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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
#1
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
https://www.readbyqxmd.com/read/28029143/troxerutin-attenuates-enhancement-of-hepatic-gluconeogenesis-by-inhibiting-nod-activation-mediated-inflammation-in-high-fat-diet-treated-mice
#2
Zifeng Zhang, Xin Wang, Guihong Zheng, Qun Shan, Jun Lu, Shaohua Fan, Chunhui Sun, Dongmei Wu, Cheng Zhang, Weitong Su, Junwen Sui, Yuanlin Zheng
Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks...
December 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28024508/-reconstruction-of-humanized-bone-marrow-niche-in-immunodeficiency-mouse
#3
Huan Chen, Zheng Tian, Bin Li, Hai-Yan Xing, Huan Li, Ke-Jing Tang, Min Wang, Qing Rao
OBJECTIVE: To reconstruct a human bone marrow niche in immunodeficiency mouse (NOD/SCID) so as to provide a model for observing the effect of abnormal BM niche on the occurence and development of leukemia. METHODS: Human platelet lysate(HPL) was obtained by repeated freezing and thawing of concentrated platelet. Bone marrow-derived mesenchymal stem cells were cultured in α-minimal essential medium (α-MEM) containing 10% HPL or 10% FBS. The morphology, cell phenotype, multilineage differentiation potential in vitro and proliferation capacity between the mesenchymal stem cells cultured with HPL or FBS were compared...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28006671/recapitulation-of-treatment-response-patterns-in-a-novel-humanized-mouse-model-for-chronic-hepatitis-b-virus-infection
#4
Benjamin Y Winer, Tiffany Huang, Benjamin E Low, Cindy Avery, Mihai-Alexandru Pais, Gabriela Hrebikova, Evelyn Siu, Luis Chiriboga, Michael V Wiles, Alexander Ploss
There are ~350 million chronic carriers of hepatitis B (HBV). While a prophylactic vaccine and drug regimens to suppress viremia are available, chronic HBV infection is rarely cured. HBV's limited host tropism leads to a scarcity of susceptible small animal models and is a hurdle to developing curative therapies. Mice that support engraftment with human hepatoctyes have traditionally been generated through crosses of murine liver injury models to immunodeficient backgrounds. Here, we describe the disruption of fumarylacetoacetate hydrolase directly in the NOD Rag1(-/-) IL2RγNULL (NRG) background using zinc finger nucleases...
December 19, 2016: Virology
https://www.readbyqxmd.com/read/28006000/glibenclamide-prevents-diabetes-in-nod-mice
#5
Smaragda Lamprianou, Conny Gysemans, Joanna Bou Saab, Helena Pontes, Chantal Mathieu, Paolo Meda
Previous work has revealed that Cx36, the sole connexin expressed in the insulin-producing beta cells, enhances the secretion of insulin, and promotes the resistance of beta cells against pro-inflammatory cytokines. In parallel, the anti-diabetic sulphonylurea glibenclamide was shown to promote the assembly and function of Cx36 channels. Here, we assessed whether glibenclamide could protect the insulin-producing cells against conditions mimicking those expected at the onset of type 1 diabetes. We found that the drug 1) protected in vitro the mouse MIN6 cells from the apoptosis and loss of Cx36, which are induced by Th1 cytokines; 2) prevented the development of hyperglycemia as well as the loss of beta cells and Cx36, which rapidly develop with aging in untreated NOD mice; 3) modified the proportion of effector CD4+ and CD8+ T cells in pancreatic draining lymph nodes...
2016: PloS One
https://www.readbyqxmd.com/read/28004787/cross-protective-efficacy-of-dendritic-cells-targeting-conserved-influenza-virus-antigen-expressed-by-lactobacillus-plantarum
#6
Wen-Tao Yang, Shao-Hua Shi, Gui-Lian Yang, Yan-Long Jiang, Liang Zhao, Yu Li, Chun-Feng Wang
Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27998968/drug-sensitive-fgfr3-mutations-in-lung-adenocarcinoma
#7
P Chandrani, K Prabhash, A Choughule, R Prasad, V Sethunath, M Ranjan, P Iyer, J Aich, H Dhamne, D N Iyer, P Upadhyay, B Mohanty, P Chandna, R Kumar, A Joshi, V Noronha, V Patil, A Ramaswamy, A Karpe, R Thorat, P Chaudhari, A Ingle, A Dutt
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths across the world. In this study we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. MATERIALS AND METHODS: Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500X (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27980777/improved-b-cell-development-in-humanized-nod-scid-il2r%C3%AE-null-mice-transgenically-expressing-human-stem-cell-factor-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-3
#8
Sonal Jangalwe, Leonard D Shultz, Anuja Mathew, Michael A Brehm
INTRODUCTION: Immunodeficient mice engrafted with human immune systems support studies of human hematopoiesis and the immune response to human-specific pathogens. A significant limitation of these humanized mouse models is, however, a severely restricted ability of human B cells to undergo class switching and produce antigen-specific IgG after infection or immunization. METHODS: In this study, we have characterized the development and function of human B cells in NOD-scid IL2Rγ(null) (NSG) mice transgenically expressing human stem cell factor (SCF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-3 (NSG-SGM3) following engraftment with human hematopoietic stem cells, autologous fetal liver, and thymic tissues (bone marrow, liver, thymus or BLT model)...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27975325/studying-hbv-infection-and-therapy-in-immune-deficient-nod-rag1-il2rgammac-null-nrg-fumarylacetoacetate-hydrolase-fah-knockout-mice-transplanted-with-human-hepatocytes
#9
Feng Li, Kouki Nio, Fumihiko Yasui, Christopher M Murphy, Lishan Su
Chimeric mouse models with a humanized liver provide a unique tool to study hepatic virus diseases, including viral infection, viral pathogenesis, and antiviral therapy. Here we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (Fah) knockout mice repopulated with human hepatocytes. The procedures include (1) maintenance and genotyping of the homozygous NRG-fah/fah mutant mice (NRG/F), (2) intrasplenic injection of human hepatocytes, (3) NTBC drug reduction cycling to improve human hepatocyte repopulation, (4) human albumin detection, and (5) HBV infection and detection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27966604/endogenous-programmed-death-ligand-1-restrains-the-development-and-onset-of-sj%C3%B3-gren-s-syndrome-in-non-obese-diabetic-mice
#10
Jing Zhou, Jun-O Jin, Toshihisa Kawai, Qing Yu
Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27940204/potentiation-of-hepatic-stellate-cell-activation-by-extracellular-atp-is-dependent-on-p2x7r-mediated-nlrp3-inflammasome-activation
#11
Shuang Jiang, Yu Zhang, Jin-Hua Zheng, Xia Li, You-Li Yao, Yan-Ling Wu, Shun-Zong Song, Peng Sun, Ji-Xing Nan, Li-Hua Lian
Purinergic receptor P2x7 (P2x7R) is a key modulator of liver inflammation and fibrosis. The present study aimed to investigate the role of P2x7R in hepatic stellate cells activation. Lipopolysaccharide (LPS) or the conditioned medium (CM) from LPS-stimulated RAW 264.7 mouse macrophages was supplemented to human hepatic stellate cells, LX-2 for 24h and P2x7R selective antagonist A438079 (10μM) was supplemented to LX-2 cells 1h before LPS or CM stimulation. In addition LX-2 cells were primed with LPS for 4h and subsequently stimulated for 30min with 3mM of adenosine 5'-triphosphate (ATP)...
December 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27939129/guillain-barr%C3%A3-syndrome-is-induced-in-non-obese-diabetic-nod-mice-following-campylobacter-jejuni-infection-and-is-exacerbated-by-antibiotics
#12
J L St Charles, J A Bell, B J Gadsden, A Malik, H Cooke, L K Van de Grift, H Y Kim, E J Smith, L S Mansfield
Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues...
December 8, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27935859/histone-deacetylase-inhibitors-inhibit-metastasis-by-restoring-a-tumor-suppressive-microrna-150-in-advanced-cutaneous-t-cell-lymphoma
#13
Fumito Abe, Akihiro Kitadate, Sho Ikeda, Junsuke Yamashita, Hiroki Nakanishi, Naoto Takahashi, Chikara Asaka, Kazuaki Teshima, Tomomitsu Miyagaki, Makoto Sugaya, Hiroyuki Tagawa
Tumor suppressive microRNA (miR)-150 inhibits metastasis by combining with the C-C chemokine receptor 6 (CCR6) "seed sequence" mRNA of the 3'-untranslated region (3'-UTR) in advanced cutaneous T-cell lymphoma (CTCL). Because the histone deacetylase inhibitor (HDACI) vorinostat showed excellent outcomes for treating advanced CTCL, HDACIs may reduce the metastasis of CTCL by targeting miR-150 and/ or CCR6. To examine whether these candidate molecules are essential HDACI targets in advanced CTCL, we used the My-La, HH, and HUT78 CTCL cell lines for functional analysis because we previously demonstrated that their xenografts in NOD/Shi-scid IL-2γnul mice (CTCL mice) induced multiple metastases...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935045/patient-derived-xenografts-of-gastrointestinal-cancers-are-susceptible-to-rapid-and-delayed-b-lymphoproliferation
#14
Sebastian M Dieter, Klara M Giessler, Mark Kriegsmann, Taronish D Dubash, Lino Möhrmann, Erik R Schulz, Christine Siegl, Sarah Weber, Hendrik Strakerjahn, Ava Oberlack, Ulrike Heger, Jianpeng Gao, Eva-Maria Hartinger, Felix Oppel, Christopher M Hoffmann, Nati Ha, Benedikt Brors, Felix Lasitschka, Alexis Ulrich, Oliver Strobel, Manfred Schmidt, Christof von Kalle, Martin Schneider, Wilko Weichert, K Roland Ehrenberg, Hanno Glimm, Claudia R Ball
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro...
December 9, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27934918/targeting-asc-in-nlrp3-inflammasome-by-caffeic-acid-phenethyl-ester-a-novel-strategy-to-treat-acute-gout
#15
Hye Eun Lee, Gabsik Yang, Nam Doo Kim, Seongkeun Jeong, Yunjin Jung, Jae Young Choi, Hyun Ho Park, Joo Young Lee
Gouty arthritis is caused by the deposition of uric acid crystals, which induce the activation of NOD-like receptor family, pyrin domain containing 3(NLRP3) inflammasome. The NLRP3 inflammasome, composed of NLRP3, the adaptor protein ASC, and caspase-1, is closely linked to the pathogenesis of various metabolic diseases including gouty arthritis. We investigated whether an orally administrable inhibitor of NLRP3 inflammasome was effective for alleviating the pathological symptoms of gouty arthritis and what was the underlying mechanism...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27933491/nlrp3-is-required-for-complement-mediated-caspase-1-and-il-1beta-activation-in-ich-short-title-for-running-head-nlrp3-is-required-for-ich
#16
Sheng-Tao Yao, Fang Cao, Jia-Lin Chen, Wei Chen, Rui-Ming Fan, Gang Li, You-Chao Zeng, Song Jiao, Xiang-Ping Xia, Chong Han, Qi-Shan Ran
Complement-mediated inflammation plays a vital role in intracerebral hemorrhage (ICH), implicating pro-inflammatory factor interleukin-1beta (IL-1β) secretion. Brain samples and contralateral hemiencephalon were all collected and detected by Western blot. NLRP3 expression was located by dual immunofluorescence staining at 1, 3, and 5 days post-ICH. Brain water content was examined post-ICH. The neural deficit scores were evaluated by observers blindly. ILs were detected by ELISA. SiRNAs targeting NLRP3 (siNLRP3), siASC, and siControl were injected to inhibit NLRP3 function...
December 8, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#17
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#18
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27889607/leptin-ob-r-signaling-is-elevated-in-mice-with-sj%C3%A3-gren-s-syndrome-and-is-implicated-in-disease-pathogenesis
#19
Ting Xu, Wen Xie, Yingchun Ma, Shiliang Zhou, Lu Zhang, Jinyun Chen, Mingyuan Cai, Rurong Sun, Peirong Zhang, Shaobo Yu, Zheng Xu, Wanlan Jiang, Min Wu
Sjögren's syndrome (SjS) is a systemic autoimmune disease resulting in a severe dry mouth and dry eyes. Currently, care for patients with SjS is palliative, as no established therapeutics target the disease directly, and its pathogenetic mechanisms are uncertain. Leptin activates B cells to induce the secretion of proinflammatory and anti-inflammatory cytokines and is elevated in several autoimmune diseases. In this study, we found the expression of leptin and its receptor OB-R in mouse models of SjS are elevated both locally and systemically during SjS progression...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27889463/noncanonical-fungal-autophagy-inhibits-inflammation-in-response-to-ifn-%C3%AE-via-dapk1
#20
Vasilis Oikonomou, Silvia Moretti, Giorgia Renga, Claudia Galosi, Monica Borghi, Marilena Pariano, Matteo Puccetti, Carlo A Palmerini, Lucia Amico, Alessandra Carotti, Lucia Prezioso, Angelica Spolzino, Andrea Finocchi, Paolo Rossi, Andrea Velardi, Franco Aversa, Valerio Napolioni, Luigina Romani
Defects in a form of noncanonical autophagy, known as LC3-associated phagocytosis (LAP), lead to increased inflammatory pathology during fungal infection. Although LAP contributes to fungal degradation, the molecular mechanisms underlying LAP-mediated modulation of inflammation are unknown. We describe a mechanism by which inflammation is regulated during LAP through the death-associated protein kinase 1 (DAPK1). The ATF6/C/EBP-β/DAPK1 axis activated by IFN-γ not only mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation...
December 14, 2016: Cell Host & Microbe
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