Enas Samir Nabih

Evaluation of nestin in lung adenocarcinoma: relation to VEGF and Bcl-2

Abstract Context: Nestin is a marker of multipotent precursor cells that is up regulated in cancer. Objective: To explore its diagnostic role and its relationship to vascular endothelial growth factor (VEGF) and Bcl-2 in lung adenocarcinoma. Materials and methods: Evaluation of nestin expression in lung biopsies by real-time PCR and serum VEGF and Bcl-2 by ELISA in 27 adenocarcinoma patients and 15 control subjects. Results: Nestin was significantly higher in lung adenocarcinoma patients especially with advanced grade and stage and it was significantly correlated to VEGF and Bcl-2. Conclusion: Nestin can be considered as a potential diagnostic marker in lung adenocarcinoma.

Association of Second Hand Smoking with Mental Disorders in Children- An Egyptian Study

Background: Second hand smoke (SHS) might affect mental health of children as many mental disorders have an onset in youth, a time when SHS exposure is high. Objectives: Investigation of the potential association of SHS exposure with children’s mental health disorders. Methodology: Forty five SHS exposed Egyptian children were enrolled as group I; all of them had at least one smoking parent and or were exposed to environmental tobacco smoke while group II included thirty age and sex well matched controls, with neither history of parental smoking nor exposures to environmental tobacco smoke. For all studied children, complete history taking, thorough clinical examination, psychometric assessment using Pediatric Symptom Checklist (PSC), Strengths and Difficulties Questionnaire (SDQ), and IQ measurement were done. DSM IV TR criteria were used to confirm any suspected behavioral and or psychiatric disorder. Laboratory assessment of second hand smoke was carried out measuring urinary cotinine levels. Results: SHS exposed children had significantly higher mean value of urinary cotinine level, total PSC, and SDQ scores compared to controls (p<0.001, p<0.001, p<0.05 respectively). Mean values of Attention Deficit Hyperactivity Disorder (ADHD), internalization, and externalization behaviors’ sub-scores of PSC were significantly higher in SHS children compared to controls. Meanwhile, mean values of emotion, conduct, ADHD, and peer problem SDQ subscores were higher in SHS children compared to controls but the comparison was only statistically significant for ADHD sub-score while prosocial problem sub-score was significantly lower in SHS children compared to controls. In studied SHS children, degree of smoking significantly positively correlated with PSC internalization behavior subscore and emotion subscore of SDQ while smoking index significantly positively correlated with ADHD subscore of SDQ. Meanwhile, prosocial subscore of SDQ and urinary cotinine level were significantly negatively correlated. In conclusion, SHS exposure significantly compromised mental health of the studied sample of Egyptian SHS exposed children.

The diagnostic efficacy of nectin 4 expression in ovarian cancer patients

Abstract Context: Nectin 4 plays a significant role in cancer cell growth and invasion. Objective: To explore its diagnostic role in ovarian cancer. Materials and methods: Evaluation of nectin 4 expression in ovarian biopsies by real-time PCR and serum nectin 4 and CA-125 by ELISA in 39 ovarian cancer patients, 21 females with benign ovarian neoplasms and 25 control females. Results: Nectin 4 expression was significantly higher in ovarian cancer patients and it was significantly correlated to serum nectin 4 and CA-125. Conclusions: Ovarian tissue expression and serum nectin 4 appear to be potential markers in ovarian cancer.

Potential involvement of JNK1 repression in the hepatic effect of sitagliptin and metformin in rats subjected to high fat diet and chronic mild distress

BACKGROUND Depression and non-alcoholic steatohepatitis (NASH) are highly co-morbid, and hepatic JNK pathway may be involved in their relation. AIM To evaluate the impact of depression on NASH through the involvement of JNK1 and to assess the effect of sitagliptin and metformin on hepatic JNK1 expression in both NASH and NASH associated with depression. METHODS Eight groups of male Wistar rats were used: naïve rats, non-stressed NASH, non-stressed NASH sitagliptin treated, non-stressed NASH metformin treated, stressed, stressed NASH untreated, stressed NASH sitagliptin treated and stressed NASH metformin treated. Behavioral, biochemical, molecular and histopathological studies were performed. RESULTS Non-stressed NASH group showed depressive like symptoms, disturbed glucose homeostasis, impairment of liver functions, decrease adiponectin and increase malondialdehyde, which were aggreviated by stress. Sitagliptin produced significant improvement compared to metformin regarding biochemical and histopathological parameters. Furthermore, sitagliptin significantly decreased expression of hepatic JNK1 in both stressed and non-stressed rats. All these changes were accompanied by significant improvement of behavioral changes. CONCLUSIONS The link between NASH and depression raised the role of JNK activation through increase expression of JNK1. Since sitagliptin was associated with preferable effects than metformin, therefore, it is potentially preferred in the management of either NASH or NASH associated with depression.

The Association Between Circulating Levels of miRNA‐181a and Pancreatic Beta Cells Dysfunction via SMAD7 in Type 1 Diabetic Children and Adolescents

miRNA‐181a has been implicated in autoimmunity and apoptosis. Therefore, this study was conducted to explore its possible role in pancreatic beta‐cells dysfunction.

Helicobacter pylori seropositivity protects against childhood asthma and inversely correlates to its clinical and functional severity

BACKGROUND In recent years, the prevalence of asthma has risen in developed countries, and its extent related to a change in our indigenous microbiota. Helicobacter pylori disappearance across the population represents a fundamental change in our human microbiota and has preceded the rise in asthma prevalence. OBJECTIVE To assess the relationship between childhood asthma and Helicobacter pylori infection. METHODS Quantitative determination of Helicobacter pylori IgG among 90 asthmatic children and 90 - age and gender - matched non-atopic, non-asthmatic healthy children was performed using ELISA in serum of all participants. RESULTS Helicobacter pylori IgG seropositivity was found in 25.6% of asthmatics compared to 44.4% of controls. Asthmatics showed lower median Helicobacter pylori IgG titre compared to healthy controls. We also detected a significant inverse relationship between Helicobacter pylori IgG titre and asthma severity. CONCLUSION Helicobacter pylori seropositivity protects against childhood asthma and inversely correlates to its clinical and functional severity.

Up-regulation of circulating miRNA146a correlates with viral load via IRAK1 and TRAF6 in hepatitis C virus-infected patients

BACKGROUND Hepatitis C virus (HCV) is a life threatening human pathogen. It has been found that miRNA146a regulates innate immunity, inflammatory response and antiviral pathway. We evaluated miRNA146a expression by real-time PCR and IL-1 receptor associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) levels by ELISA in serum of 36 HCV viremia patients and 42 age and gender matched healthy controls. RESULTS miRNA146a expression was significantly higher in HCV patients with a best cut off value 1.63 to discriminate between HCV patients and healthy controls. Meanwhile, it was negatively correlated to IRAK1 and TRAF6 levels and positively correlated to viral load in HCV patients. CONCLUSIONS miRNA146a has a potential role in HCV infection and viral replication through IRAK1 and TRAF6. It can also serve as a new screening method for HCV.

Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating cholestatic liver injury in a rat model of bile duct ligation

Many pathways are involved in the association between biliary obstruction and liver injury. We investigated the intervention influence and effect of rosuvastatin (Rvs) on the high mobility group protein 1 (HMGB1)/toll-like receptor-4 (TLR4) axis and microRNA-21 (miR-21) in cholestatic liver injury. This model was performed by ligating common bile duct of Wistar rats. Saline and Rvs were orally administrated by gastric gavages. Liver and blood samples were collected and subjected to molecular and biochemical evaluation. We found that the daily oral administration of Rvs was protective against the occurrence of cholestatic liver injury. This was evident from the results of hepatic, oxidative stress, and inflammatory biomarkers. This study also revealed the Rvs inhibitory effect on the HMGB1/TLR4 intracellular signaling axis as evidenced by decreasing the levels of nuclear factor κβ (NFκβ), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) production. Furthermore, Rvs-treated group showed a significant reduction in the expression of miR-21 in comparison to the untreated group. Accordingly, rosuvastatin interference with the HMGB1/TLR4 and miR-21 expression could explain its hepatoprotective effect in cholestatic liver injury.

The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study

Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic β-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the β-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic β-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against β-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine.

Insights into hepatic and renal FXR/DDAH-1/eNOS pathway and its role in the potential benefit of rosuvastatin and silymarin in hepatic nephropathy

OBJECTIVES The repression of renal Farnesoid X Receptor (FXR) had been shown to result from lack of bile acid production from cirrhotic liver. We hypothesized that silymarin and rosuvastatin (Rvs) could have a hepatorenal therapeutic effects in hepatic nephropathy through induction of FXR. METHODS Forty two male Wistar rats were used; naïve (n = 12); six of them were sacrificed after 4 weeks and six continued till the end of the experiment. Thirty rats were treated as follows: Rvs, silymarin, thioacetamide (TAA), TAA + Rvs and TAA + silymarin. Liver and kidney function tests as well as the renal and hepatic expression of transforming growth factor β1 (TGFβ1), FXR, dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and eNOS were performed. Histological and immuno-histochemical studies of liver and kidney were also done. RESULTS TAA-inducted liver cirrhosis was associated with significant deterioration of liver and renal functions together with increasing expression of hepatic and renal TGFβ1 and decreasing expression of hepatic and renal FXR, DDAH-1 and eNOS. Giving silymarin or Rvs induced hepatic and renal improvement which was evidenced biochemically and histologically. Significant positive correlation was detected between all the investigated biomarkers except for the correlation between FXR and TGFβ1 which was negative. CONCLUSIONS In conclusion, liver cirrhosis is associated with deterioration of renal functions. Silymarin and Rvs have a potential hepatorenal therapeutic benefit through simultaneous enhancement of FXR/DDAH-1/eNOS pathway in both organs.