nr1h4

2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100 mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e...

Increasing evidence supports a neuroprotective role for bile acids in major neurodegenerative disorders. We studied major human bile acids as signaling molecules for their two cellular receptors, farnesoid X receptor (FXR or NR1H4) and G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5), as potential neurotrophic agents. Using quantitative image analysis, we found that 20 μM deoxycholic acid (DCA) could induce neurite outgrowth in NSC-34 cells that was comparable to the neurotrophic effects of the culture control 1 μM retinoic acid (RA), with lesser effects observed for chenodexoycholic acid (CDCA) at 20 μM, and similar though less robust neurite outgrowth in SH-SY5Y cells...

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico...

Farnesoid X receptor (FXR, NR1H4) is generally considered as a tumor suppressor of colorectal and liver cancers. The interaction between FXR, bile acids (BAs) and gut microbiota is closely associated with an increased risk of colorectal and liver cancers. Increasing evidence shows that FXR agonists may be potential therapeutic agents for colorectal and liver cancers. However, FXR agonists alone do not produce the desired results due to the complicated pathogenesis and single therapeutic mechanism, which suggests that effective treatments will require a multimodal approach...

The Worldwide spread of the Omicron lineage variants has now been confirmed. It is crucial to understand the process of cellular life and to discover new drugs need to identify the important proteins in a protein interaction network (PPIN). PPINs are often represented by graphs in bioinformatics, which describe cell processes. There are some proteins that have significant influences on these tissues, and which play a crucial role in regulating them. The discovery of new drugs is aided by the study of significant proteins...

The functional versatility of the liver is paramount for organismal homeostasis. Adult liver functions are controlled by a tightly regulated transcription factor network including nuclear receptors (NRs), which orchestrate many aspects of hepatic physiology. NRs are transcription factors sensitive to extracellular cues such as hormones, lipids, xenobiotics etc. and are modulated by intracellular signaling pathways. While liver functional zonation and adaptability to fluctuating conditions rely on a sophisticated cellular architecture, a comprehensive knowledge of NR functions within liver cell populations is still lacking...

Globally, cervical cancer (CC) ranks as the fourth most common cancer and the most lethal malignancy among females of reproductive age. The incidence of CC is increasing in low-income countries, with unsatisfactory outcomes and long-term survival for CC patients. Circular RNAs (CircRNAs) are promising therapeutics that target multiple cancers. In this study, we investigated the tumorigenic role of circRHOBTB3 in CC, showing that circRHOBTB3 is highly expressed in CC cells and circRHOBTB3 knockdown also repressed CC proliferation, migration, invasion, and the Warburg effects...

INTRODUCTION: Obesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism. METHODS: In the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation...

Cigarette smoke exposure is a well-recognized causative factor for Chronic obstructive pulmonary disease (COPD), but the molecular mechanisms responsible for this effect need to be further investigated. An expanding number of studies suggest that m6A modification is involved in the progression of various diseases. Nevertheless, evidence on the regulatory function of m6A modification in human bronchial epithelial cells exposed to cigarette smoke is scarce. In this study, we investigated for the first time the effect of cigarette smoke exposure on contributing to high Mettl3 expression in HBE cells in vitro, an essential m6A writer...

Based on the postulate that glioblastoma (GBM) tumors generate anti-inflammatory prostaglandins and bile salts to gain immune privilege, we analyzed 712 tumors in-silico from three GBM transcriptome databases for prostaglandin and bile synthesis/signaling enzyme-transcript markers. A pan-database correlation analysis was performed to identify cell-specific signal generation and downstream effects. The tumors were stratified by their ability to generate prostaglandins, their competency in bile salt synthesis, and the presence of bile acid receptors nuclear receptor subfamily 1, group H, member 4 (NR1H4) and G protein-coupled bile acid receptor 1 (GPBAR1)...

BACKGROUND: We aimed to assess the interactions between mixed heavy metals, genes, and miRNAs implicated in depression development and to design and create miRNA sponges. METHODS: The key data-mining approaches in this study were the Comparative Toxicogenomics Database (CTD), MIENTURNET, GeneMania, Metascape, Webgestalt, miRNAsong, and Cytoscape software. RESULTS: A mixture of cadmium, lead, mercury, and arsenic was related to the development of depression...

The prevalence of kidney diseases has been increasing worldwide due to the aging population and has results in an increased socioeconomic burden as well as increased morbidity and mortality. A deep understanding of the mechanisms underlying the physiological regulation of the kidney and the pathogenesis of related diseases can help identify potential therapeutic targets. The farnesoid X receptor (FXR, NR1H4) is a primary nuclear bile acid receptor that transcriptionally regulates bile acid homeostasis as well as glucose and lipid metabolism in multiple tissues...

Non-alcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. The gut-liver axis is a potential therapy for NASH. Sodium cholate (SC) is a choleretic drug whose main component is bile acids and has anti-inflammatory, antifibrotic, and hepatoprotective effects. This study aimed to investigate whether SC exerts anti-NASH effects by the gut-liver axis. Mice were fed with an high-fat and high-cholesterol (HFHC) diet for 20 weeks to induce NASH. Mice were daily intragastric administrated with SC since the 11th week after initiation of HFHC feeding...

Understanding the regulation of the testicular endocrine function leading to testosterone production is a major objective as the alteration of endocrine function is associated with the development of many diseases such as infertility. In the last decades, it has been demonstrated that several endogenous molecules regulate the steroidogenic pathway. Among them, bile acids have recently emerged as local regulators of testicular physiology and particularly endocrine function. Bile acids act through the nuclear receptor FXRα (Farnesoid-X-receptor alpha; NR1H4) and the G-protein-coupled bile acid receptor (GPBAR-1; TGR5)...

Protostane-type triterpenoids are antifibrotic nature components with unique structures in Alismatis Rhizoma. However, the underlying mechanisms of them against liver fibrosis are not well illustrated. The present study aims to study the targets and mechanisms of Alismatis Rhizoma triterpenes responsible for their antifibrotic effects by network pharmacology, molecular docking, and luciferase assay. As a result, six molecular targets responsible for the antifibrotic effects of alisols against liver fibrosis were uncovered by network pharmacology, among which the activation of farnesoid X receptor (FXR/NR1H4) was highlighted and further confirmed by molecular docking and luciferase assay...

The nuclear receptor farnesoid X receptor (FXR, NR1H4) is a bile acid (BA) sensor that links the enterohepatic circuit that regulates BA metabolism and elimination to systemic lipid homeostasis. Furthermore, FXR represents a real guardian of the hepatic function, preserving, in a multifactorial fashion, the integrity and function of hepatocytes from chronic and acute insults. This review summarizes how FXR modulates the expression of pathway-specific as well as polyspecific transporters and enzymes, thereby acting at the interface of BA, lipid and drug metabolism, and influencing the onset and progression of hepatotoxicity of varying etiopathogeneses...

Alternative polyadenylation (APA) affects the composition of cis-elements in 3'-untranslated region (3'-UTR), to regulate gene expression and localization, and subsequently the downstream biological processes. Acute heat stress could change rapidly the cellular transcriptome, however the underlying molecular changes are less explored. Here, we systematically catalogued the global 3'-UTRome dynamics, by analyzing our previously reported transcriptome sequencing data of porcine immature Sertoli (iST) cells before (Control group), acute heat stress treatment at 43 °C for 0...

OBJECTIVE: To detect differentially expressed genes in patients with neonatal necrotizing enterocolitis (NEC) by bioinformatics methods and to provide new ideas and research directions for the prevention, early diagnosis and treatment of NEC. METHODS: Gene chip data were downloaded from the Gene Expression Omnibus database. The genes that were differentially expressed in NEC compared with normal intestinal tissues were screened with GEO2R. The functions, pathway enrichment and protein interactions of these genes were analyzed with DAVID and STRING...

Herein, we show that profound afferent long-term peanut-allergen-specific IgE immunological tolerance for 3 to 9 months induced sustained unresponsiveness (SU) in naïve or peanut-sensitized rodents after peanut allergen immunization. Rodents were vaccinated sublingually with a peanut allergen extract or recombinant peanut allergen in chenodeoxycholate (CDCA), a fanesoid X receptor (FXR, NR1H4) agonist that downregulates SREBP-1c (sterol regulatory element binding protein-1c) and upregulates SHP in bone marrow-derived tolerogenic dendritic cells (DCs)...

BACKGROUND: Nuclear receptor subfamily 1 group H member 4 (NR1H4) have been reported in various cancer types, however, little is known about the clinical values and biological function in clear cell Renal cell carcinoma (ccRCC). METHODS: The expression pattens of NR1H4 in ccRCC were investigated in clinical specimens, cell lines and publicly‑available databases. Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2' -deoxyuridine (EdU), transwell and cell wound healing assays were performed to assess the biological functions of NR1H4 in 786-O ccRCC cells...