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https://www.readbyqxmd.com/read/28738417/a-pharmacodynamic-analysis-of-choroidal-neovascularization-in-a-porcine-model-using-three-targeted-drugs
#1
Jeffrey Tran, Caroline Craven, Kathy Wabner, Jenn Schmit, Brock Matter, Uday Kompella, Hans E Grossniklaus, Timothy W Olsen
Purpose: To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods: Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28738166/ablation-of-toll-like-receptor-4-mitigates-cardiac-mitochondrial-dysfunction-in-hyperhomocysteinemia
#2
Nevena Jeremic, Gregory J Weber, Suresh C Tyagi
Hyperhomocysteinemia is a risk factor for adverse cardiovascular events; however, the mechanism for development of this disease is still unknown. Toll-like receptor 4 is a molecule involved in the immune response pathway and is quickly becoming a receptor of interest in the field of hypertension. In this study, we hypothesized that ablation of TLR4 mitigates cardiac mitochondrial dysfunction in a model of hyperhomocysteinemia. Five strains of mice (C57BL/6J, CBS+/-, C3H, CBS+/-/C3H and C3H/HeOuJ) 10-12 weeks old were utilized...
July 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28737448/mast-cell-and-m1-macrophage-infiltration-and-local-pro-inflammatory-factors-were-attenuated-with-incretin-based-therapies-in-obesity-related-glomerulopathy
#3
Jiao He, Geheng Yuan, Fangxiao Cheng, Junqing Zhang, Xiaohui Guo
BACKGROUND: The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal injury independent of glucose control in diabetic nephropathy. There are limited studies focusing on their effects on ORG. We explored the effects of incretin-based therapies on early ORG and the inflammatory responses involved mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local pro-inflammatory factors...
July 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28736998/evasin-displaying-lactic-acid-bacteria-bind-different-chemokines-and-neutralize-cxcl8-production-in-caco-2-cells
#4
Katja Škrlec, Anja Pucer Janež, Boris Rogelj, Borut Štrukelj, Aleš Berlec
Chemokines are key signals in the immune system and play an important role as proinflammatory mediators in the pathology of inflammatory bowel disease and colorectal cancer, making them an important target for therapy. Recombinant lactic acid bacteria (LAB) were engineered to bind CC and CXC chemokines by displaying chemokine-binding proteins evasin-1, evasin-3 and evasin-4 on their surface. Evasin genes were cloned into lactococcal surface display vector and overexpressed in L. lactis NZ9000 and NZ9000ΔhtrA in fusion with secretion signal and surface anchor...
July 24, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28736882/the-clinical-significance-of-monitoring-the-expression-of-the-sil-tal1-fusion-gene-in-t-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
X Zhao, Y Hong, Y Qin, Y Xu, Y Chang, Y Wang, X Zhang, L Xu, X Huang
INTRODUCTION: SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL). However, whether this fusion gene might be used as a reliable marker of minimal residual disease (MRD) following allogeneic stem cell transplantation (allo-HSCT) remains unknown METHODS: The clinical data of consecutive 29 patients with T-ALL who received allo-HSCT were collected. Their MRD were evaluated by SIL-TAL1, Wilms' tumor 1 (WT1) expression, and the leukemia-associated immunophenotype (LAIP) ...
July 24, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28736824/evaluation-of-lumazine-synthase-from-bacillus-anthracis-as-a-presentation-platform-for-polyvalent-antigen-display
#6
Yangjie Wei, Newton Wahome, Greta VanSlyke, Neal Whitaker, Prashant Kumar, Michael L Barta, Wendy L Picking, David B Volkin, Nicholas J Mantis, C Russell Middaugh
Polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. This strategy results in a higher local density of antigens, increased high avidity interactions with B cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. In the present study, we used lumazine synthase (LS), an icosahedral symmetry capsid derived from Bacillus anthracis, as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C terminus of LS via four different linkers...
July 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28736630/current-biologics-for-treatment-of-biliary-tract-cancers
#7
REVIEW
Diana Y Zhao, Kian-Huat Lim
Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736577/optimization-of-proximity-ligation-assay-pla-for-detection-of-protein-interactions-and-fusion-proteins-in-non-adherent-cells-application-to-pre-b-lymphocytes
#8
Lydie Debaize, Hélène Jakobczyk, Anne-Gaëlle Rio, Virginie Gandemer, Marie-Bérengère Troadec
BACKGROUND: Genetic abnormalities, including chromosomal translocations, are described for many hematological malignancies. From the clinical perspective, detection of chromosomal abnormalities is relevant not only for diagnostic and treatment purposes but also for prognostic risk assessment. From the translational research perspective, the identification of fusion proteins and protein interactions has allowed crucial breakthroughs in understanding the pathogenesis of malignancies and consequently major achievements in targeted therapy...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28736549/cloning-expression-isotope-labeling-and-purification-of-transmembrane-protein-merf-from-mercury-resistant-enterobacter-sp-az-15-for-nmr-studies
#9
Aatif Amin, Zakia Latif
Mercury resistant (Hg(R)) Enterobacter sp. AZ-15 was isolated from heavy metal polluted industrial wastewater samples near to districts Kasur and Sheikhupura, Pakistan. 16S rDNA ribotyping and phylogentic analysis showed 98% homology with already reported Enterobacter species. The merF gene encoding transmembrane protein-MerF was amplified from genomic DNA and ligated into pET31b+ vector using restriction endonucleases, SphI and XhoI. The genetic codons of merF gene encoding cysteine residues were mutated into codons, translating into serine residues by site-directed mutagenesis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28736295/digital-multiplex-ligation-dependent-probe-amplification-for-detection-of-key-copy-number-alterations-in-t-and-b-cell-lymphoblastic-leukemia
#10
Anne Benard-Slagter, Ilse Zondervan, Karel de Groot, Farzaneh Ghazavi, Virinder Sarhadi, Pieter Van Vlierberghe, Barbara De Moerloose, Claire Schwab, Kim Vettenranta, Christine J Harrison, Sakari Knuutila, Jan Schouten, Tim Lammens, Suvi Savola
Recurrent and clonal genetic alterations are characteristic of different subtypes of T- and B-cell lymphoblastic leukemia (ALL), and several subtypes are strong independent predictors of patient outcome. A next-generation sequencing-based multiplex ligation-dependent probe amplification variant (digitalMLPA) has been developed enabling simultaneous detection of copy number alterations (CNAs) of up to 1000 target sequences. This novel digitalMLPA assay was designed and optimized to detect CNAs of 56 key target genes and regions in ALL...
July 19, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28736197/characterization-of-an-escherichia-coli-derived-human-papillomavirus-type-16-and-18-bivalent-vaccine
#11
Ying Gu, Minxi Wei, Daning Wang, Zhihai Li, Minghui Xie, Huirong Pan, Ting Wu, Jun Zhang, Shaowei Li, Ningshao Xia
Human papillomavirus (HPV) types 16 and 18 account for approximately 70% of cervical cancer worldwide. Neutralizing HPV prophylactic vaccines offer significant benefit, as they block HPV infection and prevent subsequent disease. However, the three licensed HPV vaccines that cover these two genotypes were produced in eukaryotic cells, which is expensive, particularly for low-income countries where HPV is highest. Here, we report a new HPV16 and -18 bivalent candidate vaccine produced from Escherichia coli. We used two strategies of N-terminal truncation of HPV L1 proteins and soluble non-fusion expression to generate HPV16 and HPV18 L1-only virus-like particles (VLPs) in a scalable process...
July 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28733985/lalf32-51-e7-a-hpv-16-therapeutic-vaccine-candidate-forms-protein-body-like-structures-when-expressed-in-nicotiana-benthamiana-leaves
#12
Romana J R Yanez, Renate Lamprecht, Milaid Granadillo, Isis Torrens, Elsa Arcalís, Eva Stöger, Edward P Rybicki, Inga I Hitzeroth
High-risk Human papillomaviruses (HPVs) cause cervical cancer, and while there are good prophylactic vaccines on the market, these are ineffective against established infections, creating a clear need for therapeutic vaccines. The HPV E7 protein is one of the essential oncoproteins for the onset and maintenance of malignancy, and is therefore an ideal therapeutic vaccine target. We fused the HPV-16 E7 protein to the Limulus polyphemus anti-lipopolysaccharide factor (LALF32-51 ), a small hydrophobic peptide that can penetrate cell membranes and that has immunomodulatory properties...
July 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28733901/current-knowledge-on-exosome-biogenesis-and-release
#13
REVIEW
Nina Pettersen Hessvik, Alicia Llorente
Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis...
July 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28733655/lectin-mediated-reversible-immobilization-of-human-cells-into-a-glycosylated-macroporous-protein-hydrogel-as-a-cell-culture-matrix
#14
Nicholas Bodenberger, Dennis Kubiczek, Laura Trösch, Ali Gawanbacht, Susanne Wilhelm, Denis Tielker, Frank Rosenau
3D cell culture is a helpful approach to study cell-cell interaction in a native-like environment, but is often limited due the challenge of retrieving cells from the material. In this study, we present the use of recombinant lectin B, a sugar-binding protein with four binding cavities, to enable reversible cell integration into a macroporous protein hydrogel matrix. By functionalizing hydrogel precursors with saccharose, lectin B can both bind to sugar moieties on the cellular surface as well as to the modified hydrogel network...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733553/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#15
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#16
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733441/molecular-screening-for-cancer-treatment-optimization-moscato-01-in-pediatric-patients-a-single-institutional-prospective-molecular-stratification-trial
#17
Anne Catherine Harttrampf, Ludovic Lacroix, Marc Deloger, Frederic Deschamps, Stéphanie Puget, Nathalie Auger, Philippe Vielh, Pascale Varlet, Zsofia Balogh, Samuel Abbou, Adrien Allorant, Dominique Valteau-Couanet, Sabine Sarnacki, Louise Galmiche, Guillaume Meurice, Véronique Minard-Colin, Jacques Grill, Laurence Brugières, Christelle Dufour, Nathalie Gaspar, Stefan Michiels, Gilles Vassal, Jean-Charles Soria, Birgit Geoerger
This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy.<br /><br />Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site.  These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733400/visualization-of-a-specific-genome-locus-by-the-laco-laci-gfp-system
#18
Da-Qiao Ding, Yasushi Hiraoka
Observing the dynamics of a specific chromosome locus in living cells can provide important information as to the molecular mechanisms underlying events such as chromosome segregation, homologous chromosome pairing, chromosome arrangement, and gene expression. The lacO/LacI-GFP system provides a simple and useful method in which a chromosome locus is visualized by inserting lacO repeat arrays and then expressing an LacI-GFP fusion that specifically binds to the lacO sequence. This system has been adapted for use in Schizosaccharomyces pombe by expressing the LacI-GFP under a promoter of the dis1(+) gene...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28732013/the-kp1_4563-gene-is-regulated-by-the-camp-receptor-protein-and-controls-type-3-fimbrial-function-in-klebsiella-pneumoniae-ntuh-k2044
#19
Mei Luo, Shiya Yang, Xuan Li, Pin Liu, Jian Xue, Xipeng Zhou, Kewen Su, Xuan Xu, Ying Qing, Jingfu Qiu, Yingli Li
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that can adhere to host cells or extracellular matrix via type 1 and type 3 fimbriae. KP1_4563 is a gene encoding a hypothetical protein in K. pneumoniae NTUH-K2044. KP1_4563 is located between the type 1 and type 3 fimbrial gene clusters and is likely associated with fimbrial function given its putative conserved domains of unknown function (DUF1471). Cyclic AMP receptor protein (CRP) regulates virulence-related gene expression and is a crucial transcriptional regulator in many bacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28731988/roles-of-mitogen-activating-protein-kinase-kinase-kinase-kinase-3-map4k3-in-preterm-skeletal-muscle-satellite-cell-myogenesis-and-mammalian-target-of-rapamycin-complex-1-mtorc1-activation-regulation
#20
Chu-Yi Guo, Mu-Xue Yu, Jie-Min Dai, Si-Nian Pan, Zhen-Tong Lu, Xiao-Shan Qiu, Si-Qi Zhuang
BACKGROUND Preterm skeletal muscle genesis is a paradigm for myogenesis. The role of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cells myogenesis or its relationship to mammalian target of rapamycin complex 1 (mTORC1) activity have not been previously elaborated. MATERIAL AND METHODS Small interfering RNA (siRNA) interference technology was used to inhibit MAP4K3 expression. Leucine stimulation experiments were performed following MAP4K3-siRNA interference...
July 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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