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https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#1
Neal Van Hoeven, Christopher B Fox, Brian Granger, Tara Evers, Sharvari W Joshi, Ghislain I Nana, Sarah C Evans, Susan Lin, Hong Liang, Li Liang, Rie Nakajima, Philip L Felgner, Richard A Bowen, Nicole Marlenee, Airn Hartwig, Susan L Baldwin, Rhea N Coler, Mark Tomai, James Elvecrog, Steven G Reed, Darrick Carter
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#2
Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean-Alexis Grimaud
Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the three-dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL-1β, were not expressed in keratinocytes...
April 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28424222/randomized-comparison-of-paclitaxel-eluting-balloon-angioplasty-plus-stenting-versus-standard-balloon-angioplasty-plus-stenting-versus-directional-atherectomy-for-symptomatic-femoral-artery-disease-isar-stath
#3
Ilka Ott, Salvatore Cassese, Philipp Groha, Birgit Steppich, Martin Hadamitzky, Tareq Ibrahim, Sebastian Kufner, Karl Dewitz, Regina V Hiendlmayer, Karl-Ludwig Laugwitz, Heribert Schunkert, Adnan Kastrati, Massimiliano Fusaro
Background -Atherosclerosis in the superficial femoral artery (SFA) is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting and directional atherectomy (DA) have provided new options for the treatment of SFA disease, however the comparative efficacy remains uncertain. Methods -One hundred and fifty five patients with symptomatic peripheral artery disease with de novo SFA stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA followed by stenting (n=52) or directional DA with distal protection and bailout stenting (n=55)...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#4
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28413476/the-mechanism-of-human-%C3%AE-defensin-3-in-mrsa-induced-infection-of-implant-drug-resistant-bacteria-biofilm-in-the-mouse-tibial-bone-marrow
#5
Chen Zhu, Ni-Rong Bao, Shuo Chen, Jian-Ning Zhao
The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group)...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410580/lactobacillus-casei-dg-and-its-postbiotic-reduce-the-inflammatory-mucosal-response-an-ex-vivo-organ-culture-model-of-post-infectious-irritable-bowel-syndrome
#6
Debora Compare, Alba Rocco, Pietro Coccoli, Debora Angrisani, Costantino Sgamato, Barbara Iovine, Umberto Salvatore, Gerardo Nardone
BACKGROUND: The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model. METHODS: Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB...
April 14, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28409540/comparison-of-cellular-assays-for-tlr-activation-and-development-of-a-species-specific-reporter-cell-line-for-cattle
#7
Kata Tombácz, Duncan Mwangi, Dirk Werling, Amanda J Gibson
PRRs are sentinels of the innate immune system, with TLRs being the most important. Assays for TLR ligand interactions have been used to gain insights into their function and signaling pathways. As significant differences exist between species with regard to ligand recognition, it is necessary to adapt these tools for TLRs of other species. In the present work, we describe a species-specific cell-based assay adapted for the analysis of single PRRs. Human embryonic kidney 293T cells were stably transfected with the NF-κB-inducible reporter gene secreted embryonic alkaline phosphatase (SEAP) together with bovine TLR2...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#8
Mari Falck, Damjan Osredkar, Elke Maes, Torun Flatebø, Thomas Ragnar Wood, Hemmen Sabir, Marianne Thoresen
Perinatal infection increases the vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury. Hypothermia treatment (HT) does not provide neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide (LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2...
April 14, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28404732/roles-of-the-traf6-and-pellino-e3-ligases-in-myd88-and-rankl-signaling
#9
Sam Strickson, Christoph H Emmerich, Eddy T H Goh, Jiazhen Zhang, Ian R Kelsall, Thomas Macartney, C James Hastie, Axel Knebel, Mark Peggie, Francesco Marchesi, J Simon C Arthur, Philip Cohen
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells...
April 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28400218/outcomes-of-the-japanese-multicenter-viabahn-trial-of-endovascular-stent-grafting-for-superficial-femoral-artery-lesions
#10
Takao Ohki, Kimihiko Kichikawa, Hiroyoshi Yokoi, Masaaki Uematsu, Terutoshi Yamaoka, Koji Maeda, Yuji Kanaoka
OBJECTIVE: The objective of this study was to assess 1-year safety, efficacy, and invasiveness outcomes of endovascular stent grafting of symptomatic long lesions (≥10 cm) in the superficial femoral artery (SFA) as a substitute for above-knee open bypass surgery. METHODS: This prospective, multicenter (15 hospitals) study assessed heparin-coated stent grafts for the treatment of long SFA lesions in Japanese subjects with peripheral arterial disease. Inclusion criteria were Rutherford category 2 to 5 symptoms (grade 5 without active infection), ankle-brachial index ≤0...
April 8, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28384159/3lps-binding-protein-and-its-interactions-with-p-gingivalis-lps-modulate-pro-inflammatory-response-and-toll-like-receptor-signaling-in-human-oral-keratinocytes
#11
Pei-Hui Ding, Richard P Darveau, Cun-Yu Wang, Lijian Jin
Lipopolysaccharide (LPS)-binding protein (LBP) as an acute-phase protein plays a crucial role in innate host response to bacterial challenge. Our previous study shows that LBP expression in human gingiva is associated with periodontal status. Porphyromonas gingivalis is a keystone periodontopathogen, and its LPS with lipid A structural heterogeneity critically accounts for periodontal pathogenesis. This study investigated the effects of LBP and its interactions with two featured isoforms of P. gingivalis LPS (tetra-acylated LPS1435/1449 and penta-acylated LPS1690) on the expression of pro-inflammatory cytokines in human oral keratinocytes (HOKs), and the involvement of Toll-like receptor (TLR) signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28382025/starter-feeding-supplementation-alters-colonic-mucosal-bacterial-communities-and-modulates-mucosal-immune-homeostasis-in-newborn-lambs
#12
Junhua Liu, Gaorui Bian, Daming Sun, Weiyun Zhu, Shengyong Mao
This study aims to investigate the effect of starter feeding supplementation on colonic mucosal bacterial communities and on mucosal immune homeostasis in pre-weaned lambs. We selected eight pairs of 10-day-old lamb twins. One twin was fed breast milk (M, n = 8), while the other was fed breast milk plus starter (M+S, n = 8). The lambs were sacrificed at 56 days age. Colonic content was collected to determine the pH and the concentrations of volatile fatty acids (VFA) and lactate. The colonic mucosa was harvested to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and toll-like receptors (TLR) using quantitative real-time PCR...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28373780/drug-eluting-stents-or-balloon-angioplasty-for-drug-eluting-stent-associated-restenosis-an-observational-follow-up-study-of-first-time-versus-repeated-restenosis
#13
Mohamed Aboel-Kassem F Abdelmegid, Tarek A N Ahmed, Masashi Kato, Kenji Ando, Takenori Domei, Masashi Iwabuchi, Masakiyo Nobuyoshi
BACKGROUND: The treatment of patients with repeated drug-eluting stent-in stent restenosis (DES-ISR) remains a challenge and a burdensome clinical problem. METHODS: Over a 3-year period, 130 lesions in 123 patients who underwent target lesion revascularization (TLR) for DES restenosis were included in the study. They were classified into two main groups: the first group having first-time DES-ISR (n = 84), and the second group having rerestenosis of DES-treated DES-ISR (n = 39)...
April 2017: Journal of the Saudi Heart Association
https://www.readbyqxmd.com/read/28362018/il-37-suppresses-myd88-mediated-inflammatory-responses-in-human-aortic-valve-interstitial-cells
#14
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A Fullerton, Charles A Dinarello, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists...
March 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28359672/cloning-and-expression-analysis-of-a-toll-like-receptor-21-tlr21-gene-from-turbot-scophthalmus-maximus
#15
Song Li, Guanjie Wang, Dahai Liu, Qiuming Liu, Guobin Hu
Toll-like receptor 21 (TLR21) is a non-mammalian TLR recognizing unmethylated CpG DNA and considered as a functional homolog of mammalian TLR9. In the present study, a TLR21 gene was cloned from turbot, Scophthalmus maximus, its immune responsive expression was subsequently studied in vivo. The turbot (Sm)TLR21 gene is an intronless gene with a length of 3527 bp and encodes a peptide of 984 amino acids. The deduced protein possesses a signal peptide sequence, a leucine-rich repeat (LRR) domain composed of 16 LRR motifs, a transmembrane (TM) region and a Toll/interleukin-1 receptor (TIR) domain...
March 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28359324/cerebrospinal-fluid-cell-free-mitochondrial-dna-is-associated-with-hiv-replication-iron-transport-and-mild-hiv-associated-neurocognitive-impairment
#16
Sanjay R Mehta, Josué Pérez-Santiago, Todd Hulgan, Tyler R C Day, Jill Barnholtz-Sloan, Haley Gittleman, Scott Letendre, Ronald Ellis, Robert Heaton, Stephanie Patton, Jesse D Suben, Donald Franklin, Debralee Rosario, David B Clifford, Ann C Collier, Christina M Marra, Benjamin B Gelman, Justin McArthur, Allen McCutchan, Susan Morgello, David Simpson, James Connor, Igor Grant, Asha Kallianpur
BACKGROUND: Mitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort...
March 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28352660/tlr7-8-adjuvant-overcomes-newborn-hyporesponsiveness-to-pneumococcal-conjugate-vaccine-at-birth
#17
David J Dowling, Simon D van Haren, Annette Scheid, Ilana Bergelson, Dhohyung Kim, Christy J Mancuso, Willemina Foppen, Al Ozonoff, Lynn Fresh, Terese B Theriot, Andrew A Lackner, Raina N Fichorova, Dmitri Smirnov, John P Vasilakos, Joe M Beaurline, Mark A Tomai, Cecily C Midkiff, Xavier Alvarez, James L Blanchard, Margaret H Gilbert, Pyone Pyone Aye, Ofer Levy
Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13)...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28351208/angiographic-dissection-patterns-and-patency-outcomes-after-balloon-angioplasty-for-superficial-femoral-artery-disease
#18
Masahiko Fujihara, Mitsuyoshi Takahara, Shinya Sasaki, Kiyonori Nanto, Makoto Utsunomiya, Osamu Iida, Yoshiaki Yokoi
PURPOSE: To investigate the angiographic dissection patterns after balloon angioplasty for superficial femoral artery (SFA) lesions, the clinical outcome associated with each dissection pattern, and the predictive factors for severe dissection. METHODS: A retrospective, multicenter analysis examined 621 patients (mean age 72.8±9.5 years; 414 men) with 748 symptomatic de novo SFA lesions treated with endovascular therapy. Vessel dissection after the initial balloon angioplasty procedure was graded into 7 types according to a modified version of the coronary artery classification types A to F...
March 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28351204/results-from-the-visibility-iliac-study
#19
John H Rundback, Patrick Peeters, Jon C George, Michael R Jaff, Peter L Faries
PURPOSE: To evaluate the safety and effectiveness of primary stenting of the common (CIA) or external iliac artery (EIA) using the Visi-Pro Balloon-Expandable Peripheral Stent System for treatment of stenotic, restenotic, or occluded lesions. METHODS: Between 2011 and 2012, 75 patients (mean age 64.2±8.9 years; 46 men) with Rutherford category 2-4 ischemia and atherosclerotic lesions ≤10 cm in length underwent iliac artery stenting at 17 centers in the United States and Europe...
February 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28344208/clinical-outcomes-of-repetition-of-drug-coated-balloon-for-femoropopliteal-restenosis-after-drug-coated-balloon-treatment
#20
Shih-Jung Jang, Hsin-Hua Chou, Jyh-Ming Jimmy Juang, Chien-An Hsieh, De-Min Duan, Hsuan-Li Huang, Yu-Lin Ko
BACKGROUND: To compare the clinical outcomes of patients undergoing repeated drug-coated balloon (DCB) treatment for femoropopliteal (FP) DCB restenosis with those of patients without repetition-DCB.Methods and Results:From March 2013 to September 2014, 102 patients (118 affected legs) underwent DCB for symptomatic FP disease; 47 patients had restenosis, and 37 underwent reintervention over a 45-month follow-up. We compared the outcomes of repetition-DCB for DCB restenosis with those of patients without repetition...
March 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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