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https://www.readbyqxmd.com/read/29786555/innate-immunity-in-stem-cell-derived-hepatocytes
#1
REVIEW
Lena Fischer, David C Hay, Cliona O'Farrelly
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784886/-legionella-pneumophila-is-directly-sensitive-to-2-deoxyglucose-phosphate-via-its-uhpc-transporter-but-is-indifferent-to-shifts-in-host-cell-glycolytic-metabolism
#2
Jordan V Price, Kallie Jiang, Abigail Galantowicz, Alana Freifeld, Russell E Vance
Toll-like receptor stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow-derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila ( L. pneumophila ), but the role of host macrophage glycolysis on intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29784770/tlr-activated-repression-of-fe-s-cluster-biogenesis-drives-a-metabolic-shift-and-alters-histone-and-tubulin-acetylation
#3
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29783985/the-doses-of-plasmid-backbone-plays-a-major-role-in-determining-the-hbv-clearance-in-hydrodynamic-injection-mouse-model
#4
Xian Wang, Jianmin Zhu, Yong Zhang, Yue Li, Tai Ma, Qun Li, Jiegou Xu, Long Xu
BACKGROUND: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. METHODS: In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence...
May 21, 2018: Virology Journal
https://www.readbyqxmd.com/read/29781148/improved-osteogenesis-of-boron-incorporated-calcium-silicate-coatings-via-immunomodulatory-effects
#5
Xiang Lu, Kai Li, Youtao Xie, Shengcai Qi, Qingyi Shen, Jiangming Yu, Liping Huang, Xuebin Zheng
Osteoimmunology has revealed the importance of a favorable immune response for successful biomaterial-mediated osteogenesis. Boron-incorporated calcium silicate (Ca11 Si4 B2 O22 , B-CS) coating has been reported as a potential candidate for improving osteogenesis in orthopedic applications in vitro. However, relatively little is known about its effects on the immune response and subsequent osteogenesis. In this work, the immunomodulatory properties of the B-CS coating and its specific mechanism of action were explored...
May 20, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29779962/implementation-of-drug-eluting-stents-for-the-treatment-of-femoropopliteal-disease-provides-significant-cost-to-system-savings-in-a-single-state-outpatient-simulation
#6
Natalie Domenick Sridharan, Nathan Liang, Darve Robinson, Efthymios Avgerinos, Edith Tzeng, Michel S Makaroun, Rabih A Chaer, Mohammad H Eslami
OBJECTIVES: Initial data on drug-eluting stents (DES) shows that they may increase the durability of endovascular treatment of superficial femoral artery disease compared with traditional bare metal stents (BMS). Observed decreased target lesion revascularization (TLR) rates have potential for cost savings despite an increased initial cost. The purpose of this study was to run a simulation model of progressive transition from BMS to DES over 5 years evaluating the overall cost impact of that transition...
May 18, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29778672/defective-myd88-and-irak4-but-not-tlr-2-expression-in-hiv-individuals-with-latent-tuberculosis-infection
#7
Kamakshi Prudhula Devalraju, Venkata Sanjeev Kumar Neela, Ramulu Gaddam, Arunabala Chaudhury, Abhinav Van, Siva Sai Krovvidi, Ramakrishna Vankayalapati, Vijaya Lakshmi Valluri
HIV infection markedly increases the likelihood of latent tuberculosis infection progressing to active TB. Information on expression of TLR-2, myeloid differentiation factor (MyD88), IL-1R- associated kinase-4 (IRAK4) and nuclear factor kappa B (NF-kB) in HIV+LTBI+ and HIV+ patients with active TB disease is limited. We found significantly higher percentages of CD14+TLR2+ cells in PBMCs of HIV+LTBI+ patients compared to HIV-LTBI+ individuals. γ-irradiated Mtb was unable to induce MyD88, IRAK4 expression and IL-1β, MCP-1, IP-10 production in HIV+LTBI+ patients...
May 17, 2018: Cytokine
https://www.readbyqxmd.com/read/29777767/biglycan-is-a-new-high-affinity-ligand-for-cd14-in-macrophages
#8
Heiko Roedig, Madalina V Nastase, Helena Frey, Kristin Moreth, Jinyang Zeng-Brouwers, Chiara Poluzzi, Louise Tzung-Harn Hsieh, Christian Brandts, Simone Fulda, Malgorzata Wygrecka, Liliana Schaefer
Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Here we discovered that soluble biglycan is a novel high-affinity ligand for CD14, a well-known GPI-anchored co-receptor for TLRs...
May 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29777458/increased-vitamin-d-receptor-gene-expression-and-rs11568820-and-rs4516035-promoter-polymorphisms-in-autistic-disorder
#9
Burhan Balta, Hakan Gumus, Ruslan Bayramov, Keziban Korkmaz Bayramov, Murat Erdogan, Didem Behice Oztop, Muhammet Ensar Dogan, Serpil Taheri, Munis Dundar
Although there are a large number of sequence variants of different genes and copy number variations at various loci identified in autistic disorder (AD) patients, the pathogenesis of AD has not been elucidated completely. Recently, in AD patients, a large number of expression array and transcriptome studies have shown an increase in the expression of genes especially related to innate immune response. Antimicrobial effects of vitamin D and VDR are exerted through Toll-Like-Receptors (TLR) which have an important role in the innate immune response, are expressed by antigen presenting cells and recognize foreign microorganisms...
May 18, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29774159/toll-like-receptors-2-and-4-modulate-intestinal-il-10-differently-in-ileum-and-colon
#10
Eva Latorre, Elena Layunta, Laura Grasa, Julián Pardo, Santiago García, Ana I Alcalde, José E Mesonero
Background: Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis...
April 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29772941/recent-advances-in-the-discovery-and-development-of-tlr-ligands-as-novel-therapeutics-for-chronic-hbv-and-hiv-infections
#11
Keye Du, Jia Liu, Ruth Broering, Xiaoyong Zhang, Dongliang Yang, Ulf Dittmer, Mengji Lu
Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands ...
May 17, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29771684/antibiotic-treatment-induced-secondary-iga-deficiency-enhances-susceptibility-to-pseudomonas-aeruginosa-pneumonia
#12
Oliver H Robak, Markus M Heimesaat, Andrey A Kruglov, Sandra Prepens, Justus Ninnemann, Birgitt Gutbier, Katrin Reppe, Hubertus Hochrein, Mark Suter, Carsten J Kirschning, Veena Marathe, Jan Buer, Mathias W Hornef, Markus Schnare, Pascal Schneider, Martin Witzenrath, Stefan Bereswill, Ulrich Steinhoff, Norbert Suttorp, Leif E Sander, Catherine Chaput, Bastian Opitz
Broad-spectrum antibiotics are widely used in patients on intensive care units (ICU), many of which develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29770768/treatment-of-femoro-popliteal-lesions-with-scoring-and-drug-coated-balloon-angioplasty-12-month-results-of-the-dcb-trak-registry
#13
Magnus Baumhäkel, Shalva Chkhetia, Michael Kindermann
PURPOSE: Debulking strategies prior to drug-coated balloon (DCB) angioplasty were suggested to improve clinical results in femoro-popliteal lesions. Currently, there are no data regarding plaque modification with a scoring balloon with subsequent DCB-angioplasty. Recently published 6-month results of the DCB-Trak registry in patients treated with scoring-balloon angioplasty and DCB-angioplasty were promising without any safety concerns. Herein, we report the 12-month follow-up data. METHODS: In a single center registry, 29 consecutive patients with 32 femoro-popliteal lesions were treated with a scoring-balloon (VascuTrak®) and a DCB subsequently...
May 2018: Diagnostic and Interventional Radiology: Official Journal of the Turkish Society of Radiology
https://www.readbyqxmd.com/read/29769561/transcriptome-analysis-of-circulating-pbmcs-to-understand-mechanism-of-high-altitude-adaptation-in-native-cattle-of-ladakh-region
#14
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Ranjit S Kataria, Saket K Niranjan, Vijay K Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Manishi Mukesh
Ladakhi cattle is native population of Leh and Ladakh region and constantly exposed to hypobaric hypoxia over many generations. In present study, transcriptome signatures of cattle from Ladakh region (~5500 m) and Sahiwal cattle from tropical regions were evaluated using Agilent 44 K microarray chip. The top up-regulated genes in Ladakhi cows were INHBC, ITPRI, HECA, ABI3, GPR171, and HIF-1α involved in hypoxia and stress response. In Sahiwal cows, the top up-regulated genes eEF1A1, GRO1, CXCL2, DEFB3 and BOLA-DQA3 were associated with immune function and inflammatory response indicating their strong immune potential to combat the pathogens prevalent in the tropical conditions...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769448/tlr-adjuvanted-nanoparticle-vaccines-differentially-influence-the-quality-and-longevity-of-responses-to-malaria-antigen-pfs25
#15
Elizabeth A Thompson, Sebastian Ols, Kazutoyo Miura, Kelly Rausch, David L Narum, Mats Spångberg, Michal Juraska, Ulrike Wille-Reece, Amy Weiner, Randall F Howard, Carole A Long, Patrick E Duffy, Lloyd Johnston, Conlin P O'Neil, Karin Loré
Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)-based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769270/effective-combination-adjuvants-engage-both-tlr-and-inflammasome-pathways-to-promote-potent-adaptive-immune-responses
#16
Emilie Seydoux, Hong Liang, Natasha Dubois Cauwelaert, Michelle Archer, Nicholas D Rintala, Ryan Kramer, Darrick Carter, Christopher B Fox, Mark T Orr
The involvement of innate receptors that recognize pathogen- and danger-associated molecular patterns is critical to programming an effective adaptive immune response to vaccination. The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation to induce strong adaptive responses. Although TLR4 signaling through MyD88 and TIR domain-containing adapter inducing IFN-β are essential for GLA-SE activity, the mechanisms underlying the synergistic activity of GLA and SE are not fully understood...
May 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29768176/the-chaperone-unc93b1-regulates-toll-like-receptor-stability-independently-of-endosomal-tlr-transport
#17
Karin Pelka, Damien Bertheloot, Elisa Reimer, Kshiti Phulphagar, Susanne V Schmidt, Anette Christ, Rainer Stahl, Nicki Watson, Kensuke Miyake, Nir Hacohen, Albert Haas, Melanie M Brinkmann, Ann Marshak-Rothstein, Felix Meissner, Eicke Latz
Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29767533/sirt1-controls-poly-i-c-dependent-mmp9-activation-in-primary-human-nasal-epithelial-cells
#18
Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, Alkis Psaltis, Peter-John Wormald, Sarah Vreugde
BACKGROUND: Matrix metalloproteinase 9 (MMP9) is thought to be involved in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and cleaves collagen IV causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP9 expression is negatively affected by sirtuin-1 (SIRT-1) in human monocytotic cells, retinal endothelial cells and epithelial carcinoma cells. However, it is unknown which factors affect MMP9 expression and activity in human nasal epithelial cells (HNECs)...
May 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29767353/influences-of-temporal-lobe-epilepsy-and-temporal-lobe-resection-on-olfaction
#19
Richard L Doty, Isabelle Tourbier, Jessica K Neff, Jonathan Silas, Bruce Turetsky, Paul Moberg, Taehoon Kim, John Pluta, Jaqueline French, Ashwini D Sharan, Michael J Sperling, Natasha Mirza, Anthony Risser, Gordon Baltuch, John A Detre
Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test...
May 16, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29767328/a-placebo-controlled-efficacy-study-of-the-intravesical-immunomodulators-tmx-101-and-tmx-202-in-an-orthotopic-bladder-cancer-rat-model
#20
Johannes Falke, Christina A Hulsbergen-van de Kaa, Roberto Maj, Egbert Oosterwijk, J Alfred Witjes
PURPOSE: TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. METHODS: Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0...
May 16, 2018: World Journal of Urology
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