The Role of Mesenchymal Stem Cells with Ascorbic Acid and N-Acetylcysteine on TNF-α, IL 1ß, and NF-κß Expressions in Acute Pancreatitis in Albino Rats.

Severe acute pancreatitis (SAP) is a necrotic pancreatic inflammation associated with high mortality rate (up to 70%). Bone marrow (BM) mesenchymal stem cells (MSCs) have been investigated in pancreatic cellular regeneration, but still their effects are controversial. Therefore, the present study is aimed at examining the enrichment of the stem cells with ascorbic acid (AA) and N-acetylcysteine (NAC) and explore their combined action on the expression of the inflammatory cytokines: interleukin 1ß (IL 1ß), tumor necrosis factor-α (TNF-α), and nuclear factor-κß (NF-κß). A total of twenty adult male Sprague-Dawley albino rats were divided into four groups: the control group, cerulein group (to induce acute pancreatitis), BM-MSCs group, and combined BM-MSCs with AA and NAC group. Homing and proliferation of stem cells were revealed by the appearance of PKH26-labelled BM-MSCs in the islets of Langerhans. AA and NAC combination with BM-MSCs (group IV) was demonstrated to affect the expression of the inflammatory cytokines: IL 1ß, TNF-α, and NF-κß. In addition, improvement of the biochemical and histological parameters is represented in increasing body weight, normal blood glucose, and insulin levels and regeneration of the islet cells. Immunohistochemical studies showed an increase in proliferating cell nuclear antigen (PCNA) and decrease in caspase-3 reactions, detected markedly in group IV, after the marked distortion of the classic pancreatic lobular architecture was induced by cerulein. It could be concluded that treatment with BM-MSCs combined with antioxidants could provide a promising therapy for acute pancreatitis and improve the degeneration, apoptosis, necrosis, and inflammatory processes of the islets of Langerhans. TNF-α, IL 1ß, and NF-κß are essential biomarkers for the evaluation of MSC regenerative effectiveness.

lnc-HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct-acting antivirals therapy.

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.

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.

Dysregulation of miR-125b predicts poor response to therapy in pediatric acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most well-known sort of leukemia in children. In spite of favorable survival rates, some patients relapse and achieve a poor outcome. METHODS: We analyzed miR-125b and Bcl-2 expressions in pediatric patients with ALL and evaluated their clinical utility as molecular markers for the prediction of disease outcomes. RESULTS: Downregulation of miR-125b and increased Bcl-2 expression levels in pediatric patients with ALL were associated with poor prognosis at diagnosis. At day 28 of induction, miR-125b was significantly increased, whereas Bcl-2 was downregulated. Loss of miR-125b during diagnosis and its elevation after therapy are strongly correlated with short leukemia-free survival and worse survival. Moreover, the combination of miR-125b with Bcl-2 markers can clearly enhance the prediction of the disease outcome. Finally, a univariate analysis highlighted the independent prognostic value of miR-125 in a pediatric patient with ALL. CONCLUSIONS: miR-125b and Bcl-2 together are potent predictors for the prognosis and, therefore, can be used as therapeutic targets in childhood ALL.

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.

The effect of exposure to sub-inhibitory concentrations of hypochlorite and quaternary ammonium compounds on antimicrobial susceptibility of Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas is a group of medically important species that inhabit a wide range of niches, including hospital environments. Controversies have emerged about the possible link between improper use of disinfectants and the emergence of antibiotic resistance in bacteria. The aim of this study was to assess the effect of exposure of antibiotic-susceptible Pseudomonas isolates to sub-inhibitory concentrations of 2 disinfectants-didecyldimonium chloride and sodium hypochlorite-on their antibiotic susceptibility patterns. METHODS: This study involved 50 Pseudomonas isolates. The antibiotic susceptibility patterns of the isolates were assessed using broth microdilution method. The minimal inhibitory concentrations (MICs) of each antibiotic were compared before and after exposure to sub-inhibitory concentrations of didecyldimonium chloride and sodium hypochlorite. RESULTS: After overnight incubation with sub-inhibitory concentrations of sodium hypochlorite, a statistically significant increase was observed in the MICs of colistin (P = .012), ceftazidime (P < .001), amikacin (P < .001), meropenem (P < .001), gentamicin (P < .001), piperacillin-tazobactam (P = .003), and ciprofloxacin (P = .004). In contrast, exposure to sub-inhibitory concentrations of didecyldimonium chloride showed a statistically significant increase in the MICs of amikacin (P < .001), gentamicin (P < .001), meropenem (P = .041), and ciprofloxacin (P = .008). CONCLUSIONS: The use of suboptimal concentrations of sodium hypochlorite and didecyldimonium chloride can lead to the evolution of antibiotic-resistant Pseudomonas strains.

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.