Faten Zahran

Characterization of mesenchymal stem cells derived from rat bone marrow and adipose tissue: a comparative study.

Background and Objectives: Stem cell technology offers a new hope for many chronic disorders patients. The types of stem cells are different with many differences existing between each type. Mesenchymal stem cells (MSCs) represent one type of adult stem cells that can be easily isolated, then re-transplanted to the patients. This offers potential for their future application in treating many disorders without fear of rejection possibility. MSCs can be isolated from different sources e.g. bone marrow (BMSCs) and adipose tissue (ADSCs). In the present study we compared BMSCs and ADSCs isolated from Sprague-Dawley rats. Methods and Results: For this comparison, immunophenotyping, the analysis of growth rates, proliferation by colony forming unit-fibroblast assay, population doubling time, and trilineage differentiation assays were performed for both BMSCs and ADSCs. The findings revealed that despite no difference in immunphenotypic character between BMSC and ADSC, a better proliferative capacity was observed for ADSCs which would advocate their better use in regenerative applications. On the other hand, BMSCs showed more potential for osteogenic and chondrogenic differentiation. Conclusions: Our study showed that, despite many similarities between both types of cells, there are differences existing which can offer assistance on choosing type of cell to be used in specific diseases. Although ADSCs seem more promising for regenerative application generally, BMSCs may represent a better choice for treating bone disorders.

Effect of Cinnamon (Cinnamomum zeylanicum) on Growth Performance, Feed Utilization, Whole-Body Composition, and Resistance to Aeromonas hydrophila in Nile Tilapia

Four isonitrogenous (30% crude protein) and isocaloric (4.40 kcal/g) experimental diets were formulated to contain 0.0% (control), 0.5%, 1.0%, or 1.5% cinnamon. The diet containing 1% cinnamon resulted in significantly greater (P < 0.05) specific growth rate (SGR), feed conversion ratio (FCR), feed efficiency ratio (FER), protein efficiency ratio (PER), apparent protein utilization (APU), and energy utilization (EU). In regard to body composition, there was no significant difference in dry matter, protein, lipids, and ash (P > 0.05) contents due to cinnamon supplementation. Blood plasma profile showed an improvement in hemoglobin (HB), red blood cell (RBCS), hematocrite (PCV), total protein, and total lipids, while there was a decrease in creatinin, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose in fish fed 1% cinnamon. Cinnamon was found to have an antibacterial activity antagonistic to Aeromonas hydrophila infection in fish. Performance and FCR improvement translated into a 10% decrease in feed costs associated with the 1% cinnamon diet.

Evaluation of cytokeratin-1 in the diagnosis of hepatocellular carcinoma

BACKGROUND This study was undertaken to investigate whether serum cytokeratin-1 (CK1) could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC). METHODS CK1 was identified using western blot and ELISA in serum samples from 250 Egyptian patients including 150 with HCC, 100 with liver cirrhosis (LC) and 50 healthy controls. Multivariate discriminant analysis (MDA) and ROC curve analyses were used to create a predictive model including CK1 in addition to a panel of routine blood markers. RESULTS CK1 was identified at 67 kDa and quantified in sera of HCC patients using western blot and ELISA. MDA selected a score for the prediction of HCC from LC patients based on levels of CK1, albumin and AFP. An area under the ROC curves (AUC) of the score was 0.87. The score showed a sensitivity of 87% vs 39% sensitivity of AFP at cutoff value of 200 IU/ml for prediction HCC. Absolute specificity (100%) was obtained to discriminate HCC from healthy individuals. CONCLUSIONS This study suggests that the use of a combination of score including CK1, AFP and albumin in clinical practice provides a non invasive and simple test that could increase significantly the sensitivity of HCC diagnosis.

Immunochemical identification and detection of serum fibronectin in liver fibrosis patients with chronic hepatitis C.

Abstract Serum tests measuring the dynamic processes of fibrogenesis and fibrolysis may reflect the severity of liver disease. Fibronectin plays a role in liver fibrosis. The aim of this study was to assess the diagnostic value of fibronectin in chronic HCV infection among Egyptian patients. Fibronectin was identified using specific monoclonal antibody and Western blot at 90‐kDa in sera of HCV infected patients with liver fibrosis. The purified serum fibronectin showed one peak at 8 min when analyzed by capillary zone electrophoresis. Fibronectin was quantified in serum using ELISA. The mean (±SD) serum level of fibronectin (mg/L) in liver fibrosis patients were 450.9 (±170.3) and 230.5 (±90.3) in control individuals, respectively. There was a significant correlation between METAVIR score and serum fibronectin (r=0.401; P<0.0001). The area under the receiver operating characteristic (ROC) curve of fibronectin for discriminating patients with liver fibrosis from those with no fibrosis livers and its p value were 0.78 and P<0.0001. The efficiency of fibronectin for discriminating patients with liver fibrosis from those with non fibrosis livers was 75%. In conclusion, serum fibronectin can differentiate HCV infected patients with liver fibrosis from patients with non fibrosis.

Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats

Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250–300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×106 ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.

Interferon-gamma is associated with hepatic dysfunction in fibrosis, cirrhosis, and hepatocellular carcinoma

ABSTRACT The relation between interferon–gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97–0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Role of myeloperoxidase in early diagnosis of acute myocardial infarction in patients admitted with chest pain

ABSTRACT Myeloperoxidase (MPO) is an inflammatory marker, elevated in acute coronary syndromes (ACSs), especially in acute myocardial infarction (AMI) cases. This study aimed to evaluate the diagnostic power of MPO in AMI patients. MPO, creatine kinase (CK) MB, and Troponin I (cTn I) were performed for all study patients. Area under the curves (AUCs) and 95% confidence intervals (CI); P values of baseline levels of MPO for discriminating AMI patients from noncoronary chest pain (NCCP) patients, stable angina (SA) patients, and unstable angina (UA) patients were 0.91, 95% CI: 0.82–0.99; P < 0.0001, 0.87, 95% CI: 0.77–0.98; P < 0.0001, and 0.72, 95% CI: 0.58–0.85; P = 0.002, respectively. For diagnosing AMI from ACS patients, MPO was the most efficient marker than others markers with efficiency 82.5% within 0–6 hr after the onset time of chest pain. A predictive score that depends on a combination of baseline levels of three markers (MPO, CK-MB, and TnI) was correctly discriminated 91% of the AMI patients with high specificity 76%. In conclusion, the use of baseline levels of three biomarkers in combination could confer the information that is required for best available early diagnosis of AMI.

Effect of nano-formulated antioxidant on development of renal fibrosis induced by cisplatin

Cisplatin causes renal fibrosis, but the development mechanism of interstitial fibrosis is not yet understood. We examined the effect of nano form antioxidant, N, N’diphenyl-1, 4-phenylenediamine (Nano-DPPD), on development of interstitial fibrosis induced by cisplatin. Cisplatin increased blood urea nitrogen (BUN), serum creatinine, serum magnesium and serum chemoattractant protein (MCP-1) on the other hand it decreased creatinine clearance levels. Also administration of cisplatin made many pathological abnormalities represented in increasing collagen deposition, α-smooth muscle actin, Ki67 and renal tubular injury. Administration of Nano-DPPD, which was started at 3 days after cisplatin treatment, significantly inhibited the increase in renal collagen contents and the expansion of the interstitial fibrosis area. These results indicate that anti-fibrotic action of Nano-DPPD is not secondary due to the inhibition of acute renal injury but is rather a direct effect on renal fibrogenesis. Nano-DPPD prevent the infiltration of macrophages by cisplatin, suggesting that anti-fibrotic action of Nano-DPPD was not mediated by the inhibition of inflammatory cellular influx. It is suggested that reactive oxygen species and collagen deposition are involved in cisplatin-induced renal interstitial fibrosis. Correspondence to: Dr. Ahmed Nabil, Faculty of Postgraduate Studies for Advanced Science Beni-Suef University, Egypt, Tel: (+20)1000618349, E-mail: drnabil_100@hotmail.com

Potassium salt of 2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine and 9-bromo-2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine inhibits tumor growth in vitro and in vivo

Coumarin and their derivatives are important and useful compounds with diverse pharmacological properties. In the present study, we evaluated the in vitro cytotoxic activity of new Coumarin derivatives: Potassium salt of 2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine and 9-bromo-2-thioxo-4-hydroxycoumarin [3, 4-b] pyrimidine against MCF-7 (human breast cancer), HePG2 (Hepatocellular carcinoma), HCT116 (human colon cancer), PC3 (human prostate cancer). In order to find new drugs with anticancer activities prepared compounds were evaluated for their in vitro and in vivo anticancer activities. Coumarino[3, 4-b] pyrimidine -2-thioles (4a,b) were prepared via cyclocondensation of 6-substituted-3-ethoxycarbonylcoumarin (2a, b) with thiourea in the presence of anhydrous potassium carbonate to give the potassium salt of Coumarino[3, 4-b] pyrimidine -2-thioles (3a, b), followed by acidification of (3a, b), with 2 N hydrochloric acid . The compounds [3a & 3b] exhibited a significant anticancer activity towards MCF-7, HEPG2, HCT116 and PC3 cancer cell lines. Also, in vivo study of, [3a & 3b] compounds revealed a significant anticancer activity towards Ehrlich ascites carcinoma (EAC) cells by reduction of its volume to 55.5% and 73.3% (p<0.001), in the treated groups; respectively. And significantly decrease in the cell count by 65.9% and 78.9%, in treated groups (p<0.001); respectively, compared to the positive control group. It turned out that they reduced cell viability of cancer cells in a time and concentration dependent manner in vitro and in vivo studies.