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Objective: Cancer treatment using a targeted inducer of apoptosis like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) faced the obstacle of resistance, thus providing a plus drug like Thymoquinone (TQ) could be of great interest to tackle breast cancer cells. The aim of the present work is to examine the genetic modulation impacts of the TRAIL receptors and apoptotic markers upon the combinatorial remedy of TRAIL plus TQ on human breast cancer cell lines. Methods: To achieve this rationale, the protein content-based cytotoxicity using SRB assay, as well as the genetic expressions of the TRAIL receptors (DR4 and DR5) and apoptotic markers (Bcl-2, Cas-8, and FADD) using real time qRT-PCR technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results: The current study showed that the combination therapy of TQ+TRAIL significantly inhibited the protein content-based proliferation of MDA-MB-231 cells more than MCF-7 cells. The synergistic effect of them significantly up-regulated the genetic expressions of DR4, DR5, Cas-8, and FADD genes and inhibited the genetic expression of the Bcl-2 gene in the proposed cell lines treated for 24 h. The induction of the apoptotic genes using the combined therapy was stimulated by the elevation of the reactive oxygen species (ROS); nitric oxide (NO) and malondialdehyde (MDA) levels. Conclusions: The synergistic influence between TQ which induced the DR5 and TRAIL, facilitating the connection between TRAIL and its receptors on the cancerous cell membrane. Hence, the proposed combination therapy induced the ROS-mediated apoptotic stimulus.

Objective: Cancer is one of the leading causes of mortality in both developed and developing nations. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is characterized by its ability to selectively trigger apoptosis in cancer cells. TRAIL-based interventions have led to the development of recombinant human (rhTRAIL) as a promising therapy for different types of human cancer. Thymoquinone (TQ) has been shown to exert anticancer effect. The aim of the current study is to investigate the anticancer effect of the combinatorial therapy of TRAIL+TQ against human breast cancer cells. Methods: To achieve this hypothesis, cytotoxicity using MTT assay, as well as apoptosis and cell cycle using flow cytometric technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results: The current study showed that TRAIL induced cell cycle arrest and apoptosis. Moreover, it inhibited proliferation of MDA-MB-231 cells more than MCF-7 cells. Adding TQ to TRAIL increased the chemo-sensitivity of MDA-MB-231, while overcame the MCF-7 resistance to TRAIL. Conclusion: In conclusion, there is a synergistic effect between TRAIL and TQ playing a therapeutic role in killing resistant breast cancer cells.

Objectives Stunting affects 32% of children living in developing countries and has a major impact on child health and development. In this study, we aimed to assess the pro-inflammatory cytokines and some micronutrients among the healthy control and nutritionally stunted Egyptian children. Subjects and methods A total of 88 children were enrolled; 60 stunted children and 28 non-stunted of matched age and sex. Clinical, demographic characteristics, serum levels of calcium, magnesium, and zinc were measured. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and C – reactive protein (CRP) were measured in these subjects. Results Stunted children showed a marked decrease in weight and weight-for-age Z score (WAZ) versus healthy one. Significant reduction in the serum level of Ca, Mg, and Zn was detected in stunted children compared to those of the healthy control subjects. Moreover, the mean serum levels of IL-6 (pg/ml) (1.5 Vs 1.6), TNFα (pg/ml) (1.7 Vs 1.8) and CRP (mg/l) (0.7 Vs 1) were significantly higher among the stunted group compared to control. Conclusion Nutritionally stunted Egyptian children have lowered serum levels of Zn. Ca, and Mg, in addition to elevated serum levels of proinflammatory cytokines (Il-6, TNFα, and CRP).

Childhood nutritional stunting, an indicator of chronic malnutrition, has been suggested as one factor that can contribute to high incidences of obesity, and impaired lipid and glucose metabolism in developing countries. This study aimed to determine health risks of developing hyperlipidemia, obesity, and diabetes as non-communicable diseases (NCDs) among nutritionally stunted Egyptian children. A total of 90 children were enrolled; 60 nutritional stunted children and 30 non- stunted of matched age and sex. Clinical, demographic characteristics were determined for the studied children. Lipid profile levels, fasting plasma levels of glucose, and insulin were measured in these subjects. Pancreatic beta cells’ function (HOMA-β) and insulin resistance (HOMA-IR) were calculated by homeostasis model assessment (HOMA). Stunted children exhibited significantly lower values for weight, weight-for-age Z score (WAZ), height, and height-for-age Z score (HAZ) as compared to normal ones. Significant elevation in total cholesterol (TC), and low density lipoprotein cholesterol (LDL-c), significant decrease in high density lipoprotein cholesterol (HDL-c) and HDL/LDL ratio were detected compared to that of the healthy control subjects. There were no significant differences in the levels of fasting glucose, fasting insulin, homeostasis model assessment of beta-cell function (HOMA-β), and homeostasis model assessment of insulin resistance (HOMA-IR) between the two compared groups. Conclusion: Alterations in lipid pattern among nutritionally stunted Egyptian children may predict the future of NCDs later in life.

Background and Aims Hepatitis C virus (HCV) has emerged as the major pathogen of liver disease worldwide. The aim of this study was to quantitate and evaluate the performance of HCV-NS4 antigen as an alternative approach for confirmation of viremia. Methods Detection of HCV-NS4 was assessed in 883 patients with chronic hepatitis C. Areas under the ROC curves (AUC) were used to assess and compare diagnostic accuracy of ELISA for HCV-NS4 with quantitative HCV-RNA as a gold standard. Results HCV-NS4 was identified at 27 kDa using Western blot. AUC for HCV-NS4 detection was 0.95 for all patients with different liver pathologies: 0.93 for liver fibrosis (LF), 0.95 for liver cirrhosis (LC) and 0.98 for hepatocellular carcinoma (HCC). The mean ± SD (μg/mL) of HCV-NS4 in LF was 94.2 ± 55.6; in LC was 99.3 ± 64.8 and in HCC was 124.9 ± 70.3. Conclusions HCV-NS4 antigen detection using ELISA is a reliable test in the confirmation of HCV infection.

Plasma Vascular endothelial growth factors (p VEGFs) as well as plasma insulin like growth factors- I (pIGFs- I) has been implicated in the pathogenesis of diabetes mellitus. This study was performed to determine whether alternations of p VEGFs and pIGFs are related to diabetic nephropathy in type 2 diabetic patients.Patients & Methods:We examined the association of pVEGFs and pIGFs concentrations with fasting glucose levels, glycosylated hemoglobin (HbA1c %), urinary measured renal parameters i.e. creatinine clearance and albuminuria in 75 patients with type 2 diabetes and 25 healthy controls. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR). Results:We confirmed that (i) both pVEGFs and pIGFs showed remarkable increase in all diabetic groups with worsen A/Cr ratio, as compared with controls. (ii) p VEGFs and pIGFs were increased in diabetic patients as long as glycemic control was not achieved. (iii) Vascular endothelial growth factor in plasma as well as plasma insulin like growth factors elevations were also revealed statistically. (iv) Direct positive correlation between pVEGFs and pIGFs-I with glycemic control index, albuminuria were noticed. Conclusion:The release of both p VEGFs as well as pIGFs was increased during the earlier stage of diabetic nephropathy and were significantly correlated with urinary albumin excretion. This suggested that pVEGFs could be used as an early sensitive marker for the diagnosis before the stage of microalbuminuria. and for predicting disease progression to start therapy very early.

Background: Breast cancer is the most common malignancy in Egyptian females. A wealth of literature is available on various diagnostic and prognostic parameters including clinical, pathological and biological factors. The present study focuses on markers of cell cycle proteins as cyclin B1 and parameters of cell cycle kinetics, related growth factors and tissue polyamines in relation to hormone receptor status.Patients and methods: A total of 102 females made the subject of the study, 72 females with breast cancer, 14 with benign lesions and 16 healthy subjects serving as controls for serum arameters. Normal breast tissue served as control for breast cancer tissues. Tissue polyamines were measured by HPLC. yclin B1 was measured by Flow cytometry (FCM) and Western Blotting (WB). Insulin-like Growth factor 1(IGF1) was easured by enzyme immunoassay (EIA). Tumor markers (CEA and CA 15.3), estradiol and progesterone levels were measured by microparticle enzyme immune assay (MEIA).Results: Cyclin B1 was detected in 17/34 (50%) of the cases tested by FCM and only in 10% of the cases evaluated by WB. Cyclin B1 positivity tended to be associated with high grade tumors. The mean percentage of cyclin B1 positivity was higher in aneuploid tumors than in diploid ones, as well as in tumors with ≥ 10% S-phase fraction (SPF) compared to those with < 10 % SPF. Cyclin B1 positivity was significantly associated with patients of high G2/M phase (p=0.05). Cell cycle analysis showed that ER-ve tumors were significantly associated with high SPF. Tissues polyamines showed significantly increased levels when compared to both benign and normal groups (p< 0.001). Polyamines showed a significant association with ER status (p= 0.04), tumor size (p=0.04) and histopathologic type (p= 0.05). Serum IGF 1 showed insignificant increased level in breast cancer patients less than 45 yrs when compared to the age matched control group. Serum estrogen level showed no change in the breast cancer patients ≥ 45yrs compared to age matched control group, while progesterone level was significantly lower (p< 0.02) in breast cancer patients less than 45yrs old compared to age matched benign and control groups. Serum CEA and CA 15.3 showed significant increase in the breast cancer patients < 45yrs old compared to age matched benign and control groups (p=0.03 and 0.06, respectively).Conclusion: Polyamines proved value as markers of proliferative activity of breast cancer but their testing needs further standardization. Cyclin B1 is associated with aggressive tumors. Its assessment by FCM proved superior to western blotting. IGF1 might be better used to assess tumor recurrence and monitor cancer patients, and its use needs further evaluation. This study may contribute to understanding breast cancer cell growth biology in Egyptian females in view of improving therapeutic and chemopreventive strategies.

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors.

A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels — a finding referred to as ‘metabolic memory'. This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to “metabolic memory.” Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.6 mM and high glucose (H-Glc): 17.5 mM, with low (0.2 mM) and high (2 mM) SFA for 48 h. Abd Sc explants and Ads were also exposed to the aforementioned treatment regimen for 12-h periods, with alternating rest periods of 12 h in L-Glc. Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the nuclear factor-κB (NFκB) pathway in Abd Sc AT and Ads (TLR4, NFκB; P

Background Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. Methods Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8). Results Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004). Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. Conclusions Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.

Background Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Methods The activity of different MMPs including HMW species was determined using zymographic analysis technique in the urine samples procured from sixty six bladder cancer patients (bilharzial and non-bilharzial) as well as hundred healthy control subjects. Also, the correlation between these HMW MMPs activities and different clinico-pathological parameters was investigated. Results High frequency of urine MMPs (uMMPs) activity was determined in 63.6% of examined tumor cases, however, none of the control cases showed any uMMPs activity. MMP-9 had the highest activity (62%) followed by MMP9/NGAL (60%), MMP-2 (54.5%), MMP-9 dimer (53%), ADAMTS (25.6%), and the lowest one was MMP-9/TIMP-1 (12%) only. There was no correlation between uMMPs and any of clinico-pathological parameters including age, gender, tumor size and type, bilharziasis, grade, lymph node involvement, and invasion to the prostate. A significant correlation was established only between MMP-9/TIMP-1 activities with the tumor size. Conclusions This study revealed that the detection of urinary MMPs including HMWs activity might be sensitive biomarkers for prediction of bladder cancer. It is also demonstrate that the detection of these urinary HMW gelatinases could not differentiate between bilharzial and non bilharzial bladder cancer subtypes.