In multiple myeloma (MM) blood-borne malignant plasma cells home to bone marrow (BM), where they
accumulate in close contact with stromal cells. Nevertheless, the mechanisms responsible for MM cell
chemotaxis are still poorly defined. In the present study we explored the mechanisms involved in the
chemotaxis of RPMI 8226 cell line, RPMI 8226 cell line was found to express CCR3, CCR5, CCR9, CXCR3
and CXCR4, but these cells were migrated only towards CXCL12 (the ligand for CXCR4). To clarify the
signaling pathways involved in the regulation of MM cell chemotaxis, we therefore analyzed the effect of
various inhibitors targeting intracellular effectors proteins on the CXCL12-mediated RPMI 8226
chemotaxis using flow cytometry and western blot analysis. Using flow cytometry, we observed that the
chemotaxis of RPMI 8226 cell to CXCL12 was completely abrogated by adding AMD (CXCR4
antagonist), PTX (G-protein coupled receptor inhibitor) and U73122 (phospholipase C beta; PLC

inhibitor), moreover, CXCL12-mediated RPMI 8226 chemotaxis was partially inhibited by 1 μM
wortmannin (WM, Class II PI3K inhibitor)), SH5 (AKT inhibitor), Y27632 (Rho-A inhibitor), SN50 (IkB
inhibitor), PD98059 (ERK1/2 MAPK inhibitor) and Na3VO4 (phosphatase inhibitor). These results were
further confirmed by using western blot analysis where we observed that triggering of CXCR4 by
CXCL12 resulted in the activation of PLC
3, PI3K/AKT, RhoA, IB and ERK1/2. In conclusion, our
results revealed that PLC
3, PI3K/AKT, RhoA, IKB and ERK1/2 are crucial effectors for CXCL12-
mediating MM cell chemotaxis.

Malnutrition in children is frequently associated with an
increased incidence of infection. Apoptosis of immune cells in
undernourished organisms may cause an increase in the organism's
susceptibility to diseases related to immune suppression. Lymphocyte
apoptosis was described in malnutrition. The role of factor of apoptosis
signal (fas,CD95) in apoptosis of lymphocyte populations in malnourished
children is still unclear.
Objective: This study investigated apoptosis in T lymphocytes in different
types of malnutrition and the role of Fas in lymphocyte apoptosis and its
relation to clinical and laboratory parameters of malnutrition.
Study design: Sixty-three malnourished infants and children were compared
to 27 healthy controls. Beside thorough history and clinical examination,
laboratory investigations and flow cytometry assessment of T lymphocytes
were done. The viability of T lymphocytes was determined by combination of
fluorescence dye 7-amino actinomycin, CD95 and CD3.
Results: There was significant increase in apoptotic T-cells in the patients
compared to the controls. There was up-regulation of Fas expression in
CD3+ cells. Furthermore CD3+/CD95+ cells were less viable than
CD3+/CD95- cells of the patients and than CD3+/CD95+ cells of the
controls. All the clinical and laboratory parameters of the studied patients
showed no significant correlations with any of the apoptotic indices.
Conclusion: Increased apoptosis in T lymphocytes in malnourished children
may be the cause of the decrease in lymphocyte count in their peripheral
blood. This in turn may be the cause of decreased cell mediated immunity
and the more common occurrence of infection in such patients. Upregulation
of Fas may be the cause of apoptosis in T lymphocytes in these
malnourished children.

Imidacloprid (IC) is a relatively new systemic insecticide related to the tobacco toxin nicotine. The effects of repeated oral administration of IC over 4 weeks on immune response, oxidative stress and hepatotoxicity were assessed. Forty-eight adult male albino rats were divided into two groups of twenty-four animals each. The control group was orally administered distilled water, while the IC-treated group was orally administered 1/100 LD50 (0.21 mg/ kg body weight) of IC insecticide daily. We found a significant increase in the total leukocyte count, total immunoglobulins (Igs) especially IgG. In contrast, significant decreases in phagocytic activity, chemokinesis and chemotaxis were observed in the IC-treated group compared to the control group. Histopathologically, the spleen tissues of the IC-treated rats displayed low numbers of lymphocytes, some of which appeared to be pyknotic. However, both fibroblasts and bundles, such as trabeculae, occurred in greater numbers. Similarly, thymus tissues in the IC-treated group showed lymphocytic depletion with pyknotic nuclei. Additionally, significant increases in the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase (ALP) and malondialdehyde (MDA) were observed in the IC-treated group. Accordingly, in the IC-treated group, heavily congested central vein and blood sinusoids were observed in the liver tissues; pyknotic nuclei were found throughout the hepatic tissue, and leukocyte infiltration was observed. In summary, these results suggest that exposure to 1/100 LD50 of IC induces immunotoxicity, oxidative stress, lipid peroxidation and hepatotoxicity.

Previous studies have shown that heat stress can lead to tissue damage and multiple organ dysfunctions. The present study elucidates the negative effects of heat stress and the possible protective effects of vitamin E or thymoquinone against the physiological and histological consequences of heat stress. Forty male mice were distributed into four groups as follows: group I was a control group that was orally supplemented with distilled water; group II was subjected to heat stress (HS) (at a humidity of 50 to 55% and a temperature of 42°C) for 75 days; group III was subjected to heat stress and was orally supplemented with vitamin E (20 IU/kg body weight/day for 75 days); and group IV was subjected to heat stress and was orally supplemented with thymoquinone (TQ) (5 mg/kg body weight/day for 75 days). We found that the leucocyte count, Hb, and alanine aminotransferase (ALT) were significantly decreased in the HS-treated group. In contrast, the free radical (FR) levels were significantly elevated. Moreover, histopathological and ultrastructural studies of the HS-treated group revealed dilatation of the hepatic sinusoids, interstitial hemorrhage, hepatocytes that were infiltrated with fat droplets in the liver, hemorrhage enlargement of the mitochondria and dilatation of the renal tubules. Notably, supplementation with either TQ or vitamin E completely reversed the biochemical, histopathological and ultrastructural changes that were induced by heat stress yielding levels that were similar to the control values. Taken together, our data revealed the benefits of vitamin E or TQ supplementation as a means to ameliorate the negative effects of heat stress.

Previous studies have shown that dietary supplementation with antioxidants such as vitamin E affects the reproduction parameters in heat stressed males mice Nevertheless, the impact of thymoquinone (TQ) on the reproductive system during head stress is still poorly studied. Therefore, the aim of current study was to investigate changes in the reproductive parameters during heat stress and the impact of vitamin E (positive control) and TQ during this period. Forty male mice were distributed into four groups: group I was a control group that was orally supplemented with distilled water; group 2 was subjected to HS (at a humidity of 50 to 55% and a temperature of 42°C) for 75 days; Group 3 was subjected to HS and orally supplemented with vitamin E (20 IU/kg/day for 75 days) and group 4 was subjected to HS and orally supplemented with TQ (5 mg/kg body weight/day for 75 days). We found that HS significantly increased free radicals (FR) without significant effect on the testosterone level. Additionally, semen analysis of the heat stressed mice revealed a significant decrease in sperm concentration, sperm velocity straight line (SVSL), sperm velocity curved line (SVCL), and sperm velocity average path (SVAP). Moreover, histopathological examination of seminiferous tubules of heat stressed mice presented maturation arrest in the germinal layers. Notably, supplementation with either TQ or vitamin E completely restored the FR levels, semen quality and histopathological changes that were induced by HS. Our data revealed the beneficial impacts of TQ and vitamin E supplementation in improving heat stress-induced complications.

In multiple myeloma (MM), malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. Chemotaxis of malignant plasma cells and stromal cells in the surrounding microenvironment is an essential component of tumour dissemination during progression and metastasis. The mechanisms responsible for the chemotaxis of malignant plasma cells in the bone marrow are still poorly understood. Thus, in the present study, we investigated the mechanisms involved in the chemotaxis of U266 MM cell line. U266 cells strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors, but only migrated toward CXCL12 (the sole ligand for CXCR4). To clarify the signaling pathways involved in the regulation of MM cell chemotaxis, we therefore analyzed the effect of various inhibitors targeting intracellular effector proteins on the CXCL12-mediated chemotaxis of U266 using flow cytometry and Western blot analysis. Using flow cytometry, we observed that the chemotaxis of U266 cell towards CXCL12 was completely abrogated by adding AMD (CXCR4 antagonist), PTX (G-protein coupled receptor inhibitor) and U73122 (Phospholipase C inhibitor). Moreover, CXCL12-mediated U266 chemotaxis was partially inhibited by 1 μM wortmannin (WM, Class II PI3K inhibitor), SH5 (AKT inhibitor), Y27632 (RhoA inhibitor), SN50 (NFκB inhibitor) and PD98059 (ERK1/2 MAPK inhibitor). Similar results were obtained using Western blot analysis where we observed that triggering of CXCR4 by CXCL12 resulted in the activation of PLCβ3, AKT, RhoA, NFκB and ERK1/2. Taken together, our results revealed that PLCβ3, PI3K/AKT, RhoA, NFκB and ERK1/2 are crucial effectors for CXCL12-mediating MM cell chemotaxis.

Impaired wound healing is considered as one of the most serious diabetes-associated complications. Defensins, the anti-microbial peptides, have potent bactericidal activity against a wide spectrum of bacterial and fungal organisms commonly responsible for wound infections. We recently demonstrated that Whey proteins (WPs) enhance immune response during diabetes and have a protective role in some diabetic complications. In the present study, we further investigated the effect of a camel WP on the wound healing process in a streptozotocin (STZ)-induced type I diabetic mouse model. Three groups of mice were used (10 mice in each group): group 1, control non-diabetic mice; group 2, diabetic mice; and group 3, diabetic mice orally supplemented with undenatured WP (100 mg/kg body weight/day for one month through oral gavage). We found that diabetic mice exhibited delayed wound closure characterized by significant reduction in the expression of β-defensin 2, 3 and VEGF; prolonged elevation in free radical levels and obvious reduction in the level of glutathione in the wounded tissue as compared to control mice. Interestingly, supplementation of diabetic mice with WP significantly accelerated the closure and healing of the diabetic wounds. WP significantly restored the expression of β-defensin 2, 3 and VEGF; decreased the level of free radical and enhanced glutathione level in the wounded tissue as compared to diabetic mice. Our data revealed the benefits of WP supplementation in improving the healing and closure of diabetic wounds.

The effects of an acute LD50 dose of Walterennesia aegyptia crude venom was studied in male albino rats over a period of seven days. The following analyses were performed at timed intervals of 1 h, 3 h, 6 h, 12 h, 24 h, 72 h and 7 days: white blood cells (WBC), red blood cells (RBC), Platelets count, hemoglobin content (Hb), hematocrit (Hct) and blood indices [Mean Cell Volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC)]. Serum enzymatic activities include alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyl transferase (γ-GT) and alkaline phosphatase (ALP), with the following metabolites concentrations (glucose, total protein, triglycerides and creatinine). These parameters were found to fluctuate with time, with tendency to regain normal control level within the first 6 h. The 12 to 24 h seems to be crucial for the process of physiological recovery. The process of physiological adaptation and recovery from LD50 venom dose seems to stabilize after one week, leaving the animal alive with several lesions and disturbed physiological profile.

Data have demonstrated that whey protein (WP) enhances the immune system. The aim of this study was
to investigate and compare the effects of WP from three camel breeds on oxidative stress, blood lipid profile and the
cytokine levels. Seventy five male mice were randomly split into five groups. The first served as a control group. The second, the third and the fourth groups were orally administrated the WP from Majaheim, Maghateer and Soffer camel breeds,respectively, at a dose of 100 mg/kg mouse body weight. The fifth group was supplemented with bovine serum albumin(BSA). Results showed similar electrophoretic patterns of the three whey proteins. WP was found to significantly inhibit
the hydroperoxide and the Reactive Oxygen Species (ROS) in leukocytes, liver and skin as well as the blood cholesterol
level in a time dependent manner. A significant enhancement of glutathione was revealed in WP groups. Furthermore, WP
was found to significantly elevate the IL-2 with a significant time dependent enhance of IL-8. On contrast, a significant lowering effect of whey proteins on the pro-inflammatory cytokines, IL-1α, IL-1β, IL-6 and IL-10 was detected. Moreover, a mitogenic activity of WP was observed on the lymphocytes. Non-significant changes were observed in AST, ALT, creatinine and glucose level. These findings suggest that WP significantly improved the levels of the oxidative markers and the immune functions without any difference in the bioactivities of the three studied whey proteins.

ent studies indicate an ectopic upregulation of the human leukocyte antigen G (HLA-G) in tumor cells that may favor their escape from antitumor immune responses. The role of HLA-G in breast cancer has not been defined. Other studies showed that HLA-G transcription may be silenced by epigenetic mechanisms or activated by stress. This work aimed to clarify the expression of HLA-G protein, estimate the possible prognostic role of HLA-G expression and identify if this expression is linked to the DNA index (DI) and S phase fraction (SPF) in breast cancer. HLA-G protein expression and the DNA parameters were studied by flow cytometry and serum secreted HLA-G (sHLA-G) levels were detected by enzyme-linked immunosorbent assay (ELISA) in 45 breast cancer patients and 40 female blood donors as healthy donors. Surface HLA-G was expressed on 40% and the cytoplasmic pattern with no membrane association in 24.4% of the malignant specimens. There was an increased serum sHLA-G level in patients as compared with controls. There were negative correlations between cytoplasmic HLA-G and both DI and SPF and between preoperative sHLA-G and SPF with no relations with patients' clinical outcome. We cannot establish that HLA-G protein can be a useful prognostic marker, but sHLA-G may be used as a tumor marker in breast cancer patients.