S.K.a, D., Y. A.a, S. M.a, Z. N.a, K. A.a, A. A.b, M. M.a, and A. A.a, "Acoustic radiation forced impulse-based splenic prediction model using data mining for the noninvasive prediction of esophageal varices in hepatitis C virus advanced fibrosis", European Journal of Gastroenterology and Hepatology, vol. 31, issue 12, pp. 1533–1539, 2019.
Farouk, S., A. Khairy, A. M. Salem, A. F. Soliman, and N. B. E. G. Din, "Differential Expression of miR-21, miR-23a, and miR-27a, and Their Diagnostic Significance in Egyptian Colorectal Cancer Patient", GENETIC TESTING AND MOLECULAR BIOMARKERS, vol. 24, issue 12, pp. 825-834, 2020.
El-Din, N. B. G., S. Farouka, L. O. Abdel-Salam, and A. Khairy, "The potential value of miRNA-223 as a diagnostic biomarker for Egyptian colorectal patients", European Journal of Gastroenterology & Hepatology, vol. 33, pp. 25-31, 2020.
Bader El Din, N. G., M. K. Ibrahim, R. El-Shenawy, G. M. Salum, S. Farouk, N. Zayed, A. Khairy, and M. El Awady, "MicroRNAs expression profiling in Egyptian colorectal cancer patients.", IUBMB life, vol. 72, issue 2, pp. 275-284, 2020. Abstract

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). The expression profiles of 84 miRNAs were studied by miRNA PCR array in the screening set. Then four miRNAs (let-7c, 21, 26a, 146a) were selected to be studied by quantitative real-time PCR in the validation set. The PCR array results revealed significant up regulation of 20 miRNAs and downregulation of two miRNAs in CRC patients compared to the healthy subjects. Moreover, the expression levels of the four selected miRNAs were significantly higher in CRC serum samples than controls. The ROC analysis revealed that miRNAs (let-7c, 21, 26a and 146a) can effectively discriminate between CRC patients and the controls. The combination of the four miRNAs showed AUC of 0.950 (95% CI [0.898-1.002], p = .001). However, the combination of miR-21 and miR-26a showed the best diagnostic accuracy with AUC of 0.953 (95% CI [0.908-0.999], p = .001). The current data suggest that miRNAs (let-7c, 21, 26a, 146a) could play an important role in CRC development and they can be used as diagnostic biomarkers for CRC.

Nasser, M. Z., N. A. Zayed, A. M. Mohamed, D. Attia, G. Esmat, and A. Khairy, "Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 20, issue 4, pp. 198-204, 2019. Abstract

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease.

PATIENTS AND METHODS: Serum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30).

RESULTS: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = -0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups.

CONCLUSION: Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

Salem, A. E., R. Singh, Y. K. Ayoub, A. M. Khairy, and G. E. Mullin, "The gut microbiome and irritable bowel syndrome: State of art review.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 19, issue 3, pp. 136-141, 2018. Abstract

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract, the physiology of which is not very well understood. There are multiple factors and pathways involved in pathogenesis of this entity. Among all, dysmotility, dysregulation of the brain-gut axis, altered intestinal microbiota and visceral hypersensitivity play a major role. Over the last years, research has shown that the type of gut microbiome present in an individual plays a significant role in the pathophysiology of IBS. Multiple studies have consistently shown that subjects diagnosed with IBS have disruption in gut microbiota balance. It has been established that host immune system and its interaction with metabolic products of gut microbiota play an important role in the gastrointestinal tract. Therefore, probiotics, prebiotics and antibiotics have shown some promising results in managing IBS symptoms via modulating the interaction between the above. This paper discusses the various factors involved in pathophysiology of IBS, especially gut microbiota.

Salum, G. M., N. G. Bader El Din, M. K. Ibrahim, M. A. Anany, R. M. Dawood, A. Khairy, and M. K. El Awady, "Vascular Endothelial Growth Factor Expression in Hepatitis C Virus-Induced Liver Fibrosis: A Potential Biomarker.", Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, vol. 37, issue 7, pp. 310-316, 2017 Jul. Abstract

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). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure VEGFA mRNA in peripheral blood mononuclear cells, while enzyme-linked immunosorbent assay (ELISA) was used to measure the secreted VEGFA protein in serum. Both qRT-PCR and ELISA results showed that HCV patients have significantly higher VEGFA expression than that of controls (P = 0.036 and 0.043, respectively). Moreover, patients with late fibrotic stages (F2-F4) exhibited the highest levels of VEGFA mRNA and protein (P = 0.008 and 0.041, respectively) when compared with controls. An area under the receiver operating characteristic curve (AUC of the ROC) for the circulatory VEGFA protein between HCV patients with fibrosis and healthy controls was 0.92 (P = 0.043). Our data suggest that VEGFA protein is a promising noninvasively diagnostic biomarker for HCV-induced liver fibrosis.

Bader El Din, N. G., S. Farouk, R. El-Shenawy, M. K. Ibrahim, R. M. Dawood, M. M. Elhady, A. M. Salem, N. Zayed, A. Khairy, and M. K. El Awady, "Tumor necrosis factor-α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients.", World journal of gastroenterology, vol. 22, issue 34, pp. 7767-77, 2016 Sep 14. Abstract

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. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα -G308A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.

RESULTS: Current data showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients (F2-F4, n = 60) than in early fibrosis patients (F0-F1, n = 60) (P = 0.05, 0.04 respectively). Moreover, the GA or AA genotypes increased the TNFα serum level greater than the GG genotype (P = 0.002). The results showed a clear association between severe liver pathological conditions (inflammation, steatosis and fibrosis) and (GA + AA) genotypes (P = 0.035, 0.03, 0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes (GA + AA) were significantly associated with liver inflammation (OR = 3.776, 95%CI: 1.399-10.194, P = 0.009), severe steatosis (OR = 4.49, 95%CI: 1.441-14.0, P = 0.010) and fibrosis progression (OR = 2.84, 95%CI: 1.080-7.472, P = 0.034). Also, the A allele was an independent risk factor for liver inflammation (P = 0.003), steatosis (P = 0.003) and fibrosis (P = 0.014).

CONCLUSION: TNFα SNP at nucleotide -308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients.

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