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https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#1
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#2
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28698470/real-time-amperometric-recording-of-extracellular-h%C3%A2-o%C3%A2-in-the-brain-of-immunocompromised-mice-an-in-vitro-ex-vivo-and-in-vivo-characterisation-study
#3
Caroline H Reid, Niall J Finnerty
We detail an extensive characterisation study on a previously described dual amperometric H₂O₂ biosensor consisting of H₂O₂ detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H₂O₂ sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes...
July 8, 2017: Sensors
https://www.readbyqxmd.com/read/28692149/animal-models-of-human-type-1-diabetes-for-evaluating-combination-therapies-and-successful-translation-to-the-patient-with-type-1-diabetes
#4
REVIEW
Sigurd Lenzen
Animal models of human type 1 diabetes will be of a great importance for the evaluation of new combination therapies with curative potential. However, reliable predictive power for successful translation to patients with type 1 diabetes is crucial. This will be particularly important in the future when evaluating success of new combination therapies which show great promise for preservation and restoration of beta cell mass and thereby reverse the type 1 diabetic hyperglycaemia. But not all spontaneous animal models are equally well suited for this purpose...
July 10, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28686488/contribution-of-both-b-cell-intrinsic-alterations-as-well-as-non-hematopoietic-derived-factors-in-the-enhanced-immune-response-of-the-nod-mouse
#5
Viqar Showkat Banday, Radha Thyagarajan, Kristina Lejon
The underlying cellular and molecular mechanism for the development of Type 1 diabetes is still to be fully revealed. We have previously demonstrated that the NOD mouse, a model for Type 1 diabetes, display a prolonged and enhanced immune response to both self and non-self-antigens. The molecular explanation for this defect however, has not been determined. In this study we immunized NOD and C57BL/6 (B6) with the conventional antigen i.e. hen egg lysozyme (HEL) and analyzed B cell activation, germinal center reaction and antibody clearance...
July 7, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28677920/the-genetic-heterogeneity-among-different-mouse-strains-impacts-the-lung-injury-potential-of-multiwalled-carbon-nanotubes
#6
Xiang Wang, Yu-Pei Liao, Donatello Telesca, Chong Hyun Chang, Tian Xia, André E Nel
Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the pro-fibrogenic effects of a library of MWCNTs in vitro and in vivo are chosen...
July 5, 2017: Small
https://www.readbyqxmd.com/read/28666189/oral-metronomic-topotecan-sensitizes-crizotinib-antitumor-activity-in-alk-f1174l-drug-resistant-neuroblastoma-preclinical-models
#7
Libo Zhang, Bing Wu, Sylvain Baruchel
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models. METHODS: We selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro...
June 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28665482/the-p2x7-receptor-antagonist-brilliant-blue-g-reduces-serum-human-interferon-%C3%AE-in-a-humanized-mouse-model-of-graft-versus-host-disease
#8
N J Geraghty, L Belfiore, D Ly, S R Adhikary, S J Fuller, W Varikatt, M L Sanderson-Smith, V Sluyter, S I Alexander, R Sluyter, D Watson
Graft-versus-host disease (GVHD) remains a major problem after allogeneic haematopoietic stem cell transplantation, a curative therapy for haematological malignancies. Previous studies have demonstrated a role for the adenosine triphosphate (ATP)-gated P2X7 receptor channel in allogeneic mouse models of GVHD. In this study, injection of human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD-SCID-IL2Rγ(null) (NSG) mice established a humanized mouse model of GVHD. This model was used to study the effect of P2X7 blockade in this disease...
June 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28659311/memory-t-cells-expressing-an-nkg2d-car-efficiently-target-osteosarcoma-cells
#9
Lucía Fernández, Jean-Yves Metais, Adela Escudero, Maria Vela, Jaime Valentín, Isabel Vallcorba, Alejandra Leivas, Juan Torres, Antonio Valeri, Ana Patiño-García, Joaquín Martínez-López, Wing Leung, Antonio Pérez-Martínez
NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK cell elimination of osteosarcoma tumor initiating cells. In this report, we used NKG2D-NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA- memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR)...
June 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28653829/development-and-characterization-of-a-hydroxyl-sulfonamide-analogue-5-chloro-n-2-4-hydroxysulfamoyl-phenyl-ethyl-2-methoxy-benzamide-as-a-novel-nlrp3-inflammasome-inhibitor-for-potential-treatment-of-multiple-sclerosis
#10
Chunqing Guo, Jacob W Fulp, Yuqi Jiang, Xia Li, Jeremy E Chojnacki, Jingde Wu, Xiang-Yang Wang, Shijun Zhang
In our efforts to develop novel small-molecule inhibitors for the NOD-like receptor family pyrin-domain-containing 3 (NLRP3) inflammasome as potential disease-modifying agents to treat neurological disorders including multiple sclerosis (MS), a hydroxyl sulfonamide analogue JC-171 has been rationally designed and biologically characterized both in vitro and in vivo. Our studies established that JC-171 dose dependently inhibited LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8...
July 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28649577/in%C3%A2-vivo-murine-matured-human-cd3-cells-as-a-preclinical-model-for-t-cell-based-immunotherapies
#11
Kevin G Haworth, Christina Ironside, Zachary K Norgaard, Willimark M Obenza, Jennifer E Adair, Hans-Peter Kiem
Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#12
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646023/amlexanox-downregulates-s100a6-to-sensitize-kmt2a-aff1-positive-acute-lymphoblastic-leukemia-to-tnf-%C3%AE-treatment
#13
Hayato Tamai, Hiroki Yamaguchi, Koichi Miyake, Miyuki Takatori, Tomoaki Kitano, Satoshi Yamanaka, Syunsuke Yui, Keiko Fukunaga, Kazutaka Nakayama, Koiti Inokuchi
Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This poor prognosis is due to one of two factors, either resistance to TNF-α which mediates a graft-versus-leukemia (GVL) response after allo-HSCT, or immune resistance due to upregulated expression of the immune escape factor S100A6. Here we report an immune stimulatory effect against KMT2A/AFF1-positive ALL cells by treatment with the anti-allergy drug amlexanox, which we found to inhibit S100A6 expression in the presence of TNF-α...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28634110/pharmacological-rescue-of-ductal-cftr-rescue-pancreatic-and-salivary-glands-acinar-cells-and-tissue-function-in-mouse-models-of-autoimmune-diseases
#14
Mei Zeng, Mitchell Szymczak, Malini Ahuja, Changyu Zheng, Hongen Yin, William Swaim, John A Chiorini, Robert J Bridges, Shmuel Muallem
BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis (AIP) are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. NOD/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of AIP. CFTR is a ductal Cl(-) channel essential for ductal fluid and HCO3(-) secretion. We used these models to ask: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function...
June 17, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28633442/continuous-glucose-monitoring-in-female-nod-mice-reveals-daily-rhythms-and-a-negative-correlation-with-body-temperature
#15
Ron Korstanje, Jennifer L Ryan, Holly S Savage, Bonnie L Lyons, Kevin G Kane, Stacey J Sukoff Rizzo
Previous studies with continuous glucose monitoring in mice have been limited to several days or weeks, with the mouse's physical attachment to the equipment impacting behavior and measurements. In the current study we measured blood glucose and body temperature at 10-second intervals for 12 weeks in a cohort of NOD/ShiLtJ female mice using wireless telemetry. This allowed us, for the first time, to obtain a high-resolution profile of the circadian rhythm of these two parameters and the onset of hyperglycemic development in real time...
June 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#16
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#17
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#18
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28594903/the-role-of-bone-marrow-mesenchymal-stromal-cell-derivatives-in-skin-wound-healing-in-diabetic-mice
#19
Tomas de Mayo, Paulette Conget, Silvia Becerra-Bayona, Claudia L Sossa, Virgilio Galvis, Martha L Arango-Rodríguez
Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×106 cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8-10 week old female NOD mice...
2017: PloS One
https://www.readbyqxmd.com/read/28592649/oas1b-dependent-immune-transcriptional-profiles-of-west-nile-virus-infection-in-the-collaborative-cross
#20
Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Duncan M Hendrick, Kathleen Voss, Renee C Ireton, Michael Mooney, Jennifer T Go, Gabrielle Choonoo, Sophia Jeng, Fernando Pardo-Manuel de Villena, Martin T Ferris, Shannon McWeeney, Michael Gale
The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds...
June 7, 2017: G3: Genes—Genomes—Genetics
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