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Arsenic (As) readily crosses the placenta and exposure of the fetus may cause adverse consequences later in life, including immunomodulation. In the current study, the question was asked how the immune repertoire might respond in postnatal life when there is no further As exposure. Here, pregnant mice (Balb/c [H-2d]) were exposed to arsenic trioxide (As2O3) through their drinking water from time of conception until parturition. Their offspring, 4-week-old mice who had not been exposed again to As, were used for functional analyses of innate, humoral and cellular immunity. Compared to cells from non-As-exposed dam offspring, isolated peritoneal macro-phages (Mϕ) displayed no differences in T-cell stimulating ability. Levels of circulating IgG2a but not IgG1 were decreased in As-exposed dam offspring as compared to control offspring counterparts. Mixed-leukocyte reactions (MLR) indicated that CD4+ T-cells from the prenatal As-exposed mice were significantly less responsive to allogenic stimulation as evidenced by decreases in interferon (IFN)-γ and IL-2 production and in expression of CD44 and CD69 (but not CD25) activation markers. Interestingly, the Mϕ from the prenatal As-exposed mice were capable of stimulating normal allogenic T-cells, indicating that T-cells from these mice were refractory to allogenic signals. There was also a significant decrease in absolute numbers of splenic CD4+ and CD8+ T-cells due to prenatal As exposure (as compared to control). Lastly, the impaired immune function of the prenatal As-exposed mice was correlated with a very strong susceptibility to Escherichia coli infection. Taken together, the data from this study clearly show that in utero As exposure may continue to perpetuate a dampening effect on the immune repertoire of offspring, even into the early stages of postnatal life. [ABSTRACT FROM AUTHOR]

The gut microbiome derived short chain fatty acids perform multitude of functions to maintain gut homeostasis. Here we studied how butyrate stymie enteric bacterial invasion in cell using a simplistic binary model. The surface of the mammalian cells is enriched with microdomains rich in cholesterol that are known as rafts and act as entry points for pathogens. We showed that sodium butyrate treated RAW264.7 cells displayed reduced membrane cholesterol and less cholera-toxin B binding coupled with increased membrane fluidity compared to untreated cells indicating that reduced membrane cholesterol caused disruption of lipid rafts. The implication of such cellular biophysical changes on the invasion of enteric pathogenic bacteria was assessed. Our study showed, in comparison to untreated cells, butyrate-treated cells significantly reduced the invasion of Shigella and Salmonella, and these effects were found to be reversed by liposomal cholesterol treatment, increasing the likelihood that the rafts' function against bacterial invasion. The credence of ex vivo studies found to be in concordance in butyrate fed mouse model as evident from the significant drift towards a protective phenotype against virulent enteric pathogen invasion as compared to untreated mice. To produce a cytokine balance towards anti-inflammation, butyrate-treated mice produced more of the gut tissue anti-inflammatory cytokine IL-10 and less of the pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ. In histological studies of Shigella infected gut revealed a startling observation where number of neutrophils infiltration was noted which was correlated with the pathology and was essentially reversed by butyrate treatment. Our results ratchet up a new dimension of our understanding how butyrate imparts resistance to pathogen invasion in the gut. [ABSTRACT FROM AUTHOR]

This discourse attempts to capture a few important dimensions of gut physiology like microbial homeostasis, short chain fatty acid (SCFA) production, occludin expression, and gut permeability in post-natal life of mice those received arsenic only during pre-natal life. Adult Balb/c mice were fed with 4 ppm arsenic trioxide in drinking water during breeding and gestation. After the birth of the pups, the arsenic water was withdrawn and replaced with clean drinking water. The pups were allowed to grow for 28 days (pAs-mice) and age matched Balb/c mice which were never exposed to arsenic served as control The pAs-mice showed a striking reduction in Firmicutes to Bacteroidetes (F/B) ratio coupled with a decrease in tight junction protein, occludin resulting in an increase in gut permeability, increased infiltration of inflammatory cells in the colon and decrease in common SCFAs in which butyrate reduction was quite prominent in fecal samples as compared to normal control. The above phenotypes of pAs-mice were mostly reversed by supplementing 5% sodium butyrate (w/w) with food from 21st to 28th day. The ability of butyrate in enhancing occludin expression, in particular, was dissected further. As miR122 causes degradation of Occludin mRNA, we transiently overexpressed miR122 by injecting appropriate plasmids and showed reversal of butyrate effects in pAs-mice. Thus, pre-natal arsenic exposure orchestrates variety of effects by decreasing butyrate in pAs-mice leading to increased permeability due to reduced occludin expression. Our research adds a new dimension to our understanding that pre-natal arsenic exposure imprints in post-natal life while there was no further arsenic exposure. • Prenatal Arsenic exposure decreases prevalence of butyrate producing bacteria and butyrate production in the gut. • Lack of butyrate production in the gut is responsible for increased permeability and decreased occludin expression. • Oral supplementation with butyrate reverses the prenatal arsenic induced changes in the gut. • Butyrate increases Occludin gene expression by downregulating miR122 in the gut. [ABSTRACT FROM AUTHOR]

The breakout of the pandemic COVID-19 has affected numerous countries and territories worldwide. As COVID-19 specific medicines yet to be invented, at present the treatment is case specific, hence identification and evaluation of different prevalent treatment options based on various criteria and attributes are very important not only from the point of view of present pandemic but also for futuristic pandemic preparedness. The present study focuses on identifying, evaluation and ranking of treatment options using Multi Criteria Decision Making (MCDM). In this regard, the existing literature, doctors and scientist were interviewed to know the current treatment options in vogue and the scale of their importance with respect to the criteria. The criteria taken are side effect, regime cost, treatment duration, plasma stability, plasma turnover, time of suppression, ease of application, drug-drug interaction, compliance, fever, pneumonia, intensive care, organ failure, macrophage activation syndrome, hemophagocytic syndrome, pregnancy, kidney problem, age. This study extended Hesitant Fuzzy Set (HFS) to Generalized Hesitant Fuzzy Sets (GHFS). Generalized Hesitant Pentagonal Fuzzy Number (GHPFN) is developed. The properties of GHPFN are demonstrated. Two types of GHPFN has been described. The GHPFN (2nd type) along with MCDM tool Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) has been applied to rank the treatment options. The result of the study ranked 'Hydroxychloroquine' as the first alternative followed by, 'Plasma Exchange', 'Tocilizumab', 'Remdesivir' and 'Favipravir'. To check the robustness and steadiness of the proposed methodology, comparative analysis and sensitivity analysis has been conducted. [ABSTRACT FROM AUTHOR]