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.

BACKGROUND: Placental growth responds to maternal influences. Ramadan is an annual period of day-time fasting during which people in Saudi Arabia, including pregnant women, change their diets and physical activity. Little is known about the effects of this altered lifestyle on placental development. METHODS: We studied the birth records of 7083 babies born over a four-year period to Saudi nationals in Unizah, a small city 350km to the north of Riyadh, the capital city of Saudi Arabia. The records included birth weight, placental weight and gestational age. RESULTS: Mean birth weight was similar to European values but the mean placental weight and ratio of placental weight to birth weight were lower. Among babies who were in the second or third trimester of gestation during Ramadan the mean placental weight and ratio were below those of babies who were not in utero during Ramadan. Among boys the mean placental ratios were 14.4 percent (second trimester) and 14.5 percent (third trimester) compared with 14.9 percent (p=0.001 and 0.002). The corresponding figures for girls were 14.8 and 14.6 percent compared with 15.1 percent (p=0.02 and 0.001). CONCLUSIONS: In Saudi Arabia placentas respond to mothers' limited ability to deliver nutrients to them. Placental growth slows but efficiency is increased so that fetal growth is sustained, albeit with a reduced reserve capacity. The lifestyle changes associated with Ramadan further slow placental growth. Ramadan may influence placental growth through dietary changes other than day-time fasting. Changes in placental growth during Ramadan could be associated with altered fetal programming, and may therefore have long-term implications for the health of the next generation.

In this study, we show that IFNalpha increases the chemotaxis of human B cells to CCL20, CCL21 and CXCL12 in a dose- and time-dependent manner. The effect was maximal with 2000 IU ml(-1) IFNalpha. It peaked at 24 h and decreased thereafter. At 24 h, IFNalpha had increased B-cell chemotaxis to CCL20 by 20 +/- 6.2% (n = 9, P 0.002), to CCL21 by 20 +/- 8.5% (n = 14, P 0.0001) and to CXCL12 by 16.3 +/- 4.2% (n = 12, P 0.003) without changing CCR6, CCR7 or CXCR4 expression. IFNalpha enhanced the migration of memory B cells to CCL20, CCL21 and CXCL12 2.6-fold more strongly than that of naive B cells. The triggering of chemokine receptors by their ligands resulted in the activation of phosphatidylinositide-3 kinase (PI3K)/protein kinase B (PKB), inhibitory NF-kappaB (IkappaBalpha) RhoA and extracellular signal-regulated protein kinase 1/2 (ERK1/2). All these effectors except ERK1/2 are crucial for B-cell chemotaxis. IFNalpha modulated the requirements for B-cell chemotaxis, which became dependent on ERK1/2, more dependent on PI3K, RhoA and nuclear factor-kappaB but less dependent on Gbetagamma and phospholipase C activation. IFNalpha also decreased ligand-induced chemokine receptor internalization in a manner dependent on PI3K/AKT and RhoA but not on IkappaBalpha and ERK1/2. Our data characterize chemokine receptor signaling in human B cells and clarify the relevance of downstream pathways in B-cell chemotaxis and chemokine receptor internalization. They also suggest that non-class I PI3K are involved in B-cell chemotaxis.

We analyzed the modulation of human B cell chemotaxis by the gp120 proteins of various HIV-1 strains. X4 and X4/R5 gp120 inhibited B cell chemotaxis toward CXCL12, CCL20, and CCL21 by 40-50%, whereas R5 gp120 decreased inhibition by 20%. This gp120-induced inhibition was strictly dependent on CXCR4 or CCR5 and lipid rafts but not on CD4 or V(H)3-expressing BCR. Inhibition did not impair the expression or ligand-induced internalization of CCR6 and CCR7. Our data suggest that gp120/CXCR4 and gp120/CCR5 interactions lead to the cross-desensitization of CCR6 and CCR7 because gp120 does not bind CCR6 and CCR7. Unlike CXCL12, gp120 did not induce the activation of phospholipase Cbeta3 and PI3K downstream from CXCR4, whereas p38 MAPK activation was observed. Similar results were obtained if gp120-treated cells were triggered by CCL21 and CCL20. Our results are consistent with a blockade restricted to signaling pathways using phosphatidylinositol-4,5-bisphosphate as a substrate. X4 and X4/R5 gp120 induced the cleavage of CD62 ligand by a mechanism dependent on matrix metalloproteinase 1 and 3, CD4, CXCR4, Galpha(i), and p38 MAPK, whereas R5 gp120 did not. X4 and X4/R5 gp120 also induced the relocalization of cytoplasmic CD95 to the membrane and a 23% increase in CD95-mediated apoptosis. No such effects were observed with R5 gp120. The gp120-induced decrease in B cell chemotaxis and CD62 ligand expression, and increase in CD95-mediated B cell apoptosis probably have major deleterious effects on B cell responsiveness during HIV infection and in vaccination trials.

B-cell-activating factor of the TNF family, (BAFF), and a proliferation-inducing ligand (APRIL) regulate B-lymphocyte survival and activation. We report that BAFF, but not APRIL, increased the chemotactic response of primary human B cells to CCL21, CXCL12, and CXCL13. The BAFF-induced increase in B-cell chemotaxis was totally abolished by blockade of BAFF-R and was strongly dependent on the activation of PI3K/AKT, NF-kappaB, and p38MAPK pathways. BAFF had similar effects on the chemotaxis of naive and memory B cells in response to CCL21 but increased more strongly that of memory B cells to CXCL13 than that of naive B cells. Our findings indicate a previously unreported role for the BAFF/BAFF-R pair in mature B-cell chemotaxis. The synergy between CXCL13 and BAFF produced by stromal cells and follicular dendritic cells may have important implications for B-cell homeostasis, the development of normal B-cell areas, and for the formation of germinal center-like follicles that may be observed in various autoimmune diseases.

The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-alpha) antiviral therapy achieves the highest rate of success when IFN-alpha is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-gamma- and IL-2-producing and CD107a(+)) virus-specific CD8(+) T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8(+) T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-alpha rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.

Although IFN-alpha was reported to promote the survival of peripheral B-lymphocytes via the PI3-kinase-Akt pathway, the triggered signalling pathways involved in the protection of B cell from apoptosis need to be clarified. Using flow cytometry and western blot analysis, we have found that type 1 IFNs (IFN-alpha/beta) protect human B cells in culture from spontaneous apoptosis and from apoptosis mediated by anti-CD95 agonist, in a dose- and time-dependant manner. IFN-alpha/beta-mediated anti-apoptotic effect on human B cells was totally abrogated by blockade of IFNR1 chain. Our data indicate that PI3Kdelta, Rho-A, NFkappaB and Bcl-2/Bcl(XL) are active downstream of IFN receptors and are the major effectors of IFN-alpha/beta-rescued B cells from apoptosis. Furthermore, immunohistochemical results show marked reduction in numbers of CD20 positive B cell in both spleen and Peyer's patches from mice treated with anti-IFNR1 blocking antibody compared with control group. Moreover, ultrastructural observations of these organs show an obvious increase in apoptotic cells from mice treated with anti-IFNR1 blocking antibody. Our results provide more details about the triggered signalling pathways and the phosphorylation cascade which are involved in the protection of B cell from apoptosis after treatment with IFN-alpha/beta. Copyright 2010 Elsevier Inc. All rights reserved.