cyp26a1

Enniatins are emerging mycotoxins that contaminate foods. The present study investigated the oral pharmacokinetics and 28-day repeated-dose oral toxicity of enniatin B (ENNB) in CD1 (ICR) mice. In the pharmacokinetic study, male mice received a single oral or intravenous dose of ENNB [30 mg/kg body weight (BW) and 1 mg/kg BW, respectively]. After oral dosing, ENNB exhibited 139.9% bioavailability, a 5.1-hr elimination half-life, 5.26% fecal excretion from 4 to 24 h post-dose, and upregulation of Cyp7a1, Cyp2a12, Cyp2b10, and Cyp26a1 in the liver 2 h post-dosing...

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry...

Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in post-natal liver as a potential major RA catabolizing enzyme, and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 contributes only marginally to endogenous RA homeostasis postnatally. We report re-evaluation of a conditional Cyp26a1 knockdown in the postnatal mouse. The current results show that Cyp26a1 mRNA in wild-type (WT) mouse liver increases 16-fold upon re-feeding after a fast, accompanied by an increased rate of RA elimination and a 41% decrease in the RA concentration...

Cyanobacterial blooms are known sources of environmentally-occurring retinoid compounds, including all-trans and 9-cis retinoic acids (RAs). The developmental hazard for aquatic organisms has been described, while the implications for human health hazard assessment are not yet sufficiently characterized. Here, we employ a human neural stem cell model that can differentiate in vitro into a mixed culture of neurons and glia. Cells were exposed to non-cytotoxic 8-1000nM all-trans or 9-cis RA for 9-18 days (DIV13 and DIV22, respectively)...

The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling...

As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms...

Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives...

Despite being used for many decades, there is a lack of poultry research investigating the effects of dietary palmitic, carotenoid and vitamin E-rich palm oils and medium-chain fatty acid-rich PKO. The current study aimed to elucidate the influence of different dietary oils in layers on production performance, egg quality, serum biochemicals and expression of genes related to β-carotene, retinol and α-tocopherol in the liver. A total of 150 Hisex brown laying hens were fed diets containing CPO, RPO, RBD, PKO or SBO at a similar level for 16 weeks...

BACKGROUND: To establish a treatment option for liver fibrosis, the possibility of the drug repurposing theory was investigated, with a focus on the off-target effects of active pharmaceutical ingredients. METHODS: First, several active pharmaceutical ingredients were screened for their effects on the gene expression in the hepatocytes using chimeric mice with humanized hepatocytes. As per the gene expression-based screening assay for 36 medications, we assessed the mechanism of the antifibrotic effect of letrozole, a third-generation aromatase inhibitor, in mouse models of liver fibrosis induced by carbon tetrachloride (CCl4 ) and a methionine choline-deficient (MCD) diet...

We investigated the effects of vitamin A (VA) status on metabolism of Zucker rats with different genders and genotypes, and of short-term refeeding of a VA sufficient (VAS) diet on VA deficient (VAD) animals. First, male and female Zucker lean (ZL) and fatty (ZF) rats at weaning were fed a VAD or VAS diet for 8 weeks. Second, male VAD ZL rats were fed a VAS diet for 3 (VAD-VAS3d) or 7 (VAD-VAS7d) days. The body weight (BW), blood parameters, and hepatic expressions of genes for metabolism were determined. VA deficiency reduced BW gain in ZL and ZF rats of either gender...

Non-human primates are important models for investigations of neural development and evolution, and the use of Japanese macaque monkeys has especially contributed to the advancement of neuroscience studies. However, these studies are restricted by the number of animals able to be evaluated and the invasiveness of the methodologies. Induced pluripotent stem cells (iPSCs) can provide an alternative strategy for investigating neural development in vitro. We have established direct neurosphere (dNS) formation cultures of primate iPSCs as an in vitro model of early neurodevelopment in primate species...

We previously used microarrays to show that high expression of DHRS3 , NROB1 , and CYP26A1 predicts favorable NB outcomes. Here, we investigated whether expression of these genes was associated with suppression of NB cell (SK-N-SH, NB12, and TGW) growth. We assessed morphology and performed growth, colony-formation, and migration assays, as well as RNA sequencing. The effects of the transient expression of these genes were also assessed with a tetracycline-controlled expression (Tet-On) system. Gene overexpression reduced cell growth and induced morphological senescence...

Objective: To offer new prognostic evaluations by exploring potentially distinctive genetic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods: There were 12 samples for gene expression profiling processes in this study. These included three HCC lesion samples and their matched adjacent nontumor liver tissues obtained from patients with HCC, as well as three ICC samples and their controls collected similarly. In addition to the expression matrix generated on our own, profiles of other cohorts from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus (GEO) were also employed in later bioinformatical analyses...

The prognosis of AML patients with adverse genetics, such as a complex, monosomal karyotype and TP53 lesions, is still dismal even with standard chemotherapy. DNA-hypomethylating agent monotherapy induces an encouraging response rate in these patients. When combined with decitabine (DAC), all-trans retinoic acid (ATRA) resulted in an improved response rate and longer overall survival in a randomized phase II trial (DECIDER; NCT00867672). The molecular mechanisms governing this in vivo synergism are unclear...

Traumatic brain injury (TBI) is known to impair synaptic function, and subsequently contribute to observed cognitive deficits. Retinoic Acid (RA) signaling modulates expression of synaptic plasticity proteins and is involved in hippocampal learning and memory. All trans-retinoic acid (ATRA), a metabolite of Vitamin A, has been identified as a potential pharmacotherapeutic for other neurological disorders due to this role. This study conducted an ATRA dose response to determine its therapeutic effects on cognitive behaviors and expression of hippocampal markers of synaptic plasticity and RA signaling proteins after experimental TBI...

The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes...

Retinoic acid (RA) counters insulin's metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced CYP26A1 transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses CYP26A1 expression, increasing RA's elimination half-life...

Natural killer (NK) cells present in large quantities, accounting for 70% of the maternal immune cells during the first trimester of pregnancy. With the development of single-cell sequencing technology, the researchers identified three groups of uterus NK cells with different phenotypes and functions in human uterus. decidual NK1 (dNK1) subsets produce growth promoting factors which regulate T helper type 2(Th2)cell immunity and thus facilitate pregnancy. dNK2 and dNK3 subsets secrete inflammatory cytokines that are regulators of Th2 cell immunity, not conductive to establishing and maintaining pregnancy...

BACKGROUND: CYP26A1 has been reported in multiple cancers. However, the role of CYP26A1 in pancreatic cancer (PC) has not been explored. METHOD: The public data used for this study was obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Cancer Cell Line Encyclopedia (CCLE) cell lines. CCK8, colony formation, and EdU assay were used to assess the proliferation ability of cancer cells. Transwell and wound healing assays were used to evaluate the invasion and migration ability of cancer cells...

Retinoic acid, an active form of vitamin A, plays very important roles in mammalian embryogenesis. The concentration of retinoic acid is extremely low and strictly regulated by enzymes of cytochrome P450 (CYP) family, CYP26s (CYP26A1, CYP26B1 and CYP26C1) in the cells. Therefore, it is thought that changes in CYP26s activities due to exposure to a wide variety of drugs and chemicals exhibit teratogenicity. In this study, to easily detect the changes in retinoic acid level, we constructed an adenovirus-mediated reporter assay system using the promoter region of the CYP26A1 gene and inserting retinoic acid response element (RARE) and retinoid X response element (RXRE) into the downstream of the luciferase gene of reporter plasmid, which highly increased the response to retinoic acid...