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https://www.readbyqxmd.com/read/28303005/ligand-co-crystallization-of-aminoacyl-trna-synthetases-from-infectious-disease-organisms
#1
Spencer O Moen, Thomas E Edwards, David M Dranow, Matthew C Clifton, Banumathi Sankaran, Wesley C Van Voorhis, Amit Sharma, Colin Manoil, Bart L Staker, Peter J Myler, Donald D Lorimer
Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#2
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28294433/transcriptional-regulation-of-adhesive-properties-of-bacillus-subtilis-to-extracellular-matrix-proteins-through-the-fibronectin-binding-protein-yloa
#3
Facundo Rodriguez Ayala, Carlos Bauman, Marco Bartolini, Ester Saball, Marcela Salvarrey, Cecilia Leñini, Sebastián Cogliati, Mark Strauch, Roberto Grau
Bacterial adherence to extracellular matrix proteins (ECMp) plays important roles during host-pathogen interaction, however its genetic regulation remains poorly understood. yloA of the model bacterium Bacillus subtilis shows high homology to genes encoding fibronectin-binding proteins of Gram-positive pathogens. Here, we characterized the regulatory network of YloA-dependent adhesive properties of the probiotic B. subtilis natto (Bsn). YloA-proficient, but not YloA-deficient, Bsn specifically bound to ECMp in a concentration-dependent manner and were proficient in biofilm formation...
March 13, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28292720/clinical-relevance-of-hypogammaglobulinemia-clinical-and-biologic-variables-on-the-infection-risk-and-outcome-of-patients-with-stage-a-chronic-lymphocytic-leukemia
#4
Francesca R Mauro, Fortunato Morabito, Iolanda D Vincelli, Luigi Petrucci, Melissa Campanelli, Adriano Salaroli, Giuseppina Uccello, Annamaria Petrungaro, Francesca Ronco, Sara Raponi, Mauro Nanni, Antonino Neri, Manlio Ferrarini, Anna R Guarini, Robin Foà, Massimo Gentile
The prognostic effect of hypogammaglobulinemia (HGG), clinical and biologic characteristics on the infection risk and outcome has been retrospectively analyzed in 899 patients with stage A chronic lymphocytic leukemia (CLL). Low levels of IgG were recorded in 19.9% of patients at presentation, low levels of IgM and/or IgA in 10.4% and an additional 20% of patients developed HGG during the course of the disease. Before the start of any treatment, 160 (12.9%) patients experienced at least one grade ≥3 infection requiring a systemic anti-infective treatment and/or hospitalization...
February 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28274219/a-household-survey-of-medicine-storage-practices-in-gondar-town-northwestern-ethiopia
#5
Fitsum Sebsibe Teni, Abdrrahman Shemsu Surur, Assefa Belay, Dawit Wondimsigegn, Dessalegn Asmelashe Gelayee, Zewdneh Shewamene, Befikadu Legesse, Eshetie Melese Birru
BACKGROUND: Household surveys are crucial to get accurate information on how medicines are acquired, and used by consumers, as they provide the best evidence in the area. The objective of this study was to document household medicine storage practices in Gondar town, northwestern Ethiopia. METHODS: A cross-sectional household survey was conducted from April 5 to May 6, 2015. In the study, 809 households were surveyed from four sub-cities in the town selected through multistage sampling with 771 included in the final analysis...
March 9, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28273806/antimicrobial-dendrimeric-peptides-structure-activity-and-new-therapeutic-applications
#6
REVIEW
Mariano A Scorciapino, Ilaria Serra, Giorgia Manzo, Andrea C Rinaldi
Microbial resistance to conventional antibiotics is one of the most outstanding medical and scientific challenges of our times. Despite the recognised need for new anti-infective agents, however, very few new drugs have been brought to the market and to the clinic in the last three decades. This review highlights the properties of a new class of antibiotics, namely dendrimeric peptides. These intriguing novel compounds, generally made of multiple peptidic sequences linked to an inner branched core, display an array of antibacterial, antiviral and antifungal activities, usually coupled to low haemolytic activity...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28262425/sex-differences-in-transplantation
#7
REVIEW
Jeremiah D Momper, Michael L Misel, Dianne B McKay
Sex plays a role in the incidence and progression of a wide variety of diseases and conditions related to transplantation. Additionally, a growing body of clinical and experimental evidence suggests that sex can impact the pharmacokinetics and pharmacodynamics of several commonly used immunosuppressive and anti-infective drugs in transplant recipients. A better understanding of these sex differences will facilitate advances in individualizing treatment for patients and improve outcomes of solid organ transplantation...
February 20, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28261167/discovery-and-characterization-of-diazenylaryl-sulfonic-acids-as-inhibitors-of-viral-and-bacterial-neuraminidases
#8
Anja Hoffmann, Martina Richter, Susanne von Grafenstein, Elisabeth Walther, Zhongli Xu, Lilia Schumann, Ulrike Grienke, Christina E Mair, Christian Kramer, Judith M Rollinger, Klaus R Liedl, Michaela Schmidtke, Johannes Kirchmair
Viral neuraminidases are an established drug target to combat influenza. Severe complications observed in influenza patients are primarily caused by secondary infections with e.g., Streptococcus pneumoniae. These bacteria engage in a lethal synergism with influenza A viruses (IAVs) and also express neuraminidases. Therefore, inhibitors with dual activity on viral and bacterial neuraminidases are expected to be advantageous for the treatment of influenza infections. Here we report on the discovery and characterization of diazenylaryl sulfonic acids as dual inhibitors of viral and Streptococcus pneumoniae neuraminidase...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28254074/development-of-antibacterial-conjugates-using-sulfamethoxazole-with-monocyclic-terpenes-a-systematic-medicinal-chemistry-based-computational-approach
#9
Shasank S Swain, Sudhir K Paidesetty, Rabindra N Padhy
BACKGROUND AND OBJECTIVE: To develop 6 conjugate agents of the moribund antibiotic sulfamethoxazole (SMZ) joined to 6 individual monoterpenes, followed by protocols of medicinal chemistry as potent antibacterials, against multidrug resistant (MDR) human gruesome pathogenic bacteria. METHODS: Antibacterial activities of the proposed conjugates were ascertained by the 'prediction of activity spectra of substances' (PASS) program. Drug-likeness parameters and toxicity profiles of conjugates were standardized with the Lipinski rule of five, using cheminformatic tools, Molsoft, molinspiration, OSIRIS and ProTox...
March 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28253432/spectroscopic-and-computational-investigations-of-ligand-binding-to-isph-discovery-of-non-diphosphate-inhibitors
#10
Bing O'Dowd, Sarah Williams, Hongxin Wang, Joo Hwan No, Guodong Rao, Weixue Wang, J Andrew McCammon, Stephen P Cramer, Eric Oldfield
Isoprenoid biosynthesis is an important area for anti-infective drug development and one target is IspH, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) reductase, which forms isopentenyl diphosphate and dimethylallyl diphosphate from HMBPP in a 2H+/2e- reduction. IspH contains a 4Fe-4S cluster and here, we first investigated how small molecules can bind to the cluster using HYSCORE and NRVS spectroscopies. The results of these as well as other structural and spectroscopic investigations led to the conclusion that in most cases, ligands bind to IspH 4Fe-4S clusters via 1 coordination, forming tetrahedral geometries at the unique 4th Fe, ligand side-chains preventing further ligand (e...
March 2, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28246361/new-mouse-model-for-chronic-infections-by-gram-negative-bacteria-enabling-the-study-of-anti-infective-efficacy-and-host-microbe-interactions
#11
Daniel Pletzer, Sarah C Mansour, Kelli Wuerth, Negin Rahanjam, Robert E W Hancock
Only a few, relatively cumbersome animal models enable long-term Gram-negative bacterial infections that mimic human situations, where untreated infections can last for weeks. Here, we describe a simple murine cutaneous abscess model that enables chronic or progressive infections, depending on the subcutaneously injected bacterial strain. In this model, Pseudomonas aeruginosa cystic fibrosis epidemic isolate LESB58 caused localized high-density skin and soft tissue infections and necrotic skin lesions for up to 10 days but did not disseminate in either CD-1 or C57BL/6 mice...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28245269/chemogenomics-driven-discovery-of-endogenous-polyketide-anti-infective-compounds-from-endosymbiotic-emericella-variecolor-clb38-and-their-rna-secondary-structure-analysis
#12
H C Yashavantha Rao, Devaraju Rakshith, Ballagere Puttaraju Harini, Doddahosuru Mahadevappa Gurudatt, Sreedharamurthy Satish
In the postgenomic era, a new strategy for chemical dereplication of polyketide anti-infective drugs requires novel genomics and chromatographic strategies. An endosymbiotic fungal strain CLB38 was isolated from the root tissue of Combretum latifolium Blume (Combretaceae) which was collected from the Western Ghats of India. The isolate CLB38 was then identified as Emericella variecolor by its characteristic stellate ascospores culture morphology and molecular analysis of ITS nuclear rDNA and intervening 5.8S rRNA gene sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28238872/endovascular-treatment-of-intracavernous-internal-carotid-aneurysm-secondary-to-pituitary-infection-a-case-report
#13
Ligen Shi, Mading Zhou, Shenbin Xu, Qun Wu, Wei Yan, Jianmin Zhang
Intracavernous internal carotid artery (ICICA) aneurysm secondary to pituitary infection is exceedingly rare. We report an unusual case of a 63-year-old man who presented with acute left blepharoptosis and imaging findings of a pituitary infection. Interestingly, sudden onset of right blepharoptosis occurred after anti-infective therapy for ten days. Digital subtraction angiography revealed a right ICICA aneurysm. After six months of follow-up visits, enlargement of the ICICA aneurysm was observed, and the endovascular technique of a low-profile visualized intraluminal support (LVIS) stent combined with five detachable coils was successfully performed to treat the ICICA aneurysm with preservation of the internal carotid artery...
February 23, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28235746/exploring-the-binding-sites-of-staphylococcus-aureus-phenylalanine-trna-synthetase-a-homology-model-approach
#14
Samar S Elbaramawi, Samy M Ibrahim, El-Sayed M Lashine, Mohamed E El-Sadek, Efi Mantzourani, Claire Simons
Increased resistance of MRSA (multidrug resistance Staphylococcus aureus) to anti-infective drugs is a threat to global health necessitating the development of anti-infectives with novel mechanisms of action. Phenylalanine tRNA synthetase (PheRS) is a unique enzyme of the aminoacyl-tRNA synthetases (aaRSs), which are essential enzymes for protein biosynthesis. PheRS is an (αb)2 tetrameric enzyme composed of two alpha subunits (PheS) and two larger beta subunits (PheT). Our potential target in the drug development for the treatment of MRSA infections is the phenylalanine tRNA synthetase alpha subunit that contains the binding site for the natural substrate...
February 10, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28228724/drug-utilization-on-neonatal-wards-a-systematic-review-of-observational-studies
#15
Rosliana Rosli, Ahmad Fauzi Dali, Noorizan Abd Aziz, Amir Heberd Abdullah, Long Chiau Ming, Mohamed Mansor Manan
Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28228072/curcumin-and-endothelial-function-evidence-and-mechanisms-of-protective-effects
#16
Maryam Saberi Karimian, Matteo Pirro, Thomas P Johnston, Muhammed Majeed, Amirhossein Sahebkar
BACKGROUND: The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by non-invasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions...
February 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28223377/exopolysaccharide-repressing-small-molecules-with-antibiofilm-and-antivirulence-activity-against-pseudomonas-aeruginosa
#17
Erik van Tilburg Bernardes, Laetitia Charron-Mazenod, David J Reading, Shauna L Reckseidler-Zenteno, Shawn Lewenza
Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. Pseudomonas aeruginosa is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in Cystic Fibrosis (CF) patients. The extracellular matrix of P. aeruginosa biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and non-mucoid isolates of P...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28221753/structure-activity-relationships-of-the-competence-stimulating-peptides-csps-in-streptococcus-pneumoniae-reveal-motifs-critical-for-intra-group-and-cross-group-comd-receptor-activation
#18
Yifang Yang, Bimal Koirala, Lucia A Sanchez, Naiya R Phillips, Sally R Hamry, Yftah Tal-Gan
Streptococcus pneumoniae is a highly recombinogenic human pathogen that utilizes the competence stimulating peptide (CSP)-based quorum sensing (QS) circuitry to acquire antibiotic resistance genes from the environment and initiate its attack on the human host. Modulation of QS in this bacterium, either inhibition or activation, can therefore be used to attenuate S. pneumoniae infectivity and slow down pneumococcal resistance development. In this study we set to determine the molecular mechanism that drives CSP:receptor binding and identify CSP-based QS modulators with distinct activity profiles...
February 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28219144/-advances-in-the-research-of-antibacterial-function-of-silver-nanoparticle-and-its-application-in-burn-treatment
#19
M Z Liu, M X Liu, X L Wang, G H Guo
Silver has received much attention for its great anti-infection effect in wound. With the development of nanotechnology, the advantages of silver nanoparticles have gradually arisen in scientific practice and clinical application due to their large specific surface area etc. In this article, we conclude the antibacterial mechanisms of silver nanoparticles, the factors influencing their antibacterial effects, the methods of improving their performance and safety, and their application in burn treatment.
February 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28218496/functional-analysis-of-bioactivated-surfaces
#20
Selgai Haidari, Marko Boskov, Ulrike Schillinger, Klaus-Dietrich Wolff, Christian Plank, Andreas Kolk
Common scaffold surfaces, such as titanium, can have side effects, e.g., infections, cytotoxicity, impaired osseointegration or low regeneration rates for bone tissue. These effects lead to poor implant integration or even implant loss. Therefore, bioactive implants are promising instruments in tissue regeneration. Osteoinductive elements, such as growth factors and anti-infectives, support wound healing and bone growth and thereby enable faster osseointegration, even in elderly patients. In this study, titanium surfaces were coated with a poly-(D,L-lactide) (PDLLA) layer containing different concentrations of copolymer-protected gene vectors (COPROGs) to locally provide bone morphogenetic protein-2 (BMP-2) or activated anti-infective agents, such as chlorhexidine gluconate, triclosan and metronidazole, to prevent peri-implantitis...
February 20, 2017: Journal of Biomedical Materials Research. Part A
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