Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase, which metabolizes arginine to nitric oxide (NO) and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline–NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and anti-inflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th)1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions, and cancer.

Background Microglia are the resident immune cells in the brain where they play essential roles in the development and maintenance of physiological functions of this organ. Aberrant activation of microglia is speculated to be involved in the pathogenesis of a variety of neurological disorders, including alcohol use disorders. Repeated binge ethanol (EtOH) consumption can have a profound impact on the function and integrity of the brain resulting in changes in behaviors such as withdrawal and reward. However, the microglial molecular and cellular pathways associated with EtOH binge consumption remain poorly understood. Method In this study, adult C57BL/6J male and female mice were subjected daily to a gelatin‐based drinking‐in‐the‐dark voluntary EtOH consumption paradigm (3 h/d for 4 months) to characterize EtOH consumption and withdrawal‐associated and anxiety‐like behaviors. Brain microglia were isolated at the end and analyzed for protein expression profile changes using unbiased mass spectrometry‐based proteomic analysis. Results Both male and female mice consistently consumed binge quantities of EtOH daily, resulting in blood EtOH levels > 80 mg/dl measured at the end of the 3‐hour daily consumption period. Although female mice consumed a significantly greater amount of EtOH than male mice, EtOH withdrawal‐associated anxiety‐like behaviors measured by marble‐burying, light‐dark box, and elevated plus maze tests were predominantly observed in male mice. Proteomic analysis of microglia isolated from the brains of animals at the end of the 4‐month binge EtOH consumption identified 117 and 37 proteins that were significantly up‐ or downregulated in EtOH‐exposed male and female mice, respectively, compared to their pair‐fed controls. Protein expression profile‐based pathway analysis identified several cellular pathways that may underlie the sex‐specific and EtOH withdrawal‐associated behavioral abnormalities. Conclusion Taken together, our findings revealed sex‐specific changes in EtOH withdrawal‐associated behaviors and signaling pathways in the mouse brain microglia and may help advance our understanding of the molecular, cellular, and behavioral changes related to human binge EtOH consumption.

Background:Clerodendrum viscosum is commonly found in India and Bangladesh. Previously, various parts of this plant were reported for treatment of different types of diseases and there was no report on GC-Ms analysis.Objective:To analyze and characterize the phytochemical compounds of methanol extract of Clerodendrum viscosum using GC-MS.Materials and Methods:The preliminary phytochemical screening of methanol extract was carried out according to standard procedures described in WHO guidelines. Various bioactive compounds of the extract were determined by GC-MS technique.Results:The presence of steroids, triterpenoids, alkaloids, saponins, flavonoids, tannins and carbohydrate was found on phytochemical screening of methanol extract of the leaves. The GC-MS analysis showed 16 peaks of different phytoconstituents namely acetamide, N, N-carbonylbis-, 4-Pyranone,2,3-dihydro-, alpha-D-Galactofuranoside, methyl 2,3,5,6-tetra-O-methyl-, Glycerin, Xylitol, N, N-Dimethylglycine, 4H-Pyran-4-one,2,3-dihydro-3, 5-dihydroxy-6-methyl-, Benzofuran,2,3-dihydro-, 5-Hydroxymethylfurfural, 2(1H)Pyrimidinone,1-methyl-, 2,4-Dihydroxy-5,6-dimethylpyrimidine, 3-Deoxy-d-mannoic lactone, 1,3-Methylene-d-arabitol, Orcinol, n-Hexadecanoic acid and Phenol,4,4’-(1-methyl ethylidene) bis etc.Conclusion:The bioactive compounds present in the methanol extract of Clerodendrum viscosum suggest the application of this extract for the treatment of various diseases by the aborigine tribes.

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Alcohol overconsumption is a major cause of preventable mental disorders and death in the United States and around the world. The pathogenesis of alcohol dependence, abuse, and toxicity to the central nervous system remains incompletely understood. Cell culture-based models have been highly valuable in studying the molecular and cellular mechanisms underlying the contribution of individual CNS cell types to ethanol’s effects on the brain. However, conventional cell culture model systems carry the inherent disadvantage of rapid loss of ethanol due to evaporation following a bolus addition of ethanol at the start of the treatment. In this study, we have established a multi-well cell culture plate-based ethanol evaporation compensation model that utilizes the inter-well space as a reservoir to compensate for the evaporative loss of ethanol in the cell treatment wells. Following a single bolus addition at the start, ethanol concentration in the treatment wells rapidly decreased over time. Through compensation using the multi-well plate platform, maintenance of ethanol concentrations ranging from 10–100 mM was achieved for up to 72 h in a cell-free system. Furthermore, greater effects on ethanol-induced decrease in the viability of human dopaminergic neuronal cells were observed with than without evaporation compensation. Our method effectively compensates for the evaporative loss of ethanol typically observed in the traditional treatment method and provides a simple and economic in vitro model system for ethanol treatment over an extended timeframe where maintenance of a relatively constant concentration of ethanol is desired.