Posts

Vol.9 No.4-4: MiRNA-122 association with TNF-α in some liver diseases of Egyptian patients

/0 Comments/in , , /by

By: Ahmed Abdelhalim Yameny1, Sabah Farouk Alabd1, and Magda Ahmed M. Mansor2

1Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of      Sadat City, Egypt

2Department of Histology, Faculty of Medicine, Menoufia University, Egypt

Abstract:

Background:  Due to the high frequency of HCC, ongoing research is needed to find precise, non-invasive biomarkers for early identification and follow-up that will improve prognostic results. Patients and methods: this study was conducted on 90 patients with liver diseases and 25 healthy control G1, patients divided into 4 groups, (G2) 25 patients with HCV infection, (G3) 25 HCC+HCV infection, (G4) 25 patients with HBV infection, (G5) 15 patients with HCC + HBV. Results: Serum miR-122 and TNF-α levels were increased in HCV and HBV infection significantly with p-value >0.001*compared to the control group, and their levels decreased when developed into HCC but still higher than the healthy subjects significantly with p-value >0.001. For discriminating HCV from HCV+HCC the cut-off for miR-122 was >7.1 at sensitivity 100%, specificity 100%, and the AUC was 1.0 (Excellent) P-value <0.001, also the sensitivity and specificity for TNF-α 72%, and 60% respectively with cut off >12.1 and AUC of 0.745 (Good) p-value 0.003. For discriminating HBV from HBV+HCC the cut-off for miR-122 was ≤6.4 at a sensitivity of 86.67% and specificity of 96%, and the AUC of miR-122 was 0.99 (Excellent) P-value <0.001, also the sensitivity and specificity for TNF-α 93.33%, and 48.0% respectively with cut-off ≤15.73, TNF-α has AUC of 0.527 (fair) it was not significant p-value 0.780.

MiRNA-122-association-with-TNF-α-in-some-liver-diseases-of-Egyptian-patients

Download PDF

Vol.8 No.3 – 11:Interference between miR-21/PTEN/E-Cadherin and Epithelial-Mesenchymal Transition in Various Stages of Chronic HCV Infection

/0 Comments/in , , /by

By: Yasser B.M. Ali1, Mohamed G.Thabet1, Abeer M. El-Maghraby1, Asmaa Gomaa2, Omaima A. Khamiss3, Roba M. Talaat1

1Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.

2Hepatology and Gastroenterology Department, National Live Institute (NLI), Menufyia University, Shebeen-Elkom, Egypt

3Animal Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt

Abstract:

Hepatocellular carcinoma (HCC) is a major complication associated with hepatitis C viral infection (HCV). The epithelial-mesenchymal transition (EMT) is critical in HCC invasion and metastasis. Several microRNAs (miRNAs) have been linked to HCV-related HCC. This study aimed to evaluate the relation between miR-21, phosphatase, tensin homolog deleted on chromosome ten (PTEN), and E-Cadherin with a flashlight on their role in the EMT process in HCV infection at different stages. One hundred HCV-infected patients were studied, 75 had HCV-induced cirrhosis (classified into Child A, B, and C), and 25 had HCC. In parallel, 45 healthy volunteers were considered normal controls. Circulating miR-21was detected by quantitative Reverse Transcription Polymerase Chain Reaction (qRT–PCR).PTEN and E-cadherin serum levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). A significant elevation in miR-21 was observed in HCC patients compared with control ones(P˂0.01). HCC patients had the lowest E-cadherins and PTEN (P<0.01) compared with cirrhotic and normal subjects. In HCC patients, PTEN was positively correlated with E-cadherin (r= 0.501; p<0.01).  On the other hand, a negative correlation between miR-21 and both E-cadherins (r= -0.455; p<0.01) and PTEN (r= -0.255; p<0.05) was observed. Accordingly, up-regulation of miR-21 in the tumor is an important step in HCV-positive cirrhotic hepatocarcinogenesis and might result in concomitant down-regulation of PTEN and E-cadherin in favor of tumor promotion. Our data might be the first study that correlates miR-21, PTEN, and E-cadherin in different stages of HCV infection (from cirrhosis to HCC).

Interference-between-miR-21PTENE-Cadherin-and-Epithelial-Mesenchymal-Transition-in-Various-Stages-of-Chronic-HCV-Infection

Download PDF

Vol.8 No.1 – 3: 8-hydroxy-2′-deoxyguanosine and TP53 in Egyptian Patients with Hepatitis C Viral Chronic Liver Diseases: Insight into the Pathogenesis and Predictive Force

/0 Comments/in , , /by

By : Hoda M. El-Emshaty1,*, Somaia M. Osman 2, Fathy M. El-Taweel2, Mohamed M. El-Hemaly1, Hisham Ismail 3

1Gastrointestinal Surgery Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

2Chemistry Dept., Faculty of Science, Damietta University, New Damietta, Egypt.

3Biochemistry Division, Chemistry Dept., Faculty of Science, Minia University, Minia, Egypt.

Abstract

Reactive oxygen species (ROS) is excessively generated during tumor development yielding the oxidatively modified products of proteins and DNA. These DNA alterations could contribute to the development of cancer through the activation of oncogenes and inactivating tumor suppressor genes (TSGs). Therefore, 8-OHdG DNA oxidative damage and TP53 protein expression were evaluated amongst HCV-Chronic liver disease patients to explore their possible role in hepatocarcinogenesis and to predict HCC development at early stages. A total of 141 patients with HCV-related liver diseases; 69 with hepatocellular carcinoma and 72 with liver cirrhosis were enrolled in this study in addition to 56 healthy subjects.Serum 8-OHdG and TP53 expression by ELISA were markedly elevated in HCC patients compared to LC and healthy individuals (p<0.0001). A significant correlation was noted for 8-OHdG and TP53 with disease progression and tumor differentiation but not with tumor site. 8-OHdG and TP53 were highly (p<0.05) predicting for HCC at early stages and the diagnostic performance for discriminating HCC from LC by ROC curve showed the best AUC was recorded for 8-OHdG (0.745) followed by TP53 (0.667) with accuracy (87.2% and 82% respectively). Therefore, HCV-induced oxidative DNA damage could increase the carcinogenic potential of HCC development through the activation of TP53.

8-hydroxy-2-deoxyguanosine-and-TP53-in-Egyptian-Patients-with-Hepatitis-C-Viral-Chronic-Liver-Diseases-Insight-into-the-Pathogenesis-and-Predictive-Force-converted

Download PDF

Vol.5 No.3 – 5 : Serum cytokine profile during disease progression stages in male and female hepatitis C patients

/0 Comments/in , , /by

By: Abdel-Rahman N. Zekri1, Abeer M. Badr2*, Shimaa Rabah2, Maysa El Razky3, Somaya El Deeb2

1Molecular Virology and Immunology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt.

2Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.

3Hepatology Department and Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, 11441, Egypt.

Abstract

T helper (Th) cytokines play a key role in the immunological aspects of hepatitis C virus (HCV) pathogenesis. The pattern of Th1 (IL-2, interferon (IFN)-γ), Th2 (IL-10), and immunomodulatory cytokines (IL-12, IL-1β, IFN-α and tumor necrosis factor-α receptor (TNF-αR2) balance participated in the outcome of host immune responses. The study aimed toinvestigate the serum levels of Th1/Th2 and immunomodulatory cytokines in HCV infected patients in both genders during various liver disease stages compared to healthy controls. Blood samples were collected from 16 healthy individuals and 77 patients at different disease stages including chronic, cirrhosis, and hepatocellular carcinoma (HCC). Serum cytokine levels were measured by ELISA. Levels of serum IL-12 and IL-10 were significantly higher in both genders in all groups than those in corresponding healthy subjects. Whereas, HCV infected female patients showed significant lower levels of IL-2, IL-1β, IFN-α in chronic and cirrhosis stages than corresponding males. Serum level of IFN-γ could be utilized as biomarker for early detection of HCC. Finally, cytokine response variation in gender during various stages of disease, imply that the subsequent activation and attenuated functional immune responses displayed differences in the balance of Th1 and immunomodulatory related cytokines between females and males upon infection.

Serum cytokine profile during disease progression stages in male and female hepatitis C patients-converted

Download PDF

Vol.3 No.4 – 2: miRNA-122 from Laboratory biomarker to the treatment of HCV

/0 Comments/in , , /by

By : Ahmed Abdelhalim Yameny

Abstract

     Hepatitis C virus (HCV) is an important human pathogen that infects as many as 185 million persons worldwide, In the long-term, this can lead to advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma HCC, there is currently no vaccine for hepatitis C. About 15–45% of infected persons spontaneously clear the virus within 6 months of infection without any treatment, miRNAs are endogenous short single-stranded noncoding RNAs and they are post-transcriptional negative regulators of gene expression, about18-22 nucleotides long, and play a crucial role in the regulation of gene expression. Now there are over 2500  mature potential human microRNAs recorded in miRBase (version 20, accessed January 2014), 84 miRNAs in serum and plasma of HCV-infected patients to identify miRNAs that correlated with different stages histologically assessed liver disease severity and during HCV infection, miRNA-122 is the most abundant in the liver,miRNA-122 is responsible, for liver homeostasis, several studies showed that miRNA-122 is required for HCV replication in infected cells, it can use as a serum biomarker over alanine leucine transaminase(ALT) in predicting the presence of chronic HCV infection, miR-122 also plays a crucial role in the regulation of cholesterol and fatty acid metabolism in the adult liver, and was identified as a regulator for systematic iron homeostasis, therapies that target it could present an effective approach for the development of new HCV antiviral drugs, Recently, the development of the anti-miR122 therapeutic miravirsen. Miravirsen (formerly SPC3649) is a 15-base oligonucleotide that is complementary to part of miR-122 and is the first miRNA-targeting agent administered to patients. Miravirsen has demonstrated in vitro antiviral activity against all HCV genotypes, Miravirsen interferes with the functions of miR-122 both in viral proliferation and in cholesterol homeostasis, miravirsen has demonstrated broad antiviral activity and a relatively high genetic barrier to resistance.

miRNA-122-from-Laboratory-diagnosis-to-treatment-of-HCV-converted

Download PDF