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https://www.readbyqxmd.com/read/29232587/discovery-of-naphtho-1-2-d-oxazole-derivatives-as-potential-anti-hcv-agents-through-inducing-heme-oxygenase-1-expression
#1
Chih-Hua Tseng, Chun-Kuang Lin, Yeh-Long Chen, Chin-Kai Tseng, Jar-Yu Lee, Jin-Ching Lee
A number of naphtho[1,2-d]oxazole derivatives were synthesized and evaluated for their anti-HCV virus activity. Among them, compound 18 was the most active, exhibited approximately 21-folds more active anti-HCV activity (IC50 of 0.63 μM) than that of ribavirin (IC50 = 13.16 μM). Compound 18 was less cytotoxic than ribavirin, and the selective index (SI) of 18 is approximately 28-folds higher than that of ribavirin (229.10 v.s. 8.08). By using heme oxygenase-1 (HO-1) promoter-based assay and western blotting, compound 18 could induce HO-1 promoter activity, and protein expression...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29196031/effects-of-various-feeding-patterns-of-bacillus-coagulans-on-growth-performance-antioxidant-response-and-nrf2-keap-1-signaling-pathway-in-juvenile-gibel-carp-carassius-auratus-gibelio
#2
Yebing Yu, Changhai Wang, Aimin Wang, Wenping Yang, Fu Lv, Fei Liu, Bo Liu, Cunxin Sun
The present study was conducted to evaluate the effects of various Bacillus coagulans feeding patterns on growth, antioxidant parameter and Nrf2 pathway in juvenile gibel carp. The similar size of gibel carp (initial weight: 14.33 ± 0.15 g) were subjected to three levels of B. coagulans supplementation (0, 500, and 1000 mg/kg) and two feeding modes (supplementing B. coagulans continuously or for two days of B. coagulans after 5 days of a basal diet) according to a 3 × 2 factorial design. The fish that were continuously fed 500 mg/kg B...
November 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29186203/chl1-dna-helicase-and-scc2-function-in-chromosome-condensation-through-cohesin-deposition
#3
Donglai Shen, Robert V Skibbens
Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair...
2017: PloS One
https://www.readbyqxmd.com/read/29125538/cigarette-smoke-regulates-the-competitive-interactions-between-nrf2-and-bach1-for-heme-oxygenase-1-induction
#4
Wen-Hsin Chang, Philip Thai, Jihao Xu, David C Yang, Reen Wu, Ching-Hsien Chen
Cigarette smoke has been shown to trigger aberrant signaling pathways and pathophysiological processes; however, the regulatory mechanisms underlying smoke-induced gene expression remain to be established. Herein, we observed that two smoke-responsive genes, HO-1 and CYP1A1, are robustly induced upon smoke by different mechanisms in human bronchial epithelia. CYP1A1 is mediated by aryl hydrocarbon receptor signaling, while induction of HO-1 is regulated by oxidative stress, and suppressed by N-acetylcysteine treatment...
November 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29113307/prediction-of-clinical-outcome-and-survival-in-soft-tissue-sarcoma-using-a-ten-lncrna-signature
#5
Rong-Quan He, Qing-Jun Wei, Rui-Xue Tang, Wen-Jie Chen, Xia Yang, Zhi-Gang Peng, Xiao-Hua Hu, Jie Ma, Gang Chen
The prognostic value of long non-coding RNAs (lncRNAs) in patients with soft-tissue sarcoma has rarely been unraveled. The aim of the study was to find a lncRNA signature to predict the clinical outcome and survival in soft-tissue sarcoma based on the high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA) database. The lncRNAs which closely correlated with overall survival in 258 soft-tissue sarcoma patients were identified with Cox proportional regression model. Ten lncRNAs, including RP11-560J1...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028112/the-role-of-declining-adaptive-homeostasis-in-ageing
#6
Laura C D Pomatto, Kelvin J A Davies
Adaptive homeostasis is, 'the transient expansion or contraction of the homeostatic range for any given physiological parameter in response to exposure to sub-toxic, non-damaging, signalling molecules or events, or the removal or cessation of such molecules or events (Davies, 2016a)." Adaptive homeostasis enables biological systems to make continuous short-term adjustments for optimal functioning despite ever-changing internal and external environments. Initiation of adaptation in response to an appropriate signal allows organisms to successfully cope with much greater, normally toxic, stresses...
October 13, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28955775/dynamics-of-absorption-metabolism-and-excretion-of-5-aminolevulinic-acid-in-human-intestinal-caco-2-cells
#7
Kei Saito, Tohru Fujiwara, Urara Ota, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Masahiro Ishizuka, Tohru Tanaka, Hideo Harigae
5-Aminolevulinic acid (ALA) is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC) for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28889753/silencing-of-bach1-inhibits-invasion-and-migration-of-prostate-cancer-cells-by-altering-metastasis-related-gene-expression
#8
Neda Shajari, Sadaf Davudian, Tohid Kazemi, Behzad Mansoori, Shima Salehi, Vahid Khaze Shahgoli, Dariush Shanehbandi, Ali Mohammadi, Pascal Duijf, Behzad Baradaran
BACKGROUND: Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. BACH1, a basic leucine zipper transcription factor, has been shown to transcriptionally regulate expression of a range of genes that are associated with breast cancer metastasis. However, the exact role and the underlying molecular mechanism of BACH1 in prostate cancer remain unclear. This study aims to explore the expression of BACH1 in prostate cancer tissues and the effect of BACH1 suppression on prostate cancer cell behavior...
September 11, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28863281/aging-related-decline-in-the-induction-of-nrf2-regulated-antioxidant-genes-in-human-bronchial-epithelial-cells
#9
Lulu Zhou, Hongqiao Zhang, Kelvin J A Davies, Henry Jay Forman
Evidence from animal studies suggests that stress-induced increases in Nrf2-regulated antioxidant gene expression, a critical mechanism of cellular protection, declines with aging. This study examined whether this also occurs in humans. We measured the basal and inducible levels of Nrf2-regulated antioxidant genes in human bronchial epithelial (HBE) cells from subjects of young adult (21-29 years) and older (60-69 years) non-smokers, and explored factors affecting expresion. The basal expression of three representative Nrf2-regulated genes, the catalytic and modulator subunits of glutamate cysteine ligase (GCLC and GCLM, respectively), and NAD(P)H quinone oxidoreductase 1 (NQO1), was higher in cells from the older donors compared with cells from the young adult donors...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28808058/reductions-in-the-mitochondrial-abc-transporter-abcb10-affect-the-transcriptional-profile-of-heme-biosynthesis-genes
#10
Alexandra Seguin, Naoko Takahashi-Makise, Yvette Y Yien, Nicholas C Huston, Jared C Whitman, Gabriel Musso, Jared A Wallace, Thomas Bradley, Hector A Bergonia, Martin D Kafina, Mitsuyo Matsumoto, Kazuhiko Igarashi, John D Phillips, Barry H Paw, Jerry Kaplan, Diane M Ward
ATP-binding cassette subfamily B member 10 (Abcb10) is a mitochondrial ATP-binding cassette (ABC) transporter that complexes with mitoferrin1 and ferrochelatase to enhance heme biosynthesis in developing red blood cells. Reductions in Abcb10 levels have been shown to reduce mitoferrin1 protein levels and iron import into mitochondria, resulting in reduced heme biosynthesis. As an ABC transporter, Abcb10 binds and hydrolyzes ATP, but its transported substrate is unknown. Here, we determined that decreases in Abcb10 did not result in protoporphyrin IX accumulation in morphant-treated zebrafish embryos or in differentiated Abcb10-specific shRNA murine Friend erythroleukemia (MEL) cells in which Abcb10 was specifically silenced with shRNA...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28790431/differentiation-impairs-bach1-dependent-ho-1-activation-and-increases-sensitivity-to-oxidative-stress-in-sh-sy5y-neuroblastoma-cells
#11
Sabrina Piras, Anna Lisa Furfaro, Lorenzo Brondolo, Mario Passalacqua, Umberto Maria Marinari, Maria Adelaide Pronzato, Mariapaola Nitti
Neuronal adaptation to oxidative stress is crucially important in order to prevent degenerative diseases. The role played by the Nrf2/HO-1 system in favoring cell survival of neuroblastoma (NB) cells exposed to hydrogen peroxide (H2O2) has been investigated using undifferentiated or all-trans retinoic acid (ATRA) differentiated SH-SY5Y cells. While undifferentiated cells were basically resistant to the oxidative stimulus, ATRA treatment progressively decreased cell viability in response to H2O2. HO-1 silencing decreased undifferentiated cell viability when exposed to H2O2, proving the role of HO-1 in cell survival...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28704479/dynamic-changes-in-bach1-expression-in-the-kidney-of-rhabdomyolysis-associated-acute-kidney-injury
#12
Masakazu Yamaoka, Hiroko Shimizu, Toru Takahashi, Emiko Omori, Hiroshi Morimatsu
Free heme, a pro-oxidant released from myoglobin, is thought to contribute to the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI), because renal overexpression of heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, confers protection against RM-AKI. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that represses HO-1. Here, we examined the changes with time in the gene expression of Bach1, HO-1, and δ-aminolevulinate synthase (ALAS1, a heme biosynthetic enzyme) in the rat kidney using an RM-AKI model induced by the injection of 50% glycerol (10 mL/kg body weight) into bilateral limbs...
2017: PloS One
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#13
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28685309/mir-155-enhances-phagocytic-activity-of-%C3%AE-thalassemia-hbe-monocytes-via-targeting-of-bach1
#14
Kanitta Srinoun, Chamnong Nopparatana, Malai Wongchanchailert, Suthat Fucharoen
Abnormal red blood cell (RBC) clearance in β-thalassemia is triggered by activated monocytes. Recent reports indicate that miRNA (miR-) plays a role in monocyte activation. To study phagocytic function, we co-cultured monocytes of normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals with RBCs obtained from normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals. The phagocytic activity of β-thalassemia/HbE monocytes co-cultured with β-thalassemia/HbE RBCs was significantly higher than that of normal monocytes co-cultured with normal RBCs...
November 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28645578/the-electrophilic-character-of-quinones-is-essential-for-the-suppression-of-bach1
#15
Chuanyang Su, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important cellular defense mechanisms against oxidative attack. BTB and CNC homology-1 (Bach1), like Kelch-like ECH-associated protein 1 (Keap1), is one of a negative regulator of Nrf2 that control antioxidant response elements (ARE)-dependent gene expressions. In the current study, we found that quinones show greater capacity than hydroquinones in nuclear Bach1 export, as well as ubiquitin-dependent Bach1 degradation in our experimental time frame...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28598815/prediction-of-clinical-outcome-and-survival-in-soft-tissue-sarcoma-using-a-ten-lncrna-signature
#16
Rong-Quan He, Qing-Jun Wei, Rui-Xue Tang, Wen-Jie Chen, Xia Yang, Zhi-Gang Peng, Xiao-Hua Hu, Jie Ma, Gang Chen
The prognostic value of long non-coding RNAs (lncRNAs) in patients with soft-tissue sarcoma has rarely been unraveled. The aim of the study was to find a lncRNA signature to predict the clinical outcome and survival in soft-tissue sarcoma based on the high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA) database. The lncRNAs which closely correlated with overall survival in 258 soft-tissue sarcoma patients were identified with Cox proportional regression model. Ten lncRNAs, including RP11-560J1...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588024/bromodomain-and-extraterminal-inhibitors-block-the-epstein-barr-virus-lytic-cycle-at-two-distinct-steps
#17
COMPARATIVE STUDY
Kristin M Keck, Stephanie A Moquin, Amanda He, Samantha G Fernandez, Jessica J Somberg, Stephanie M Liu, Delsy M Martinez, Jj L Miranda
Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. Proteins in the bromodomain and extraterminal (BET) family regulate multiple stages of viral life cycles and provide promising intervention targets. Synthetic small molecules can bind to the bromodomains and disrupt function by preventing recognition of acetylated lysine substrates. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV lytic cycle...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28576353/reprint-of-heme-oxygenase-1-affects-granulopoiesis-in-mice-through-control-of-myelocyte-proliferation
#18
Karolina Bukowska-Strakova, Maciej Ciesla, Krzysztof Szade, Witold Norbert Nowak, Robert Straka, Agata Szade, Malgorzata Tyszka-Czochara, Karolina Najder, Anna Konturek, Maciej Siedlar, Jozef Dulak, Alicja Jozkowicz
Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe(2+). We showed that HO-1 knock-out mice (HO-1(-/-)) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced surface expression of G-CSF receptor on the hematopoietic precursors. This suggests the effect of HO-1 on granulopoiesis. Here we aimed to determine the stage of granulopoiesis regulated by HO-1...
June 2017: Immunobiology
https://www.readbyqxmd.com/read/28536120/hepatocyte-specific-sirtuin-6-deletion-predisposes-to-nonalcoholic-steatohepatitis-by-up-regulation-of-bach1-an-nrf2-repressor
#19
Sun-O Ka, In Hyuk Bang, Eun Ju Bae, Byung-Hyun Park
Sirtuin (Sirt)6 has been implicated in negative regulation of inflammation and lipid metabolism, although its function in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains to be defined. To explore the role of hepatocyte Sirt6 in NASH development, we generated hepatocyte-specific Sirt6-knockout (KO) mice that were fed a high-fat and high-fructose (HFHF) diet for 16 wk. HFHF-fed KO mice had increased hepatic steatosis and inflammation and aggravated glucose intolerance and insulin resistance compared with wild-type mice...
September 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28420366/pirfenidone-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice-by-regulating-nrf2-bach1-equilibrium
#20
Yuan Liu, Fuai Lu, Lirong Kang, Zhihua Wang, Yongfu Wang
BACKGROUND: Oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the expression level of antioxidant factors, further regulating the function of oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for IPF therapy approved drugs...
April 18, 2017: BMC Pulmonary Medicine
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