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Nassim Mahtal, Clémence Brewee, Sylvain Pichard, Orane Visvikis, Jean-Christophe Cintrat, Julien Barbier, Emmanuel Lemichez, Daniel Gillet
Cytotoxic necrotizing factor 1 (CNF1) is a toxin produced by pathogenic strains of Escherichia coli responsible for extra-intestinal infections. CNF1 deamidates Rac1, thereby triggering its permanent activation and worsening inflammatory reactions. Activated Rac1 is prone to proteasomal degradation. There is no targeted therapy against CNF1, despite its clinical relevance. In this work we developed a fluorescent cell-based immunoassay to screen for inhibitors of CNF1-induced Rac1 degradation among 1120 mostly approved drugs...
April 6, 2018: ChemMedChem
Francesca L Short, Chidiebere Akusobi, William R Broadhurst, George P C Salmond
Bacteria have evolved numerous defense systems to protect themselves from viral (bacteriophage) infection. The ToxIN system of Pectobacterium atrosepticum is a Type III toxin-antitoxin complex and "altruistic suicide" anti-phage system, which kills phage-infected cells through the release of a ribonuclease toxin, ToxN. ToxN is counteracted by a co-transcribed antitoxic RNA pseudoknot, ToxI, which self-assembles with ToxN into an inactive 3 ToxI:3 ToxN complex in vitro. However it is not known whether this complex is predominant in vivo, or how the complex is disassembled following infection to trigger a lethal, "altruistic" response...
January 17, 2018: Scientific Reports
Mengjie Zhang, Wang Wei, Yingming Sun, Xiu Jiang, Xiu Ying, Rui Tao, Longxing Ni
OBJECTIVES: Fish epidermal antimicrobial peptides, such as pleurocidin, are cathelicidins with broad-spectrum antimicrobial activity against gram negative and gram-positive bacteria, as well as fungi. In the current study, we attempted to optimize peptide bioactivity by sequence modification and assess the antimicrobial activities. METHODS: Fifteen pleurocidin analogues were designed, and the efficacy of pleurocidin congeners against common cariogenic microorganisms was tested; furthermore, we performed a preliminary study of the antimicrobial mechanism...
October 2016: Archives of Oral Biology
Jasem Al Shemaili, Khatija A Parekh, Robert A Newman, Björn Hellman, Carl Woodward, Abdu Adem, Peter Collin, Thomas E Adrian
The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was less potent (EC50 ~2...
June 17, 2016: Marine Drugs
Shin-Hyung Park, Jae-Chul Kim
PURPOSE: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45-50 Gy in 25-28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. MATERIALS AND METHODS: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil...
June 2016: Radiation Oncology Journal
Si Luo, Benli Wu, Xiaoqin Xiong, Jianwei Wang
The ionic composition of water is important for all fish. In the present study, the effects of total hardness and Ca(2+):Mg(2+) ratio on early life stages of rare minnows (Gobiocypris rarus), a promising laboratory fish in China, were evaluated. Paired parent fish were transferred to spawning aquaria (16 L) containing water at different total hardness and Ca:Mg ratios, and their offspring were further cultured at 25 ± 1 °C and 12:12-h light:dark photoperiod. Fertilization rates were not affected by total hardness to 480 mg L(-1) CaCO3, but egg size decreased with increasing total hardness...
2016: Comparative Medicine
John R Perfect, Jennifer L Tenor, Yi Miao, Richard G Brennan
With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with widespread use of antifungal agents, drug-resistant fungal infections are on the rise. Therefore, there is some urgency to develop the antifungal pipeline with the goal of new antifungal agent discovery. In this review, a simple metabolic pathway, which forms the disaccharide, trehalose, will be characterized and its potential as a focus for antifungal target(s) explained...
February 17, 2017: Virulence
Josh Sanburn
No abstract text is available yet for this article.
February 1, 2016: Time
Xin Yu, Zheng Li
Thymocyte selection-associated high mobility group box factor (TOX) is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. TOX encodes a nuclear protein of the high-mobility group box superfamily. It contains a DNA-binding domain, which allows it to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. Previous studies have shown that TOX play important roles in immune system...
2015: American Journal of Cancer Research
Pierre L Goossens, Jean-Nicolas Tournier
Anthrax, caused by Bacillus anthracis, a Gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. There are three types of human infection: cutaneous, inhalational, and gastrointestinal. For each form, B. anthracis spores need to cross the cutaneous, respiratory or digestive epithelial barriers, respectively, as a first obligate step to establish infection. Anthrax is a toxi-infection: an association of toxemia and rapidly spreading infection progressing to septicemia. The pathogenicity of Bacillus anthracis mainly depends on two toxins and a capsule...
2015: Frontiers in Microbiology
A D'ors, A A Cortés, A Sánchez-Fortún, M C Bartolomé, S Sánchez-Fortún
The successful selection of a particular type of bioelement and its association to the appropriate transducer determines the specificity of a biosensor. Therefore, from a strain of chloroficea Dictyosphaerium chlorelloides, modified in laboratory to tolerate high Cr(VI) concentrations, the possible interferences of other heavy metals on photosynthetic activity were studied. After exposing wild type and Cr(VI)-resistant cells to increasing Ag(+1), Co(+2), Hg(+2), Cr(+3), Cu(+2), Zn(+2), Fe(+3) and Cd(+2) concentrations, both photosynthetic quantum yields was compared...
January 2016: Ecotoxicology
S Sharma, D Kaul, D Singh
Arsenic biology has caught the imagination of scientists across the globe because of its unique association with degenerative diseases in general and cancer in particular. Recent findings have added a new dimension to arsenic biology by revealing that most of the arsenic epigenomic effects are mediated through its ability to induce cellular miR-2909 expression at low doses. The present study was addressed to explore the molecular link that might exist between arsenic exposure, miR-2909 RNomics involving immunomodulatory genes and effector IgA class switching, revealed that arsenic-exposed Balb/c mice exhibited predominant Th1 immune response coupled with effector IgA class switching thereby tailoring their immune system to ensure increased risk to infections and chronic diseases like cancer...
October 2015: Experimental and Molecular Pathology
S Mafla, R Moraga, C G León, V G Guzmán-Fierro, J Yañez, C T Smith, M A Mondaca, V L Campos
Roxarsone is included in chicken food as anticoccidial and mainly excreted unchanged in faeces. Microorganisms biotransform roxarsone into toxic compounds that leach and contaminate underground waters used for human consumption. This study evaluated roxarsone biotransformation by underground water microorganisms and the toxicity of the resulting compounds. Underground water from an agricultural field was used to prepare microcosms, containing 0.05 mM roxarsone, and cultured under aerobic or anaerobic conditions...
August 2015: World Journal of Microbiology & Biotechnology
Valerie W C Soo, Hsin-Yao Cheng, Brian W Kwan, Thomas K Wood
The prevalence of toxin/antitoxin (TA) systems in almost all genomes suggests they evolve rapidly. Here we show that an antitoxin from a type V system (GhoS, an endoribonuclease specific for the mRNA of the toxin GhoT) can be converted into a novel toxin (ArT) simply by adding two mutations. In contrast to GhoS, which increases growth, the new toxin ArT decreases growth dramatically in Escherichia coli. Transmission electron microscopy analysis revealed that the nucleoid in ArT-producing cells is concentrated and appears hollow...
2014: Scientific Reports
María del Carmen Sánchez-Villegas, Daniel Rodríguez-Álvarez, Concepción Ortega-Carrillo, Alejandro Alagón-Cano, Jaime Zaldívar-Cervera, Jorge Loría-Castellanos, Norma Alicia Urzúa-Rodríguez
BACKGROUND: Loxoscelism is a condition caused by the inoculation of a series of proteolytic enzymes through the loxosceles spider bite (violinist). Morbidity and mortality is unknown in our country. The loxoscelism toxi-syndrome of local expression may have a good prognosis; however, viscera-cutaneus or systemic form has a serious and often fatal evolution. We report a case of a systemic variant developed in a pregnant patient. CLINICAL CASE: We present the first reported case of systemic loxoscelism in a pregnant patient, highlighting the survival of the mother-son, in the presence of viscera-cutaneus behavior...
January 2014: Revista Médica del Instituto Mexicano del Seguro Social
No abstract text is available yet for this article.
1952: Revue de Médecine Navale (métropole et Outre-mer); Travaux Scientifiques des Médecins et Pharmaciens-chimistes de la Marine
Cédric Mazoyer, Jérémy Carlier, Alexandra Boucher, Michel Péoc'h, Catherine Lemeur, Yvan Gaillard
We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC-MS/MS after liquid-liquid extraction (Toxi-tubes A(®)). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7...
November 2013: Journal of Forensic Sciences
Francesca L Short, Xue Y Pei, Tim R Blower, Shue-Li Ong, Peter C Fineran, Ben F Luisi, George P C Salmond
Bacterial small RNAs perform numerous regulatory roles, including acting as antitoxic components in toxin-antitoxin systems. In type III toxin-antitoxin systems, small processed RNAs directly antagonize their toxin protein partners, and in the systems characterized the toxin and antitoxin components together form a trimeric assembly. In the present study, we sought to define how the RNA antitoxin, ToxI, inhibits its potentially lethal protein partner, ToxN. We show through cross-inhibition experiments with the ToxIN systems from Pectobacterium atrosepticum (ToxIN(Pa)) and Bacillus thuringiensis (ToxIN(Bt)) that ToxI RNAs are highly selective enzyme inhibitors...
January 15, 2013: Proceedings of the National Academy of Sciences of the United States of America
Tim R Blower, Terry J Evans, Rita Przybilski, Peter C Fineran, George P C Salmond
Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III protein-RNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that "escaped" ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN...
2012: PLoS Genetics
N Kaushal, S Naz, Ak Tiwary
BACKGROUND AND PURPOSE OF THE STUDY: Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells...
2011: Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
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