In vitro knock-out of miR-155 suppresses leukemic and HCV virus loads in pediatric HCV-4-associated acute lymphoid leukemia: A promising target therapy.

Hepatitis C virus (HCV) infection is a major public health problem, having a high prevalence in Egypt. Leukemia and lymphoma have been associated with HCV infection. MicroRNA-155 (miR-155) has been reported to play a regulatory role in cancer, inflammation, and immune response to infection. The expression level of miR-155 in HCV viremic patients is controversial; although high miR-155 levels were demonstrated in HCV genotypes 1,2, and 3, low levels of miR-155 were detected in Egyptian patients with HCV genotype 4. Several studies have investigated the correlation between the levels of miRNA-155 and the replication of HCV, others have evaluated miRNA-155 as a prognostic biomarker in different types of cancer. No studies have investigated the impact of miRNA-155 knockdown on HCV pediatric patients associated with childhood acute lymphoblastic leukemia (ALL). We knocked-out the miR_155a in cultured polymorphonuclear cells (PBMCs) obtained from 60 children with ALL; 30 were associated with HCV-4 infection and 30 were HCV negative. The miR_155a, HCV viral load, and cell proliferation werre assessed in treated and untreated cells using TaqMan assay quantitative polymerase chain reaction. We found that miRNA-155 was significantly upregulated by seven folds in the HCV-4 associated ALL group; while being linked to high HCV viral load and leukemic burden, miR_155a knock-out can improve the disease outcome. We conclude that miR-155 is a critical miRNA that is considered a therapeutic target in pediatric HCV leukemic patients.

Molecular Characterization of Extended-Spectrum ß-Lactamase Enterobacteriaceae Isolated from Egyptian Patients with Community- and Hospital-Acquired Urinary Tract Infection.

Extended-spectrum ß-lactamases (ESßLs) pose a serious problem in the treatment of urinary tract infections (UTIs). The ESßL-producing organism is an expanding global health problem. Therefore, screening for ESßL, detection of their drug-resistance pattern, and molecular characterization should be a continuous process. The present study was performed to determine the antibiotic resistance profile and the genetic characterization of ESßL isolates from hospital- and community-acquired UTIs. Two hundred fifty Enterobacteriaceae isolates were obtained from urine samples of outpatient clinic attendants and hospitalized patients at Kasr Al-Aini Hospital. By phenotypic screening tests, 100 ESßL isolates were detected among the studied groups. Furthermore, detection of beta-lactamase (bla) cefotaxime (CTX)-M, sulfhydryl variable, and temoneira ESßL genes was investigated by polymerase chain reaction. A subset of 25 CTX-M-positive isolates was further identified by gene sequencing technology. Among the 100 ESßL isolates, 66% were Escherichia coli and 34% were Klebsiella spp. There was no statistical difference in the prevalence of ESßL Enterobacteriaceae in community-acquired versus hospital-acquired UTIs. The susceptibility of all ESßL isolates to carbapenems was the most prevalent finding. In addition, all ESßL E. coli isolates were susceptible to fosfomycin, whereas all community-acquired ESßL isolates were susceptible to nitrofurantoin. A total of 98% of the ESßL isolates harbored bla-CTX-M genes, with CTX-M-15 being the most prevalent. It could be concluded that ESßL production is present at a high rate among Egyptian patients with hospital- and community-acquired UTI. The high prevalence of bla-CTX-M may suggest it as a candidate for molecular screening of ESßL.

Association between Severity of Liver Disease, Frequency of Helicobacter pylori Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B Virus Infection.

The relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child-Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori-infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child-Pugh A, 70% of Child-Pugh B, and 100% of Child-Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.