Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract: [Figure not available: see fulltext.

Potential Role of New Anthropometric Parameters in Childhood Obesity with or Without Metabolic Syndrome

BACKGROUND: Obese children and adolescents are more prone to have metabolic syndrome (MS).MS is a cluster of cardiovascular risk factors associated with insulin resistance. Body round index [BRI], visceral adiposity index [VAI] and a body shape index [ABSI] are among the new obesity anthropometric parameters. AIM: To evaluate the new markers for obesity in children and their possible association with other laboratory and clinical variables of MS. METHODS: Eighty nine obese children and 40 controls aged 10-18 years were recruited. Full history taking, thorough clinical examination, anthropometric and biochemical features were performed in the studied groups. Subcutaneous fat thickness (SFT) and visceral fat thickness (VFT) were estimated by ultrasonography. RESULTS: Obese children, exhibited significantly higher values in all anthropometric measurements (P < 0.001). Diastolic and systolic blood pressure were significantly higher (P < 0.001) in the obese group. ABSI, BRI and VAI have been found to be significantly higher in obese subjects (P < 0.001), with no significant gender difference. BMI, WHtR, WC/HR, SBP, DBP, subcutaneous fat thickness and visceral fat thickness, Liver Span, ABSI, BRI, VAI and HOMA_IR were significantly higher among children with MS than those without MS. Positive significant correlations of VAI with BMI, WC/Ht, WC/Hip, SBP, DBP, SFT, VFT, Liver size and HOMA-IR (r = 0.384, 0.239, 0.268, 0.329, 0.516, 0.320, 0.254, 0.251, and 0.278 respectively) are shown. The area under the ROC curve (AUC) of BMI, VAI, ABSI, BRI for predicting MS was 0.802 (0.701-0.902), 0.737 (0.33-0.841), 0.737 (0.620-0.855), 0.816 (0.698-0.934). CONCLUSION: We suggest using the VAI and WHtR indexes, as they are better predictor of MS

Open-array analysis of genetic variants in Egyptian patients with type 2 diabetes and obesity

Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants.Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 diabetes (T2D) and obesity susceptibility loci by GWAS in a sample of Egyptian patients to find out if there is shared genetic background underlying both disease entities.Methods: Genotyping was performed using OpenArray protocol on the QuantStudioTM 12K Flex Real- Time PCR System. In the present case control study a custom array was designed to facilitate costeffective analysis of selected SNPs related to glycolysis, gluconeogenesis, inflammation, insulin signalling, and immune function.Results: Seven gene variants showed significant association with the risk of T2D patients including FCGRA2, STAT4, CELSR2, PPARG, EXT2 rs3740878, GCKR, PTGS1. Factors that significantly affect T2D were obesity (p < 0.001) and GCKR (p = 0.001) and PTGS1 (p = 0.001) gene variants. Gene variants that showed significant or borderline effect on obesity were MTHFD1, EXT2 rs3740878, GCKR and PTGS1 (p = 0.03, 0.017, 0.059, 0.006) respectively.Conclusions/interpretation: Overlapping genetic aspects should be considered and the presence of risk alleles of different genes together could contribute to the risk of T2D or obesity or both. The MTHFD1 and EXT2rs3740878 gene variants significantly affect obesity and not shared with T2D. Gene variants that showed combined effect on both disease entities were GCKR and PTGS1. These findings provide a basis for future studies on a larger scale. More stress on the risk gene variants that have a combined impact on both diabetes and obesity is recommended to improve risk prediction and preventive strategies

Study of nonstandard auto-antibodies as prognostic markers in auto immune hepatitis in children

<p>Abstract</p> <p>Background</p> <p>Antibodies to chromatin and soluble liver antigen have been associated with severe form of autoimmune hepatitis and/or poor treatment response and may provide guidance in defining subsets of patients with different disease behaviors. The major clinical limitation of these antibodies is their lower individual occurrence in patients with autoimmune hepatitis.</p> <p>Aim</p> <p>To estimate the value of detection of these non-standard antibodies in autoimmune hepatitis as prognostic markers.</p> <p>Methods</p> <p>Both antibodies were tested by enzyme immunoassay in 20 patients with autoimmune hepatitis.</p> <p>Results</p> <p>Antibodies to soluble liver antigen were not detected in any of our patients. On the other hand anti chromatin antibodies were present in 50% (10/20). Antibodies to chromatin occurred more commonly in females than males (8/14 versus 2/6). Of the 14 patients who relapsed 8(57%) had antichromatin antibodies while they were present in only 2 out of 6(33.3%) non relapsers. Antichromatin antibodies were found more in patients with antinuclear (3/4) and anti smooth muscle antibodies (9/13) more than in those with liver kidney microsomal antibodies (1/4) and those seronegative (1/4) i.e. they were +ve in patients with type I (8/12(66.6%)) more than those with type II (1/4(25%)) and those seronegative (1/4(25%)). Antibodies to chromatin are associated with high levels of γ globulin but yet with no statistical difference between seropositive and seronegative counterparts (p = 0.65).</p> <p>Conclusion</p> <p>Antibodies to chromatin may be superior than those to soluble liver antigen in predicting relapse and may be useful as prognostic marker. Further studies with larger number of patients and combined testing of more than one antibody will improve the performance parameters of these antibodies and define optimal testing conditions for them before they can be incorporated into management algorithms that project prognosis.</p

Attenuation of Smad, Wnt and E2F Signaling by Egyptian Riverhemp Triterpenes in Leukemia Cells

Presenter: Ospanov Meirambekhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1012/thumbnail.jp

Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia

Presenter: Ospanov Meirambekhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1013/thumbnail.jp

Diagnostic efficacy of monoclonal antibody based sandwich enzyme linked immunosorbent assay (ELISA) for detection of Fasciola gigantica excretory/secretory antigens in both serum and stool

<p>Abstract</p> <p>Background</p> <p>This research was carried out to develop a reliable monoclonal antibody (MoAb)-based sandwich enzyme linked immunosorbent assay (ELISA) for the diagnosis of active <it>Fasciola gigantica </it>infection in both serum and stool for comparative purposes.</p> <p>Methods</p> <p>From a panel of MoAbs raised against <it>F. gigantica </it>excretory/secretory antigens (ES Ags), a pair (12B/11D/3F and 10A/9D/10G) was chosen due to its high reactivity and strict specificity to <it>F. gigantica </it>antigen by indirect ELISA.</p> <p>Results</p> <p>The two MoAbs were of the IgG₁and IgG_2asubclasses, respectively. Using SDS-PAGE and EITB, the selected MoAbs recognized 83, 64, 45 and 26 kDa bands of ES Ags. The lower detection limit of ELISA assay was 3 ng/ml. In stool, the sensitivity, specificity and diagnostic efficacy of ELISA was 96%, 98.2 and 97.1%; while in serum they were 94%, 94.6% and 94.3%, respectively. Moreover, a positive correlation was found between ova count in stool of <it>F. gigantica </it>infected patients and the OD readings of ELISA in both stool and serum samples (<it>r </it>= 0.730, p < 0.01 and r = 0.608; p < 0.01, respectively).</p> <p>Conclusions</p> <p>These data showed that the use of MoAb-based sandwich ELISA for the detection of <it>F. gigantica </it>coproantigens in stool specimens was superior to serum samples; it provides a highly efficient, non-invasive technique for the diagnosis of active <it>F. gigantica </it>infection.</p

Study of Visfatin Level in Type 1 Diabetic Children and Adolescents

BACKGROUND: Visfatin is an intracellular enzyme, known as nicotinamide phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF-1). It has insulin-mimetic effects and lowers plasma glucose levels.AIM: The aim of the work was to assess serum concentration of Visfatin in type 1 diabetic children and adolescents and study its relationships with duration of diabetes, body mass index (BMI), glycemic control, insulin dosage, lipid profile and microvascular complications.MATERIAL AND METHODS: Fifty children and adolescents with type 1 diabetes mellitus were recruited with 30 ages and gender-matched healthy subjects. They were subjected to history taking; anthropometric measurements and chronic diabetic complications were recorded if present. Laboratory analysis included urinary microalbumin, serum triglycerides, HDL, LDL, cholesterol, fasting blood glucose, glycosylated Hb (HbA1c) and serum visfatin which was measured with enzyme-linked immunosorbent assay.RESULTS: Diabetic patients showed highly significant decrease in the level of visfatin compared to the control group (P = 0.0001).There was significant further decrease in visfatin level in diabetics with microalbuminuria (n = 13) compared to normoalbuminuric patients (n = 37) (P = 0.015). There was highly significant inverse correlation between visfatin level with age (r = -0.379, p = 0.007), BMI (r = -0.418, p = 0.003), waist circumference (r = -0.430, p = 0.002), hip circumference (r = -0.389, p = 0.005) and microalbuminuria (r = -0.323, p = 0.022).CONCLUSIONS: Type 1 diabetic children and adolescents had a significantly lower visfatin level compared to controls. A marked decrease in the level of visfatin was shown in patients with microalbuminuria with an inverse correlation with BMI suggesting an important role of visfatin in the pathogenesis of type 1 diabetics and type 1 diabetic nephropathy