ABSTRACT While alternative methods for toxicity testing using re-constructed human skin and cornea have been written into guidelines and adopted by regulatory authorities, three-dimensional (3D) liver models are currently applied in the industrial settings for hepatotoxicity screening and prediction. These 3D liver models can recapitulate the architecture, functionality and toxicity response of the native liver,Read More
Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells
ABSTRACT Intestinal health relies on the immunosuppressive activity of CD4+ regulatory T (Treg) cells. Expression of the transcription factor Foxp3 defines this lineage, and can be induced extrathymically by dietary or commensal-derived antigens in a process assisted by a Foxp3 enhancer known as conserved non-coding sequence 1 (CNS1). Products of microbial fermentation including butyrate facilitate the generationRead More
Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli
ABSTRACT Escherichia coli broadly colonize the intestinal tract of humans and produce a variety of small molecule signals. However, many of these small molecules remain unknown. Here, we describe a family of widely distributed bacterial metabolites termed the “indolokines.” In E. coli, the indolokines are upregulated in response to a redox stressor via aspC and tyrB transaminases. Although indolokine 1 represents a previouslyRead More
Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders
ABSTRACT Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPARα is a promising drug target for diabetic retinopathy and age-related macularRead More
Breastmilk-promoted bifidobacteria produce aromatic lactic acids in the infant gut
ABSTRACT Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previouslyRead More
Structure Based Multitargeted Molecular Docking Analysis of Selected Furanocoumarins against Breast Cancer
ABSTRACT Breast cancer is one of the biggest global dilemmas and its current therapy is to target the hormone receptors by the use of partial agonists/antagonists. Potent drugs for breast cancer treatment are Tamoxifen, Trastuzumab, Paclitaxel, etc. which show adverse effects and resistance in patients. The aim of the study has been on certain phytochemicalsRead 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
Detection and Removal of Biologically Active Organic Micropollutants from Hospital Wastewater
ABSTRACT The presence of contaminants of emerging concern (CECs), such as antibiotics, antimicrobial disinfectants, nonprescription drugs, personal care products, pharmaceuticals, and steroids, in water resources can impact aquatic and human health. A large portion of the CECs entering regional wastewater treatment plants originate from hospitals. The purposes of this study were to conduct exploratory analyticalRead 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
Correlation Between Cytochrome P450 Inducers and Nuclear Receptor Activation – a Screening Approach
View Full Size Research conducted by: Shantanu Roychowdhury (1); Casidy M. Ward (1); Kevin J. Kennedy (1); & Yong Zhao (1) (1) Eurofins Discovery, 6 Research Park Drive, St. Charles, MO 63304 Date of Publication: 2019 Presented at: ISSX 2019 in Portland, OR