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https://www.readbyqxmd.com/read/28213871/thieno-2-3-b-pyridine-derivatives-a-new-class-of-antiviral-drugs-against-mayaro-virus
#1
Raquel Amorim, Marcelo Damião Ferreira de Meneses, Julio Cesar Borges, Luiz Carlos da Silva Pinheiro, Lucio Ayres Caldas, Claudio Cesar Cirne-Santos, Marcos Vinícius Palmeira de Mello, Alessandra Mendonça Teles de Souza, Helena Carla Castro, Izabel Christina Nunes de Palmer Paixão, Renata de Mendonça Campos, Ingrid E Bergmann, Viviana Malirat, Alice Maria Rolim Bernardino, Moacyr Alcoforado Rebello, Davis Fernandes Ferreira
Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28213636/decrease-of-glial-cell-derived-neurotrophic-factor-contributes-to-anesthesia-and-surgery-induced-learning-and-memory-dysfunction-in-neonatal-rats
#2
Lingli Gui, Xi Lei, Zhiyi Zuo
: Long duration of anesthesia may induce toxicity in the developing brain. However, little is known about the effects of the combination of surgery and anesthesia on the developing brain. The mechanisms for the effects are not clear. To determine these effects, postnatal day 7 male and female Sprague-Dawley rats were exposed to 3% sevoflurane for 2 h with or without right common carotid exposure. Pyrrolidine dithiocarbamate (PDTC), an anti-inflammatory agent, was given 30 min before and 6 h after the carotid exposure...
February 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28213321/effects-of-selenium-lead-interaction-on-the-gene-expression-of-inflammatory-factors-and-selenoproteins-in-chicken-neutrophils
#3
Xiaojing Li, Mengyuan Xing, Menghao Chen, Jinxin Zhao, Ruifeng Fan, Xia Zhao, Changyu Cao, Jie Yang, Ziwei Zhang, Shiwen Xu
Lead (Pb) is one of the most highly toxic metal pollutant that can cause damage to the immune system. It is known that selenium (Se) can antagonize heavy metals. To explore the toxic effects of Pb poisoning on bird immune cells, as well as the alleviating effects of Se on Pb, Se supplement and/or Pb poisoning chicken models were established. One hundred and eighty Hyline 7-day-old male chickens received either Se (1mg Se per kg of diet), Pb (350mg Pb per liter water) or Se+Pb in their diet and water for 90 days...
February 14, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28213156/myotonic-dystrophy-disease-repeat-range-penetrance-age-of-onset-and-relationship-between-repeat-size-and-phenotypes
#4
REVIEW
Kevin Yum, Eric T Wang, Auinash Kalsotra
Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease primarily characterized by myotonia and progressive muscle weakness. The pathogenesis of DM involves microsatellite expansions in noncoding regions of transcripts that result in toxic RNA gain-of-function. Each successive generation of DM families carries larger repeat expansions, leading to an earlier age of onset with increasing disease severity. At present, diagnosis of DM is challenging and requires special genetic testing to account for somatic mosaicism and meiotic instability...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28213126/the-galactose-induced-decrease-in-phosphate-levels-leads-to-toxicity-in-yeast-models-of-galactosemia
#5
Caio M Machado, Evandro A De-Souza, Ana Luiza F V De-Queiroz, Felipe S A Pimentel, Guilherme F S Silva, Fabio M Gomes, Mónica Montero-Lomelí, Claudio A Masuda
Classic galactosemia is an inborn error of metabolism caused by deleterious mutations in the GALT gene. A number of evidences indicate that the galactose-1-phosphate accumulation observed in patient cells is a cause of toxicity in this disease. Nevertheless, the consequent molecular events caused by the galactose-1-phosphate accumulation remain elusive. Here we show that intracellular inorganic phosphate levels decreased when yeast models of classic galactosemia were exposed to galactose. The decrease in phosphate levels is probably due to the trapping of phosphate in the accumulated galactose-1-phosphate since the deletion of the galactokinase encoding gene GAL1 suppressed this phenotype...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#6
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28212817/in-vivo-toxicity-of-copper-oxide-lead-oxide-and-zinc-oxide-nanoparticles-acting-in-different-combinations-and-its-attenuation-with-a-complex-of-innocuous-bio-protectors
#7
Ilzira A Minigalieva, Boris A Katsnelson, Vladimir G Panov, Larisa I Privalova, Anatoly N Varaksin, Vladimir B Gurvich, Marina P Sutunkova, Vladimir Ya Shur, Ekaterina V Shishkina, Irene E Valamina, Ilya V Zubarev, Oleg H Makeyev, Ekaterina Y Meshtcheryakova, Svetlana V Klinova
Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.t.) (for performing a broncho-alveolar lavage in 24hrs to estimate the cytological and biochemical indices of the response of the lower airways), while in the other, Me-NPs were repeatedly injected intraperitoneally (i...
February 14, 2017: Toxicology
https://www.readbyqxmd.com/read/28212723/redox-dynamics-of-manganese-as-a-mitochondrial-life-death-switch
#8
REVIEW
Matthew Ryan Smith, Jolyn Fernandes, Young-Mi Go, Dean P Jones
Sten Orrenius, M.D., Ph.D., pioneered many areas of cellular and molecular toxicology and made seminal contributions to our knowledge of oxidative stress and glutathione (GSH) metabolism, organellar functions and Ca(+2)-dependent mechanisms of cell death, and mechanisms of apoptosis. On the occasion of his 80(th) birthday, we summarize current knowledge on redox biology of manganese (Mn) and its role in mechanisms of cell death. Mn is found in all organisms and has critical roles in cell survival and death mechanisms by regulating Mn-containing enzymes such as manganese superoxide dismutase (SOD2) or affecting expression and activity of caspases...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212704/neurochemical-differences-in-learning-and-memory-paradigms-among-rats-supplemented-with-anthocyanin-rich-blueberry-diets-and-exposed-to-acute-doses-of-56-fe-particles
#9
Shibu M Poulose, Bernard M Rabin, Donna F Bielinski, Megan E Kelly, Marshall G Miller, Nopporn Thanthaeng, Barbara Shukitt-Hale
The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to "accelerated aging." One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as (56)Fe, within 24-48h after exposure, and found that radiation primarily affects memory and not learning...
February 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/28212632/exome-wide-association-study-identifies-genetic-polymorphisms-of-c12orf51-myl2-and-aldh2-associated-with-blood-lead-levels-in-the-general-korean-population
#10
Sang-Yong Eom, Myung Sil Hwang, Ji-Ae Lim, Byung-Sun Choi, Ho-Jang Kwon, Jung-Duck Park, Yong-Dae Kim, Heon Kim
BACKGROUND: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population. METHODS: The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb...
February 17, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28211874/datf4-regulation-of-mitochondrial-folate-mediated-one-carbon-metabolism-is-neuroprotective
#11
Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha Hy Loh, L Miguel Martins
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211535/arylmethylamino-steroids-as-antiparasitic-agents
#12
Reimar Krieg, Esther Jortzik, Alice-Anne Goetz, Stéphanie Blandin, Sergio Wittlin, Mourad Elhabiri, Mahsa Rahbari, Selbi Nuryyeva, Kerstin Voigt, Hans-Martin Dahse, Axel Brakhage, Svenja Beckmann, Thomas Quack, Christoph G Grevelding, Anthony B Pinkerton, Bruno Schönecker, Jeremy Burrows, Elisabeth Davioud-Charvet, Stefan Rahlfs, Katja Becker
In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1-5 nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211448/cx-5461-is-a-dna-g-quadruplex-stabilizer-with-selective-lethality-in-brca1-2-deficient-tumours
#13
Hong Xu, Marco Di Antonio, Steven McKinney, Veena Mathew, Brandon Ho, Nigel J O'Neil, Nancy Dos Santos, Jennifer Silvester, Vivien Wei, Jessica Garcia, Farhia Kabeer, Daniel Lai, Priscilla Soriano, Judit Banáth, Derek S Chiu, Damian Yap, Daniel D Le, Frank B Ye, Anni Zhang, Kelsie Thu, John Soong, Shu-Chuan Lin, Angela Hsin Chin Tsai, Tomo Osako, Teresa Algara, Darren N Saunders, Jason Wong, Jian Xian, Marcel B Bally, James D Brenton, Grant W Brown, Sohrab P Shah, David Cescon, Tak W Mak, Carlos Caldas, Peter C Stirling, Phil Hieter, Shankar Balasubramanian, Samuel Aparicio
G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28210953/combined-toxicity-of-imidacloprid-and-three-insecticides-to-the-earthworm-eisenia-fetida-annelida-oligochaeta
#14
Tao Cang, Dejiang Dai, Guiling Yang, Yijun Yu, Lu Lv, Leiming Cai, Qiang Wang, Yanhua Wang
Although the earthworm Eisenia fetida has been used in many ecotoxicological studies in recent years, most of these studies have only focused on assessing the effects of individual insecticides. In the present study, we aimed to compare the individual and combined toxic effects of imidacloprid and three insecticides (phoxim, chlorpyrifos, and lambda-cyhalothrin) on E. fetida. We showed that imidacloprid had the highest intrinsic toxicity to the worms in filter paper contact test, followed by phoxim and lambda-cyhalothrin, while the least toxicity was found from chlorpyrifos...
February 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28210931/serotonin-syndrome-from-5-hydroxytryptophan-supplement-ingestion-in-a-9-month-old-labrador-retriever
#15
Hopkins Jennifer, Pardo Mariana, Bischoff Karyn
INTRODUCTION: 5-Hydroxytryptophan (5-HTP) supplements are available over the counter and labeled as sleeping aids and anxiolytics for human use. 5-HTP is a serotonin precursor and overdose can lead to serotonin syndrome. CASE REPORT: A 9-month-old female Labrador retriever was evaluated after ingestion of a 5-HTP supplement. Signs of agitation developed within 1 h of ingestion, and emesis was attempted by the owner with  3% hydrogen peroxide (H2O2) orally. On presentation, the dog was obtunded, bilaterally mydriatic and salivating...
February 16, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28210905/hypermagnesemia-disturbances-in-rats-no-related-pentadecapeptide-bpc-157-abrogates-l-name-and-l-arginine-worsen
#16
Maria Medvidovic-Grubisic, Vasilije Stambolija, Danijela Kolenc, Jadranka Katancic, Tamara Murselovic, Ivna Plestina-Borjan, Sanja Strbe, Domagoj Drmic, Ivan Barisic, Aleksandra Sindic, Sven Seiwerth, Predrag Sikiric
AIM: Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects...
February 16, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28209108/acute-temozolomide-induced-liver-injury%C3%A2-mixed-type-hepatocellular-and-cholestatic-toxicity
#17
C Aygun, A Y Altınok, A Çakır, A F Agan, Y Balaban
Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28208796/recent%C3%A2-trends%C3%A2-in%C3%A2-marine%C3%A2-phycotoxins%C3%A2-from%C3%A2-australian%C3%A2-coastal%C3%A2-waters
#18
Penelope Ajani, D Tim Harwood, Shauna A Murray
Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years...
February 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#19
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208145/carfilzomib-inhibits-constitutive-nf-%C3%AE%C2%BAb-activation-in-mantle-cell-lymphoma-b-cells-and-leads-to-the-induction-of-apoptosis
#20
Yong-Li Zhang, Matthew Ho Zhi Guang, Hui-Qin Zhuo, Xiang-Hui Min, Qin Yao, Ai-Qi Gu, Sheng-Hua Wu, Dai-Bo Zhang, Jing-Yuan Lu, Yan Chen, Yu-Han Chen, Ke-Jie Zhang
Mantle cell lymphoma (MCL) remains incurable and new treatments are needed, especially in the relapsed/refractory setting. We therefore investigated the effects of carfilzomib, a novel, long-acting, second-generation proteasome inhibitor, in MCL cells. Eight established MCL cell lines and freshly isolated primary MCL cells were treated with carfilzomib. Cell proliferation was assessed by a 3H-thymidine incorporation assay. Cell apoptosis was evaluated by flow cytometry with annexin V and propidium iodide. Electrophoresis mobility shift (EMSA), Western blot, and luciferase assays were used to analyze NF-κB activation and related signaling proteins...
February 17, 2017: Acta Haematologica
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