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https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#1
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#2
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346102/phage-display-derived-ligand-for-mucosal-transcytotic-receptor-gp-2-promotes-antigen-delivery-to-m-cells-and-induces-antigen-specific-immune-response
#3
Inam Ullah Khan, Jiansheng Huang, Rui Liu, Jingbo Wang, Jun Xie, Naishuo Zhu
Successful oral immunization depends on efficient delivery of antigens (Ags) to the mucosal immune induction site. Glycoprotein-2 (GP-2) is an integral membrane protein that is expressed specifically on M cells within follicle-associated epithelium (FAE) and serves as transcytotic receptor for luminal Ags. In this study, we selected peptide ligands against recombinant human GP-2 by screening a phage display library and evaluated their interaction with GP-2 in vitro and ex vivo. Selected peptides were conjugated to the C-terminal of enhanced green fluorescence protein (EGFP) and evaluated for their ability to induce an immune response in mice...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345878/multispectral-optical-tweezers-for-biochemical-fingerprinting-of-cd9-positive-exosome-subpopulations
#4
Randy P Carney, Sidhartha Hazari, Macalistair Colquhoun, Di Tran, Billanna Hwang, Michael S Mulligan, James D Bryers, Eugenia Girda, Gary S Leiserowitz, Zachary James Smith, Kit S Lam
Extracellular vesicles (EVs), including exosomes, are circulating nanoscale particles heavily implicated in cell signaling, and can be isolated in vast numbers from human biofluids. Study of their molecular profiling and materials properties is currently underway for purposes of describing a variety of biological functions and diseases. However, the large, and as yet unquantified, variety of EV subpopulations differing in composition, size, and likely function, necessitates characterization schemes capable of measuring single vesicles...
March 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28345657/multicolor-bioimaging-with-biosynthetic-zinc-nanoparticles-and-their-application-in-tumor-detection
#5
Yanjun Kang, Yi-Zhou Wu, Xianyun Hu, Xueqin Xu, Jie Sun, Rong Geng, Tongxing Huang, Xiaohang Liu, Yichen Ma, Ying Chen, Quan Wan, Xiaobang Qi, Gen Zhang, Xiaohui Zhao, Xin Zeng
Because they generate excellent images, nanoparticles (NPs), especially biosynthesized NPs, provide a new solution for tumor imaging. In this research, we unveil a novel type of biosynthesized NPs featuring multicolor fluorescence. These NPs exhibit little cytotoxicity to cells. The explored NPs, designated Zn-ZFP-GST NPs (Zinc NPs in abbreviation), are generated from leukemia cells treated with a Zn(2+) solution, while zinc-finger protein and glutathione S-transferase (GST) were also identified in the Zinc NPs...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345468/surface-bound-galectin-4-regulates-gene-transcription-and-secretion-of-chemokines-in-human-colorectal-cancer-cell-lines
#6
U Subrahmanyeswara Rao, Prema S Rao
One long-term complication of chronic intestinal inflammation is the development of colorectal cancer. However, the mechanisms linking inflammation to the colorectal tumorigenesis are poorly defined. Previously, we have demonstrated that galectin-4 is predominantly expressed in the luminal epithelia of the gastrointestinal tract, and its loss of expression plays a key role in the colorectal tumorigenesis. However, the mechanism by which galectin-4 regulates inflammation-induced tumorigenesis is unclear. Here, we show that galectin-4 secreted by the colorectal cancer cell lines was bound to the cell surface...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345293/detection-of-zaire-ebolavirus-in-swine-assay-development-and-optimization
#7
B S Pickering, B Collignon, G Smith, P Marszal, G Kobinger, H M Weingartl
Ebolaviruses (family Filoviridae, order Mononegavirales) cause often fatal, haemorrhagic fever in primates including humans. Pigs have been identified as a species susceptible to Reston ebolavirus (RESTV) infection, with indicated transmission to humans in the Philippines; however, their role during Ebola outbreaks in Africa needs to be clarified. To perform surveillance studies, detection of ebolavirus requires a prerequisite validation of viral RNA and antibody detection methods in swine samples. These diagnostic tests also need to be suitable for deployment to low-level containment laboratories...
March 27, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28345271/immunosuppression-with-mtor-inhibitors-prevents-the-development-of-donor-specific-antibodies-after-liver-transplant
#8
Katharina Willuweit, Andreas Heinold, Jassin Rashidi-Alavijeh, Falko M Heinemann, Peter A Horn, Andreas Paul, Guido Gerken, Kerstin Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are an important cause of complications after solid-organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined. METHODS: The DSA status of 400 patients who underwent LT at the outpatient clinic of the University Hospital Essen, was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity (MFI)...
March 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#9
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344998/low-dose-liver-targeted-gene-therapy-for-pompe-disease-enhances-therapeutic-efficacy-of-ert-via-immune-tolerance-induction
#10
Sang-Oh Han, Giuseppe Ronzitti, Benjamin Arnson, Christian Leborgne, Songtao Li, Federico Mingozzi, Dwight Koeberl
Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10(11) vector genomes [vg]/kg)...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344991/antibody-directed-glucocorticoid-targeting-to-cd163-in-m2-type-macrophages-attenuates-fructose-induced-liver-inflammatory-changes
#11
Pia Svendsen, Jonas H Graversen, Anders Etzerodt, Henrik Hager, Rasmus Røge, Henning Grønbæk, Erik I Christensen, Holger J Møller, Hendrik Vilstrup, Søren K Moestrup
Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory changes in rats on a high-fructose diet...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344977/chromatographic-studies-of-protein-based-chiral-separations
#12
Cong Bi, Xiwei Zheng, Shiden Azaria, Sandya Beeram, Zhao Li, David S Hage
The development of separation methods for the analysis and resolution of chiral drugs and solutes has been an area of ongoing interest in pharmaceutical research. The use of proteins as chiral binding agents in high-performance liquid chromatography (HPLC) has been an approach that has received particular attention in such work. This report provides an overview of proteins that have been used as binding agents to create chiral stationary phases (CSPs) and in the use of chromatographic methods to study these materials and protein-based chiral separations...
September 2016: Separations
https://www.readbyqxmd.com/read/28344834/ligature-associated-bacterial-profiles-are-linked-to-type-2-diabetes-mellitus-in-a-rat-model-and-influenced-by-antibody-treatment-against-tnf-%C3%AE-or-rage
#13
M B Grauballe, D Belstrøm, J A Østergaard, B J Paster, S Schou, A Flyvbjerg, P Holmstrup
There is a bidirectional relationship between periodontal disease (PD) and type 2 diabetes mellitus (T2D). T2D may lead to ecological perturbations in the oral environment, which may facilitate an altered microbiota. However, previous studies have been inconclusive in determining the effect of T2D on oral bacterial profiles. Therefore, we aimed to evaluate the influence of T2D on the ligature-associated bacterial profile in a diabetic rat model with PD and investigated the impact of blocking inflammatory pathways with antibodies targeting either Tumor Necrosis Factor α (TNF-α) or the receptor of advanced glycation end-products (RAGE)...
February 2017: Clinical and Experimental Dental Research
https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#14
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344667/m%C3%A3-ller-cells-and-retinal-axons-can-be-primary-targets-in-experimental-neuromyelitis-optica-spectrum-disorder
#15
REVIEW
Bleranda Zeka, Hans Lassmann, Monika Bradl
Recent work from our laboratory, using different models of experimental neuromyelitis optica spectrum disorder (NMOSD), has led to a number of observations that might be highly relevant for NMOSD patients. For example: (i) in the presence of neuromyelitis optica immunoglobulin G, astrocyte-destructive lesions can be initiated by CD4+ T cells when these cells recognize aquaporin 4 (AQP4), but also when they recognize other antigens of the central nervous system. The only important prerequisite is that the T cells have to be activated within the central nervous system by "their" specific antigen...
January 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28344593/agaricus-brasiliensis-polysaccharides-stimulate-human-monocytes-to-capture-candida-albicans-express-toll-like-receptors-2-and-4-and-produce-pro-inflammatory-cytokines
#16
Priscila Raquel Martins, Ângela Maria Victoriano de Campos Soares, Andrea Vanessa da Silva Pinto Domeneghini, Márjorie Assis Golim, Ramon Kaneno
BACKGROUND: Agaricus brasiliensis is a medicinal mushroom with immunomodulatory and antitumor activities attributed to the β-glucans presented in the polysaccharide fraction of its fruiting body. Since β-glucans enhance cellular immunoresponsiveness, in this study we aimed to evaluate the effect of an acid-treated polysaccharide-rich fraction (ATF) of A. brasiliensis on the ability of human monocytes to adhere/phagocyte C. albicans yeast cells, their expression of pattern recognition receptors and their ability to produce cytokines...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28344580/a-perspective-on-the-development-of-plant-made-vaccines-in-the-fight-against-ebola-virus
#17
REVIEW
Sergio Rosales-Mendoza, Ricardo Nieto-Gómez, Carlos Angulo
The Ebola virus (EBOV) epidemic indicated a great need for prophylactic and therapeutic strategies. The use of plants for the production of biopharmaceuticals is a concept being adopted by the pharmaceutical industry, with an enzyme for human use currently commercialized since 2012 and some plant-based vaccines close to being commercialized. Although plant-based antibodies against EBOV are under clinical evaluation, the development of plant-based vaccines against EBOV essentially remains an unexplored area...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344579/reslizumab-and-eosinophilic-asthma-one-step-closer-to-precision-medicine
#18
REVIEW
Gilda Varricchi, Gianenrico Senna, Stefania Loffredo, Diego Bagnasco, Matteo Ferrando, Giorgio Walter Canonica
Human eosinophils represent approximately 1% of peripheral blood leukocytes. However, these cells have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophilic inflammation is present in a significant proportion of patients with severe asthma. Asthma is a chronic inflammatory disorder that affects more than 315 million people worldwide, with 10% having severe uncontrolled disease. Although the majority of patients can be efficiently treated, severe asthmatics continue to be uncontrolled and are at risk of exacerbations and even death...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344577/linear-epitopes-of-paracoccidioides-brasiliensis-and-other-fungal-agents-of-human-systemic-mycoses-as-vaccine-candidates
#19
REVIEW
Luiz R Travassos, Carlos P Taborda
Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South America; Histoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344403/toxoplasma-gondii-infection-in-meat-animals-from-africa-systematic-review-and-meta-analysis-of-sero-epidemiological-studies
#20
Aretas Babatoundé Nounnagnon Tonouhewa, Yao Akpo, Philippe Sessou, Camus Adoligbe, Eric Yessinou, Yaovi Gildas Hounmanou, Marc Napoléon Assogba, Issaka Youssao, Souaïbou Farougou
AIM: Toxoplasma gondii is an ubiquitous apicomplexan parasite which causes toxoplasmosis in humans and animals. Felids especially cats are definitive hosts and almost all warm-blooded mammals, including livestock and human can serve as intermediate hosts. Food animals can be reservoirs for T. gondii and act as one of the sources for parasite transmission to humans. The objective of this study is to collect serological data on the prevalence of anti-T. gondii antibody, and risk factors for certain food animals from Africa to provide a quantitative estimate of T...
February 2017: Veterinary World
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