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https://www.readbyqxmd.com/read/28424681/the-spontaneous-autoimmune-neuromyopathy-in-icosl-nod-mice-is-cd4-t-cell-and-interferon-%C3%AE-dependent
#1
Claire Briet, Gwladys Bourdenet, Ute C Rogner, Chantal Becourt, Isabelle Tardivel, Laurent Drouot, Christophe Arnoult, Jean-Claude do Rego, Nicolas Prevot, Charbel Massaad, Olivier Boyer, Christian Boitard
Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the development of a spontaneous autoimmune neuromyopathy. At the pathological level, ICOSL(-/-) NOD mice show stronger protection from insulitis than their ICOS(-/-) counterparts. Also, the ICOSL(-/-) NOD model carries a limited C57BL/6 region containing the Icosl nul mutation, but, in contrast to ICOS(-/-) NOD mice, no gene variant previously reported as associated to NOD diabetes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28412308/genistein-prevention-of-hyperglycemia-and-improvement-of-glucose-tolerance-in-adult-non-obese-diabetic-mice-are-associated-with-alterations-of-gut-microbiome-and-immune-homeostasis
#2
Guannan Huang, Joella Xu, Daniel E Lefever, Travis C Glenn, Tamas Nagy, Tai L Guo
Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse model was employed to investigate the effects of GEN exposure on blood glucose level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male and female NOD mice were fed with either soy-based or casein-based diet, and received GEN at 20mg/kg body weight by gavage daily...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28392419/early-phase-dynamics-of-traceable-mcherry-fluorescent-protein-carrying-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells-transplanted-nod-scid-jak3-mice
#3
Nobuyo Higashi-Kuwata, Hiromi Ogata-Aoki, Shin-Ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Tatsuyoshi Kawamura, Hironobu Ihn, Hisataka Kobayashi, Seiji Okada, Hiroaki Mitsuya
We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FL(mC)) and NOD/SCID/Jak3(-/-) mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FL(mC) inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FL(mC)-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6)...
April 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28390927/a-novel-hemolytic-complement-sufficient-nsg-mouse-model-supports-studies-of-complement-mediated-antitumor-activity-in-vivo
#4
Mohit K Verma, Julia Clemens, Lisa Burzenski, Stephen B Sampson, Michael A Brehm, Dale L Greiner, Leonard D Shultz
Monoclonal antibodies (mAbs) have emerged as a mainstream therapeutic option against cancer. mAbs mediate tumor cell-killing through several mechanisms including complement-dependent cytotoxicity (CDC). However, studies of mAb-mediated CDC against tumor cells remain largely dependent on in vitro systems. Previously developed and widely used NOD-scid IL2rγ(null) (NSG) mice support enhanced engraftment of many primary human tumors. However, NSG mice have a 2-bp deletion in the coding region of the hemolytic complement (Hc) gene, and it is not possible to evaluate CDC activity in NSG mice...
April 6, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28381471/sox17-regulates-conversion-of-human-fibroblasts-into-endothelial-cells-and-erythroblasts-via-de-differentiation-into-cd34-progenitor-cells
#5
Lianghui Zhang, Ankit Jambusaria, Zhigang Hong, Glenn Marsboom, Peter T Toth, Brittney-Shea Herbert, Asrar B Malik, Jalees Rehman
Background -The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28380378/targeting-abl-ire1%C3%AE-signaling-spares-er-stressed-pancreatic-%C3%AE-cells-to-reverse-autoimmune-diabetes
#6
Shuhei Morita, S Armando Villalta, Hannah C Feldman, Ames C Register, Wendy Rosenthal, Ingeborg T Hoffmann-Petersen, Morvarid Mehdizadeh, Rajarshi Ghosh, Likun Wang, Kevin Colon-Negron, Rosa Meza-Acevedo, Bradley J Backes, Dustin J Maly, Jeffrey A Bluestone, Feroz R Papa
In cells experiencing unrelieved endoplasmic reticulum (ER) stress, the ER transmembrane kinase/endoribonuclease (RNase)-IRE1α-endonucleolytically degrades ER-localized mRNAs to promote apoptosis. Here we find that the ABL family of tyrosine kinases rheostatically enhances IRE1α's enzymatic activities, thereby potentiating ER stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α's RNase. Imatinib-an anti-cancer tyrosine kinase inhibitor-antagonizes the ABL-IRE1α interaction, blunts IRE1α RNase hyperactivity, reduces pancreatic β cell apoptosis, and reverses type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28378202/exercise-training-but-not-curcumin-supplementation-decreases-immune-cell-infiltration-in-the-pancreatic-islets-of-a-genetically-susceptible-model-of-type-1-diabetes
#7
Leandro Kansuke Oharomari, Camila de Moraes, Anderson Marliere Navarro
BACKGROUND: The main mechanism involved in the pathogenesis of autoimmunity is an uncontrolled inflammatory response against self-antigens. Therefore, anti-inflammatory factors, such as the intake of bioactive compounds and a physically active lifestyle, may decrease or cease the development of autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic β cell destruction. The non-obese diabetic (NOD) mouse is a model of spontaneous T1D and is the model most similar to human disease...
December 2017: Sports Medicine—Open
https://www.readbyqxmd.com/read/28365567/use-of-p53-silenced-endothelial-progenitor-cells-to-treat-ischemia-in-diabetic-peripheral-vascular-disease
#8
Nabanita Kundu, Cleyton C Domingues, Cyril Chou, Neeki Ahmadi, Sara Houston, D Joseph Jerry, Sabyasachi Sen
BACKGROUND: Peripheral vascular disease is a major diabetes mellitus-related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53- and p21-silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53- and p21-silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso-occlusive peripheral vascular disease mouse models...
April 1, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28360906/efficacy-of-resistance-to-francisella-imparted-by-ity-nramp-slc11a1-depends-on-route-of-infection
#9
Daniel A Powell, Jeffrey A Frelinger
Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1(Gly169), which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1(Asp169), that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1(Gly169) (B6-Slc11a1(G169) ) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28352127/insights-from-engraftable-immunodeficient-mouse-models-of-hyperinsulinaemia
#10
Michelle L Maugham, Patrick B Thomas, Gabrielle J Crisp, Lisa K Philp, Esha T Shah, Adrian C Herington, Chen Chen, Laura S Gregory, Colleen C Nelson, Inge Seim, Penny L Jeffery, Lisa K Chopin
Hyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. Here, the long-term effects of a 23% Western high-fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1 (-/-)) suitable for engraftment with human-derived tissue xenografts, and the effect of diet-induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1 (-/-)and NOD/SCID HFD-fed mice demonstrated diet-induced impairments in glucose tolerance at 16 and 23 weeks post weaning...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28348600/delivery-of-bone-marrow-derived-mesenchymal-stem-cells-improves-tear-production-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#11
Hema S Aluri, Mahta Samizadeh, Maria C Edman, Dillon R Hawley, Helene L Armaos, Srikanth R Janga, Zhen Meng, Victor G Sendra, Pedram Hamrah, Claire L Kublin, Sarah F Hamm-Alvarez, Driss Zoukhri
The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren's syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n = 20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 10(6) cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28348460/epac1-blocks-nlrp3-inflammasome-to-reduce-il-1%C3%AE-in-retinal-endothelial-cells-and-mouse-retinal-vasculature
#12
Youde Jiang, Li Liu, Elizabeth Curtiss, Jena J Steinle
Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compound 49b, reduced Toll-like receptor 4 (TLR4) signaling in retinal endothelial cells (REC) grown in high glucose. Others reported that TLR4 activates high-mobility group box 1 (HMGB1), which has been associated with the NOD-like receptor 3 (NLRP3) inflammasome. Thus, we hypothesized that Epac1, a downstream mediator of β-adrenergic receptors, would block TLR4/HMGB1-mediated stimulation of the NLRP3 inflammasome, leading to reduced cleavage of caspase-1 and interleukin-1 beta (IL-1β)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28341862/follistatin-like-1-aggravates-silica-induced-mouse-lung-injury
#13
Yinshan Fang, Si Zhang, Xiaohe Li, Fangxin Jiang, Qiao Ye, Wen Ning
Occupational inhalation of dust, such as crystalline silica, for prolonged periods in the workplace leads to fibrotic lung diseases worldwide. The mechanisms underlying the diseases are unknown, so that no effective treatment exists for these conditions. We found elevated levels of follistatin like 1 (FSTL1) in serum from patients with silicosis and in lungs from silica-induced mouse model. The induced Fstl1 regulated inflammation response via activation of nod-like receptor family, pyrin domain containing 3v (NLRP3) inflammasome-mediated IL-1β production from macrophages...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341731/targeting-the-5t4-oncofoetal-glycoprotein-with-an-antibody-drug-conjugate-a1mcmmaf-improves-survival-in-patient-derived-xenograft-models-of-acute-lymphoblastic-leukemia
#14
Owen J McGinn, Shekhar Krishnan, Jean-Pierre Bourquin, Puja Sapra, Clare Dempsey, Vaskar Saha, Peter L Stern
Outcome in childhood acute lymphoblastic leukemia is prognosticated on levels of minimal residual disease after remission induction therapy. Higher minimal residual disease levels are associated with inferior results even with intensification of therapy and suggest identification and targeting of minimal residual disease cells as a therapeutic strategy. Here we identify high expression of 5T4 in subclonal populations of patient derived xenografts from patients with high minimal residual disease post induction...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28336807/pmp22-regulates-self-renewal-and-chemoresistance-of-gastric-cancer-cells
#15
Wangyu Cai, Gang Chen, Qicong Luo, Jun Liu, Xiaofeng Guo, Tian Zhang, Fei Ma, Liang Yuan, Boan Li, Jianchun Cai
Cancer stem cells (CSCs) possess self-renewal and chemoresistance activities. However, the manner in which these features are maintained remains obscure. We sought to identify cell surface protein(s) that mark self-renewing and chemoresistant gastric cancer cells using the Explorer Antibody Microarray. We identified PMP22, a target gene of the Wnt/β-catenin pathway, as the most upregulated cell surface protein in gastric cancer xenografts exposed to cisplatin (DDP). PMP22 expression was markedly upregulated in tumorspheric cells and declined with differentiation...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28319642/therapeutic-efficacy-of-nanocomplex-of-poly-ethylene-glycol-and-catechin-for-dry-eye-disease-in-a-mouse-model
#16
Hyesook Lee, Whuisu Shim, Chae Eun Kim, So Yeon Choi, Haeshin Lee, Jaewook Yang
Purpose: We investigated the possibility of the nanocomplex of poly(ethylene glycol) (PEG) and catechin as a new biomedical material to treat dry eye disease. Methods: NOD.B10.H2b mice were exposed to an air draft and injected with scopolamine for 10 days. Ten days later, the mice were treated with normal saline (n = 11), 1% catechin (n = 11), 1% PEG (n = 11), and 1% catechin/PEG nanocomplex solution mixture containing catechin and PEG at weight ratios of 1:1 (CP1, n = 11), 1:5 (CP5, n = 11), and 1:10 (CP10, n = 11)...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28306193/diphtheria-toxin-based-anti-human-cd19-immunotoxin-for-targeting-human-cd19-tumors
#17
Qian Zheng, Zhaohui Wang, Huiping Zhang, Qi Huang, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19(+) tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19(+) tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28292965/repurposed-jak1-jak2-inhibitor-reverses-established-autoimmune-insulitis-in-non-obese-diabetic-mice
#18
Prerak M Trivedi, Kate L Graham, Nicholas A Scott, Misty R Jenkins, Suktilang Majaw, Robyn M Sutherland, Stacey Fynch, Andrew M Lew, Christopher J Burns, Balasubramanian Krishnamurthy, Thomas C Brodnicki, Stuart I Mannering, Thomas W Kay, Helen E Thomas
Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics from other diseases to type 1 diabetes, especially when there is evidence for overlapping mechanisms. JAK1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and STAT1 pathway in human type 1 diabetes and in mouse models, especially in beta cells...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28291161/development-of-the-nonobese-diabetic-mouse-and-contribution-of-animal-models-for-understanding-type-1-diabetes
#19
Yoko Mullen
In 1974, the discovery of a mouse and a rat that spontaneously developed hyperglycemia led to the development of 2 autoimmune diabetes models: nonobese diabetic (NOD) mouse and Bio-Breeding rat. These models have contributed to our understanding of autoimmune diabetes, provided tools to dissect autoimmune islet damage, and facilitated development of early detection, prevention, and treatment of type 1 diabetes. The genetic characterization, monoclonal antibodies, and congenic strains have made NOD mice especially useful...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28281688/effects-of-silk-fibroin-in-murine-dry-eye
#20
Chae Eun Kim, Ji Hyun Lee, Yeung Kyu Yeon, Chan Hum Park, JaeWook Yang
The study aimed to investigate the effects of silk fibroin in a mouse model of dry eye. The experimental dry eye mouse model was developed using more than twelve-weeks-old NOD.B10.H2(b) mice exposing them to 30-40% ambient humidity and injecting them with scopolamine hydrobromide for 10 days. Tear production and corneal irregularity score were measured by the instillation of phosphate buffered saline or silk fibroin. Corneal detachment and conjunctival goblet cell density were observed by hematoxylin and eosin or periodic acid Schiff staining in the cornea or conjunctiva...
March 10, 2017: Scientific Reports
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