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Xiuxuan Zhang, Yan Zhou, Xiaofei Gu, Yu Cheng, Manxin Hong, Liqiang Yan, Fulong Ma, Zhengjian Qi
Cytochrome P450s have brought considerable attention to researchers for their significant correlations with metabolic behaviors of procarcinogenic chemicals. To better understand the roles of CYP1A in biological and physiological systems, we developed a novel ratiometric fluorescence probe N-((2-hydroxyl ethoxy) ethyl)- 4-methoxy-1, 8-naphthalimide (NEMN) allowing for selectively and sensitively monitoring the target enzymes under physiological conditions and living cells. The probe was designed based on substrate predilection of CYP1A and its outstanding O-dealkylation capacity, and 1, 8-naphthalimide was chosen as fluorophore on account of its desirable photophysical properties...
August 15, 2018: Talanta
Canan Sapmaz, Tulin Firat, Aysel Kukner, Azra Bozcaarmutlu
Morin is a flavonoid which is present in many plants. Endosulfan and 7,12-dimethylbenz[a]anthracene (DMBA) are toxic chemicals that humans are exposed to in their daily lives. In this study, the protective role of morin was investigated in endosulfan and DMBA treated rats. Eight groups, each comprising seven 2.5-month-old adult male Wistar rats (weighing 170-255 g), were used. Endosulfan, morin, and DMBA were administered individually or in combinations, at 5 mg/kg body weight (bw) (three times/week), 25 mg/kg bw (three times/week), and 30 mg/kg bw (once/week for three weeks) via oral gavage, respectively...
May 18, 2018: Drug and Chemical Toxicology
Mingzhe Zhu, Qianlei Wang, Wenjun Zhou, Tao Liu, Lili Yang, Peiyong Zheng, Li Zhang, Guang Ji
To enhance our understanding of molecular mechanisms and mine novel biomarkers of non-alcoholic fatty liver disease (NAFLD), RNA sequencing was performed to gain hepatic expression profiles of mRNAs and miRNAs in NAFLD and normal rats. Using DESeq with thresholds of a two-fold change and a false discovery rate (FDR) less than 0.05, 336 mRNAs and 21 miRNAs were identified as differentially expressed. Among those, 17 miRNAs (e.g., miR-144-3p, miR-99a-3p, miR-200b-3p, miR-200b-5p, miR-200c-3p, etc.) might serve as novel biomarkers of NAFLD...
May 16, 2018: Scientific Reports
Yan Qin Tan, Leo Clement Chiu-Leung, Shu-Mei Lin, Lai K Leung
The environmental polycyclic aromatic hydrocarbons (PAH) and dioxins are carcinogens and their adverse effects have been largely attributed to the activation of AhR. Hesperetin is a flavonone found abundantly in citrus fruits and has been shown to be a biologically active agent. In the present study, the effect of hesperetin on the nuclear translocation of AhR and the downstream gene expression was investigated in MCF-7 cells. Confocal microscopy indicated that 7, 12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) -induced nuclear translocation of AhR was deterred by hesperetin treatment...
May 16, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Ang Zhou, Amy E Taylor, Ville Karhunen, Yiqiang Zhan, Suvi P Rovio, Jari Lahti, Per Sjögren, Liisa Byberg, Donald M Lyall, Juha Auvinen, Terho Lehtimäki, Mika Kähönen, Nina Hutri-Kähönen, Mia Maria Perälä, Karl Michaëlsson, Anubha Mahajan, Lars Lind, Chris Power, Johan G Eriksson, Olli T Raitakari, Sara Hägg, Nancy L Pedersen, Juha Veijola, Marjo-Riitta Järvelin, Marcus R Munafò, Erik Ingelsson, David J Llewellyn, Elina Hyppönen
Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests...
May 14, 2018: Scientific Reports
Sneha Budhwar, Charu Bahl, Siddharth Sharma, Navneet Singh, Digambar Behera
Background: AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer...
May 2018: Current Genomics
Priya Tripathi, Furong Deng, Anne M Scruggs, Yahong Chen, Steven K Huang
Exposure to particulate matter < 2.5 μm (PM2.5 ) is associated with a variety of airway diseases. Although studies have demonstrated that high doses of PM2.5 cause cytotoxicity and changes to gene expression in bronchial epithelial cells, the effect of lower doses and repeated exposure to PM2.5 are less well studied. Here, we treated BEAS-2B cells with varying doses of PM2.5 for 1-7 days and examined the expression of a variety of genes implicated in airway disorders. At high doses, PM2.5 increased the expression of IL6, TNF, TSLP, CSF2, PTGS2, IL4R, and SPINK5...
May 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Stefanie Hessel-Pras, Anke Ehlers, Albert Braeuning, Alfonso Lampen
The epithelium of the small intestine plays an important role in detoxification processes due to the presence of various xenobiotic-metabolizing enzymes from phase I and II, as well as transport proteins of the ATP-binding cassette superfamily. Exposure to xenobiotics induces the expression of these proteins in the small intestine, with multiple signaling pathways stimulated by exogenous compounds converging at individual gene promoters by mechanisms which have not been fully understood yet. In this context the promoter region of the CYP1A1 gene, encoding the phase I monooxygenase cytochrome P450 1A1, was analyzed by chromatin immunoprecipitation with regard to binding of xeno-sensing receptors following stimulation of Caco-2 cells with agonists of the aryl hydrocarbon receptor (AHR) and retinoid receptors...
2018: EXCLI Journal
Simona Strapáčová, Petra Brenerová, Pavel Krčmář, Patrik Andersson, Karin I van Ede, Majorie B M van Duursen, Martin van den Berg, Jan Vondráček, Miroslav Machala
Toxicity of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls, is largely mediated via aryl hydrocarbon receptor (AhR) activation. AhR-mediated gene expression can be tissue-specific; however, the inducibility of AhR in the lungs, a major target of DLCs, remains poorly characterized. In this study, we developed relative effective potencies (REPs) for a series of DLCs in both rodent (MLE-12, RLE-6TN) and human (A549, BEAS-2B) lung and bronchial epithelial cell models, using expression of both canonical (CYP1A1, CYP1B1) and less well characterized (TIPARP, AHRR, ALDH3A1) AhR target genes...
May 5, 2018: Toxicology
B Huang, J Bao, Y-R Cao, H-F Gao, Y Jin
Nonalcoholic fatty liver disease (NAFLD) is a chronic hepatic disease associated with excessive accumulation of lipids in hepatocytes. As the disease progresses, oxidative stress plays a pivotal role in the development of hepatic lipid peroxidation. Cytochrome P450 1A1 (CYP1A1), a subtype of the cytochrome P450 family, has been shown to be a vital modulator in production of reactive oxygen species. However, the exact role of CYP1A1 in NAFLD is still unclear. The aim of this study was to investigate the effects of CYP1A1 on lipid peroxidation in oleic acid (OA)-treated human hepatoma cells (HepG2)...
May 2018: Biochemistry. Biokhimii︠a︡
María-Aránzazu Martínez, Irma Ares, José-Luis Rodríguez, Marta Martínez, David Roura-Martínez, Victor Castellano, Bernardo Lopez-Torres, María-Rosa Martínez-Larrañaga, Arturo Anadón
This study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8mg/kg bw for 6days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β- (CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2)...
August 1, 2018: Science of the Total Environment
Yu Zhou, Shijin Li, Lulin Huang, Yeming Yang, Lin Zhang, Mu Yang, Wenjing Liu, Kim Ramasamy, Zhilin Jiang, Periasamy Sundaresan, Xianjun Zhu, Zhenglin Yang
Retinitis pigmentosa (RP) refers to a group of retinal degenerative diseases, which often lead to vision loss. Although 70 genes have been identified in RP patients, the genetic cause of approximately 30% of RP cases remains unknown. We aimed to identify the cause of the disease in a cohort of RP families by whole exome sequencing. A rare homozygous splicing variant, c.1160 + 1G>A, which introduced skipping of exon 9 of the aryl hydrocarbon receptor (AHR), was identified in family RD-134. This variant is very rare in several exome databases and leads to skipping of exon 9 in the transcript...
May 2, 2018: Human Molecular Genetics
Sridhar Jaligama, Vivek S Patel, Pingli Wang, Asmaa Sallam, Jeffrey Harding, Matthew Kelley, Skylar R Mancuso, Tammy R Dugas, Stephania A Cormier
BACKGROUND: Pollutant particles containing environmentally persistent free radicals (EPFRs) are formed during many combustion processes (e.g. thermal remediation of hazardous wastes, diesel/gasoline combustion, wood smoke, cigarette smoke, etc.). Our previous studies demonstrated that acute exposure to EPFRs results in dendritic cell maturation and Th17-biased pulmonary immune responses. Further, in a mouse model of asthma, these responses were enhanced suggesting exposure to EPFRs as a risk factor for the development and/or exacerbation of asthma...
May 3, 2018: Particle and Fibre Toxicology
Le Du, Lei Lei, Xiaojuan Zhao, Hongjuan He, Erfei Chen, Jing Dong, Yuan Zeng, Jin Yang
The main purpose of this study was to perform a meta-analysis to assess the interaction between smoking and nine genes ( GSTM1 , GSTT1 , GSTP1 , CYP1A1 , NAT2 , SULT1A1 , hOGG1 , XRCC1 and p53 ) on colorectal cancer, gastric cancer, liver cancer and oesophageal cancer. Published articles from the PubMed, ISI and EMBASE databases were retrieved. A total of 67 case-control studies or nested case-control studies were identified for the analysis. The pooled jodds ratio (OR) with 95% confidence interval (CI) was calculated using the random effect model...
2018: Journal of Cancer
Jee-Hyun Jung, Young-Sun Moon, Bo-Mi Kim, Young-Mi Lee, Moonkoo Kim, Jae-Sung Rhee
Flounder is a promising model species for environmental monitoring of coastal regions. To assess the usefulness of liver transcriptome profiling, juvenile olive flounder Paralichthys olivaceus were exposed to two pollutants, bisphenol S (BPS) and benzo[a]pyrene (BaP), which have different chemical characteristics and have distinct modes of metabolic action in teleost. Six hours after intraperitoneal injection with BPS (50 mg/kg bw) or BaP (20 mg/kg bw), liver transcriptomes were analyzed using the Illumina Hiseq 3000 platform...
2018: PloS One
Hassan M Naif, Mohammed A I Al-Obaide, Hayfa H Hassani, Abdualghani S Hamdan, Zainab S Kalaf
Background: CYP1A1 gene polymorphisms and tobacco smoking are among several risk factors for various types of cancers, but their influence on breast cancer remains controversial. We analyzed the possible association of CYP1A1 gene polymorphisms and tobacco smoking-related breast cancer in women from Iraq. Materials and methods: In this case-control study, gene polymorphism of CYP1A1 gene ( CYP1A1m1 , T6235C and CYP1A1m2 , A4889G) of 199 histologically verified breast cancer patients' and 160 cancer-free control women's specimens were performed by using PCR-based restriction fragment length polymorphism...
2018: Frontiers in Public Health
A Yeong Lee, Won Park, Tae-Wook Kang, Min Ho Cha, Jin Mi Chun
ETHNOPHARMACOLOGICAL RELEVANCE: Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued. AIM OF THE STUDY: To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach...
July 15, 2018: Journal of Ethnopharmacology
Stephanie H Witt, Josef Frank, Maria Gilles, Maren Lang, Jens Treutlein, Fabian Streit, Isabell A C Wolf, Verena Peus, Barbara Scharnholz, Tabea S Send, Stefanie Heilmann-Heimbach, Sugirthan Sivalingam, Helene Dukal, Jana Strohmaier, Marc Sütterlin, Janine Arloth, Manfred Laucht, Markus M Nöthen, Michael Deuschle, Marcella Rietschel
BACKGROUND: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight...
April 25, 2018: BMC Genomics
Wen-Yao Zhang, Hao Wang, Shaopei Qi, Xixi Wang, Xueru Li, Kun Zhou, Yong Zhang, Ming-Qing Gao
The expression of cytochrome P4501A1 (CYP1A1) enzyme is changed in various organs during the host response to inflammation or infection, leading to alterations in the metabolism of endogenous and exogenous compounds. Results of this study showed that CYP1A1 expression was significantly downregulated in the mammary tissue of bovine with mastitis, in inflammatory epithelial cells (INEs) extracted from the tissue, and in lipopolysaccharide- (LPS-) induced INEs compared with their corresponding counterparts. Overexpression of CYP1A1 in bovine mammary epithelial cells alleviated the LPS-induced inhibition of epithelial proliferation, abated the LPS-induced increase of gene expression and protein secretion of inflammatory cytokine tumor necrosis factor- α and interleukin-6, and attenuated the LPS-induced activation of NF- κ B signaling...
2018: Mediators of Inflammation
Amy M Padula, Wei Yang, Kathleen Schultz, Fred Lurmann, S Katharine Hammond, Gary M Shaw
Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene-environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population-based case-control (86 cases of spina bifida and 208 non-malformed controls) study...
May 2018: American Journal of Medical Genetics. Part A
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