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https://www.readbyqxmd.com/read/28319642/therapeutic-efficacy-of-nanocomplex-of-poly-ethylene-glycol-and-catechin-for-dry-eye-disease-in-a-mouse-model
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28280903/microrna-21-targets-bcl2-mrna-to-increase-apoptosis-in-rat-and-human-beta-cells
#6
Emily K Sims, Alexander J Lakhter, Emily Anderson-Baucum, Tatsuyoshi Kono, Xin Tong, Carmella Evans-Molina
AIMS/HYPOTHESIS: The role of beta cell microRNA (miR)-21 in the pathophysiology of type 1 diabetes has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in type 1 diabetes and the phenotype of beta cell miR-21 overexpression through target identification. METHODS: Islets were isolated from NOD mice and mice treated with multiple low doses of streptozotocin, as a mouse model of diabetes. INS-1 832/13 beta cells and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the milieu of early type 1 diabetes...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28275508/targeting-cd47-the-achievements-and-concerns-of-current-studies-on-cancer-immunotherapy
#7
COMMENT
Yuting Huang, Yuchi Ma, Peng Gao, Zhi Yao
Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction...
February 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28273882/inhibition-of-nlrp3-inflammasome-pathway-by-butyrate-improves-corneal-wound-healing-in-corneal-alkali-burn
#8
Fang Bian, Yangyan Xiao, Mahira Zaheer, Eugene A Volpe, Stephen C Pflugfelder, De-Quan Li, Cintia S de Paiva
Epithelial cells are involved in the regulation of innate and adaptive immunity in response to different stresses. The purpose of this study was to investigate if alkali-injured corneal epithelia activate innate immunity through the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. A unilateral alkali burn (AB) was created in the central cornea of C57BL/6 mice. Mice received either no topical treatment or topical treatment with sodium butyrate (NaB), β-hydroxybutyric acid (HBA), dexamethasone (Dex), or vehicle (balanced salt solution, BSS) quater in die (QID) for two or five days (d)...
March 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28273875/characterization-of-ace-and-ace2-expression-within-different-organs-of-the-nod-mouse
#9
Heleia Roca-Ho, Marta Riera, Vanesa Palau, Julio Pascual, Maria Jose Soler
Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression...
March 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28272423/small-molecule-inhibitors-block-gas6-inducible-tam-activation-and-tumorigenicity
#10
Stanley G Kimani, Sushil Kumar, Nitu Bansal, Kamalendra Singh, Vladyslav Kholodovych, Thomas Comollo, Youyi Peng, Sergei V Kotenko, Stefan G Sarafianos, Joseph R Bertino, William J Welsh, Raymond B Birge
TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264583/crispr-mediated-knockout-of-i-cybb-i-in-nsg-mice-establishes-a-model-of-chronic-granulomatous-disease-for-human-stem-cell-gene-therapy-transplants
#11
Colin L Sweeney, Uimook Choi, Chengyu Liu, Sherry M Koontz, Seung-Kwon Ha, Harry L Malech
Chronic granulomatous disease (CGD) is characterized by defects in production of microbicidal reactive oxygen species (ROS) by phagocytes. Testing of gene and cell therapies for treatment of CGD in human hematopoietic cells requires pre-clinical transplant models. The use of the lymphocyte-deficient NOD.Cg-Prkdc<sup>scid</sup> Il2rg<sup>tm1Wjl</sup>/SzJ (NSG) mouse strain for human hematopoietic cell xenografts to test CGD therapies is complicated by the presence of functional mouse granulocytes capable of producing ROS for subsequent bacterial and fungal killing...
March 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28258056/novel-immunodeficient-pde6b-rd1-mouse-model-of-retinitis-pigmentosa-to-investigate-potential-therapeutics-and-pathogenesis-of-retinal-degeneration
#12
Alaknanda Mishra, Barun Das, Madhu Nath, Srikanth Iyer, Ashwani Kesarwani, Jashdeep Bhattacharjee, Shailendra Arindkar, Preeti Sahay, Kshama Jain, Parul Sahu, Prakriti Sinha, Thirumurthy Velpandian, Perumal Nagarajan, Pramod Upadhyay
Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for elucidation of effective therapeutics and factors regulating retinal degeneration to prohibit or renew the damaged retina. However, controversies over immune privilege of retina during cell transplantation and role of immune modulation during RP still remain largely uninvestigated due to lack of proper animal models...
March 3, 2017: Biology Open
https://www.readbyqxmd.com/read/28249000/stabilization-of-hif-1%C3%AE-and-hif-2%C3%AE-up-regulation-of-mycc-and-accumulation-of-stabilized-p53-constitute-hallmarks-of-cns-pnet-animal-model
#13
Sergey Malchenko, Simone Treiger Sredni, Yingtao Bi, Naira V Margaryan, Jerusha Boyineni, Indra Mohanam, Tadanori Tomita, Ramana V Davuluri, Marcelo B Soares
Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice's brain sub-ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients' PNETs. Moreover, we found that (i) stabilization of HIF-1α and HIF-2α, which are involved in mediation of the hypoxic responses in the majority of cell types, (ii) up-regulation of MYCC, a key onco-protein whose dysregulation occurs in ~70% of human tumors, and (iii) accumulation of stabilized p53, which is commonly altered in human cancers, constitute hallmarks of our tumor model, and might represent the basis for CNS-PNET tumorigenesis in this model...
2017: PloS One
https://www.readbyqxmd.com/read/28247187/development-of-novel-immunopet-tracers-to-image-human-pd-1-checkpoint-expression-on-tumor-infiltrating-lymphocytes-in-a-humanized-mouse-model
#14
Arutselvan Natarajan, Aaron T Mayer, Robert E Reeves, Claude M Nagamine, Sanjiv Sam Gambhir
PURPOSE: It is well known that cancers exploit immune checkpoints (programmed death 1 receptor (PD-1) and its ligand (PD-L1)) to evade anti-tumor immune responses. Although immune checkpoint (IC) blockade is a promising approach, not all patients respond. Hence, imaging of tumor-infiltrating lymphocytes (TILs) is of high specific interest, as they are known to express PD-1 during activation and subsequent exhaustion in the tumor microenvironment and are thought to be potentially predictive of therapeutic responses to IC blockade...
February 28, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28236454/il-15-super-agonist-alt-803-enhances-natural-killer-nk-cell-function-against-ovarian-cancer
#15
M Felices, S Chu, B Kodal, L Bendzick, C Ryan, A J Lenvik, K L M Boylan, H C Wong, A P N Skubitz, J S Miller, M A Geller
OBJECTIVE: Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. METHODS: NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation...
February 21, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28230260/elevation-of-sharpin-protein-levels-in-prostate-adenocarcinomas-promotes-metastasis-and-impairs-patient-survivals
#16
Hai Huang, Tao Du, Yiming Zhang, Yiming Lai, Kaiwen Li, Xinxing Fan, Dingjun Zhu, Tianxin Lin, Kewei Xu, Jian Huang, Leyuan Liu, Zhenghui Guo
BACKGROUND: SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model...
February 23, 2017: Prostate
https://www.readbyqxmd.com/read/28229405/compact-bone-derived-multipotent-mesenchymal-stromal-cells-mscs-for-the-treatment-of-sjogren-s-like-disease-in-nod-mice
#17
Ghada Abu Elghanam, Younan Liu, Saeed Khalili, Dongdong Fang, Simon D Tran
Compact bone (cortical or dense bone) is among the organs that contain multipotent mesenchymal stromal cells (MSCs). Unlike bone marrow plugs where MSCs were initially isolated, compact bone has minimal (amount of) hematopoietic cells and thus facilitates the MSCs isolation process. In vitro, MSCs from compact bone show multipotency and differentiation into mesenchymal tissues such as bone, adipose, and cartilage, under certain conditions. MSCs therapy has been promising in preclinical and clinical studies against autoimmune diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#18
Elisabeth Schrumpf, Xiaojun Jiang, Sebastian Zeissig, Marion J Pollheimer, Jarl Andreas Anmarkrud, Corey Tan, Mark A Exley, Tom H Karlsen, Richard S Blumberg, Espen Melum
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d(-/-) mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28218739/suppression-of-islet-homeostasis-protein-thwarts-diabetes-mellitus-progression
#19
Seh-Hoon Oh, Marda L Jorgensen, Clive H Wasserfall, Altin Gjymishka, Bryon E Petersen
During progression to type 1 diabetes, insulin-producing β-cells are lost through an autoimmune attack resulting in unrestrained glucagon expression and secretion, activation of glycogenolysis, and escalating hyperglycemia. We recently identified a protein, designated islet homeostasis protein (IHoP), which specifically co-localizes within glucagon-positive α-cells and is overexpressed in the islets of both post-onset non-obese diabetic (NOD) mice and type 1 diabetes patients. Here we report that in the αTC1...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28210258/human-gingiva-derived-mesenchymal-stem-cells-inhibit-xeno-graft-versus-host-disease-via-cd39-cd73-adenosine-and-ido-signals
#20
Feng Huang, Maogen Chen, Weiqian Chen, Jian Gu, Jia Yuan, Yaoqiu Xue, Junlong Dang, Wenru Su, Julie Wang, Homayoun H Zadeh, Xiaoshun He, Limin Rong, Nancy Olsen, Song Guo Zheng
Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease...
2017: Frontiers in Immunology
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