Feeding enhances fibronectin adherence of quiescent lymphocytes through non-canonical insulin signalling.

Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue-resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty.

Two novel cell culture models of buccal mucosal oral cancer from patients with no risk-habits of tobacco smoking or chewing.

Objective: Tobacco consumption is one of the major etiological factors for oral cancer, but it also develops in non-tobacco users, with unknown etiologies. Cellular models for tobacco associated oral cancer are available, however; reports of cellular models for studying non-tobacco associated oral cancer are limiting. We report here the establishment and characterization of two novel buccal mucosal cancer cell lines 'GBC02' and 'GBC035' derived from non-tobacco users.

miR-3666 inhibits development of hepatic steatosis by negatively regulating PPARγ.

Aims: PPARγ is a crucial transcription factor involved in development of hepatic steatosis, an early stage of NAFLD. PPARγ is tightly regulated through various positive and negative regulators including miRNAs. In this study, we report for the first time miR-3666 as a negative regulator of PPARγ and its involvement in development of hepatic steatosis.

Vitexin alleviates non-alcoholic fatty liver disease by activating AMPK in high fat diet fed mice.

Non-alcoholic fatty liver disease (NAFLD) is a most common liver disorder characterized by accumulation of fat in the liver and currently there is no approved treatment for it. Obesity and diabetes being leading cause of NAFLD, compounds having anti-obesity activity and potential to reduce insulin resistance are considered suitable candidate for NAFLD treatment. In this study, we checked effect of vitexin, a naturally occurring flavonoid, on high fat diet (HFD) induced NAFLD in C57BL/6J mice.

F-box protein FBXO16 functions as a tumor suppressor by attenuating nuclear β-catenin function.

Aberrant activation of β-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/β-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor.

Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis.

With the advent of synthetic biology in medicine many synthetic or engineered proteins have made their way to therapeutics and diagnostics. In this paper, the downstream gene network of CD14-TNF-EGFR pathway in leishmaniasis, a tropical disease, is reconstructed. Network analysis showed that NFkB links the signaling and gene network, used as a point of intervention through a synthetic circuit embedded within the negative autoregulatory feedback loop.

CCR6 signaling inhibits suppressor function of induced-Treg during gut inflammation.

CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3CD4 T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6 Tregs enhanced the expression of RORγt.

Mediation of transitional B cell maturation in the absence of functional Bruton's tyrosine kinase.

X-linked immune-deficient (Xid) mice, carrying a mutation in Bruton's tyrosine kinase (Btk), have multiple B cell lineage differentiation defects. We now show that, while Xid mice showed only mild reduction in the frequency of the late transitional (T2) stage of peripheral B cells, the defect became severe when the Xid genotype was combined with either a CD40-null, a TCRbeta-null or an MHC class II (MHCII)-null genotype. Purified Xid T1 and T2 B cells survived poorly in vitro compared to wild-type (WT) cells.

Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma.

A Hyperglycemic condition in diabetes promotes formation of advanced glycation end products, which are known to elicit immune response and form complexes with immunoglobulins called circulating immune complexes. To investigate the involvement of advanced glycation end product (AGE)-modified proteins in the elicitation of an immune response, circulating immune complexes were isolated and proteins associated were identified and characterized. Label-free-based mass spectrometric analysis of circulating immune complexes in clinical plasma of prediabetic, newly diagnosed diabetes, and diabetic microalbuminurea revealed elevated levels of serum albumin in the circulating immune complexes, which were also observed to be AGE modified.

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights.

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O.

Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor.

Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation.

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine.

Low plasma albumin levels are associated with increased plasma protein glycation and HbA1c in diabetes.

Albumin is one of the most abundant plasma proteins and is heavily glycated in diabetes. In this study, we have addressed whether variation in the albumin levels influence glycation of plasma proteins and HbA1c. The study was performed in three systems: (1) streptozotocin (STZ)-induced diabetic mice plasma, (2) diabetic clinical plasma, and (3) in vitro glycated plasma.

Proteomic analysis of glycated proteins from streptozotocin-induced diabetic rat kidney.

Glycation of proteins leading to formation of advanced glycation end products (AGEs) has been considered as one of the important causes of diabetic nephropathy. Therefore, in this study, glycated proteins were detected by anti-AGE antibodies from kidney of streptozotocin-induced diabetic rat showing nephropathic symptoms, by using two dimensional electrophoresis and western blot analysis. These glycated proteins were identified and characterized by using combination of peptide mass finger printing and tandem mass spectrometric approaches.

Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression.

Background: p53 is the most studied tumor suppressor and its overexpression may or may not cause cell death depending upon the genetic background of the cells. p53 is degraded by human papillomavirus (HPV) E6 protein in cervical carcinoma. Several stress activated kinases are known to phosphorylate p53 and, among them cyclin dependent kinase 5 (Cdk5) is one of the kinase studied in neuronal cell system.

Discovery of rifampicin as a new anti-glycating compound by matrix-assisted laser desorption/ionization mass spectrometry-based insulin glycation assay.

An in vitro insulin glycation assay was developed for screening glycation inhibitors. The assay involves the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for monitoring the formation of glycated insulin. The assay is simple, rapid and amenable for high throughput screening.

Albumin competitively inhibits glycation of less abundant proteins.

Glycation, a non-enzymatic reaction between glucose and protein is the primary cause of diabetic complications. Albumin, the most abundant plasma protein undergoes glycation both in vivo and in vitro. The influence of albumin on glycation of less abundant proteins has not been addressed.

Interleukin-12 is necessary for the priming of CD4+ T cells required during the elicitation of HIV-1 gp120-specific cytotoxic T-lymphocyte function.

The mechanism of the T-cell response and cytokine induction to restrict human immunodeficiency virus 1 (HIV-1) infection is not clear. During early infection, HIV-infected individuals have a high frequency of virus-specific cytotoxic T lymphocytes (CTLs) that effectively reduces the viral load. However, the CTLs are unable to clear the virus at later stages of infection, leading to disease progression.

HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner.

A large number of multicomponent vaccine candidates are currently in clinical evaluation, many of which also include the HIV-1 Tat protein, an important regulatory protein of the virus. However, whether Tat, a known immune effector molecule with a well-conserved sequence among different HIV subtypes, affects the immune response to a coimmunogen is not well understood. In this study, using a bicistronic vector expressing both gp120 and Tat, we have analyzed the role of Tat in elicitation of the gp120-specific immune response.

TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma.

We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (TbetaRI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity.

SMAR1-derived P44 peptide retains its tumor suppressor function through modulation of p53.

The use of pharmacologically active short peptide sequences is a better option in cancer therapeutics than the full-length protein. Here we report one such 44-mer peptide sequence of SMAR1 (TAT-SMAR1 wild type, P44) that retains the tumor suppressor activity of the full-length protein. The protein transduction domain of human immunodeficiency virus, type 1, Tat protein was used here to deliver the 33-mer peptide of SMAR1 into the cells.

CD40 signaling is impaired in L. major-infected macrophages and is rescued by a p38MAPK activator establishing a host-protective memory T cell response.

Leishmania, a protozoan parasite, lives and multiplies as amastigote within macrophages. It is proposed that the macrophage expressed CD40 interacts with CD40 ligand on T cells to induce IFN-gamma, a Th1-type cytokine that restricts the amastigote growth. Here, we demonstrate that CD40 cross-linking early after infection resulted in inducible nitric oxide synthetase type-2 (iNOS2) induction and iNOS2-dependent amastigote elimination.