Synthetic non-toxic anti-biofilm agents as a strategy in combating bacterial resistance.

The tremendous increase in the bacterial resistance to the available antibiotics is a serious problem for the treatment of various infections. Biofilm formation in bacteria significantly contributes to the bacterial survival in host cells, and is considered as an crucial factor, responsible for bacterial resistance. The response of the bacterial cells in the biofilm to antibiotics is completely different from that of the free floating planktonic cells of the same strain. The anti-biofilm agents that could inhibit the biofilm production without affecting the bacterial growth, apply less selective pressure over the bacterial strains than the traditional antibiotics; thus the development of bacterial resistance would be of low incidence. Many attempts have been performed to discover novel agents capable of interfering with the bacterial biofilm life cycle, and several compounds have shown promising activities in suppressing the biofilm production or in dispersing mature existing biofilms. This review describes the different chemical classes that have anti-biofilm effects against different Gram-positive and Gram-negative bacteria without affecting the bacterial growth.

Frequency and risk factors of H. pylori infection among dental students: an observational cross-sectional study.

Despite Helicobacter pylori infection remains asymptomatic in most people, it is associated with an increased risk of gastric cancer. Considering Egypt had the highest prevalence of H. pylori in healthy asymptomatic population in adults and pediatric age in past studies and currently salivary ELISA could be used for diagnosis of Oral H. pylori infection. Moreover, some researchers speculated that dentists and dental students might be at a higher risk for oral H. pylori infection because they are the most frequently exposed ones to saliva and dental plaque. This study aimed to determine risk factors associated with frequency of H. pylori among a sample of dental students for better management of the disease. 83 participants, with age (21-25 years), attending Faculty of Dentistry, Fayoum University were recruited. A structured questionnaire was used to collect information on sociodemographic parameters and risk factors for H. pylori. Direct inquiry about dyspeptic symptoms were done. Saliva samples were collected and tested for H. pylori antibodies. Overall seroprevalence was 22.9%. Participants in internship were more prone to be positive (p = 0.005). 32.6% of urban residents versus 10.8% of rural were H. pylori positive (p = 0.019). 75.0% of previous history of H. pylori infection versus 14.1% of those with no history were H. pylori positive p < 0.001. 70% of positive H. pylori participants reported positive clinical symptoms that were statistically significant. This study suggests that middle income, previous history of H. pylori and clinical symptoms of dyspepsia are risk factors of oral H. pylori with a decline in its prevalence in Egypt.

Significance of MiRNA-34a and MiRNA-192 as a risk factor for nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: NAFLD is one of the fast-growing health problems that affects up to 25% of people worldwide. Numerous miRNAs have been clarified as important regulators of liver pathophysiology, including NAFLD. Thus, we investigated the expression of the MiRNA-34a and MiRNA-192 as diagnostic markers for NAFLD. PATIENTS AND METHODS: Blood samples were collected from NAFLD cases and healthy controls. The expression profile of both studied miRNAs was detected via real-time PCR analysis. RESULTS: The present study showed that both studied miRNAs were upregulated in NAFLD patients compared to controls. Interestingly, miRNA-34a and MiRNA-192 are upregulated in NAFLD patients with early fibrosis compared to controls [with a fold change of 4.02 ± 11.49 (P = 0.05) and 18.43 ± 47.8 (P = 0.017), respectively]. However, miRNA-34a is downregulated in NAFLD patients with advanced fibrosis compared to controls, with fold expression of 0.65 ± 1.17 (P = 0.831). The area under the receiver operating characteristics (AUROC) for miRNA-34a and miRNA-192 were 0.790 and 0.643, respectively; furthermore, the sensitivities and specificities were 76.7%, 100% for miRNA-34a and 63.3%, and 93.3% for miRNA-192 (P < 0.05). Additionally, MiRNA34a was positively correlated with hypertension and fasting blood sugar, and it also was negatively correlated with hemoglobin level and total leucocyte count (P < 0.05). CONCLUSION: The results obtained indicated that both studied miRNAs could potentially be used as diagnostic biomarkers for the early stage of liver fibrosis in NAFLD cases. Also, miRNA-34a was positively correlated with metabolic disorders associated with NAFLD such as hypertension and diabetes. However, their expression showed no association with advanced fibrosis. Thus, larger cohorts are necessitated to certify the utility of serum MiRNA-34a and MiRNA-192 in monitoring the deterioration of NAFLD.

Clinical Spectrum of Nonalcoholic Fatty Liver Disease in Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: The purpose of this study was to determine the prevalence of nonalcoholic fatty liver disease in a group of chronic obstructive pulmonary disease patients. MATERIAL AND METHODS: This study comprised 48 stable chronic obstructive pulmonary disease patients who were diagnosed and categorized using the Global Initiative for Chronic Obstructive Lung Disease 2017 criteria. The prevalence of nonalcoholic fatty liver disease in chronic obstructive pulmonary disease patients was determined using noninvasive biomarkers and imaging methods. Steatosis was detected using magnetic resonance mDIXON-Quant sequence imaging, while fibrosis was detected using the acoustic radiation force impulse and FIB-4 index. RESULTS: A total of 58.3% of the patients investigated had a fat level of 5%, and nearly a quarter of them had a fat content of 10% or more, and 45.8% of the patients studied had severe hepatic fibrosis. The Fibrosis-4 (FIB-4) index revealed advanced fibrosis in 18.75% of them. No statistically significant association was found between chronic obstructive pulmonary disease groups of studied patients and the presence of steatosis and fibrosis (≥F2) using acoustic radiation force impulse. The presence of fibrosis, however, was statistically significant linked with chronic obstructive pulmonary disease groups of examined patients using the FIB-4 index. γ-Glutamyl transferase and alkaline phosphatase levels were greater in Global Initiative for Chronic Obstructive Lung Disease 3/4 and C/D groups. CONCLUSION: Nonalcoholic fatty liver disease is a common comorbidity in chronic obstructive pulmonary disease and should be included in the list of chronic obstructive pulmonary disease comorbidities.

Interferon lambda 4 gene polymorphisms as a predicting tool of response to hepatitis C virus genotype 4 patients treated with Sofosbuvir and Ribavirin.

The relation between interferon lambda 4 gene (IFNL4) and direct acting antiviral (DAA) regimens in hepatitis C virus (HCV) infected patients is not clear. So, a single nucleotide polymorphisms (SNP) of IFNL4 gene genotypes and its relationship with Sofosbuvir (SOF) and Ribavirin (RBV) treatment response is under consideration. This study aims to investigate the relation between IFNL4 polymorphisms and clearance of HCV genotype 4 for HCV patients. Hence, the appropriate drug can be chosen for each patient. SNP genotyping assay for IFNL4 which formerly known as IL28B (rs368234815) was examined for genomic DNA. The DNA was extracted from whole blood of one hundred patients who documented to have infection with chronic HCV genotype 4 (positive PCR) and treated with SOF and RBV. Patients were diagnosed, previously, as HCV genotype 4 and classified according to drug response into two groups (responders, non-responders). All samples were compared with 50 of non-infected (negative PCR) people (control group). The TT/TT homozygous represents 48% of patients and 66% of non-infected people while the homozygous ∆G/∆G is 21% and 12%, respectively. There is significance to IFNL4 genotypes for the treatment response with the probability value p < 0.001. The percentages of the appearance of genotypes TT/TT, TT/∆G and ∆G/∆G for responders were 60%, 28% and 12%, respectively. There is no significance for gender, age, ALT and PLC to treatment response to SOF and RBV, while INR has.

Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus.

BACKGROUND: Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs (miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis. AIM: To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C. METHODS: This prospective study included 208 patients and 82 age- and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring. RESULTS: The ADC value decreased significantly with the progression of fibrosis, from controls (F0) to patients with early fibrosis (F1 and F2) to those with late fibrosis (F3 and F4) (median 1.92, 1.53, and 1.25 × 10-3 mm2/s, respectively) (P = 0.001). The cut-off ADC value used to differentiate patients from controls was 1.83 × 10-3 mm2/s with an area under the curve (AUC) of 0.992. Combining ADC and miR-200b revealed the highest AUC (0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10-3 mm2/s with an AUC of 0.866. The combination of ADC and miR-200b revealed the best AUC (0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200b (r = - 0.61, P = 0.001), miR-21 (r = - 0.62, P = 0.001), and miR-29 (r = 0.52, P = 0.001). CONCLUSION: Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.

Does steatosis affect the performance of diffusion-weighted MRI values for fibrosis evaluation in patients with chronic hepatitis C genotype 4?

BACKGROUND/AIMS: To evaluate the effect of hepatic steatosis on the apparent diffusion coefficient (ADC) of hepatic fibrosis in patients with HCV genotype 4-related chronic hepatitis. MATERIALS AND METHODS: Overall, 268 chronic hepatitis C patients (164 males and 104 females) underwent liver biopsy for fibrosis assessment by the METAVIR score and grading for hepatic steatosis. They were classified into early fibrosis stage (F1, F2) and advanced fibrosis stage (F3, F4). Diffusion-weighted MRI (DWI) of the liver was performed using 1.5-Tesla scanners, and the ADC value of the patients with and without steatosis in different stages of fibrosis was estimated and compared. RESULTS: In patients with early fibrosis, the ADC value significantly decreased in patients with steatosis (1.52±0.17×10-3 mm2/s) compared to that in patients without steatosis (1.65±0.11×10-3 mm2/s) (p<0.001). In those with an advanced stage of fibrosis, the ADC value was also significantly decreased in patients with steatosis (1.07±0.16×10-3 mm2/s) compared with that in patients without steatosis (1.35±0.11×10-3 mm2/s) (p≤0.001). The cutoff value for ADC for steatosis prediction in the early fibrosis group was 1.585 according to the AUROC curve, with a sensitivity of 76.8% and a specificity of 73.5%. The cutoff value for ADC for steatosis prediction in patients with an advanced stage of fibrosis was 1.17×10-3 mm2/s, with a sensitivity of 97% and a specificity of 88.5%. CONCLUSION: Histologically detected hepatic steatosis should always be considered when assessing hepatic fibrosis using diffusion-weighted MRI to avoid the underestimation of the ADC value in patients with chronic hepatitis C genotype 4.

Prediction of Fibrosis Progression Rate in Patients with Chronic Hepatitis C Genotype 4: Role of Cirrhosis Risk Score and Host Factors.

The rate of liver fibrosis progression in chronic hepatitis C (CHC) patients is highly variable and affected by different factors. This study aimed to assess the role of cirrhosis risk score (CRS) based on 7 genetic variants (7 single-nucleotide polymorphisms [SNPs]) and host factors (age and sex) in the prediction of the rate of fibrosis progression in CHC. Duration of infection was determined in 115 patients. The fibrosis progression rate (FPR) per year was calculated as the ratio between fibrosis stage and the duration of infection. SNP genotyping were performed and CRS was determined based on it. FPR was significantly elevated in patients who acquired infection at age >40 years versus those who acquired infection at 30-40 years and those who acquired infection at <30 years. Median FPR was significantly higher in males than females (0.17 vs. 0.15) with P = 0.001. CRS value ≥0.8 is predictive of patients with high risk for cirrhosis, and CRS value <0.5 is predictive of patients with low risk for cirrhosis. There was significant positive correlation between CRS and FPR (P ≤ 0.001). CRS based on 7 SNPs at cutoff value ≥0.8, age at infection >40 years, and male sex are predictors of higher FPR.

Pre-Clinical Study for the Antidiabetic Potential of Selenium Nanoparticles.

This research was delineated to explore the efficacy of selenium nanoparticles delivered in liposomes (L-Se) in the mitigation of type-2 diabetes mellitus. Adult female Wistar rats were assigned into four groups: group I, the normal control group in which the rats received normal saline solution orally; group II, the diabetic control group in which the rats were injected intraperitoneally with a single dose of streptozotocin (STZ) for induction of diabetes; group III, the metformin (Met)-treated group in which the diabetic rats were treated orally with Met; and group IV, the L-Se-treated group in which the diabetic rats were treated orally with L-Se. All treatments were delivered for 21 days. Blood and pancreas tissue samples were obtained for biochemical analysis, immunohistochemical examinations, and histopathological investigation. The L-Se-treated group showed significant drop in serum glucose and pancreatic malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and prostaglandin F2α (PGF2α) levels associated with significant rise in serum insulin and pancreatic glutathione, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) values, in addition to significant improvement in the immunohistochemical indices (insulin and glucagon). Aforementioned results are appreciated by the histopathological findings of pancreatic tissue. In conclusion, our data have brought about compelling evidence favoring the antidiabetic potency of elemental selenium nanoparticles delivered in liposomes through preservation of pancreatic ß cell integrity with consequent increment of insulin secretion and in turn glucose depletion, repression of oxidative stress, potentiation of the antioxidant defense system, and inhibition of pancreatic inflammation.

Interleukin 28B Polymorphism Predicts Treatment Outcome Among Egyptian Patients Infected With HCV Genotype 4.

BACKGROUND/AIMS: Egypt has the highest prevalence of HCV worldwide (15%) with a high morbidity and mortality from chronic liver disease, cirrhosis, and hepatocellular carcinoma. The Aim of this study was to investigate the associations between IL-28B single nucleotide polymorphisms (SNP rs12979860) and treatment outcome among Egyptian patients infected with HCV genotype 4. METHODOLOGY: HCV patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860 in unrelated case control of Egyptian population with HCV. RESULTS: By using univariate regression analysis, the minor allele of IL28B (p < 0.0001), high serum level of HCV-RNA (p = 0.035), and advanced fibrosis (p = 0.02) were associated with (NRs) (Odds ratio, 3.75 with 95% confidence nterval (2.308-6.1067). While, in multivariate logistic regression analysis, rs12979860 CC genotype was the strongest predictive of SVR (OR = 20.83, 95% CI = 11.63- 37.04, p < 0.0001). CONCLUSION: The IL28B rs12979860 SNP is the strongest predictor of an SVR among Egyptian patients infected with HCV-4.