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Autophagy is a protective mechanism important in human diseases as cancer. We evaluated the impact of khalas date extract (KDE) (20-60 mg/mL) on cell viability, morphological changes, DNA fragmentation and gene expression of LC3B-II associated with autophagosome on HepG2 cell line. The GC/MS identification of KDE showed its high content of flavonoids including quercetin, myricetin, kaempferol and catechol. KDE reduced cell viability of HepG2 with IC50 (31.52 mg/mL). Cells treated with KDE showed two band of DNA fragments at (30 and 40 mg) indicating that KDE induced DNA damage and apoptosis in HepG2. The analysis RT-PCR data showed a 0.2-fold increase in the expression of LC3-B in the cells treated with KDE versus control. We concluded that, KDE flavonoids such as quercetin, myricetin kaempferol exhibited anticancer properties manifested by inhibition of HepG2 cell viability and induction of apoptosis and upregulation of the pro-autophagy LC3-B gene. [ABSTRACT FROM AUTHOR]

Background: Carnosine is a biological active dipeptide in different tissue exert physiological role as buffer in muscle and cell cycle division. Tocopherol (vitamin E) is the potent antioxidant natural product. This study investigated the role of carnosine supplementation with vitamin E in protection against nephropathy in diabetic rats. Materials and Methods: This study was carried out on 75 rats grouped into five groups; control and the other rats groups (II-V) were received a single dose of streptozocine i.p, at dose of (65 mg/kg/b.w) for diabetogenesis. GPI were considered as diabetic untreated. Rats in groups 3-6 were treated i.p daily with carnosine (1mg/kg b.w), vitamin E (50,00 IU/kg b.w) or combined (10 mg/kg b.w) respectively for 12 weeks. Fasting serum was subjected for assay of glucose, HbA1c, AGEs, MDA, SOD, total antioxidant activity and inflammatory markers (TNF-α and IL-6). Results: Data obtained showed that, diabetic rats treated with carnosine and Vitamin E showed improvement in glucose, glycated hemoglobin, antioxidant enzymes, decreased inflammatory mediators and AGEs (p <0.001) versus untreated diabetic. In addition, combined treatment is better than individual treatment (p <0.05). Conclusion: Promising positive results were spot a new strategy of carnosine and Vitamin E rich food supplements for protection against diabetic complications. It can be used as complementary and alternative therapy for nephropathy, neuropathy and cardiomyopathy. [ABSTRACT FROM AUTHOR]

Objectives: Among tropical diseases, schistosomiasis caused by Schistosoma mansoni is the second major cause of morbidity and mortality worldwide. Inflammation was considered as an adverse event that contributes to the pathology associated with schistosomiasis. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) have been implicated in the process of angiogenesis. The current study aimed to evaluate the effect of S. mansoni infection on HO-1 gene expression, IL-4, IL-12, and VEGF to address the role of these factors in the pathogenesis of schistosomiasis. Methods: Thirty mice divided equally into three groups comprised a non-infected control group and two S. mansoni-infected groups. Infected animals were studied at 8 and 12 weeks post-infection. Serum IL-4, IL-12, and VEGF were measured. HO-1 mRNA was detected by RT-PCR of liver homogenates and HO activity was assessed as percentage of carboxy hemoglobin. Results: S. mansoni-infected mice showed a progressive increase in serum IL-4 and VEGF and decrease in IL-12 levels. In addition, HO-1 expression and activity were increased in infected mice compared to control group with the maximum increase at egg deposition stage. Conclusion: Our results suggested that the body response to acute stage of S. mansoni infection by elevating the expression of the stress gene HO-1 and that VEGF may serve as a new indicator of progression of S. mansoni associated angiogenesis which regulates granuloma and/or fibrosis development in the liver of infected mice. Understanding the role of HO-1 and VEGF in pathogenesis of S. mansoni may provide a new pharmacological target. [ABSTRACT FROM AUTHOR]

Background: Lactate dehydrogenase (LDH) is an enzyme of glycolytic pathway, ubiquitously found in living organisms. Increased glycolysis and LDH activity are associated with many pathologic conditions including inflammation and cancer, thereby making the enzyme a suitable drug target. Studies on conserved structural and functional domains of LDH from various species reveal novel inhibitory molecules. Our study describes Escherichia coli production and characterization of a moderately thermostable LDH (LDH-GT) from Geobacillus thermodenitrificans DSM-465. An in silico 3D model of recombinant enzyme and molecular docking with a set of potential inhibitors are also described. Results: The recombinant enzyme was overexpressed in E. coli and purified to electrophoretic homogeneity. The molecular weight of the enzyme determined by MALDI-TOF was 34,798.96 Da. It exhibitedmaximum activity at 65°C and pH 7.5 with a KM value for pyruvate as 45 μM. LDH-GT and human LDH-A have only 35.6% identity in the amino acid sequence. On the contrary, comparison by in silico structural alignment reveals that LDH-GT monomer has approximately 80% identity to that of truncated LDH-A. The amino acids "GEHGD" as well as His179 and His193 in the active site are conserved. Docking studies have shown the binding free energy changes of potential inhibitors with LDH-A and LDH-GT ranging from -407.11 to -127.31 kJ mol-1. Conclusions: By highlighting the conserved structural and functional domains of LDH from two entirely different species, this study has graded potential inhibitory molecules on the basis of their binding affinities so that they can be applied for in vivo anticancer studies. [ABSTRACT FROM AUTHOR]