Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.

Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes.

Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.

Nuclear receptors are a unique family of transcription factors that play cardinal roles in physiology and plethora of human diseases. The adopted orphan nuclear receptor Nr1d1 is a constitutive transcriptional repressor known to modulate several biological processes. In this study, we found that Nr1d1 plays a decisive role in T helper (Th)-cell polarization and transcriptionally impedes the formation of Th2 cells by directly binding to the promoter region of GATA binding protein 3 (GATA3) gene.

Host factors subverted by Potential targets for host directed therapy.

Introduction: Despite new approaches in the diagnosis and treatment of tuberculosis (TB), it continues to be a major health burden. Several immunotherapies that potentiate the immune response have come up as adjuncts to drug therapies against drug resistant TB strains; however, there needs to be an urgent appraisal of host specific drug targets for improving their clinical management and to curtail disease progression. Presently, various host directed therapies (HDTs) exist (repurposed drugs, nutraceuticals, monoclonal antibodies and immunomodulatory agents), but these mostly address molecules that combat disease progression.

Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment.

The escalation in living standards and adoption of 'Western lifestyle' has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes.

Vitamin D3-VDR-PTPN6 axis mediated autophagy contributes to the inhibition of macrophage foam cell formation.

Macrophage derived foam cells in atherosclerotic plaques are the major factor responsible for the pathogenesis of atherosclerosis (AS). During advanced AS, macrophage-specific macroautophagy/autophagy is dysfunctional. 1, 25-dihydroxy vitamin D3 (VitD3) and its receptor VDR (vitamin D receptor) are reported to inhibit foam cell formation and induce autophagy; however, the role of VitD3-VDR-induced autophagy and foam cell formation in AS has not been explored.

TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR.

Hepatocellular carcinoma appears as an extremely angiogenic solid tumor marked by apoptosis evasion, dysregulated cell cycle and low sensitivity to chemotherapy. TGF-β, a multifunctional cytokine, plays a pleiotropic role in the tumor microenvironment and has implications in cancer drug resistance. The current study provides novel evidence that TGF-β signaling contributes to drug resistance in liver cancer cells by inducing the expression of xenobiotic nuclear receptor PXR.

AutophagySMDB: a curated database of small molecules that modulate protein targets regulating autophagy.

Macroautophagy/autophagy is a complex self-degradative mechanism responsible for clearance of non functional organelles and proteins. A range of factors influences the autophagic process, and disruptions in autophagy-related mechanisms lead to disease states, and further exacerbation of disease. Despite in-depth research into autophagy and its role in pathophysiological processes, the resources available to use it for therapeutic purposes are currently lacking.

AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment.

Early stage prostate cancers are dependent on androgens for their growth and survival and androgen withdrawal causes them to regress. Progressive prostate cancers eventually acquire androgen independence rendering anti-androgen therapy ineffective. However, the factors leading to this have not been adequately addressed.