and severe liver fibrosis. Recent studies suggested that genetic markers may be able to define the exact stage of liver fibrosis.

Increased incidence of cytomegalovirus coinfection in HCV-infected patients with late liver fibrosis is associated with dysregulation of JAK-STAT pathway.

Herein, we examined the association between cytomegalovirus (CMV) coinfection and the progression of liver fibrosis in hepatitis C virus (HCV) infection, and investigated the effect of CMV coinfection on JAK-STAT pathway. CMV DNAemia was detected by PCR in DNA from controls (n = 120), and HCV patients with early (F0-F1, n = 131) and late (F2-F4, n = 179) liver fibrosis. By quantitative real time PCR (qRT-PCR), we examined the profile of 8 JAK-STAT transcripts in PBMCs RNA from 90 HCV patients (39 CMV positive and 51 CMV negative), 4 CMV mono-infected patients, and 15 controls.

Vascular Endothelial Growth Factor Expression in Hepatitis C Virus-Induced Liver Fibrosis: A Potential Biomarker.

The major complication of hepatitis C virus (HCV) infection is the induction of hepatic fibrosis. In this study, we investigated the correlation between the expression level of vascular endothelial growth factor (VEGFA) at mRNA and protein levels and the progression of HCV-related liver fibrosis. One hundred twenty subjects were selected for this study: 15 controls and 105 chronic HCV patients with different fibrosis grades (44 F0-F1 and 61 F2-F4).

Expression of Reactive Oxygen Species-Related Transcripts in Egyptian Children With Autism.

The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects.

Mice Antibody Response to Conserved Nonadjuvanted Multiple Antigenic Peptides Derived from E1/E2 Regions of Hepatitis C Virus.

Synthetic peptides are one of the hepatitis C virus (HCV)-specific small molecules that have antiviral activity and represent a target for HCV vaccine. This study aims to determine the lowest concentration of adjuvanted and non-adjuvanted (multiple antigenic peptide [MAP]) form of three conserved HCV envelope peptides that can induce murine immunogenic responses and evaluate the neutralization capacities of the generated antibodies (Abs) against HCV in cultured Huh7.5 cells.

Methylene Tetrahydrofolate Reductase Gene Polymorphism is Associated with Severity of Liver Steatosis in Chronically Infected Patients with HCV Genotype 4.

Background: Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was reported as a genetic variant in liver steatosis and fibrosis. This is a study of the association between MTHFR C677T polymorphism and HCV core with severity of steatosis in HCV GT4 patients.

Methods: 111 HCV patients and 112 control subjects were recruited.

The Synergistic Effect of TNFα -308 G/A and TGFβ1 -509 C/T Polymorphisms on Hepatic Fibrosis Progression in Hepatitis C Virus Genotype 4 Patients.

Tumor necrosis factor-alpha (TNFα) and transforming growth factor-beta (TGFβ1) cytokines are highly implicated in liver fibrosis. Polymorphisms in these cytokines affect their expression, secretion, and activity. This study aimed to evaluate the influence of TNFα -308 G/A and TGFβ1 -509 C/T polymorphism on hepatic fibrosis progression in Egyptian patients with hepatitis C virus (HCV) genotype 4.

Three Gene Signature for Predicting the Development of Hepatocellular Carcinoma in Chronically Infected Hepatitis C Virus Patients.

Hepatitis C virus (HCV) is the leading cause of liver fibrosis and hepatocellular carcinoma (HCC). At present, there is no predictive biomarker for the patients at high risk of developing HCC. In this study, we examined the association between single-nucleotide polymorphisms (SNPs) in 3 innate immunity genes [2'-5'oligoadenylate synthetase 1 (OAS1) rs10774671, interleukin 28B (IL28B) rs12979860, and low molecular mass polypeptide 7 (LMP-7) at codon 49] besides cytomegalovirus (CMV) coinfection and susceptibility to HCC in genotype 4 (GT4) chronically infected Egyptian patients.

Tumor necrosis factor-α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients.

Aim: To investigate the association of tumor necrosis factor alpha (TNFα) -G308A polymorphism with different liver pathological changes in treatment-naïve Egyptian patients infected with hepatitis C virus (HCV) genotype 4.

Methods: This study included 180 subjects, composed of 120 treatment-naïve chronic HCV patients with different fibrosis grades (F0-F4) and 60 healthy controls. The TNFα -G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis.

Low Molecular Mass Polypeptide 7 Single Nucleotide Polymorphism is Associated with the Progression of Liver Fibrosis in Patients Infected with Hepatitis C Virus Genotype 4.

Background: The hepatitis C virus (HCV) is a leading cause of liver disease and the consequent complications of cirrhosis. However, there is no precise biomarker to predict the patients at high risk of developing progressive disease. We showed previously the implication of low molecular mass polypeptide-7 (LMP-7) single nucleotide varia- tions in the response to combined pegylated IFN and ribavirin therapy in patients infected with HCV genotype 4.

Transcriptional Dysregulation of Upstream Signaling of IFN Pathway in Chronic HCV Type 4 Induced Liver Fibrosis.

IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects.

Alteration of the Total Nuclear DNA Ploidy in Different Histopathological Liver Tissues Negative and Positive for HCV RNA.

Background: Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-associated carcinogenesis are unknown. We aim to investigate the alteration of the total nuclear DNA content (ploidy) in different histopathological liver tissues infected with HCV and their relation to the seropositivity of HCV RNA.

Impact of OAS1 Exon 7 rs10774671 Genetic Variation on Liver Fibrosis Progression in Egyptian HCV Genotype 4 Patients.

The aim of this study was to assess the impact of genetic variants of oligoadenylate synthetase 1 (OAS1) single-nucleotide polymorphism (SNP) rs10774671 at the exon 7 splice acceptor site on liver fibrosis progression and hepatitis C virus (HCV) outcome in Egyptian HCV genotype 4 patients. In this study, 195 subjects were enrolled; 60 controls and 135 chronic HCV genotype 4 patients with different fibrosis grades. All subjects were genotyped for OAS1 SNP rs10774671 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Polymorphism in variable number of tandem repeats of dopamine d4 gene is a genetic risk factor in attention deficit hyperactive egyptian children: pilot study.

Introduction: The variable number of tandem repeats (VNTR) of the dopamine receptor D4 (DRD4) gene among humans may elucidate individual differences in susceptibility to neuropsychiatric diseases. Dopamine dysfunction may be involved with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. In this study, we report the association between the phenotype of ADHD, a condition characterized by inattentiveness, hyperactivity, and impulsiveness, and a 48-base pair VNTR in exon 3 of the DRD4 polymorphism.

Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique.

Predictors of disease recurrence post living donor liver transplantation in end stage chronic HCV patients.

HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor's age and degree of liver steatosis, recipient's age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient's postoperative levels of ALT, AST, ALP (P < 0.