Development of Peptides to Target Antigen Presenting Cells for Controlling the Immune Response in Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human disease multiple sclerosis (MS). In EAE and MS, the immune system recognizes proteins of the myelin sheath as antigenic, and an inflammatory reaction is initiated within the central nervous system (CNS), leading to demyelination of the axons. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. The objective of this project is to develop peptides that target myelin-specific antigen presenting cells (APC) in order to modulate the immune response towards the myelin sheath. Bifunctional peptide inhibitors (BPI) are molecules composed of an antigenic peptide and an adhesion peptide that are designed to target the major histocompatibility class-II molecule and adhesion receptors, respectively, on the surface of APC. The simultaneous binding to both receptors on the APC is proposed to hinder the delivery of activation signals to T cells and, therefore, attenuate the inflammatory T cell response. In this study, PLP-BPI, a well-studied BPI molecule, was tested as a peptide vaccine in preventing the onset of EAE as well as for its role in providing protection against blood-brain barrier breakdown during disease. Next, a novel BPI molecule known as PLP-B7AP, which targets costimulatory molecules, was developed and tested for the first time in suppressing EAE. Finally, to provide protection against the diverse pool of antigenic proteins of the myelin sheath, BPI molecules targeting other myelin antigens as well as a multivalent BPI molecule were developed. These novel peptides have consistently demonstrated a shift towards an immuno-tolerant state accompanied by significant suppression of EAE

Crack-entry invasion of wheat roots by Azospirillumbrasilensevia chemical-enzyme treatment: a way facilitating para-nodule formation and forced association for proper crop yield

The induction of nodule-like structures referred to para-nodules was assessed due to 2,4-D, IAA and the enzyme mixture of cellulase and pectolyase in presence of PEG treatment of wheat cultivars inoculated with Azospirillumbrasilense. In gnotobiotic model experiment; 9-18 and 6-19 para-nodule plant-1 were produced due to 2,4 D and IAA treatments respectively. Less than 7 para-nodules plant-1were attributed to Azospirllum alone, numbers increased to 26 when the diazotroph was introduced in combination with p-nodule-inducing agents. The cell wall-degrading enzyme mixture with PEG facilitated the crack-entry invasion of the diazotroph in population of > 5x105cfu g-1 root. High rates of C2H2 reductions of > 200 nmoles C2H4 g-1 root hr-1 were estimated for the enzyme mixture-PEG treated plants. The average glutamine synthetase activities of plant leaves were the highest (57.1-86.3 µ mol g-1Fw hr-1) for IAA-Azospirillum treatment. Wheat plants successfully paranodulated in pot experiment when pre-treated with IAA and enzyme mixture and inoculated with Azospirillum in presence of 50 % of recommended N, plant biomass and N yields increased as well. The highest levels of chlorophyll a (2.10 µg g-1Dw), chlorophyll b (2.28) and carotenoids (1.59) were estimated for inoculated plants pre-treated with IAA plus enzyme mixture. In the field trial, as high as > 2.0 kg plot-1 total biological yield was produced by plants initially primed by soaking in water. The superior grain yields of 441.7-571.4 g plot-1 were attributed to Azospirillum inoculation together with IAA and enzyme mixture for 50 % N-supplied plants. Seed priming somewhat raised the grain yield

Suppression of MOG- and PLP-Induced Experimental Autoimmune Encephalomyelitis Using a Novel Multivalent Bifunctional Peptide Inhibitor

Previously, bifunctional peptide inhibitors (BPI) with a single antigenic peptide have been shown to suppress experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner. In this study, a multivalent BPI (MVBMOG/PLP) with two antigenic peptides derived from myelin oligodendrocyte glycoprotein (MOG38-50) and myelin proteolipid protein (PLP139-151) was evaluated in suppressing MOG38-50- and PLP139-151-induced EAE. MVBMOG/PLP significantly suppressed both models of EAE even when there was some evidence of epitope spreading in the MOG38-50-induced EAE model. In addition, MVBMOG/PLP was found to be more effective than PLP-BPI and MOG-BPI in suppressing MOG38-50-induced EAE. Thus, the development of MVB molecules with broader antigenic targets can lead to suppression of epitope spreading in EAE

Credit of peanut to subsequent wheat under desert farming conditions in presence of diazotrophs and nitrogen fertilizers

Rotation with leguminous crops to break non-legume monocultures has been established to benefit the latter. The lacking information on this cultivation system in stressed environments encouraged the implementation of two field trials in two different locations of Ismailia desert soils. The experimental design included the cultivation of wheat subsequent to peanut in presence of diazotroph inoculation and N fertilization. Bradyrhizobial inoculation of the legume in combination with 50 kg N acre-1 resulted in the highest total biological yields of 4.24 and 5.01 kg plot-1 at the experimental sites 1 and 2, respective seed yields of 1.46 and 1.61 kg pot-1 were recorded. In case of the cereal crop, the measured acetylene reducing activities in soils of associative diazotroph-inoculated plants together with 50 kg N acre-1 were the highest being 515.8-886.2 and 616.7-1066.2 nmoles C2H4 g-1 h-1 at locations 1 and 2 respectively. The enzymatic activity of fallow-cultivated wheat generally represented ca. 95 % of that in subsequent to peanut. Irrespective of inoculation and N fertilization, the wheat biomass yield increases in residual effect-field over the fallow one were 6.4-35.1 % and 4.6-38.5 % at experimental sites 1 and 2 respectively. Increase percentages of 3.1-26.6 and 6.9-44.7 were scored as well for grain yield. The beneficial residual effect of the legume to the succeeding cereal was also extended to protein yields, increases of 4.0-14.2 % and 4.5-7.6 % were estimated for grain protein as well as 8.3-24.1 % and 8.1-35.3 % for straw protein yield. The findings of this study proved that the positively yield turnover of a legume is extended to the subsequent non-legume. Besides, the beneficial residual effects of legumes toward rotated non legumes could be magnified by diazotroph inoculation together with adequate N supply particularly in stressed environments represented, in the present study, by Ismailia sandy soil

Vitamin D and inflammation in the prevention of type 2 diabetes: public health relevance

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce the disease risk and burden at the population level, preventative strategies should be developed with minimal cost and effort and with no side-effects. Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D may represent a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. This review examines current knowledge linking T2DM to chronic low-grade inflammation and the role of vitamin D in modulating this relationship. The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to health care and public health practices

Protective effect of propolis on manganese chloride neurotoxicity of olfactory bulb in adult male albino rat

Background: Manganese (Mn) is widely used for industrial purposes and exposure to high levels of Mn may cause an irreversible brain disease. Propolis is a natural plant product; it acts as a powerful reactive oxygen species scavenger and improves the neurodegeneration process. Materials and methods: In this study 40 adult male albino rats were divided randomly into four groups 10 rats each: group I (control group), group II manganese chloride (MnCl2) received 10 mg/kg/day/orally for 4 weeks by intra-gastric tube, group III (propolis group) received 50 mg/kg/day/orally for 4 weeks by intra-gastric tube, and group IV (MnCl2 + propolis group) received the same doses with the same duration and route as in groups II and III. Rats were sacrificed after 24 h of last dose. The olfactory bulbs removed, the right bulb cut to be processed for haematoxylin and eosin, immunohistochemical staining and the left cut for electron microscopic studies. Results: Results revealed that rat olfactory bulb from MnCl2 group showed darkly stained mitral cells with dark pyknotic nuclei, some show pericellular spaces and vacuolation, dark apoptotic cells in granular cells, neuropil vacuolation and pyknotic astrocyte. Electron microscopic examination showed abnormal granular cell with irregular damaged nuclear membrane, rupture of myelin fibre. Mitral nerve cell with destructed nucleus, many cytoplasmic vacuoles, swollen rough endoplasmic reticulum, vacuolated mitochondria and neuropil were observed. Manganese chloride + propolis group showed improvement compared to MnCl2 group. Conclusions: It was concluded that propolis can ameliorate the toxic changes of manganese chloride on rat olfactory bulb

Risk Factors for Maternal Vitamin D Deficiency within the United Arab Emirates

Introduction: Vitamin D deficiency during pregnancy is a public health problem and it has been associated with negative pregnancy outcomes for both mothers and infants. Aim: To estimate the prevalence of vitamin D deficiency in pregnant women in the United Arab Emirates (UAE) and to identify the contribution of risk factors to the 25(OH)D levels. Methods: It is a cross-sectional study in which vitamin D levels of 1088 adult pregnant women were assessed. Information on vitamin D intake was available in a sub-sample of 266 women. Results: The mean serum 25(OH)D was 26.2 nmol/L (95% CI 25.2-27.1 range 5-129.1 nmol/L) with 69% of women being vitamin D deficient (<30 nmol/L). In the bivariate analysis, showed that no predictors could have been indicated as no values exceeded significance (p<0.2). Stepwise multiple linear regression analysis could not be applied to identify predictors of vitamin D levels as no values exceeded p=0.2. Conclusion: Due to the high prevalence of vitamin deficiency in UAE, there is an urge for interventions focusing on supplementation, fortification and diet diversity for preventing health consequences during a critical period of development