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https://www.readbyqxmd.com/read/27913547/new-treatment-approaches-to-von-willebrand-disease
#1
Michelle Lavin, James S O'Donnell
von Willebrand disease (VWD) is the commonest inherited bleeding disorder and results from either a quantitative or qualitative deficiency in the plasma glycoprotein von Willebrand factor (VWF). Recent large cohort studies have significantly enhanced our understanding of the molecular mechanisms involved in the pathogenesis of VWD. In contrast, however, there have been relatively few advances in the therapeutic options available for the treatment of bleeding in patients with VWD. Established treatment options include tranexamic acid, 1-deamino-8-d-arginine vasopressin (DDAVP), and plasma-derived VWF concentrates...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#2
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27908736/cd98-mediated-adhesive-signaling-enables-the-establishment-and-propagation-of-acute-myelogenous-leukemia
#3
Jeevisha Bajaj, Takaaki Konuma, Nikki K Lytle, Hyog Young Kwon, Jailal N Ablack, Joseph M Cantor, David Rizzieri, Charles Chuah, Vivian G Oehler, Elizabeth H Broome, Edward D Ball, Edward H van der Horst, Mark H Ginsberg, Tannishtha Reya
Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient-derived AML, highlighting the importance of this pathway in human disease...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27908670/proteome-of-the-rete-testis-fluid-from-tropically-adapted-morada-nova-rams
#4
Mauricio Fraga van Tilburg, Solange Damasceno Sousa, Révila Bianca Ferreira de Melo, Frederico B Moreno, Ana Cristina Monteiro-Moreira, Renato A Moreira, Arlindo de Alencar Moura
The rete testis has a close relationship with sperm development and may have other functions besides serving as an intercalated channel. The aim of this study was to identify and characterize the proteins of rete testis fluid (RTF) from tropically-adapted Morada Nova rams. Testicles obtained from six Morada Nova rams were dissected and the head of the epididymis was separated to access the efferent ducts. Rete testis fluid was obtained by gentle massage of the testis. The fluid was centrifuged to remove cell debris and sperm...
November 22, 2016: Animal Reproduction Science
https://www.readbyqxmd.com/read/27908641/free-energy-perturbation-calculation-of-relative-binding-free-energy-between-broadly-neutralizing-antibodies-and-the-gp120-glycoprotein-of-hiv-1
#5
Anthony J Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S Murret, Fang Xu, Amy Bao, Nina J Lu, Tongqing Zhou, Peter D Kwong, Lawrence Shapiro, Barry Honig, Richard A Friesner
Direct calculation of relative binding affinities between antibodies and antigens is a long-sought goal. However, despite substantial efforts, no generally applicable computational method has been described. Here we describe a systematic free energy perturbation (FEP) protocol and calculate the binding affinities between the gp120 envelope glycoprotein of HIV-1 and three broadly neutralizing antibodies (bNAbs) of the VRC01 class. The protocol has been adapted from successful studies of small molecules to address the challenges associated with modeling protein-protein interactions...
November 28, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27906723/safety-and-outcome-measures-of-first-in-human-intraperitoneal-%C3%AE-radioimmunotherapy-with-212pb-tcmc-trastuzumab
#6
Ruby F Meredith, Julien J Torgue, Tania A Rozgaja, Eileen P Banaga, Patty W Bunch, Ronald D Alvarez, J Michael Straughn, Michael C Dobelbower, Andrew M Lowy
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome...
November 30, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27904492/hydroxycitric-acid-ameliorates-inflammation-and-oxidative-stress-in-mouse-models-of-multiple-sclerosis
#7
Mahdi Goudarzvand, Sanaz Afraei, Somaye Yaslianifard, Saleh Ghiasy, Ghazal Sadri, Mustafa Kalvandi, Tina Alinia, Ali Mohebbi, Reza Yazdani, Shahin Khadem Azarian, Abbas Mirshafiey, Gholamreza Azizi
Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35-55)...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27902833/evaluation-of-ischemic-and-bleeding-risks-associated-with-2-parenteral-antiplatelet-strategies-comparing-cangrelor-with-glycoprotein-iib-iiia-inhibitors-an-exploratory-analysis-from-the-champion-trials
#8
Muthiah Vaduganathan, Robert A Harrington, Gregg W Stone, Efthymios N Deliargyris, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Alberto Menozzi, Jayne Prats, Steven Elkin, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt
Importance: In the context of contemporary pharmacotherapy, optimal antiplatelet management with percutaneous coronary intervention (PCI) has not been well established. Objective: To compare the ischemic and bleeding risks associated with glycoprotein IIb/IIIa inhibitors (GPIs) and a potent P2Y12 antagonist, cangrelor, in patients undergoing PCI. Design, Setting, and Participants: An exploratory analysis of pooled patient-level data from the 3 phase 3 Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX) trials of patients undergoing elective or nonelective PCI...
November 30, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27902713/association-of-n-linked-glycoprotein-acetyls-and-colorectal-cancer-incidence-and-mortality
#9
Paulette D Chandler, Akintunde O Akinkuolie, Deirdre K Tobias, Patrick R Lawler, Chungying Li, M Vinayaga Moorthy, Lu Wang, Daniel A Duprez, David R Jacobs, Robert J Glynn, James Otvos, Margery A Connelly, Wendy S Post, Paul M Ridker, JoAnn E Manson, Julie E Buring, I-Min Lee, Samia Mora
BACKGROUND: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker. METHODS: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA)...
2016: PloS One
https://www.readbyqxmd.com/read/27899813/the-pro-fibrotic-role-of-dipeptidyl-peptidase-4-in-carbon-tetrachloride-induced-experimental-liver-injury
#10
Xin M Wang, Lauren E Holz, Sumaiya Chowdhury, Shaun P Cordoba, Kathryn A Evans, Margaret G Gall, Ana Júlia Vieira de Ribeiro, Yuan Zhou Zheng, Miriam T Levy, Denise M T Yu, Tsun-Wen Yao, Natasa Polak, Christopher J Jolly, Patrick Bertolino, Geoffrey W McCaughan, Mark D Gorrell
Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice...
November 30, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27899485/circulating-microrna-122-is-associated-with-the-risk-of-new-onset-metabolic-syndrome-and-type-2-diabetes
#11
Peter Willeit, Philipp Skroblin, Alexander R Moschen, Xiaoke Yin, Dorothee Kaudewitz, Anna Zampetaki, Temo Barwari, Meredith Whitehead, Cristina M Ramírez, Leigh Goedeke, Noemi Rotllan, Enzo Bonora, Alun D Hughes, Peter Santer, Carlos Fernández-Hernando, Herbert Tilg, Johann Willeit, Stefan Kiechl, Manuel Mayr
MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n=810; survey year: 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type-2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-alpha-2-glycoprotein and positively with afamin, complement-factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27894861/development-of-a-competitive-double-antibody-lateral-flow-assay-for-the-detection-of-antibodies-specific-to-glycoprotein-b-of-aujeszky-s-disease-virus-in-swine-sera
#12
V V Vrublevskaya, V N Afanasyev, A A Grinevich, Yu Y Skarga, P P Gladyshev, S A Ibragimova, D V Krylsky, O S Morenkov
Three lateral flow assays (LFAs) for the detection of antibodies against glycoprotein B (gB) of Aujeszky's disease virus (ADV) in swine sera: a competitive double antibody sandwich LFA without a preincubation step (CDAS-gB-LFA), a CDAS-gB-LFA with a preincubation step (pCDAS-gB-LFA), and a competitive direct gB-LFA have been developed and were compared with each other and with a gB-ELISA. The assays are based on monoclonal antibodies to immunodominant epitopes of ADV gB. The pCDAS-gB-LFA proved to be the most specific and sensitive assay to detect antibodies directed to ADV gB...
November 25, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27894589/discovery-and-preclinical-evaluation-of-7-benzyl-n-substituted-pyrrolo-3-2-d-pyrimidin-4-amines-as-single-agents-with-microtubule-targeting-effects-along-with-triple-acting-angiokinase-inhibition-as-antitumor-agents
#13
Roheeth Kumar Pavana, Shruti Choudhary, Anja Bastian, Michael A Ihnat, Ruoli Bai, Ernest Hamel, Aleem Gangjee
The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of AA with microtubule targeting agents (MTAs) have been particularly successful. The discovery, synthesis and biological evaluations of a series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR), along with microtubule targeting in single molecules are described...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27887624/detection-and-phylogenetic-analysis-of-porcine-epidemic-diarrhea-virus-in-central-china-based-on-the-orf3-gene-and-the-s1-gene
#14
Yunfang Su, Yunchao Liu, Yumei Chen, Baolei Zhao, Pengchao Ji, Guangxu Xing, Dawei Jiang, Chang Liu, Yapeng Song, Guoqiang Wang, Dongliang Li, Ruiguang Deng, Gaiping Zhang
BACKGROUND: Porcine epidemic diarrhea (PED) has increased in severity in China since 2010. To investigate further the infectivity, genetic diversity and molecular epidemiology of its causative agent, the porcine epidemic diarrhea virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue of piglets with severe diarrhea, from 17 cities in central China. Both the spike (S) glycoprotein (S1, 1-789 amino acids (aa)) and the full-length ORF3 gene of 21 representative field strains from 21 farms in 11 cities were sequenced and analysed...
November 25, 2016: Virology Journal
https://www.readbyqxmd.com/read/27882867/subtyping-of-cryptosporidium-cuniculus-and-genotyping-of-enterocytozoon-bieneusi-in-rabbits-in-two-farms-in-heilongjiang-province-china
#15
Ziyin Yang, Wei Zhao, Yujuan Shen, Weizhe Zhang, Ying Shi, Guangxu Ren, Di Yang, Hong Ling, Fengkun Yang, Aiqin Liu, Jianping Cao
Cryptosporidium spp. and Enterocytozoon bieneusi are two prevalent opportunistic pathogens in humans and animals. Currently, few data are available on genetic characterization of both pathogens in rabbits in China. The aim of the present study was to understand prevalence and genetic characterization of Cryptosporidium spp. and E. bieneusi in rabbits. We collected 215 fecal samples from 150 Rex rabbits and 65 New Zealand White rabbits on two different farms in Heilongjiang Province, China. Cryptosporidium spp...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27882696/fetuin-a-alpha-2hs-glycoprotein-modulates-growth-motility-invasion-and-senescence-in-high-grade-astrocytomas
#16
Gladys N Nangami, Amos M Sakwe, Michael G Izban, Tanu Rana, Philip E Lammers, Portia Thomas, Zhenbang Chen, Josiah Ochieng
Glioblastomas (high-grade astrocytomas) are highly aggressive brain tumors with poor prognosis and limited treatment options. In the present studies, we have defined the role of fetuin-A, a liver-derived multifunctional serum protein, in the growth of an established glioblastoma cell line, LN229. We hereby demonstrate that these cells synthesize ectopic fetuin-A which supports their growth in culture in the absence of serum. We have demonstrated that a panel of tissue microarray (TMA) of glioblastomas also express ectopic fetuin-A...
November 23, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27880800/minimal-in-vivo-efficacy-of-iminosugars-in-a-lethal-ebola-virus-guinea-pig-model
#17
Joanna L Miller, Simon G Spiro, Stuart D Dowall, Irene Taylor, Antony Rule, Dominic S Alonzi, Andrew C Sayce, Edward Wright, Emma M Bentley, Ruth Thom, Graham Hall, Raymond A Dwek, Roger Hewson, Nicole Zitzmann
The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated...
2016: PloS One
https://www.readbyqxmd.com/read/27872839/insight-into-the-exoproteome-of-the-tissue-derived-trypomastigote-form-of-trypanosoma-cruzi
#18
Rayner M L Queiroz, Carlos A O Ricart, Mara O Machado, Izabela M D Bastos, Jaime M de Santana, Marcelo V de Sousa, Peter Roepstorff, Sébastien Charneau
The protozoan parasite Trypanosoma cruzi causes Chagas disease, one of the major neglected infectious diseases. It has the potential to infect any nucleated mammalian cell. The secreted/excreted protein repertoire released by T. cruzi trypomastigotes is crucial in host-pathogen interactions. In this study, mammalian tissue culture-derived trypomastigotes (Y strain) were used to characterize the exoproteome of the infective bloodstream life form. Proteins released into the serum-free culture medium after 3 h of incubation were harvested and digested with trypsin...
2016: Frontiers in Chemistry
https://www.readbyqxmd.com/read/27868164/efficient-production-of-recombinant-glycoprotein-d-of-herpes-simplex-virus-type-2-in-pichia-pastoris-and-its-protective-efficacy-against-viral-challenge-in-mice
#19
Man Wang, Shuai Jiang, Li Zhou, Chaoqun Wang, Ruifeng Mao, Murugavel Ponnusamy
Herpes simplex virus type 2 (HSV-2) infection is the leading cause of genital ulcer disease and a significant public health concern. However, there are no approved vaccines available to prevent HSV-2 infection. The glycoprotein D (gD) of HSV-2 is the most important candidate antigen for vaccine development. In this study, a truncated form of gD (codons 1-340, gD1-340) was produced as a secretory protein in the methylotrophic yeast Pichia pastoris. The recombinant gD1-340 with a His6 tag was purified to homogeneity by one-step affinity chromatography...
November 21, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27867186/shenmai-injection-enhances-the-cytotoxicity-of-chemotherapeutic-drugs-against-colorectal-cancers-via-improving-their-subcellular-distribution
#20
Wen-Yue Liu, Jing-Wei Zhang, Xue-Quan Yao, Chao Jiang, Ji-Chao He, Pin Ni, Jia-Li Liu, Qian-Ying Chen, Qing-Ran Li, Xiao-Jie Zang, Lan Yao, Ya-Zhong Liu, Mu-Lan Wang, Pei-Qiang Shen, Guang-Ji Wang, Fang Zhou
Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg(-1)·3d(-1)) or PTX (7...
November 21, 2016: Acta Pharmacologica Sinica
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