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Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients.This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment's effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract's apoptotic activity, and proliferation marker in the selected samples. Also, a colony formation test and stemness protein were investigated.In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients' samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P0.008) for CD138-/CD19- and 36.94% (P0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%.MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs.

An aqueous solution of magnetite (Fe3O4) nanoparticles was synthesized using the method of co-precipitation. The nanoparticles were activated with epichlorohydrin for covalently immobilizing the catalase enzyme. The immobilization conditions were optimized as 0.07 mg/ml catalase for 1 h contact time. The properties of free and immobilized catalase were also investigated. The immobilized enzyme showed enhanced activity at alkaline pH and retained about 90% of its relative activity between pH (6–8) and resisted the high temperature and retained 90% of its relative activity at 50 °C. Kinetic parameters of free and immobilized catalase were investigated. While the Vmax value of the immobilized enzyme was reduced 2.4 fold compared to the free enzyme, the KM value of the immobilized catalase was higher by 2.2 fold than the free enzyme. The formulated matrix enhanced the velocity of the immobilized catalase more than the free one and was able to be used for about 18 cycles with retention of 80% of its activity. The immobilized catalase on epoxy functionalized iron oxide nanoparticles is promising as a nano-bio-catalyst carrying out in many industries and different fields.

This study evaluated the possible neuroprotective effect of Allium atroviolaceum extract (AaE)-synthesized selenium nanoparticles (SeNPs) on aluminum (Al)-induced neurotoxicity in mice, explaining the likely mechanisms. Mice were divided into five groups: G1, control; G2, AaE group that received AaE (200 mg/kg) for 4 weeks; and groups 3, 4, and 5 received AlCl3 (100 mg/kg) for 3 weeks. After that, G4 received AaE (200 mg/kg), and G5 received SeNPs-AaE (0.5 mg/kg) for another 1 week. Exposure to AlCl3 boosted oxidative damage in brain tissue as evidenced by a reduction in glutathione concentrations and other antioxidant enzymes along with increased lipid peroxidation and nitric oxide levels. There was also a rise in the concentrations of interleukin-1β, TNF-α, and cyclooxygenase-II activities. AlCl3-treated mice showed reduced brain-derived neurotrophic factor (BDNF) and dopamine levels, increased acetylcholinesterase (AChE) activity, and reduced Bcl-2, and Bax, and caspase-3 activities. Treatment with SeNPs-AaE significantly reduced markers of oxidative stress, inflammation, and apoptosis. In addition, in SeNPs-AaE-treated rats, levels of BDNF and dopamine were significantly increased along with a reduction in AChE as compared with the AlCl3 group. Therefore, our results indicate that SeNPs-AaE has a potential neuroprotective effect against Al-mediated neurotoxic effects because of its powerful antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.

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.

Background Synthesized gallium nanoparticles synthesized by grape seed extract were characterized with spherical shape and size range less than100 nm, possessing the functional groups of the biological material. The purpose of this study is to evaluate gallium nanoparticles synthesized by grape seed extract, as an antitumor agent with low dose of γ-radiation against hepatocellular carcinoma in rats. Aim of work This work aimed to evaluate the antitumor effect of gallium nanoparticles synthesized (GaNPs) by grape seed extract and the co-binded treatment with low dose of γ-radiation on hepatocellular carcinoma in rats, through evaluating their effect on signaling pathways and tumor markers. Results Cytotoxic activity of GaNPs synthesized by grape seed extract was estimated by mediated cytotoxicity assay on HepG2 cell line that recorded IC50 of 388.8 μg/ml. To achieve these goals, eighty Wistar male rats (120−150 g) will be divided into eight groups, each of 10 rats. The animals are administered with diethylnitrosamine to induce hepatocellular carcinoma and then orally administered with GaNPs synthesized by grape seed extract (38.5 mg/kg) in combination with the exposure of the total body to a low dose of γ-radiation (0.5 Gy). The treatment modulated plasma vascular endothelial growth factor and alpha-fetoprotein. In addition, the immunoblotting results of nuclear factor-kappa beta showed a marked downregulation of extracellular signal-regulated kinase, mitogen-activated protein kinase, and c-Jun NH2-terminal kinase alongside, significantly elevating the level of Sirtuin-3 and caspase-3. Conclusions It can be concluded that the combined treatment with GaNPs synthesized by grape seed extract and low dose γ-radiation may have antineoplastic activity against hepatocarcinogenesis by inhibiting signal pathways extracellular signal-regulated kinase/mitogen-activated protein kinase/c-Jun NH2-terminal kinase and stimulating apoptotic protein.

The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.

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.

Rapid, highly sensitive, and accurate virus circulation monitoring techniques are critical to limit the spread of the virus and reduce the social and economic burden. Therefore, point-of-use diagnostic devices have played a critical role in addressing the outbreak of COVID-19 (SARS-CoV-2) viruses. This review provides a comprehensive overview of the current techniques developed for the detection of SARS-CoV-2 in various body fluids (e.g., blood, urine, feces, saliva, tears, and semen) and considers the mutations (i.e., Alpha, Beta, Gamma, Delta, Omicron). We classify and comprehensively discuss the detection methods depending on the biomarker measured (i.e., surface antigen, antibody, and nucleic acid) and the measurement techniques such as lateral flow immunoassay (LFIA), enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), microarray analysis, clustered regularly interspaced short palindromic repeats (CRISPR) and biosensors. Finally, we addressed the challenges of rapidly identifying emerging variants, detecting the virus in the early stages of infection, the detection sensitivity, selectivity, and specificity, and commented on how these challenges can be overcome in the future.

Nanomaterials are becoming important materials in several fields and industries thanks to their very reduced size and shape-related features. Scientists think that nanoparticles and nanostructured materials originated during the Big Bang process from meteorites leading to the formation of the universe and Earth. Since 1990, the term nanotechnology became very popular due to advances in imaging technologies that paved the way to specific industrial applications. Currently, nanoparticles and nanostructured materials are synthesized on a large scale and are indispensable for many industries. This fact fosters and supports research in biochemistry, biophysics, and biochemical engineering applications. Recently, nanotechnology has been combined with other sciences to fabricate new forms of nanomaterials that could be used, for instance, for diagnostic tools, drug delivery systems, energy generation/storage, environmental remediation as well as agriculture and food processing. In contrast with traditional materials, specific features can be integrated into nanoparticles, nanostructures, and nanosystems by simply modifying their scale, shape, and composition. This article first summarizes the history of nanomaterials and nanotechnology. Followed by the progress that led to improved synthesis processes to produce different nanoparticles and nanostructures characterized by specific features. The content finally presents various origins and sources of nanomaterials, synthesis strategies, their toxicity, risks, regulations, and self-aggregation.

Over the last few years, biopolymers have attracted great interest in tissue engineering and regenerative medicine due to the great diversity of their chemical, mechanical, and physical properties for the fabrication of 3D scaffolds. This review is devoted to recent advances in synthetic and natural polymeric 3D scaffolds for bone tissue engineering (BTE) and regenerative therapies. The review comprehensively discusses the implications of biological macromolecules, structure, and composition of polymeric scaffolds used in BTE. Various approaches to fabricating 3D BTE scaffolds are discussed, including solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, electrospinning, and sol–gel techniques. Rapid prototyping technologies such as stereolithography, fused deposition modeling, selective laser sintering, and 3D bioprinting are also covered. The immunomodulatory roles of polymeric scaffolds utilized for BTE applications are discussed. In addition, the features and challenges of 3D polymer scaffolds fabricated using advanced additive manufacturing technologies (rapid prototyping) are addressed and compared to conventional subtractive manufacturing techniques. Finally, the challenges of applying scaffold-based BTE treatments in practice are discussed in-depth.

Synthesized gallium nanoparticles synthesized by grape seed extract were characterized with spherical shape and size range less than100 nm, possessing the functional groups of the biological material. The purpose of this study is to evaluate gallium nanoparticles synthesized by grape seed extract, as an antitumor agent with low dose of γ-radiation against hepatocellular carcinoma in rats.This work aimed to evaluate the antitumor effect of gallium nanoparticles synthesized (GaNPs) by grape seed extract and the co-binded treatment with low dose of γ-radiation on hepatocellular carcinoma in rats, through evaluating their effect on signaling pathways and tumor markers.Cytotoxic activity of GaNPs synthesized by grape seed extract was estimated by mediated cytotoxicity assay on HepG2 cell line that recorded ICIt can be concluded that the combined treatment with GaNPs synthesized by grape seed extract and low dose γ-radiation may have antineoplastic activity against hepatocarcinogenesis by inhibiting signal pathways extracellular signal-regulated kinase/mitogen-activated protein kinase/c-Jun NH2-terminal kinase and stimulating apoptotic protein.

A new matrix formulation was devised for catalase immobilization. Carrageenan-alginate beads different ratios were developed and soaked into different ratios of CaCl(2)–KCl as a hardening solution. The best formulation for loading capacity was selected, treated with polyethylene imine followed by glutaraldehyde and further studied. The best concentration of catalase for immobilization was 300U/ml and the best loading time was 6 h. The catalytic properties increased after immobilization and the immobilized catalase achieved optimum activity at a temperature range of 30–50 °C that was compared to the optimum activity of free catalase which occurred at 40 °C. Higher catalytic activity of immobilized catalase occurred at alkaline pHs than the free one which achieved optimum catalytic activity at neutral pH. A comparison between the kinetic parameters of immobilized and free catalase showed variation. The K(M) and Vmax of the immobilized catalase were 2.4 fold and six times higher than those of free catalase. The results of the study indicate that the formulated matrix can be used as a good matrix for catalase enzyme in various industrial applications.

Objective The present work was designed to study the effect of new conjugated caffeic and folic acid with silver nanoparticles with definite molecular size applied with and without gamma radiation exposure, as an antitumor agent against experimentally induced Ehrlich tumor and attempted to identify their potential molecular mechanisms of action throughout determination of anti-tumor activities using MTT cytotoxic assay against two human carcinoma cell lines in vitro, such as apoptosis analysis by flow cytometry through caspase-8, caspase-3 and TNF determination in vivo. Materials and methods Adult female albino mice were used and divided into five groups. Animals were sacrificed and the following parameters were estimated, glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) in blood in addition to caspase8, caspase 3 and tumor necrosis factor (TNF) of tumor tissue, liver and kidney function also measured in plasma. The tumor specimens were processed for histopathological examination. Results Nano-silver folate caffeic (NSFC) complex compound treatment resulted in growth inhibition in Ehrlich solid tumor, Hep-G2, and MCF-7 cells (IC50 0.062 mg, 7.70 µM, and 14.50 µM, respectively). Flow cytometric analysis revealed that (NSFC) with radiation IR had apoptotic effects at caspases 8 (Mean±SD) (49.4±14), caspase3 (39.97±9.75), and TNF (40.1±3.4) more than any other groups. Those disturbances were found to be associated with a kinetic induction of apoptosis and showed modulation of the antioxidant system {glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) which were 60.70±0.80, 26.73±0.80, 39.52±0.58 respectively}at the group which took (NSFC+IR), besides its high percentage of necrotic cells by histopathological studies. In conclusion, the present study showed that the treatment of (NSFC) exhibits very efficient oncolytic activity in delaying tumor growth in mice bearing Ehrlich Solid Carcinoma (ESC) and the mechanisms underlying the inhibitory effect of the present compound involve both an apoptotic effect against Hep-G2 and MCF-7 cells and modulation of antioxidant system.

The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.

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.

The aim of this study was to investigate the radioprotective effect of salicin against irradiation effect on spleen tissue in male rats. Lipid peroxidation product (MDA) level was measured as thiobarbituric acid reactive substance. Ultrastructural examination was carried out in spleen tissue by scanning electron microscope (SEM). The polyacrylamide gel electrophoresis for native protein, lipoprotein and zymogram were carried out in spleen homogenate. As expected, salicin resisted the irradiation effect and declined the MDA level in spleen homogenate of all treated groups. The alterations which were occurred as a result of irradiation in the spleen tissue could not be detected microscopically but they were detected electrophoertically at levels of protein and isozymes. Salicin prevented the qualitative mutagenic effect of irradiation on the electrophoretic protein pattern in the irradiated salicin simultaneous treated group (SI = 0.73). It showed the highest protective effect against qualitative mutagenic irradiation effect in catalase pattern in irradiated salicin pre-treated group (SI = 0.80). It could not prevent the abnormalities occurred qualitatively and quantitatively as a result of irradiation in peroxidase pattern in all irradiated salicin treated groups. While the esterase pattern showed the same electrophoretic pattern in the all irradiated salicin treated groups. The results suggested the radioprotective ability of salicin against gamma irradiation effect on various ultrastructural and electrophoretic patterns in spleen tissue of male rats.

The aim of this study was to investigate the radioprotective effect of salicin against irradiation effect on brain tissue of male rats. Lipid peroxidation level was measured as thiobarbituric acid reactive substance in brain tissue. The polyacrylamide gel electrophoresis for native protein, lipoprotein and zymogram were carried out in brain homogenate. As expected, salicin resisted the irradiation effect and declined the MDA level in brain homogenate of all treated groups (especially in the irradiated salicin post-treated group). Salicin minimized the qualitative mutagenic effect of irradiation on the electrophoretic protein pattern in all irradiated salicin treated groups and it showed the highest antagonistic effect against irradiation in irradiated salicin post-treated group (SI = 0.57). It could not prevent the abnormalities occurred qualitatively and quantitatively as a result of irradiation in lipoprotein pattern in all irradiated salicin treated groups. In the electrophoretic esterase pattern, salicin prevented the qualitative effect of irradiation in irradiated salicin post-treated group (SI = 1.00). Salicin minimized the qualitative irradiation effect on the catalase pattern in the irradiated salicin pre-treated group (SI = 0.73). While in the peroxidase pattern, salicin adminstration resisted the irradiation effect in the irrradiated post-treated groups (SI = 0.67). The results suggested the radioprotective ability of salicin against gamma irradiation effect on various electrophoretic patterns in brain tissue of male rats.

Background: The folk medicine in Egypt has described several kinds of Egyptian herbs and plant prescriptions, belonging to various families to be concerned with the treatment of diabetes mellitus.The present study focuses on evaluating the chromosomal aberration in somatic cells of STZ-diabetic rats treated with Lupinus albus (termis) and Hyphaene thebaica (doum) as well as their effect on liver and pancreas histopathology. Material and methods: STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. Termis seeds suspension (75 mg/100 g b.wt.) was daily orally administered, doum fruit suspension was daily orally administered (1g/kg b.wt.) and also gliclazide, reference drug, was administered at a dose equivalent to the therapeutic dose of rat. After four weeks of administration, bone-marrow metaphases were prepared for examining chromosomal aberration. These were followed by statistical analysis. Liver and pancreas were dissected, processed and stained with H&E for investigating histopathological changes. Results: The results of chromosomal analysis showed that, diabetic rats had a highly significant increase of chromosomal aberrations compared to that of normal healthy control. Animals which were treated with Lupinus albus and Hyphaene thebaica showed significant improvements in the frequencies of chromosomal aberrations. Also, treatment of diabetic rats with termis and doum revealed marked improvement in liver and pancreas histopathology. Conclusion: It is concluded that diabetes is much harmful on the histological picture of liver and pancreas and on chromosomal aberration frequencies in the animal body, whilst the administration of termis or doum reduced these harmful effects of diabetes.

Background: Several plants have been used as dietary adjuvant and in treating the number of diseases because of their perceived effectiveness, minimal side effects in clinical experience and relatively low costs.The present study focuses on evaluating the effect of Lupinus albus (termis) and Hyphaene thebaica (doum) on STZ-diabetic rats at the level of some biochemical parameters Material and methods: STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. Termis seeds suspension (75 mg/100 g b.wt.) was daily orally administered. Doum palm fruit suspension was daily orally administered (1g/kg b.wt.) and also gliclazide (reference drug) was administered of a dose equivalent to the therapeutic dose of rat. After four weeks of administration, blood samples were collected for biochemical measurement. Results: Blood glucose level was significantly increased. Diabetes increased serum total lipids, cholesterol, triglycerides and LDL but serum HDL wasdecreased. Also activities of serum enzymes ASAT, ALAT, ALP, GGT and LDH were elevated. However, L. albus and H. thebaica improved the level of mostly all biochemical parameters. Conclusion: It is concluded that termis and doum may be dietary adjuvant in reducing the harmful of diabetes.

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.

Purpose : The purpose of this study was to evaluate the effi cacy of hesperidin (HES), a citrus fl avonoid, against the severity of biochemical disorders in the cerebral hemispheres of irradiated rats. Material and methods : Hesperidin (50 mg/kg body weight) was administered to male albino rats via gavages during 10 successive days before whole body exposure to gamma rays (5 Gy) and during 14 days after irradiation. The animals were sacrifi ced on the 14th day post-irradiation. Results : The results demonstrated a signifi cant increase of the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CO), and advanced oxidation protein products (AOPP), associated to signifi cant decreases of total superoxide dismutase (tSOD) and catalase (CAT) activities, and reduced thiols content in the cerebral hemispheres of irradiated rats indicating oxidative stress. A signifi cant decrease of the serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents and a signifi cant increase of the activity of monoamine oxidase (MAO) were recorded, also, indicating alterations in the metabolism of monoamines. Moreover, a signifi cant decrease of the activities of glutamate dehydrogenase (GDH) and creatine phophokinase (CPK), and a signifi cant increase of calcium ions (Ca 2 ) levels were recorded in the mitochondria. Hesperidin treatment has signifi cantly attenuated oxidative stress, monoamines alterations and mitochondrial damage in the cerebral hemispheres of irradiated rats. Conclusion : It could be concluded that hesperidin might attenuate the severity of radiation-induced biochemical disorders in brain tissues.

Background and Aim: Response to interferon therapy and disease progression in hepatitis C virus (HCV) infected patients differs among individuals, suggesting a possibility of a contribution of host genetic factors. 2′-5′-oligoadenylate synthetase 1 (OAS1), an important component of the innate immune system with a proven antiviral function, may therefore have a relationship with the response to interferon therapy and clinical course of HCV disease. Our aim was to determine the frequency of single nucleotide polymorphism (SNP) at exon 7 splice acceptor site (SAS) of the OAS1 gene in relation to the interferon response and status of HCV infection. Methods: A 203 bp fragment containing exon 7 SAS was amplified in 70 HCV chronic patients and 50 healthy controls. SNP was examined using restriction fragment length polymorphism (RFLP) genotyping method. Correlations of SNP genotypes with response to interferon and clinical status of patients were statistically analyzed. Results: There was an increasing trend of response from AA to AG to GG genotypes (P = 0.007). Genotype AA was associated with non-response to interferon and higher degree of liver fibrosis (P = 0.05). Multivariate analysis showed this SNP as independent and a significant determinant of the outcome of interferon therapy (odds ratio 4.913 [95% confidence interval 1.365–8.2], P = 0.006). Conclusions: This is the first study to show a significant association between the functional SNP at exon 7 SAS of OAS1 gene and the viral response to interferon in chronic HCV patients. Patients with AA genotype were associated with progressive HCV disease and viral resistance to interferon therapy. This OAS SNP is a potential bio-marker to predict IFN response in chronic hepatitis C patients.

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.

Anabasis articulata (Forssk) Moq. (Chenopodiaceae) is an herb, grows in Egypt, and used in folk medicine to treat diabetes, fever, and kidney infections. The protective and therapeutic effects of the ethanol extract of A. articulata aerial parts were evaluated against dimethylnitrosamine (DMN)-induced liver fibrosis, compared with the standard drug, silymarin. Hepatic hydroxyproline content, serum transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) and fructosamine were measured as liver fibrosis markers. Hepatic malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione reductase (GR) and glutathione content (GSH) were measured as oxidant/antioxidant markers. Parallel histopathological investigations were also performed. Protective and therapeutic administration of A. articulata (100 mg/kg daily for 4 weeks), markedly prevented DMN-induced loss in body and liver weights. The extract significantly inhibited the elevation of hepatic hydroxyproline, NO and MDA (P

Background and Aim: Response to interferon therapy and disease progression in hepatitis C virus (HCV) infected patients differs among individuals, suggesting a possibility of a contribution of host genetic factors. 2′‐5′‐oligoadenylate synthetase 1 (OAS1), an important component of the innate immune system with a proven antiviral function, may therefore have a relationship with the response to interferon therapy and clinical course of HCV disease. Our aim was to determine the frequency of single nucleotide polymorphism (SNP) at exon 7 splice acceptor site (SAS) of the OAS1 gene in relation to the interferon response and status of HCV infection. Methods: A 203 bp fragment containing exon 7 SAS was amplified in 70 HCV chronic patients and 50 healthy controls. SNP was examined using restriction fragment length polymorphism (RFLP) genotyping method. Correlations of SNP genotypes with response to interferon and clinical status of patients were statistically analyzed. Results: There was an increasing trend of response from AA to AG to GG genotypes (P = 0.007). Genotype AA was associated with non‐response to interferon and higher degree of liver fibrosis (P = 0.05). Multivariate analysis showed this SNP as independent and a significant determinant of the outcome of interferon therapy (odds ratio 4.913 [95% confidence interval 1.365–8.2], P = 0.006). Conclusions: This is the first study to show a significant association between the functional SNP at exon 7 SAS of OAS1 gene and the viral response to interferon in chronic HCV patients. Patients with AA genotype were associated with progressive HCV disease and viral resistance to interferon therapy. This OAS SNP is a potential bio‐marker to predict IFN response in chronic hepatitis C patients.

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.