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https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#1
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28074863/herb-pair-danggui-honghua-mechanisms-underlying-blood-stasis-syndrome-by-system-pharmacology-approach
#2
Shi-Jun Yue, Lan-Ting Xin, Ya-Chu Fan, Shu-Jiao Li, Yu-Ping Tang, Jin-Ao Duan, Hua-Shi Guan, Chang-Yun Wang
Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28055957/analysis-of-molecular-mechanisms-of-5-fluorouracil-induced-steatosis-and-inflammation-in-vitro-and-in-mice
#3
Judith Sommer, Abdo Mahli, Kim Freese, Tobias S Schiergens, Fulya Suzan Kuecuekoktay, Andreas Teufel, Wolfgang E Thasler, Martina Müller, Anja K Bosserhoff, Claus Hellerbrand
Chemotherapy-associated steatohepatitis is attracting increasing attention because it heralds an increased risk of morbidity and mortality in patients undergoing surgery because of liver metastases. The aim of this study was to develop in vitro and in vivo models to analyze the pathogenesis of 5-fluorouracil (5-FU)-induced steatohepatitis.Therefore, primary human hepatocytes and HepG2 hepatoma cells were incubated with 5-FU at non-toxic concentrations up to 24 h. Furthermore, hepatic tissue of C57BL/6N mice was analyzed 24 h after application of a single 5-FU dose (200 mg/kg body weight)...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999449/the-ratio-of-hmox1-nrf2-mrna-level-in-the-tumor-tissue-is-a-predictor-of-distant-metastasis-in-colorectal-cancer
#4
Liang-Che Chang, Chung-Wei Fan, Wen-Ko Tseng, Hui-Ping Chein, Tsan-Yu Hsieh, Jim-Ray Chen, Cheng-Cheng Hwang, Chung-Ching Hua
Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction...
2016: Disease Markers
https://www.readbyqxmd.com/read/27998018/genetic-polymorphism-of-heme-oxygenase-1-promoter-in-the-occurrence-and-severity-of-chronic-obstructive-pulmonary-disease-a-meta-analysis
#5
Hongbin Zhou, Xiwang Ying, Yuanshun Liu, Sa Ye, Jianping Yan, Yaqing Li
Heme oxygenase 1 (HMOX1) plays an important role in the development of chronic obstructive pulmonary disease (COPD). However, the association of HMOX1 length polymorphism in promoter region to the risk and severity of COPD has not been well studied. In this study, we searched the databases including PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) and extracted the information from related articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study the effect of HMOX1 polymorphism on the risk and severity of COPD...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27979226/fractionation-enzyme-inhibitory-and-cellular-antioxidant-activity-of-bioactives-from-purple-sweet-potato-ipomoea-batatas
#6
Tuba Esatbeyoglu, Miriam Rodríguez-Werner, Anke Schlösser, Peter Winterhalter, Gerald Rimbach
Sweet potato (Ipomoea batatas L.) is mainly cultivated in Asia. The deep purple color of purple sweet potato (PSP) is due to the high content of acylated anthocyanins. In the present study, PSP-derived polyphenols were identified using HPLC-PDA and HPLC-ESI-MS(n) analyses. After concentration of the polyphenols from PSP, preparative separation into two fractions, designated anthocyanins (AF) and copigments (CF), was carried out using adsorptive membrane chromatography. In enzyme inhibitory assays, all PSP samples inhibited the enzymes α-amylase, α-glucosidase and xanthine oxidase...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27976481/irradiation-with-uv-c-inhibits-tnf-%C3%AE-dependent-activation-of-the-nf-%C3%AE%C2%BAb-pathway-in-a-mechanism-potentially-mediated-by-reactive-oxygen-species
#7
Katarzyna Szoltysek, Anna Walaszczyk, Patryk Janus, Marek Kimmel, Piotr Widlak
Pathways depending on the NF-κB transcription factor are essential components of cellular response to stress. Plethora of stimuli modulating NF-κB includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affecting NF-κB remains relatively understudied. Here, we aim to characterize the influence of UV radiation on TNF-α-induced activity of the NF-κB pathway. We document inhibition of TNF-α-induced activation of NF-κB and subsequent suppression of NF-κB-regulated genes in cells exposed to UV-C several hours before TNF-α stimulation...
December 15, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27943244/genetic-variations-in-bilirubin-metabolism-genes-and-their-association-with-unconjugated-hyperbilirubinemia-in-adults
#8
Ashish S Chiddarwar, Selma Z D'Silva, Roshan B Colah, Kanjaksha Ghosh, Malay B Mukherjee
OBJECTIVE: The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes (UGT1A1, OATP2, HMOX1, and BLVRA) and their association with hyperbilirubinemia. MATERIAL AND METHODS: Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, GeneScan analysis, and direct DNA sequencing. RESULTS: Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls...
December 12, 2016: Annals of Human Genetics
https://www.readbyqxmd.com/read/27927768/iron-heme-bach1-axis-is-involved-in-erythroblast-adaptation-to-iron-deficiency
#9
Masahiro Kobayashi, Hiroki Kato, Hiroshi Hada, Ari Itoh-Nakadai, Tohru Fujiwara, Akihiko Muto, Yukihiro Inoguchi, Kenji Ichiyanagi, Wataru Houjou, Naohisa Tomosugi, Hiroyuki Sasaki, Hideo Harigae, Kazuhiko Igarashi
Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27829220/gene-expression-profile-induced-by-arsenic-trioxide-in-chronic-lymphocytic-leukemia-cells-reveals-a-central-role-for-heme-oxygenase-1-in-apoptosis-and-regulation-of-matrix-metalloproteinase-9
#10
Irene Amigo-Jiménez, Elvira Bailón, Noemí Aguilera-Montilla, José A García-Marco, Angeles García-Pardo
CLL remains an incurable disease in spite of the many new compounds being tested. Arsenic trioxide (ATO) induces apoptosis in all CLL cell types and could constitute an efficient therapy. To further explore this, we have studied the gene expression profile induced by ATO in CLL cells. ATO modulated many genes, largely involved in oxidative stress, being HMOX1 the most upregulated gene, also induced at the protein level. ATO also increased MMP-9, as we previously observed, both at the mRNA and protein level...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829164/molecular-effects-of-1-naphthyl-methylcarbamate-and-solar-radiation-exposures-on-human-melanocytes
#11
Bianca Ferrucio, Manoela Tiago, Richard D Fannin, Liwen Liu, Kevin Gerrish, Silvya Stuchi Maria-Engler, Richard S Paules, Silvia Berlanga de Moraes Barros
Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100μM) and solar radiation (375mJ/cm(2))...
February 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#12
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27789968/reduction-of-facial-wrinkles-by-hydrolyzed-water-soluble-egg-membrane-associated-with-reduction-of-free-radical-stress-and-support-of-matrix-production-by-dermal-fibroblasts
#13
Gitte S Jensen, Bijal Shah, Robert Holtz, Ashok Patel, Donald C Lo
OBJECTIVE: The aim of this study was to evaluate the effects of water-soluble egg membrane (WSEM) on wrinkle reduction in a clinical pilot study and to elucidate specific mechanisms of action using primary human immune and dermal cell-based bioassays. METHODS: To evaluate the effects of topical application of WSEM (8%) on human skin, an open-label 8-week study was performed involving 20 healthy females between the age of 45 years and 65 years. High-resolution photography and digital analysis were used to evaluate the wrinkle depth in the facial skin areas beside the eye (crow's feet)...
2016: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/27782264/metal-homeostasis-disruption-and-mitochondrial-dysfunction-in-hepatocytes-exposed-to-sub-toxic-doses-of-zinc-oxide-nanoparticles
#14
M Chevallet, B Gallet, A Fuchs, P H Jouneau, K Um, E Mintz, I Michaud-Soret
Increased production and use of zinc oxide nanoparticles (ZnO-NPs) in consumer products has prompted the scientific community to investigate their potential toxicity, and understand their impact on the environment and organisms. Molecular mechanisms involved in ZnO-NP toxicity are still under debate and focus essentially on high dose expositions. In our study, we chose to evaluate the effect of sub-toxic doses of ZnO-NPs on human hepatocytes (HepG2) with a focus on metal homeostasis and redox balance disruptions...
October 26, 2016: Nanoscale
https://www.readbyqxmd.com/read/27778153/phenotypic-characterization-of-a-novel-ho-1-depletion-model-in-the-rat
#15
Vassilios Atsaves, Maria G Detsika, Elpida Poulaki, Hara Gakiopoulou, Elias A Lianos
Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1 (-/-) rat model and characterizes its renal and extrarenal phenotype. Hmox1 (-/-) rats had growth retardation and splenomegaly compared to their Hmox1 (+/+) littermates...
October 24, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27760386/spatiotemporal-expression-and-transcriptional-regulation-of-heme-oxygenase-and-biliverdin-reductase-genes-in-zebrafish-danio-rerio-suggest-novel-roles-during-early-developmental-periods-of-heightened-oxidative-stress
#16
Andrew Holowiecki, Britton O'Shields, Matthew J Jenny
Heme oxygenase 1 (HMOX1) degrades heme into biliverdin, which is subsequently converted to bilirubin by biliverdin reductase (BVRa or BVRb) in a manner analogous to the classic anti-oxidant glutathione-recycling pathway. To gain a better understanding of the potential antioxidant roles the BVR enzymes may play during development, the spatiotemporal expression and transcriptional regulation of zebrafish hmox1a, bvra and bvrb were characterized under basal conditions and in response to pro-oxidant exposure. All three genes displayed spatiotemporal expression patterns consistent with classic hematopoietic progenitors during development...
January 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/27746196/influence-of-sex-and-developmental-stage-on-acute-hepatotoxic-and-inflammatory-responses-to-liver-procarcinogens-in-the-mouse
#17
Daniel Hanna, Ariane Emami Riedmaier, Kim S Sugamori, Denis M Grant
The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27740521/predictive-role-blvra-mrna-expression-in-hepatocellular-cancer
#18
Kristy Na Kubícková, Iva Subhanová, Renáta Konícková, Linda Matousová, Petr Urbánek, Hana Parobková, Martin Kupec, Jirí Pudil, Libor Vítek
:  Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. MATERIAL AND METHODS: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue)...
November 2016: Annals of Hepatology
https://www.readbyqxmd.com/read/27734935/effects-of-aged-garlic-extract-and-fruarg-on-gene-expression-and-signaling-pathways-in-lipopolysaccharide-activated-microglial-cells
#19
Hailong Song, Yuan Lu, Zhe Qu, Valeri V Mossine, Matthew B Martin, Jie Hou, Jiankun Cui, Brenda A Peculis, Thomas P Mawhinney, Jianlin Cheng, C Michael Greenlief, Kevin Fritsche, Francis J Schmidt, Ronald B Walter, Dennis B Lubahn, Grace Y Sun, Zezong Gu
Aged garlic extract (AGE) is widely used as a dietary supplement on account of its protective effects against oxidative stress and inflammation. But less is known about specific molecular targets of AGE and its bioactive components, including N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). Our recent study showed that both AGE and FruArg significantly attenuate lipopolysaccharide (LPS)-induced neuroinflammatory responses in BV-2 microglial cells. This study aims to unveil effects of AGE and FruArg on gene expression regulation in LPS stimulated BV-2 cells...
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27671773/characterization-of-heme-oxygenase-and-biliverdin-reductase-gene-expression-in-zebrafish-danio-rerio-basal-expression-and-response-to-pro-oxidant-exposures
#20
Andrew Holowiecki, Britton O'Shields, Matthew J Jenny
While heme is an important cofactor for numerous proteins, it is highly toxic in its unbound form and can perpetuate the formation of reactive oxygen species. Heme oxygenase enzymes (HMOX1 and HMOX2) degrade heme into biliverdin and carbon monoxide, with biliverdin subsequently being converted to bilirubin by biliverdin reductase (BVRa or BVRb). As a result of the teleost-specific genome duplication event, zebrafish have paralogs of hmox1 (hmox1a and hmox1b) and hmox2 (hmox2a and hmox2b). Expression of all four hmox paralogs and two bvr isoforms were measured in adult tissues (gill, brain and liver) and sexually dimorphic differences were observed, most notably in the basal expression of hmox1a, hmox2a, hmox2b and bvrb in liver samples...
November 15, 2016: Toxicology and Applied Pharmacology
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