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https://www.readbyqxmd.com/read/29160203/molecular-epidemiology-and-antimicrobial-susceptibility-of-clostridium-difficile-isolated-from-hospitals-during-a-4-year-period-in-china
#1
Yun-Bo Chen, Si-Lan Gu, Ping Shen, Tao Lv, Yun-Hui Fang, Ling-Ling Tang, Lan-Juan Li
OBJECTIVE: The aim of this study was to perform molecular characterization for and determine the antimicrobial susceptibility profiles of Clostridium difficile collected from hospitals during a 4-year period (2009-2013) in China. METHODS: Strains of toxigenic C. difficile were isolated from patients with diarrhoea, and this was followed by typing using multilocus sequence typing (MLST) and testing for susceptibility to 10 antimicrobials by using the E-test. The mechanisms of resistance to moxifloxacin, erythromycin, clindamycin and tetracycline were investigated by PCR...
November 21, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29158666/tenofovir-alafenamide-in-the-treatment-of-chronic-hepatitis-b-design-development-and-place-in-therapy
#2
REVIEW
Eiichi Ogawa, Norihiro Furusyo, Mindie H Nguyen
Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level <29 IU/mL at week 48...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29156833/targeting-aggressive-prostate-cancer-associated-cd44v6-using-phage-display-selected-peptides
#3
Ying Peng, Austin R Prater, Susan L Deutscher
There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156755/escherichia-coli-nissle-1917-engineered-to-express-tum-5-can-restrain-murine-melanoma-growth
#4
Lian He, Huijun Yang, Fei Liu, Yiyan Chen, Sijia Tang, Wei Ji, Jianli Tang, Zhudong Liu, Yunjun Sun, Shengbiao Hu, Youming Zhang, Xiong Liu, Weitao Huang, Xuezhi Ding, Liqiu Xia
Tumor growth and metastasis depend on angiogenesis. Thus, inhibiting tumor angiogenesis has become promising cancer therapeutic strategy in recent years. Tumstatin is a more powerful angiogenesis inhibitor than endostatin. Anti-angiogenic active fragment encoding amino acids 45-132 (Tum-5) of tumstatin was subcloned into four different inducible expression vectors and successfully solubly expressed in Escherichia coli BL21 (DE3) in this study. Subsequently, an anaerobic inducible expression vector was constructed under Vitreoscilla hemoglobin gene promoter Pvhb in E...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156381/structure-based-methods-to-predict-mutational-resistance-to-diarylpyrimidine-non-nucleoside-reverse-transcriptase-inhibitors
#5
Syeda Maryam Azeem, Alecia N Muwonge, Nehaben Thakkar, Kristina W Lam, Kathleen M Frey
Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29152592/revisiting-the-igf-1r-as-a-breast-cancer-target
#6
Roudy Chiminch Ekyalongo, Douglas Yee
The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation...
2017: NPJ Precis Oncol
https://www.readbyqxmd.com/read/29148694/ambient-aqueous-synthesis-of-ultrasmall-ni0-85se-nanoparticles-for-non-invasive-photoacoustic-imaging-and-combined-photothermal-chemo-therapy-of-cancer
#7
Xianwen Wang, Fei Li, Xu Yan, Yan Ma, Zhaohua Miao, Liang Dong, Huajian Chen, Yang Lu, Zhengbao Zha
Big size induced long-term retention in the body has hampered the translational applications of many reported nanomedicine. Herein, we reported a multifunctional theranostic agent composed of ultrasmall polyacrylic acid functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed a considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency (PTCE) of 54...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#8
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29142571/in-vitro-transcription-analysis-of-ns5a-from-hcv-3a-circulating-in-pakistani-patients-with-chronic-hepatitis-c-and-their-differential-response-to-antiviral-therapy
#9
Shameem Bhatti, Sobia Manzoor, Fahed Parvaiz, Javed Ashraf, Farakh Javed
Objective: Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy. Methods: In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection...
September 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29140675/identification-of-novel-allosteric-modulators-of-glutamate-transporter-eaat2
#10
Sandhya Kortagere, Ole Valente Mortensen, Jingsheng Xia, William Lester, Yuhong Fang, Yellamelli V V Srikanth, Joseph M Salvino, Andreia Cristina Karklin Fontana
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsyand neurodegenerative diseases among others. EAAT2 is the main subtype responsible for glutamate clearance in the brain, having a key role in regulating transmission and preventing excitotoxicity. Therefore, compounds that increase the expression or activity of EAAT2 have therapeutic potential for neuroprotection. Previous studies identified molecular determinants for EAAT2 transport stimulation in a structural domain that lies at the interface of the rigid trimerization domain and the central substrate binding transport domain...
November 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29133952/engaging-homeostatic-plasticity-to-treat-depression
#11
E R Workman, F Niere, K F Raab-Graham
Major depressive disorder (MDD) is a complex and heterogeneous mood disorder, making it difficult to develop a generalized, pharmacological therapy that is effective for all who suffer from MDD. Through the fortuitous discovery of N-methyl-D-aspartate receptor (NMDAR) antagonists as effective antidepressants, we have gained key insights into how antidepressant effects can be produced at the circuit and molecular levels. NMDAR antagonists act as rapid-acting antidepressants such that relief from depressive symptoms occurs within hours of a single injection...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133777/acute-lymphoblastic-leukemia-patient-with-variant-atf7ip-pdgfrb-fusion-and-favorable-response-to-tyrosine-kinase-inhibitor-treatment-a-case-report
#12
Ge Zhang, Yanle Zhang, Jianrong Wu, Yan Chen, Zhigui Ma
BACKGROUND Chromosomal translocations involving the PDGFRB gene have been reported in a broad spectrum of hematological malignancies. An ATF7IP/PDGFRB fusion was recently identified in a Philadelphia chromosome-like (Ph-like) B-progenitor acute lymphoblastic leukemia (B-ALL) patient. Here we report on a special case of a Ph-like ALL patient who had a variant ATF7IP/PDGFRB fusion. CASE REPORT In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively...
November 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29133434/pkd1-promotes-functional-synapse-formation-coordinated-with-n-cadherin-in-hippocampus
#13
Cheng Cen, Li-Da Luo, Wen-Qi Li, Gang Li, Na-Xi Tian, Ge Zheng, Dong-Min Yin, Yimin Zou, Yun Wang
Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836-871 and phosphorylates it at Ser 869, 871, 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29123174/d-cateslytin-a-new-antimicrobial-peptide-with-therapeutic-potential
#14
Abdurraouf Zaet, Pauline Dartevelle, Fadoua Daouad, Claire Ehlinger, Fabienne Quilès, Grégory Francius, Christian Boehler, Camille Bergthold, Benoît Frisch, Gilles Prévost, Philippe Lavalle, Francis Schneider, Youssef Haïkel, Marie-Hélène Metz-Boutigue, Céline Marban
The rise of antimicrobial resistant microorganisms constitutes an increasingly serious threat to global public health. As a consequence, the efficacy of conventional antimicrobials is rapidly declining, threatening the ability of healthcare professionals to cure common infections. Over the last two decades host defense peptides have been identified as an attractive source of new antimicrobials. In the present study, we characterized the antibacterial and mechanistic properties of D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122685/molecular-and-enzoinformatics-perspectives-of-targeting-polo-like-kinase-1-in-cancer-therapy
#15
REVIEW
Shazi Shakil, Mohammad H Baig, Shams Tabrez, Syed M Danish Rizvi, Syed K Zaidi, Ghulam M Ashraf, Shakeel A Ansari, Aftab Aslam Parwaz Khan, Mohammad H Al-Qahtani, Adel M Abuzenadah, Adeel G Chaudhary
Cancer is a disease that has been the focus of scientific research and discovery and continues to remain so. Polo-like kinases (PLKs) are basically serine/threonine kinase enzymes that control cell cycle from yeast to humans. PLK-1 stands for 'Polo-like kinase-1'. It is the most investigated protein among PLKs. It is crucial for intracellular processes, hence a 'hot' anticancer drug-target. Accelerating innovations in Enzoinformatics and associated molecular visualization tools have made it possible to literally perform a 'molecular level walk' traversing through and observing the minutest contours of the active site of relevant enzymes...
November 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29119048/elucidating-immunometabolic-targets-in-glioblastoma
#16
REVIEW
Pooja Agarwal, Michael J Pajor, David M Anson, Maheedhara R Guda, Collin M Labak, Andrew J Tsung, Kiran K Velpula
Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29116116/urinary-sulphatoxymelatonin-as-a-biomarker-of-serotonin-status-in-biogenic-amine-deficient-patients
#17
Marta Batllori, Marta Molero-Luis, Luisa Arrabal, Javier de Las Heras, Joaquín-Alejandro Fernandez-Ramos, Luis González Gutiérrez-Solana, Salvador Ibáñez-Micó, Rosario Domingo, Jaume Campistol, Aida Ormazabal, Frederic Sedel, Thomas Opladen, Basiliki Zouvelou, Roser Pons, Angels Garcia-Cazorla, Eduardo Lopez-Laso, Rafael Artuch
Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115374/metabolic-profiles-of-adipose-derived-and-bone-marrow-derived-stromal-cells-from-elderly-coronary-heart-disease-patients-by-capillary-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry
#18
Jian-Zhong Li, Hui Qu, Jian Wu, Fan Zhang, Zhi-Bo Jia, Jian-Yong Sun, Bo Lv, Yue Kang, Shu-Lin Jiang, Kai Kang
Adipose-tissue derived mesenchymal stem cell (ADSC)-based therapy is a promising option for patients with atherosclerotic conditions, including coronary artery disease. However, the potential differences in the metabolic characteristics between bone marrow-derived mesenchymal stem cells (BMSCs) and ADSCs have remained to be fully elucidated. The present study aimed to compare the metabolic profiles of BMSCs and ADSCs via liquid chromatography quadrupole time-of-flight mass spectrometry. BMSCs and ADSCs obtained from elderly coronary heart disease patients were cultured, and after three passages, supernatants of each cell type were collected and systematically analysed...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29111272/novel-hbv-recombinants-between-genotypes-b-and-c-in-3-terminal-reverse-transcriptase-rt-sequences-are-associated-with-enhanced-viral-dna-load-higher-rt-point-mutation-rates-and-place-of-birth-among-chinese-patients
#19
Baoming Liu, Jing-Xian Yang, Ling Yan, Hui Zhuang, Tong Li
As one of the major global public health concerns, hepatitis B virus (HBV) can be divided into at least eight genotypes, which may be related to disease severity and treatment response. We previously demonstrated that genotypes B and C HBV, with distinct geographical distribution in China, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene region, a target of antiviral therapy using nucleos(t)ide analogues. Recently recombination between HBV genotypes B and C was reported to occur in the RT region...
October 27, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29110065/fungi-in-gastrointestinal-tracts-of-human-and-mice-from-community-to-functions
#20
REVIEW
Jiayan Li, Daiwen Chen, Bing Yu, Jun He, Ping Zheng, Xiangbing Mao, Jie Yu, Junqiu Luo, Gang Tian, Zhiqing Huang, Yuheng Luo
Fungi are often ignored in studies on gut microbes because of their low level of presence (making up only 0.1% of the total microorganisms) in the gastrointestinal tract (GIT) of monogastric animals. Recent studies using novel technologies such as next generation sequencing have expanded our understanding on the importance of intestinal fungi in humans and animals. Here, we provide a comprehensive review on the fungal community, the so-called mycobiome, and their functions from recent studies in humans and mice...
November 6, 2017: Microbial Ecology
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