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https://www.readbyqxmd.com/read/28736522/gliotoxin-targets-nuclear-notch2-in-human-solid-tumor-derived-cell-lines-in-vitro-and-inhibits-melanoma-growth-in-xenograft-mouse-model
#1
Rainer Hubmann, Wolfgang Sieghart, Susanne Schnabl, Mohammad Araghi, Martin Hilgarth, Marlies Reiter, Dita Demirtas, Peter Valent, Christoph Zielinski, Ulrich Jäger, Medhat Shehata
Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28734063/atp-and-astrocytes-play-a-prominent-role-in-the-control-of-the-respiratory-pattern-generator-in-the-lamprey
#2
Elenia Cinelli, Ludovica Iovino, Donatella Mutolo
The role of ATP and astrocytes in respiratory rhythm modulation has been recently investigated in neonatal rodents. However, no information on the role of ATP and astrocytes within the respiratory network of the lamprey is available, particularly within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator. To address these issues, the present study was carried out on isolated brainstems of the adult lamprey. Bath application of ATP caused marked increases in respiratory frequency followed by decreases in the respiratory motor output, mediated by the ATP metabolite adenosine at the level of the pTRG...
July 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28720735/a-nonredundant-phosphopantetheinyl-transferase-ppta-is-a-novel-antifungal-target-that-directs-secondary-metabolite-siderophore-and-lysine-biosynthesis-in-aspergillus-fumigatus-and-is-critical-for-pathogenicity
#3
Anna Johns, Daniel H Scharf, Fabio Gsaller, Hella Schmidt, Thorsten Heinekamp, Maria Straßburger, Jason D Oliver, Mike Birch, Nicola Beckmann, Katharine S Dobb, Jane Gilsenan, Bharatkumar Rash, Elaine Bignell, Axel A Brakhage, Michael J Bromley
Secondary metabolites are key mediators of virulence for many pathogens. Aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs). Both NRPSs and PKSs harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (P-pant). The A. fumigatus P-pant PptA has been shown to prime the putative NRPS Pes1 in vitro and has an independent role in lysine biosynthesis; however, its role in global secondary metabolism and its impact on virulence has not been described...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28718218/impact-of-prenatal-immune-challenge-on-the-demyelination-injury-during-adulthood
#4
Abdeslam Mouihate, Hessah Al-Hashash, Sarah Rakhshani-Moghadam, Samah Kalakh
AIM: Brain inflammation is associated with several brain diseases such as multiple sclerosis (MS), a disease characterized by demyelination. Whether prenatal immune challenge affects demyelination-induced inflammation in the white matter during adulthood is unclear. In the present study, we used a well-established experimental model of focal demyelination to assess whether prenatal immune challenge affects demyelination-induced inflammation. METHODS: Pregnant rats were injected with either lipopolysaccharide (100 μg/kg, ip) or pyrogen-free saline...
July 17, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28640227/impact-of-mycotoxins-secreted-by-aspergillus-molds-on-the-inflammatory-response-of-human-corneal-epithelial-cells
#5
Yélian Marc Bossou, Youssra Serssar, Amel Allou, Sandrine Vitry, Isabelle Momas, Nathalie Seta, Jean Menotti, Sophie Achard
Exposure to molds and mycotoxins not only contributes to the onset of respiratory disease, it also affects the ocular surface. Very few published studies concern the evaluation of the effect of mycotoxin exposure on ocular cells. The present study investigates the effects of aflatoxin B₁ (AFB₁) and gliotoxin, two mycotoxins secreted by Aspergillus molds, on the biological activity of the human corneal epithelial (HCE) cells. After 24, 48, and 72 h of exposure, cellular viability and inflammatory response were assessed...
June 22, 2017: Toxins
https://www.readbyqxmd.com/read/28625859/harmine-produces-antidepressant-like-effects-via-restoration-of-astrocytic-functions
#6
Fengguo Liu, Jingjing Wu, Yu Gong, Peng Wang, Lei Zhu, Lijuan Tong, Xiangfan Chen, Yong Ling, Chao Huang
Depression is a world-wide disease with no effective therapeutic methods. Increasing evidence indicates that astrocytic pathology contributes to the formation of depression. In this study, we investigated the effects of harmine, a natural β-carboline alkaloid and potent hallucinogen, known to modulate astrocytic glutamate transporters, on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. Results showed that harmine treatment (10, 20mg/kg) protected the mice against the CUS-induced increases in the immobile time in the tail suspension test (TST) and forced swimming test (FST), and also reversed the reduction in sucrose intake in the sucrose preference experiment...
June 15, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28605287/prdx1-peroxiredoxin-1-deficiency-reduces-cholesterol-efflux-via-impaired-macrophage-lipophagic-flux
#7
Se-Jin Jeong, Sinai Kim, Jong-Gil Park, In-Hyuk Jung, Mi-Ni Lee, Sejin Jeon, Hyae Yon Kweon, Dae-Yeul Yu, Sang-Hak Lee, Yangsoo Jang, Sang Won Kang, Ki-Hwan Han, Yury I Miller, Young Mi Park, Cheolho Cheong, Jae-Hoon Choi, Goo Taeg Oh
Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous anti-oxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the anti-oxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other anti-oxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages...
June 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28587324/in-vitro-activity-of-chlorogenic-acid-against-aspergillus-fumigatus-biofilm-and-gliotoxin-production
#8
Jin-Liang Kong, Jing Luo, Bing Li, Bi-Ying Dong, Hong Huang, Ke Wang, Li-Hong Wu, Yi-Qiang Chen
Aspergillus (A.) fumigatus, one of the most common causes of life-threatening fungal infections in immunocompromised patients, shows resistance to antifungal agents as has a high propensity to forming a biofilm. The present study aimed to investigate the effects of chlorogenic acid (CRA) on A. fumigatus biofilm formation and integrity. Confocal laser scanning microscopy was performed to determine the inhibitory effects of CRA against A. fumigatus biofilm formation. Transmission electron microscopy was performed to investigate the ultrastructural changes of A...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28525266/gliotoxin-biosynthesis-structure-mechanism-and-metal-promiscuity-of-carboxypeptidase-glij
#9
Antoine Marion, Michael Groll, Daniel H Scharf, Kirstin Scherlach, Manuel Glaser, Holger Sievers, Michael Schuster, Christian Hertweck, Axel A Brakhage, Iris Antes, Eva M Huber
The formation of glutathione (GSH) conjugates, best known from the detoxification of xenobiotics, is a widespread strategy to incorporate sulfur into biomolecules. The biosynthesis of gliotoxin, a virulence factor of the human pathogenic fungus Aspergillus fumigatus, involves attachment of two GSH molecules and their sequential decomposition to yield two reactive thiol groups. The degradation of the GSH moieties requires the activity of the Cys-Gly carboxypeptidase GliJ, for which we describe the X-ray structure here...
June 6, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28381925/molecular-insights-into-pathogenesis-and-infection-with-aspergillus-fumigatus
#10
REVIEW
Ciamak Ghazaei
The virulence of fungi is dependent on multiple factors, including the immune status of patients and biological features of fungi. In particular, the virulence of Aspergillus fumigatus is due to the complex interaction among various molecules involved in thermotolerance (such as ribosomal biogenesis proteins, α-mannosyltransferase and heat shock proteins), pigment production (DHN-melanin), immune evasion (like melanin and hydrophobin) and nutrient uptake (such as siderophores and zinc transporters). Other molecules also play important roles in the virulence of A...
March 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28376389/identification-and-characterization-of-the-verticillin-biosynthetic-gene-cluster-in-clonostachys-rogersoniana
#11
Ying Wang, Pengjie Hu, Yuanyuan Pan, Yaxin Zhu, Xingzhong Liu, Yongsheng Che, Gang Liu
Verticillin is one of the dimeric epipolythiodioxopiperazines (ETPs) which are toxic secondary metabolites produced only by fungi. ETPs have received substantial attention since its complex molecular architecture and a wide range of biological activities. Although biosynthesis of the monomeric gliotoxin has been studied extensively, the biosynthetic pathway of dimeric ETPs is far from being studied. To investigate the biosynthesis of dimeric ETPs and expand our understanding of their dimerization, the verticillin biosynthetic gene cluster (ver) was identified and cloned from a genomic DNA fosmid library of the Cordyceps-colonizing fungus Clonostachys rogersoniana with the designed primers based on the sequence of a nonribosomal peptide synthetase (NRPS) ChaP which was predicted to be responsible for chaetocin biosynthesis in Chaetomium virescens...
June 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28301237/aspergillosis-a-natural-infection-in-poultry-mycological-and-molecular-characterization-and-determination-of-gliotoxin-in-aspergillus-fumigatus-isolates
#12
Verónica Montes de Oca, Sara Esther Valdés, Carolina Segundo, Gabriela Guadalupe Gómez, José Ramírez, Roberto Arnulfo Cervantes
Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis...
March 2017: Avian Diseases
https://www.readbyqxmd.com/read/28280460/androstenediol-reduces-demyelination-induced-axonopathy-in-the-rat-corpus-callosum-impact-on-microglial-polarization
#13
Samah Kalakh, Abdeslam Mouihate
Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28276430/beta-trace-protein-as-a-new-non-invasive-immunological-marker-for-quinolinic-acid-induced-impaired-blood-brain-barrier-integrity
#14
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Robert J Breitenecker, Tatjana Stojakovic, Winfried März, Christoph Robier, Hans-Bernd Rothenhäusler, Harald Mangge, Andreas Meinitzer
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213885/epigenetic-modifier-induced-enhancement-of-fumiquinazoline-c-production-in-aspergillus-fumigatus-ga-l7-an-endophytic-fungus-from-grewia-asiatica-l
#15
Ankita Magotra, Manjeet Kumar, Manoj Kushwaha, Praveen Awasthi, Chand Raina, Ajai Prakash Gupta, Bhahwal A Shah, Sumit G Gandhi, Asha Chaubey
Present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of Aspergillus fumigatus (GA-L7), an endophytic fungus isolated from Grewia asiatica L. Seven secondary metabolites were isolated from A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28179499/structural-mechanistic-and-functional-insight-into-gliotoxin-bis-thiomethylation-in-aspergillus-fumigatus
#16
Stephen K Dolan, Tobias Bock, Vanessa Hering, Rebecca A Owens, Gary W Jones, Wulf Blankenfeldt, Sean Doyle
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S-adenosylhomocysteine (1.33 Å) and GtmA complexed to S-adenosylmethionine (2...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28149676/genomic-insight-into-pathogenicity-of-dematiaceous-fungus-corynespora-cassiicola
#17
Hong Keat Looi, Yue Fen Toh, Su Mei Yew, Shiang Ling Na, Yung-Chie Tan, Pei-Sin Chong, Jia-Shiun Khoo, Wai-Yan Yee, Kee Peng Ng, Chee Sian Kuan
Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient's contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases...
2017: PeerJ
https://www.readbyqxmd.com/read/28068839/antituberculosis-compounds-from-a-deep-sea-derived-fungus-aspergillus-sp-scsio-ind09f01
#18
Xiaowei Luo, Xuefeng Zhou, Xiuping Lin, Xiaochu Qin, Tianyu Zhang, Junfeng Wang, Zhengchao Tu, Bin Yang, Shengrong Liao, Yongqi Tian, Xiaoyan Pang, Kumaravel Kaliyaperumal, Jian Lin Li, Huaming Tao, Yonghong Liu
Eleven diketopiperazine and fumiquinazoline alkaloids (1-11) together with a tetracyclic triterpenoid helvolic acid (12) were obtained from the cultures of a deep-sea derived fungus Aspergillus sp. SCSIO Ind09F01. The structures of these compounds (1-12) were determined mainly by the extensive NMR, ESIMS spectra data and by comparison with previously described compounds. Besides, anti-tuberculosis, cytotoxic, antibacterial, COX-2 inhibitory and antiviral activities of these compounds were evaluated. Gliotoxin (3), 12,13-dihydroxy-fumitremorgin C (11) and helvolic acid (12) exhibited very strong anti-tuberculosis activity towards Mycobacterium tuberculosis with the prominent MIC50 values of <0...
January 9, 2017: Natural Product Research
https://www.readbyqxmd.com/read/27975125/antidepressant-like-activity-of-the-neuropeptide-y-y5-receptor-antagonist-lu-aa33810-behavioral-molecular-and-immunohistochemical-evidence
#19
Helena Domin, Bernadeta Szewczyk, Bartłomiej Pochwat, Monika Woźniak, Maria Śmiałowska
RATIONALE: It has recently been found that chronic treatment with the highly selective, brain-penetrating Y5 receptor antagonist, Lu AA33810 [N-[[trans-4-[(4,5-dihydro [1] benzothiepino[5,4-d] thiazol-2-yl) amino] cyclohexyl]methyl]-methanesulfonamide], produces antidepressant-like effects in the rat chronic mild stress model. OBJECTIVE: In the present study, we investigated the possible antidepressant-like activity of Lu AA33810 in rats subjected to glial ablation in the prefrontal cortex (PFC) by the gliotoxin L-AAA, which is an astroglial degeneration model of depression...
February 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27939578/disseminated-aspergillosis-in-an-immunocompetent-patient-with-detectable-bis-methylthio-gliotoxin-and-negative-galactomannan
#20
Matxalen Vidal-García, Pilar Sáncehez-Chueca, María Pilar Domingo, Carlos Ballester, Lourdes Roc, Isabel Ferrer, María José Revillo, Julián Pardo, Eva María Gálvez, Antonio Rezusta
BACKGROUND: Disseminated invasive aspergillosis is an exceptional finding in immunocompetent hosts. As in immunocompromised patients, it has high mortality rates. Early diagnostic methods are required in order to properly manage the patient. Bis(methylthio)gliotoxin (bmGT) is a novel biomarker, useful in onco-hematological patients. CASE REPORT: A 70-year-old male, with non-insulin dependent type II diabetes mellitus and a past surgery history of aortic valve replacement with coronary by-pass five years ago, was seen in the emergency department with blurred vision...
December 8, 2016: Revista Iberoamericana de Micología
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