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Background: Ozanimod (RPC1063) is an immunomodulator that has been recently approved by the FDA (2020) for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is a selective agonist of the sphingosine-1-phophate receptors 1 and 5, expressed on naïve and central memory T and B cells, as well as natural killer (NK) cells, and is involved in lymphocyte trafficking. Oral administration of ozanimod was reported to result in rapid and reversible reduction in circulating lymphocytes in multiple sclerosis (MS) patients, however, only minimal effect on NK cells was observed. In this study, we sought to investigate the effect of ozanimod on NK cells and assess whether they play any role in ozanimod-induced remission in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Methods: Active EAE induction was done in C57BL/6 female mice, followed by daily oral treatment with ozanimod (0.6mg/kg) starting at disease onset (score 1). Flow cytometry of blood and CNS was performed 24 hours after the last oral dose of ozanimod treatment in diseased mice. Histological analysis of lumbar spinal cord was performed for evaluating the level of inflammation and demyelination. Depletion of peripheral NK cells was done using anti-NK1.1 mouse antibody (mAb) at day 5 post-EAE induction. Results: Ozanimod was effective in reducing the clinical severity of EAE and reducing the percentage of autoreactive CD4+ and CD8+ T cells along with significant inhibition of lymphocyte infiltration into the spinal cord, accompanied by reversed demyelination. Furthermore, ozanimod treatment resulted in a significant increase in the frequency of total NK cells in the blood and CNS along with upregulation of the activating receptor NKG2D on CD27low/- NK cell subset in the CNS. The effectiveness of ozanimod treatment in inhibiting the progression of the disease was reduced when NK cells were depleted using antiNK1.1 mAb Conclusion: The current study demonstrated that ozanimod treatment significantly improved clinical symptoms in EAE mice. Ozanimod and antiNK1.1 mAb appear to function in opposition to one another. Collectively, our data suggest that ozanimod-mediated remission is associated with an increased percentage of total NK cells and CD27low/- NK cells expressing the activating receptor, NKG2D in the CNS. [ABSTRACT FROM AUTHOR]

The role of vitamin C on diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin C on some of the metabolic parameters of diabetic rats. Diabetes was induced by intraperitoneal injection of STZ (60 mg [kg.sup.-1] body weight at 12 weeks of age). Vitamin C (10, 50, 100 mg [kg.sup.-1] body weight) was administered orally for a period of four weeks to normal and diabetic male Wistar rats. In some experiments vitamin C was given either before or after the induction of diabetes mellitus. Glucose tolerance test (GTT) was performed on fasted normal, diabetic and vitamin C-treated rats at the end of the experimental period. Blood sugar level and weight were also recorded on a weekly basis for each rat in different groups. Vitamin C significantly (p Key words: ROS, vitamin C, antioxidants, diabetes, glucose, INTRODUCTION Diabetes mellitus (DM) is currently taking its place as one of the main threats to human health in the 21st century. In the past two decades the number of [...]

Abstract Background A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption) in mice treated with concanavalin A (Con A). This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. Methods C57Bl/6 and C57Bl/6 IFN-γ−/− mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ) and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. Results In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pp=0.005) was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3+NKT+ cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ−/− mice treated with ConA. Conclusions Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

Abstract: Toll like receptors are primary sensors of both innate and adaptive immune systems. They activate APCs and influence T-cell function in inflammatory autoimmune response. Studies have shown that TLR manipulation may lead to either tolerance or trigger autoimmunity. Using diabetogenic and subdiabetogenic multiple low doses of streptozotocin, we demonstrate here that Pam3 CYS-CK4 a TLR-2 agonist, enhances and promotes diabetes in C57BL/6 male mice following increased apoptosis of β islet cells. FACS analysis of isolated pancreatic lymph node cells revealed significant increased number of macrophages, dendritic cells, CD4+ TNF-α+, CD4+ IFN-γ+ and most significantly, CD4+ IL-17+ and reduced number of CD25+Fox p3+ T cells after Pam3CSK4 treatment. Genetic deletion of IFN-γ prevents whereas deletion of IL-17 reduced severity of Pam3CSK4-induced enhancement of diabetes. TLR-2 agonist-enhanced diabetogenesis is also influenced by enhanced influx of antigen presenting cells and suppression of regulatory T cell activity. [Copyright &y& Elsevier]

This article reviews the patents showing the use of antimicrobial agents in processing plants to eliminate the growth of the microorganism that affects on the quality and safety of the end products. Several materials have unique antimicrobial effects, especially towards biofilms in the processing equipments. The selection of a proper antimicrobial agent is essential to obtain the best results in preserving foods. The antimicrobial agent must not be toxic, and many factors need to be considered in choosing the right antimicrobial agent.

Carbon monoxide (CO) poisoning is rare in the Arabian Peninsula and occurs almost exclusively during the winter months. Knowledge and perception of the hazards of carbon monoxide is limited. Migrant workers from warm climates appear particularly at risk. We investigated 46 cases of carbon monoxide poisoning presenting at emergency departments from 2007-2009 of the two main hospitals in Al Ain city, United Arab Emirates. Interviews, hospital records, and administered questionnaires were used to collect the data. Among the 46 cases investigated, 24 (52%) were males. Foreign nationals compromised 80% of the cases and the incidence was 3.1 cases per 100,000 residents per year. Burning charcoal in poorly ventilated residences was the predominant source of the carbon monoxide poisoning. Almost all cases (98%) were admitted during the winter months, most in the early morning hours. Carboxyhaemoglobin (COHb) was significantly increased in cases with loss of consciousness and depressed consciousness. There were no reported fatalities.

Diabetes mellitus (DM) is recognized as one of the leading causes of morbidity and mortality in the world. About 5-6% of the world population suffers from this disease and the number of people diagnosed with diabetes is rapidly increasing. Diabetes has been demonstrated to be associated with oxidative stress and hyperglycemia, one of the most important indicators of oxidative stress. The endogenous mechanisms of enzymes and antioxidants are able to destroy the reactive species and create a balance between antioxidant and free radicals. In diabetes, the oxidative stress is increased because of the deficiency in the antioxidant defense. The intake of antioxidants, such as vitamin C, may reduce the oxidative stress associated with diabetes and hence help to restore the antioxidant defense system. The aim of this article was to investigate the effect of different doses of vitamin C on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Biochemical analysis was used to study the effect of this vitamin on the biochemical parameters of normal and diabetic rats. Liver and kidney enzymes were elevated after the onset of diabetes. Moderate doses of vitamin C significantly (P < 0.0008) reduced plasma gamma-glutamyl level in diabetic rats. Moreover, vitamin C significantly (P < 0.01) reduced the blood urea nitrogen level of diabetic rats. The plasma level of electrolytes, such as calcium and sodium, also changed significantly (P < 0.00001) after oral administration of vitamin C. Antioxidants, such as vitamin C, may ameliorate the biochemical parameters of diabetic rats.