INTRODUCTION Nuclear receptors (NRs) are ligand-dependent transcription factors found in many species that regulate the expression of important target genes involved in a spectrum of developmental and physiological processes. In addition to ligand binding, the transcriptional activities of NRs are also modulated through a range of protein-protein interactions with coregulatory proteins, either with coactivator orRead More
INDIGO Expands Discovery Platform to Include Zebrafish Assays
Expansion Meets Industry Demand for Pre-Clinical Models for Cancer and Environmental Research State College, PA (23 January 2020) – INDIGO Biosciences, the recognized industry leader in nuclear receptor research, has announced the addition of four zebrafish assays to its portfolio. These additions both expand INDIGO’s robust portfolio of in vitro animal model assay systems andRead More
Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods
ABSTRACT In this paper, we evaluate the PPARα signaling network in rats, examining transcriptional responses in primary hepatocytes exposed to a PPARα specific ligand, GW7647. These transcriptomic studies were complemented with ChIP-seq studies of PPARα binding and transcription binding motif identification for PPARα responsive genes. We also conducted a limited study of GW7647 dosing the inRead More
Quinazolinone derivative BNUA‐3 ameliorated [NDEA+2‐AAF]‐ induced liver carcinogenesis in SD rats by modulating AhR‐CYP1B1‐Nrf2‐Keap1 pathway
ABSTRACT Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation ofRead More
Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice
ABSTRACT Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying.Read More
Involvement of estrogen receptor α in pro-pruritic and pro-inflammatory responses in a mouse model of allergic dermatitis
ABSTRACT It has been reported that endogenous or exogenous estrogens can affect the immune system, resulting in immune disorders; however, their direct involvement in such conditions remains to be demonstrated. The purpose of this study was to investigate whether estrogen receptors (ER) are directly implicated in pro-pruritic and pro-inflammatory reactions in cutaneous allergy. Initially, enhancement of the pro-inflammatoryRead More
Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and improves running endurance in sedentary C57BL/6 J mice
ABSTRACT The α-eleostearic acid (α-ESA) in bitter melon seed oil (BMSO) is efficiently converted by the body into rumenic acid. The objective of this study was to investigate effects of BMSO on skeletal muscle fiber-type switch and endurance capacity in mice, with or without exercise training. In a 3 x 2 factorial design, C57BL/6 JRead More
Disruption of Nuclear Receptor Signaling Alters Triphenyl Phosphate-Induced Cardiotoxicity in Zebrafish Embryos
ABSTRACT Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on (1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and (2) high-content screening to identify nuclear receptor ligands thatRead More
Sedaxane—Use of Nuclear Receptor Transactivation Assays, Toxicogenomics, and Toxicokinetics as Part of a Mode of Action Framework for Rodent Liver Tumors
ABSTRACT Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA isRead More
Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats is not Attenuated by Dietary Choline Supplementation
ABSTRACT Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for four weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementationRead More