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https://www.readbyqxmd.com/read/28732110/growth-inhibitory-effect-of-%C3%AE-eudesmol-on-cholangiocarcinoma-cells-and-its-potential-suppressive-effect-on-heme-oxygenase-1-production-stat1-3-activation-and-nf-%C3%AE%C2%BAb-downregulation
#1
Vivek Bhakta Mathema, Wanna Chaijaroenkul, Juntra Karbwang, Kesara Na-Bangchang
Cholangiocarcinoma (CCA) is a progressively fatal form of cancer originating from the malignant transformation of hepatic biliary cholangiocytes. The present study reports for the first time in vitro growth inhibitory activities of β-eudesmol, the bioactive sesquiterpenoid present in the rhizome of Atractylodes lancea (Thunb) DC., with respect to its underlying potential effects on heme oxygenase-1 (HO-1) production, STAT1/3 phosphorylation, and NF-κB protein expression in human CCA cell line CL-6. The cytotoxic effect of β-eudesmol on CL-6 cells was evaluated by MTT assay using normal human embryonic fibroblast (OUMS) as a control cell line...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28731922/a-novel-g-55040074delt-in-alas2-gene-resulting-in-a-monomeric-protein-and-severe-sideroblastic-anemia-phenotype
#2
Prateek Bhatia, Aditya Singh, Avani Hedge
Sideroblastic anemias are a rare group of disorders resulting from defective iron incorporation during heme synthesis and hence characterized by anemia and presence of ringed sideroblasts in bone marrow. The most common form is an X-linked disorder caused by mutations in ALAS2 gene. In the current paper, a case of X-linked sideroblastic anemia caused by a novel homozygous deletional mutation in exon 10 of ALAS2 gene is presented. The female infant developed moderately severe anemia at 6 months of age, which did not improve despite adequate nutritional support...
July 20, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28731684/the-binding-mode-of-n-hydroxyamidines-to-indoleamine-2-3-dioxygenase-1-ido1
#3
Ute Friederike Röhrig, Vincent Zoete, Olivier Michielin
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important target in cancer immunotherapy. The most advanced clinical compound, epacadostat (INCB024360), binds to the heme cofactor of IDO1 through a N-hydroxyamidine function. Conflicting binding modes have recently been proposed, reporting iron binding either through the hydroxyamidine oxygen or nitrogen atoms. Here, we use quantum chemical calculations, docking, and QM/MM calculations based on available X-ray data to resolve this issue and to propose a physically meaningful binding mode...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28731262/nephroprotective-effects-of-anthocyanin-from-the-fruits-of-panax-ginseng-gfa-on-cisplatin-induced-acute-kidney-injury-in-mice
#4
Zhen-Lan Qi, Zi Wang, Wei Li, Jin-Gang Hou, Ying Liu, Xin-Dian Li, Hui-Ping Li, Ying-Ping Wang
Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin...
July 21, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28730260/longer-survival-of-a-patient-with-glioblastoma-resected-with-5-aminolevulinic-acid-5-ala-guided-surgery-and-foreign-body-reaction-to-polyglycolic-acid-pga-suture
#5
Raluca Maria Munteanu, Lucian Eva, Bogdan IonuŢ DobrovăŢ, Alin Constantin Iordache, Liviu Pendefunda, Nicoleta Dumitrescu, Doina Mihăilă, Cristina Maria Gavrilescu, Elena Şapte, Ion Poeată
In recent years, there is a growing evidence that using 5-aminolevulinic acid (5-ALA)-guided resection of a cerebral glioblastoma, associated with chemoradiotherapy determine a prolonged survival of these patients, even though this period do not exceed 15 months. 5-ALA is a natural biochemical precursor of heme that is metabolized to fluorescent porphyrins, particularly protoporphyrin IX (PPIX) and no foreign reaction were noted until now. However, foreign body reaction developing in neurosurgery is documented in a few number of cases to suture material, surgical hemostatic material, or surgical glove starch, but up to now we could not find any article about granulomatous inflammation to polyglycolic acid (PGA) suture after brain tumor resection...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28727916/transient-catalytic-voltammetry-of-sulfite-oxidase-reveals-rate-limiting-conformational-changes
#6
Ting Zeng, Silke Leimkühler, Ulla Wollenberger, Vincent Fourmond
Sulfite oxidases are metalloenzymes that oxidize sulfite to sulfate at a molybdenum active site. In vertebrate sulfite oxidases, the electrons generated at the Mo center are transferred to an external electron acceptor via a heme domain, which can adopt two conformations: a "closed" conformation, suitable for internal electron transfer, and an "open" conformation suitable for intermolecular electron transfer. This conformational change is an integral part of the catalytic cycle. Sulfite oxidases have been wired to electrode surfaces, but their immobilization lead to a significant decrease in their catalytic activity, raising the question of the occurrence of the conformational change when the enzyme is on an electrode...
July 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28726208/immunolocation-of-heme-oxygenases-in-the-walls-of-cerebral-arteries-of-various-diameters-in-rats
#7
V M Chertok, A E Kotsyuba
The distribution of two enzymes involved in the formation of carbon monoxide, heme oxygenases 1 and 2, in the pial branches of orders I-V of the middle cerebral artery basin and in intracerebral vessels was studied in adult Wistar rats. Immunohistochemical studies detected hemeoxygenase-2 in the endothelium of the small pial and intracerebral arterioles and in myocytes of pial branches I-III. Heme oxygenase 1, an inducible form of the enzyme, is normally not expressed in the cerebral vessels, but the enzyme is expressed in response to sodium metaarsenite...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28724916/involvement-of-the-p62-nrf2-signal-transduction-pathway-on-erythrophagocytosis
#8
Inês B Santarino, Michelle S Viegas, Neuza S Domingues, Ana M Ribeiro, Miguel P Soares, Otília V Vieira
Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724911/honokiol-inhibits-c-met-ho-1-tumor-promoting-pathway-and-its-cross-talk-with-calcineurin-inhibitor-mediated-renal-cancer-growth
#9
Murugabaskar Balan, Samik Chakraborty, Evelyn Flynn, David Zurakowski, Soumitro Pal
Honokiol (HNK) is a small molecule with potent anti-inflammatory and anti-tumorigenic properties; yet the molecular targets of HNK are not well studied. Hyperactivation of the receptor tyrosine kinase c-Met and overexpression of the cytoprotective enzyme heme oxygenase-1 (HO-1) play a critical role in the growth and progression of renal cell carcinoma (RCC). Interestingly, the calcineurin inhibitor (CNI) cyclosporine A (CsA), an immunosuppressant used to prevent allograft rejection, can also increase the risk of RCC in transplant patients...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724407/characterization-of-the-cytochrome-p450-monooxygenase-genes-p450ome-from-the-carotenogenic-yeast-xanthophyllomyces-dendrorhous
#10
Pamela Córdova, Ana-María Gonzalez, David R Nelson, María-Soledad Gutiérrez, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno
BACKGROUND: The cytochromes P450 (P450s) are a large superfamily of heme-containing monooxygenases involved in the oxidative metabolism of an enormous diversity of substrates. These enzymes require electrons for their activity, and the electrons are supplied by NAD(P)H through a P450 electron donor system, which is generally a cytochrome P450 reductase (CPR). The yeast Xanthophyllomyces dendrorhous has evolved an exclusive P450-CPR system that specializes in the synthesis of astaxanthin, a carotenoid with commercial potential...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28722682/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#11
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720846/physiological-stress-induced-corticosterone-increases-heme-uptake-via-klf4-hcp1-signaling-pathway-in-hippocampus-neurons
#12
Hongxia Li, Caixia Zhang, Hui Shen, Zhilei Shen, Lusha Wu, Fengfeng Mo, Min Li
Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718097/regulatory-genes-and-their-roles-for-improvement-of-antibiotic-biosynthesis-in-streptomyces
#13
REVIEW
Fengjuan Lu, Yanyan Hou, Heming Zhang, Yiwen Chu, Haiyang Xia, Yongqiang Tian
The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators...
August 2017: 3 Biotech
https://www.readbyqxmd.com/read/28716864/alpha1-antitrypsin-binds-hemin-and-prevents-oxidative-activation-of-human-neutrophils-putative-pathophysiological-significance
#14
Sabina Janciauskiene, Srinu Tumpara, Malgorzata Wiese, Sabine Wrenger, Vijith Vijayan, Faikah Gueler, Rongjun Chen, Kukuh Madyaningrana, Ravi Mahadeva, Tobias Welte, Stephan Immenschuh, Joanna Chorostowska-Wynimko
Heme is a ubiquitous compound of human tissues, and it is involved in cellular physiology and metabolism. Once released from the cell, free heme oxidizes to the ferric state (hemin). High levels of hemin can cause oxidative stress and inflammation if not neutralized immediately by specialized scavenger proteins. Human alpha1-antitrypsin (A1AT), an acute-phase glycoprotein and important inhibitor of neutrophil proteases, is also a hemin-binding protein. A short-term exposure of freshly isolated human blood neutrophils to 4 µM hemin results in cell spreading, surface expression of filament protein, vimentin, free radical production, expression of heme oxygenase-1 (HO-1), release of IL-8, and enhanced neutrophil adhesion to human endothelial cells...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28715873/subcritical-water-hydrolyzed-fish-collagen-ameliorates-survival-of-endotoxemic-mice-by-inhibiting-hmgb1-release-in-a-ho-1-dependent-manner
#15
Min Young Ahn, Jung Seok Hwang, Sun Ah Ham, Jinwoo Hur, Yeonji Jo, SangYoon Lee, Mi-Jung Choi, Sung Gu Han, Han Geuk Seo
To investigate potential mechanisms underlying the bioactivity of hydrolyzed fish collagen, we examined the anti-inflammatory actions of subcritical water-hydrolyzed fish collagen (SWFC) in lipopolysaccharide (LPS)-triggered inflammation and endotoxemia. SWFC markedly inhibited LPS-stimulated release of high mobility group box 1 (HMGB1) in murine RAW264.7 macrophages, along with decreased cytosolic translocation of HMGB1. Both the protein and mRNA levels of heme oxygenase-1 (HO-1) were significantly upregulated in SWFC-treated RAW 264...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715485/characterization-of-the-maize-lipoxygenase-gene-family-in-relation-to-aflatoxin-accumulation-resistance
#16
Oluwaseun F Ogunola, Leigh K Hawkins, Erik Mylroie, Michael V Kolomiets, Eli Borrego, Juliet D Tang, W Paul Williams, Marilyn L Warburton
Maize (Zea mays L.) is a globally important staple food crop prone to contamination by aflatoxin, a carcinogenic secondary metabolite produced by the fungus Aspergillus flavus. An efficient approach to reduce accumulation of aflatoxin is the development of germplasm resistant to colonization and toxin production by A. flavus. Lipoxygenases (LOXs) are a group of non-heme iron containing dioxygenase enzymes that catalyze oxygenation of polyunsaturated fatty acids (PUFAs). LOX derived oxylipins play critical roles in plant defense against pathogens including A...
2017: PloS One
https://www.readbyqxmd.com/read/28715185/substrate-binding-primes-human-tryptophan-2-3-dioxygenase-for-ligand-binding
#17
Karin Nienhaus, Vincent Hahn, Manuel Hüpfel, Gerd Ulrich Nienhaus
The human heme enzyme tryptophan 2,3-dioxygenase (hTDO) catalyzes the insertion of dioxygen into its cognate substrate, L-tryptophan (L-Trp). Its active site structure is highly dynamic, and the mechanism of enzyme-substrate-ligand complex formation and the ensuing enzymatic reaction is not yet understood. Here we have studied complex formation in hTDO by using time-resolved optical and infrared spectroscopy with carbon monoxide (CO) as a ligand. We have observed that both substrate-free and substrate-bound hTDO co-exist in two discrete conformations with greatly different ligand binding rates...
July 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28714938/taxifolin-activates-the-nrf2-anti-oxidative-stress-pathway-in-mouse-skin-epidermal-jb6-p-cells-through-epigenetic-modifications
#18
Haixue Kuang, Zhenqiu Tang, Chengyue Zhang, Zhibin Wang, Wenji Li, Chunjuan Yang, Qiuhong Wang, Bingyou Yang, Ah-Ng Kong
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714505/the-antiproliferative-activity-of-di-2-pyridylketone-dithiocarbamate-is-partly-attributed-to-catalase-inhibition-detailing-the-interaction-by-spectroscopic-methods
#19
Cuiping Li, Youxun Liu, Yun Fu, Tengfei Huang, Lixia Kang, Changzheng Li
The bioactivity of drugs is attributed to their interaction with biological molecules, embodied in either their direct or indirect influence on enzyme activity and conformation. Di-2-pyridylketone hydrazine dithiocarbamate (DpdtC) exhibits significant antitumor activity in our preliminary study. We speculated that its activity may partly stem from enzyme inhibition due to strong metal chelating ability. To this end, we assessed its effect on catalase from erythrocytes and found evidence of inhibition, which was further confirmed by ROS determination in vivo...
July 17, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28713894/identification-of-a-compound-heterozygous-mutation-of-abcc2-in-a-patient-with-hyperbilirubinemia
#20
Rong Xiang, Jing-Jing Li, Liang-Liang Fan, Jie-Yuan Jin, Kun Xia, Fang Wang
Bilirubin is the end product of heme catabolism, which is produced primarily from the breakdown of erythrocyte hemoglobin in the reticuloendothelial system. Hyperbilirubinemia is induced not only by increased bilirubin synthesis, but can also be caused by decreased bilirubin clearance. There are several disorders, which can contribute to hyperbilirubinemia, including Dubin‑Johnson syndrome (DJS). DJS is a rare autosomal recessive disorder, which is characterized by predominantly conjugated hyperbilirubinemia without progression to end‑stage liver disease...
July 5, 2017: Molecular Medicine Reports
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