Food Drug and Chemical Toxicology

Translation is the process of translating the sequence of a messenger RNA (mRNA) molecule to a sequence of amino acids during protein synthesis. The genetic code describes the relationship between the sequence of base pairs in a gene and the corresponding amino acid sequence that it encodes.
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Epilepsy is a common chronic central nervous system disorder characterized by repeated malicious seizures. Current medications acceptable by medical practitioners till date mostly suppresses the seizures and has symptomatic relief, but no effect on epileptogenesis. In the present work, we have attempted to provide the scientific base to use the bee venom therapy (Apitherapy) which was practiced throughout ancient Egyptian, Greek and Chinese civilization to treat epilepsy. Our computational studies and molecular dynamics simulation results indicate that interaction between S100B (calcium binding protein) and melittin (a venom peptide from bee), resulted in the structural distortion and inaccessibility of calcium binding domain of S100B protein, which is required to maintain ionic imbalance due to over expressed S100B in disease conditions.

The availability of arsenic in ground water and potable water accounts many toxic effects on human health because of its high toxicity level; it has become a global concern. Previously to decrease As (III) concentration in water various removal methods were explored. In the present study baker yeast Saccharomyces cerevisiae, used as a biosorbate to remediate the Arsenic (III) in the ground water, its capability was examined to sequester the metal ions from the arsenic contaminated water. Initially yeast was grown in YEPD medium and synthetic solution of As (III) was prepared in 3 different conc. 0.2 mg/l, 0.3 mg/l and 0.4 mg/l respectively. Systematic batch kinetic experiments were conducted with various process parameters such as agitation period, pH, and temperature; all the parameters were studied and found that Saccharomyces cerevisiae had very fine competence towards arsenic removal from the contaminated water under optimized condition of agitation period 120 hours, temperature 55ºC and pH 6 were maintained. Removal of As (III) from supernatant was analyzed using the Atomic Absorption Spectrophotometer. It has been found that the percentage removal of Arsenic species (III) increases with decrease in YPD media and Saccharomyces cerevisiae removed 82.2%, 87.8% and 90.46% with respect to different concentration of synthetic solution of As (III) and it is highly effective method for the As (III) removal from the contaminated water.

Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8? T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8? T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.

Metal oxide and carbon-based nanoparticles (NP) have a wide range of application in various fields, including paint, electroluminescent, pharmaceutical, and other industries. In the last decade, there is an exceeding demand of the applications using these particles in biomedical sciences such as in drug delivery system whereas these materials are also used widely in the environmental applications. Due to their extensive applications, these materials are the class of highest global annual production. The information of the potentially harmful effect of these nanoparticles lags behind their increased use in consumer products and therefore, the safety data on various nanoparticles applicable for risk assessment is urgently needed. The availability of less information of toxicity and harmful effects on the human biological system of these particles, there is a need to understand the toxicity of metal oxides and carbon-based nanoparticles. In the present study, we elucidate the toxic impact of the metal oxide and carbon-based nanoparticles on p53 DNA binding domain protein using molecular docking approach. Furthermore, we also explore the binding phenomenon between the p53 protein and nanoparticles (metal oxide and carbon-based NP) using the same molecular docking approach. The study illustrates that metal oxide based nanomaterial has a high binding affinity toward the DNA binding domain of p53 protein as compared to carbon-based nanoparticles, this happens because the metal oxide nanoparticles formed hydrogen and metal acceptor bonds whereas in the case of carbon-based nanoparticles only van der Waal interactions were identified in the molecular interaction. Due to the binding of these nanoparticles, DNA is unable to interact with binding domain site which may lead to deactivation of the tumor suppressing nature of the p53 protein.

Oxidative stress is an important factor in the pathogenesis of asthma. Furthermore, antioxidants like GST are reduced in asthma patients. In the present study, the therapeutic effects of exogenous GST and mGST were evaluated in a mice model. GST mutated at residues 21/27 has reduced IgE binding with similar enzyme activity as that of GST. To evaluate the therapeutic effects of GST, BALB/c mice were immunized and challenged with ovalbumin. Mice were given GST, mGST, and α-lipoic acid by inhalation and sacrificed on Day 31 to evaluate inflammation and oxidative stress. Mice treated with mGST showed significantly reduced total cell count (P b 0.01) and eosinophils (P b 0.01) in BALF compared to GST-or PBS-treated groups. The lung inflammation score was lowest for the mGST-treated group along with reduced IL-4 (P b 0.01) and OVA-specific IgE than other groups. Oxidative stress as per the lipid peroxidation level in BALF of mGST-treated mice was reduced significantly in comparison to PBS-or GST-treated mice. In conclusion, inhalation of mGST reduced airway inflammation in mice. Mutated GST with reduced allergenicity has better therapeutic potential and can be explored as an adjunct therapy in asthma.

Significance The prevalence of food allergy is rising at an alarming rate; the US Centers for Disease Control and Prevention documented an 18% increase among children in the United States between 1997 and 2007. Twenty-first century environmental interventions are implicated by this dramatic generational increase. In this report we examine how alterations in the trillions of commensal bacteria that normally populate the gastrointestinal tract influence allergic responses to food. We identify a bacterial community that protects against sensitization and describe the mechanism by which these bacteria regulate epithelial permeability to food allergens. Our data support the development of novel adjunctive probiotic therapies to potentiate the induction of tolerance to dietary allergens.

Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in te...

The diversity and basic functional attributes of the gut microbiome of healthy Indians is not well understood. This study investigated the gut microbiome of three Indian communities: individuals residing in rural and urban (n = 49) sea level Ballabhgarh areas and in rural high altitude areas of Leh, Ladakh in North India (n = 35). Our study revealed that the gut microbiome of Indian communities is dominated by Firmicutes followed by Bacteroidetes, Actinobateria and Proteobacteria. Although, 54 core bacterial genera were detected across the three distinct communities, the gut bacterial composition displayed specific signatures and was observed to be influenced by the topographical location and dietary intake of the individuals. The gut microbiome of individuals living in Leh was observed to be significantly similar with a high representation of Bacteroidetes and low abundance of Proteobacteria. In contrast, the gut microbiome of individuals living in Ballabhgarh areas harbored higher...

Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder characterized by an imbalance in blood glucose level, altered lipid profile and high blood pressure. Genetic constituents, high-fat and high-energy dietary habits, and a sedentary lifestyle are three major factors that contribute to high risk of T2D. Several studies have reported gut microbiome dysbiosis as a factor in rapid progression of insulin resistance in T2D that accounts for about 90% of all diabetes cases worldwide. The gut microbiome dysbiosis may reshape intestinal barrier functions and host metabolic and signaling pathways, which are directly or indirectly related to the insulin resistance in T2D. Thousands of the metabolites derived from microbes interact with the epithelial, hepatic and cardiac cell receptors that modulate host physiology. Xenobiotics including dietary components, antibiotics and nonsteroidal anti-inflammatory drugs strongly affect the gut microbial composition and can promote dysb...

Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα-chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll-like receptor (TLR) ligand activation of TCRtransgenic murine dNKT cells. IFN-γ production by dNKT cells required dendritic cells (DC), cell-to-cell contact and presence of TLR ligands. TLR-stimulated DC activated dNKT cells to secrete IFN-γ in a CD1d-, CD80/86-and type I IFN-independent manner. In contrast, a requirement for IL-12p40, and a TLR ligand-selective dependence on IL-18 or IL-15 was observed. TLR ligand/DC stimulation provoked early secretion of pro-inflammatory cytokines by both CD62L + and CD62L − dNKT cells. However, proliferation was limited. In contrast, TCR/co-receptor-mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L − dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co-receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.

Somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID) and requires target gene transcription. A splice isoform of SRSF1, SRSF1-3, is necessary for AID-dependent SHM of IgV genes. Nevertheless, its exact molecular mechanism of action in SHM remains unknown. Our in silico studies show that, unlike SRSF1, SRSF1-3 lacks a strong nuclear localization domain. We show that the absence of RS domain in SRSF1-3 affects its nuclear localization, as compared to SRSF1. Consequently, SRSF1-3 is predominantly present in the cytoplasm. Remarkably, co-immunoprecipitation studies showed that SRSF1-3 interacts with Topoisomerase 1 (TOP1), a crucial regulator of SHM that assists in generating ssDNA for AID activity. Moreover, the immunofluorescence studies confirmed that SRSF1-3 and TOP1 are co-localized in the nucleus. Furthermore, Proximity Ligation Assay corroborated the direct interaction between SRSF1-3 and TOP1. An interaction between SRSF1-3 and TOP1 suggests that SRSF1-3 likely influences the TOP1 activity and consequently can aid in SHM. Accordingly, SRSF1-3 probably acts as a link between TOP1 and SHM, by spatially regulating TOP1 activity at the Ig locus. We also confirmed the interaction between SRSF1-3 and AID in chicken B-cells. Thus, SRSF1-3 shows dual-regulation of SHM, via interacting with AID as well as TOP1.

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Natural killer T (NKT) cells are unique unconventional T cells that are reactive to lipid antigens presented on the non-polymorphic major histocompatibility class (MHC) I-like molecule CD1d. They have characteristics of both innate and adaptive immune cells, and have potent immunoregulatory roles in tumor immunity, autoimmunity, and infectious diseases. Based on their T cell receptor (TCR) expression, NKT cells are divided into two subsets, type I NKT cells with an invariant TCRα-chain (Vα24 in humans, Vα14 in mice) and type II NKT cells with diverse TCRs. While type I NKT cells are well-studied, knowledge about type II NKT cells is still limited, and it is to date only possible to identify subsets of this population. However, recent advances have shown that both type I and type II NKT cells play important roles in many inflammatory situations, and can sometimes regulate the functions of each other. Type II NKT cells can be both protective and pathogenic. Here, we review current kno...

Mucosal surface layers are the critical borders throughout epithelial membranes. These epithelial cells segregate luminal material from external environments. However, mucosal linings are also accountable for absorbing nutrients and requiring specific barrier permeability. These functional acts positioned the mucosal epithelium at the epicenter of communications concerning the mucosal immune coordination and foreign materials, such as dietary antigens and microbial metabolites. Current innovations have revealed that external stimuli can trigger several mechanisms regulated by intestinal mucosal barrier system. Crucial constituents of this epithelial boundary are physical intercellular structures known as tight junctions (TJs). TJs are composed of different types transmembrane proteins linked with cytoplasmic adaptors which helps in attachment to the adjacent cells. Disruption of this barrier has direct influence on healthy or diseased condition, as barrier dysfunctions have been int...