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https://www.readbyqxmd.com/read/28230260/elevation-of-sharpin-protein-levels-in-prostate-adenocarcinomas-promotes-metastasis-and-impairs-patient-survivals
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28209904/noninvasive-imaging-of-human-immune-responses-in-a-human-xenograft-model-of-graft-versus-host-disease
#6
Catharina H M J Van Elssen, Mohammad Rashidian, Vladimir Vrbanac, Kai W Wucherpfennig, Zeina El Habre, Jana Sticht, Christian Freund, Johanne Jacobsen, Juanjo Cragnolini, Jessica Ingram, Loes Plaisier, Eric Spierings, Andrew M Tager, Hidde Ploegh
The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer or auto-immunity. Immuno-PET is a non-invasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28205558/plant-based-vaccines-for-oral-delivery-of-type-1-diabetes-related-autoantigens-evaluating-oral-tolerance-mechanisms-and-disease-prevention-in-nod-mice
#7
Amanda L Posgai, Clive H Wasserfall, Kwang-Chul Kwon, Henry Daniell, Desmond A Schatz, Mark A Atkinson
Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3(+) and LAP(+) regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202777/nodding-syndrome-may-be-an-autoimmune-reaction-to-the-parasitic-worm-onchocerca-volvulus
#8
Tory P Johnson, Richa Tyagi, Paul R Lee, Myoung-Hwa Lee, Kory R Johnson, Jeffrey Kowalak, Abdel Elkahloun, Marie Medynets, Alina Hategan, Joseph Kubofcik, James Sejvar, Jeffrey Ratto, Sudhir Bunga, Issa Makumbi, Jane R Aceng, Thomas B Nutman, Scott F Dowell, Avindra Nath
Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#9
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193546/contribution-of-guanine-nucleotide-exchange-factor-vav2-to-nlrp3-inflammasome-activation-in-mouse-podocytes-during-hyperhomocysteinemia
#10
Sabena M Conley, Justine M Abais-Battad, Xinxu Yuan, Qinghua Zhang, Krishna M Boini, Pin-Lan Li
NADPH oxidase (NOX)-derived reactive oxygen species (ROS) have been demonstrated to mediate the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes in podocytes in response to elevated levels of homocysteine (Hcys). However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The present study tested whether the guanine nucleotide exchange factor Vav2 mediates Rac1-mediated NOX activation in response to elevated Hcys leading to NLRP3 inflammasome activation in podocytes and consequent glomerular injury...
February 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28183848/long-term-observation-reveals-high-frequency-engraftment-of-human-acute-myeloid-leukemia-in-immunodeficient-mice
#11
Anna M Paczulla, Stephan Dirnhofer, Martina Konantz, Michael Medinger, Helmut R Salih, Kathrin Rothfelder, Dimitrios A Tsakiris, Jakob R Passweg, Pontus Lundberg, Claudia Lengerke
Repopulation of immunodeficient mice remains the primary method to func-tionally assess human acute myeloid leukemia. Published data report en-graftment of ~40-66% of cases, mostly belonging to intermediate or poor risk subtypes. Here we report that extending follow-up beyond the standard analysis end-points of 10 to 16 weeks post-transplantation permitted leukemic engraftment from nearly every xenotransplanted acute myeloid leukemia case (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune phenotypes and genetic signatures when compared to corresponding pre-transplant cells, and were furthermore able to induce leukemia in re-transplantation assays...
February 9, 2017: Haematologica
https://www.readbyqxmd.com/read/28164571/establishment-of-a-novel-myelodysplastic-syndrome-mds-xenotransplantation-model
#12
Ling Ma, Xia Zhang, Zhiqiong Wang, Yan Chen, Jia Wei, Lihua Hu
BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disease of the elderly characterized by chronic cytopenia, dysplasia, and a high risk of progression to acute myeloid leukemia (AML). Up until now, few animal models that fully recapitulate clinical features of this disease have been available. METHODS: This study aimed to establish a new MDS xenograft model utilizing a human MDS-derived cell line with heterozygous Y641C mutation of EZH2 (SKM-1). 1 x 107 SKM-1 cells were inoculated into anti-mouse CD122 monoantibody conditioned nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice by intravenous injection...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159904/innate-immune-cell-recovery-is-positively-regulated-by-nlrp12-during-emergency-hematopoiesis
#13
Brandon M L Linz, Crystal J Neely, Laurel B Kartchner, April E Mendoza, Amal L Khoury, Agnieszka Truax, Gregory Sempowski, Timothy Eitas, June Brickey, Jenny P Y Ting, Bruce A Cairns, Robert Maile
With enhanced concerns of terrorist attacks, dual exposure to radiation and thermal combined injury (RCI) has become a real threat with devastating immunosuppression. NLRP12, a member of the NOD-like receptor family, is expressed in myeloid and bone marrow cells and was implicated as a checkpoint regulator of inflammatory cytokines, as well as an inflammasome activator. We show that NLRP12 has a profound impact on hematopoietic recovery during RCI by serving as a checkpoint of TNF signaling and preventing hematopoietic apoptosis...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28139658/sc83288-is-a-clinical-development-candidate-for-the-treatment-of-severe-malaria
#14
Stefano Pegoraro, Maëlle Duffey, Thomas D Otto, Yulin Wang, Roman Rösemann, Roland Baumgartner, Stefanie K Fehler, Leonardo Lucantoni, Vicky M Avery, Alicia Moreno-Sabater, Dominique Mazier, Henri J Vial, Stefan Strobl, Cecilia P Sanchez, Michael Lanzer
Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28135669/identification-of-genetic-variation-in-nod-like-receptor-2-gene-and-influence-of-polymorphism-on-gene-structure-and-function-in-buffalo-bubalus-bubalis
#15
Asmita Dhiman, S K Mishra, P K Dubey, S Goyal, M Sehgal, S K Niranjan, M Sodhi, B P Mishra, R S Kataria
Nucleotide-binding oligomerization domain (NOD)-like receptor 2 is one of the important mediators of innate as well as adaptive immune response to microbial infections. In this study, NOD-like receptor-2 was characterized by determining the full gene sequence and analyzing genetic diversity in Indian buffaloes. Sequence analysis of buffalo NOD2 revealed 3042 nucleotides long ORF, encoding 1013 amino acids from 12 exons. Domain structure analysis indicated existence of 8 leucine-rich repeat (LRR) domains in buffalo, cattle, sheep and mouse, along with central NACHT/NOD domain and two N-terminal CARD domains...
January 22, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28125559/o-011-low-dose-il-2-administration-expands-human-regulatory-t-cells-in-patients-with-uc-and-humanized-mice-and-protects-against-experimental-colitis
#16
Jeremy Goettel, Daniel Kotlarz, David Illig, James Canavan, Jessica Allegretti, Matthew Hamilton, Ryan Kelly, Alexandra Griffith, Madeline Carellas, Anastasia Nelina, Athos Bousvaros, Joshua Korzenik, Scott Snapper
BACKGROUND: Treg dysfunction or deficiency results in unopposed immune activation and autoimmunity. Interleukin-2 (IL-2) is critical for the expansion, suppressive function, and maintenance of Tregs. Although conventional T cells and NK cells respond to IL-2, Tregs are more sensitive to lower concentrations of IL-2 due to constitutive expression of CD25, the high affinity IL-2 receptor. Low-dose IL-2 therapies have shown to preferentially expand Tregs and ameliorate manifestations of graft versus host disease (Koreth et al...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28122086/rapamycin-eye-drops-suppress-lacrimal-gland-inflammation-in-a-murine-model-of-sj%C3%A3-gren-s-syndrome
#17
Mihir Shah, Maria C Edman, Srikanth Reddy Janga, Frances Yarber, Zhen Meng, Wannita Klinngam, Jonathan Bushman, Tao Ma, Siyu Liu, Stan Louie, Arjun Mehta, Chuanqing Ding, J Andrew MacKay, Sarah F Hamm-Alvarez
Purpose: To evaluate the efficacy of topical rapamycin in treating autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. Methods: We developed rapamycin in a poly(ethylene glycol)-distearoyl phosphatidylethanolamine (PEG-DSPE) micelle formulation to maintain solubility. Rapamycin or PEG-DSPE eye drops (vehicle) were administered in a well-established Sjögren's syndrome disease model, the male nonobese diabetic (NOD) mice, twice daily for 12 weeks starting at 8 weeks of age...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28111928/electrospun-poly-hydroxybutyrate-scaffolds-promote-engraftment-of-human-skin-equivalents-via-macrophage-m2-polarization-and-angiogenesis
#18
Delia Castellano, Ana Sanchis, María Blanes, Mª Dolores Pérez Del Caz, Amparo Ruiz-Saurí, Marina Piquer, Beatriz Pelacho, B Marco, Nahuel Garcia, Imelda Ontoria-Oviedo, Vicente Cambra, Felipe Prosper, Pilar Sepúlveda
Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, we show that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-ε-caprolactone electrospun scaffolds (PCL) as a substrate for skin reconstruction...
January 23, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28109957/adoptive-transfer-of-mrna-transfected-t-cells-redirected-against-diabetogenic-cd8%C3%A2-t-cells-can-prevent-diabetes
#19
Sigal Fishman, Mark D Lewis, L Khai Siew, Evy De Leenheer, Dimitri Kakabadse, Joanne Davies, Doron Ziv, Alon Margalit, Nathan Karin, Gideon Gross, F Susan Wong
Chimeric major histocompatibility complex (MHC) molecules supplemented with T cell receptor (TCR) signaling motifs function as activation receptors and can redirect gene-modified T cells against pathogenic CD8 T cells. We have shown that β2 microglobulin (β2m) operates as a universal signaling component of MHC-I molecules when fused with the CD3-ζ chain. Linking the H-2K(d)-binding insulin B chain peptide insulin B chain, amino acids 15-23 (InsB15-23) to the N terminus of β2m/CD3-ζ, redirected polyclonal CD8 T cells against pathogenic CD8 T cells in a peptide-specific manner in the non-obese diabetic (NOD) mouse...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28081180/pi3k%C3%AE-deficient-nod-mice-are-protected-from-diabetes-by-restoring-the-balance-of-regulatory-to-effector-t-cells
#20
Jamil Azzi, Lindsay Thueson, Robert Moore, Rozita Abdoli, Helena Reijonen, Reza Abdi
With a steady increase in its incidence and lack of curative treatment, type 1 diabetes (T1D) has emerged as a major health problem worldwide. To design novel effective therapies, there is a pressing need to identify regulatory targets controlling the balance of autoreactive to regulatory-T-cells (Tregs). We previously showed that the inhibition of the γ-subunit of the Phosphoinositide-3-kinase (PI3K), significantly suppress autoimmune-diabetes. To further delineate the mechanisms and the selectivity of specific immune modulation by PI3Kγ-inhibition, we developed a new NOD mouse model of T1D lacking the γ-subunit of PI3K...
2017: PloS One
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