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https://www.readbyqxmd.com/read/28811677/the-relationship-between-vegfa-and-tgfb1-polymorphisms-and-target-lesion-revascularization-after-elective-percutaneous-coronary-intervention
#1
Tadeusz Osadnik, Andrzej Lekston, Kamil Bujak, Joanna Katarzyna Strzelczyk, Lech Poloński, Mariusz Gąsior
BACKGROUND AND AIM: The specific association between genetic variation and in-stent restenosis is still only partly understood. The aim of this study is to analyze the relationship between functional polymorphisms in the genes encoding vascular endothelial growth factor A (VEGF-A; rs699947) and transforming growth factor beta 1 (TGF-β1; rs1800470) and target lesion revascularization (TLR) risk. METHODS: A total of 676 patients (805 lesions) with stable coronary artery disease (SCAD) who received elective percutaneous coronary intervention (PCI) with at least one bare-metal stent implantation were included...
2017: Disease Markers
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#2
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28804955/3m-052-as-an-adjuvant-for-a-plga-microparticle-based-leishmania-donovani-recombinant-protein-vaccine
#3
Qian Wang, Meagan A Barry, Christopher A Seid, Elissa M Hudspeth, C Patrick McAtee, Michael J Heffernan
It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (TH 1) immune response. In this study, we investigated the adjuvanticity of the Toll-like receptor (TLR) 7/8 agonist 3M-052 in combination with the Leishmania donovani 36-kDa nucleoside hydrolase recombinant protein antigen (NH36). NH36 and 3M-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). The loading efficiency for NH36 was 83% and for 3M-052 was above 95%. In vitro stimulation of bone marrow-derived dendritic cells, measured by IL-12 secretion, demonstrated that 3M-052 (free or MP-formulated) had a concentration-dependent immunostimulatory effect with an optimum concentration of 2 µg/mL...
August 14, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28795638/short-term-results-of-the-rapid-randomized-trial-of-the-legflow-paclitaxel-eluting-balloon-with-supera-stenting-vs-supera-stenting-alone-for-the-treatment-of-intermediate-and-long-superficial-femoral-artery-lesions
#4
Sanne W de Boer, Daniel A F van den Heuvel, Debbie A B de Vries-Werson, Jan Albert Vos, Bram Fioole, Damnis Vroegindeweij, Otto E Elgersma, Rudolph P Tutein Nolthenius, Jan M M Heyligers, Gerlof P T Bosma, Bernart de Leeuw, Lee H Bouwman, Dittmar Böckler, Dmitriy I Dovzhanskiy, Floris W F Vos, Ted W F Vink, Pieter G A Hooijboer, Rutger J Hissink, Jean-Paul P M de Vries
PURPOSE: To report a randomized trial comparing the Legflow paclitaxel-eluting balloon (PEB) + Supera stenting to Supera stenting alone in patients with intermediate to long superficial femoral artery (SFA) lesions. METHODS: The multicenter RAPID trial ( controlled-trials.com ; identifier ISRCTN47846578) randomized (1:1) 160 patients (mean age 67 years; 102 men) with Rutherford category 2-6 ischemia to treatment with Legflow PEB + Supera stent or Supera stent alone in intermediate to long SFA lesions (mean lesion length 15...
August 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28794025/retrovirus-based-virus-like-particle-immunogenicity-and-its-modulation-by-toll-like-receptor-activation
#5
Fabien Pitoiset, Thomas Vazquez, Beatrice Levacher, Djamel Nehar-Belaid, Nicolas Dérian, James Vigneron, David Klatzmann, Bertrand Bellier
Retrovirus-derived virus-like particles (VLPs) are particularly interesting vaccine platforms as they trigger efficient humoral and cellular immune responses and can be used to display heterologous antigens. In this study, we characterized the intrinsic immunogenicity of VLPs and investigated their possible adjuvantization by incorporation of toll-like receptor (TLR) ligands. We designed a non-coding single-stranded RNA (ncRNA) that could be encapsidated by VLPs and induce TLR7/8-signaling. We found that VLPs efficiently induce in vitro dendritic cell activation, which can be improved by ncRNA encapsidation (ncRNAVLPs)...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28789861/anti-inflammatory-properties-of-an-extract-of-m-ilicifolia-in-the-human-intestinal-epithelial-caco-2-cell-line
#6
Ruth Wonfor, Manuela Natoli, Ifat Parveen, Manfred Beckman, Robert Nash, Deborah Nash
ETHNOPHARMACOLOGY RELEVANCE: Maytenus ilicifolia is a Celastracea plant used in traditional medicine to alleviate digestive tract inflammatory disorders. AIM OF THE STUDY: We investigated anti-inflammatory properties of M. ilicifolia crude extract towards Caco-2 cell line, as a model of Toll-like Receptor 2 (TLR-2) inflammatory pathway. MATERIALS AND METHODS: Toxicity was assessed following culture of Caco-2 with M. ilicifolia, using apparent cell permeability and trans-epithelial electric resistance...
August 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28778074/toll-like-receptor-expression-in-human-non-small-cell-lung-carcinoma-potential-prognostic-indicators-of-disease
#7
Alison K Bauer, Brad L Upham, Elizabeth A Rondini, Meredith A Tennis, Kalpana Velmuragan, David Wiese
INTRODUCTION: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. RESULTS: Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28776068/clinical-outcomes-of-left-main-crossover-stenting-for-ostial-left-anterior-descending-artery-acute-myocardial-infarction
#8
Kei Yamamoto, Kenichi Sakakura, Naoyuki Akashi, Yusuke Watanabe, Masamitsu Noguchi, Yousuke Taniguchi, Hiroshi Wada, Shin-Ichi Momomura, Hideo Fujita
Percutaneous coronary interventions to ostial left anterior descending artery (LAD)-acute myocardial infarction (AMI) were challenging, especially in crossover stenting from left main trunk (LMT) to LAD. The clinical outcomes of ostial LAD-AMI that needed crossover stenting were not well investigated. The objective of this study was to compare the clinical outcomes of LMT crossover stenting with those of ostial LAD just proximal (jp) stenting. Between January 2009 and March 2016, 1499 patients were diagnosed as AMI in our institution...
August 3, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28761685/two-year-clinical-outcomes-of-patients-treated-with-the-dual-therapy-stent-in-a-1000-patient-all-comers-registry
#9
Deborah N Kalkman, Pier Woudstra, Ian B A Menown, Peter den Heijer, Arnoud Wj Van't Hof, Andrejs Erglis, Harry Suryapranata, Karin E Arkenbout, Andrés Iñiguez, Philippe Muller, Jan G Tijssen, Marcel A M Beijk, Robbert J de Winter
OBJECTIVE: The dual-therapy stent combines an abluminal biodegradable drug-eluting coating, with a 'pro-healing' luminal layer. This bioengineered layer attracts circulating endothelial progenitor cells that can differentiate into normal endothelium. Rapid endothelialisation of the stent might allow safe short dual antiplatelet therapy. We aim to assess clinical outcomes in patients treated with this novel device at 2-year follow-up. METHODS: A total of 1000 patients were included in the REMEDEE Registry to evaluate clinical outcomes after treatment with the dual-therapy stent...
2017: Open Heart
https://www.readbyqxmd.com/read/28756925/intervention-effect-and-mechanism-of-curcumin-in-chronic-urinary-tract-infection-in-rats
#10
Wen-Yong Xue, Jin-Chun Qi, Lei Du
OBJECTIVE: To analyze the invention effect of curcumin on chronic urinary tract infection in rats and explore its possible mechanism of action. METHODS: The experimental animals were randomly divided into three groups, normal, model and curcumin group. Chronic urinary tract infection models were built for model group and curcumin group by injecting coliform fluid into the cavity of bladder. From the first day of modeling, rats in the curcumin group were injected with 150 mg/kg curcumin, while rats in normal group and model group were given no other treatment...
June 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28747347/trim8-negatively-regulates-tlr3-4-mediated-innate-immune-response-by-blocking-trif-tbk1-interaction
#11
Wen Ye, Ming-Ming Hu, Cao-Qi Lei, Qian Zhou, Heng Lin, Ming-Shun Sun, Hong-Bing Shu
TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a Trim8 gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including TNF, Il6, Rantes, and Ifnb, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as Salmonella typhimurium infection-induced loss of body weight and septic shock...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28744288/naltrexone-inhibits-il-6-and-tnf%C3%AE-production-in-human-immune-cell-subsets-following-stimulation-with-ligands-for-intracellular-toll-like-receptors
#12
Rachel Cant, Angus G Dalgleish, Rachel L Allen
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28735358/il-10-and-tgf-%C3%AE-unbalanced-levels-in-neutrophils-contribute-to-increase-inflammatory-cytokine-expression-in-childhood-obesity
#13
Nayara I Medeiros, Rafael T Mattos, Carlos A Menezes, Rafaelle C G Fares, André Talvani, Walderez O Dutra, Fabrício Rios-Santos, Rodrigo Correa-Oliveira, Juliana A S Gomes
PURPOSE: Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. METHODS: We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. RESULTS: We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW)...
July 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28734965/enhanced-immunostimulatory-activity-of-in-silico-discovered-agonists-of-toll-like-receptor-2-tlr2
#14
M S Murgueitio, S Ebner, P Hörtnagl, C Rakers, R Bruckner, P Henneke, G Wolber, S Santos-Sierra
BACKGROUND: Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28729359/the-%C3%AE-defensin-retrocyclin-101-inhibits-tlr4-and-tlr2-dependent-signaling-and-protects-mice-against-influenza-infection
#15
Daniel Prantner, Kari Ann Shirey, Wendy Lai, Wuyuan Lu, Alexander M Cole, Stefanie N Vogel, Alfredo Garzino-Demo
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729250/stellarex-drug-coated-balloon-for-treatment-of-femoropopliteal-disease-12-month-outcomes-from-the-randomized-illumenate-pivotal-and-pharmacokinetic-studies
#16
Prakash Krishnan, Peter Faries, Khusrow Niazi, Ash Jain, Ravish Sachar, William B Bachinsky, Joseph A Cardenas, Martin Werner, Marianne Brodmann, J A Mustapha, Carlos I Mena-Hurtado, Michael R Jaff, Andrew H Holden, Sean P Lyden
Background -Drug-coated balloons (DCB) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Due to differences in excipients, paclitaxel dose and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of two studies investigating the pharmacokinetic (PK) and clinical outcomes of a new DCB to treat femoropopliteal disease. Methods -In the ILLUMENATE Pivotal Study, 300 symptomatic patients (Rutherford class 2-4), were randomized to DCB (N=200) or standard angioplasty (PTA) (N=100)...
July 20, 2017: Circulation
https://www.readbyqxmd.com/read/28726298/faah-but-not-magl-inhibition-modulates-acute-tlr3-induced-neuroimmune-signaling-in-the-rat-independent-of-sex
#17
Lisa E Flannery, Rebecca J Henry, Daniel M Kerr, David P Finn, Michelle Roche
Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-α/β, IP-10, or TNF-α), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN-α expression in the spleen of female, but not male, rats 8 hr post TLR3 activation...
July 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28726115/the-impact-of-coronary-calcification-on-angiographic-and-3-year-clinical-outcomes-of-everolimus-eluting-stents-results-of-a-xience-v-promus-post-marketing-surveillance-study
#18
Nobuo Shiode, Ken Kozuma, Jiro Aoki, Masaki Awata, Mamoru Nanasato, Kengo Tanabe, Junichi Yamaguchi, Hajime Kusano, Hong Nie, Takeshi Kimura
Coronary calcification (CCA) is one of the independent predictors for major adverse cardiac events (MACEs) in coronary intervention. Post-marketing surveillance study Japan is a prospective registry designed to evaluate the safety and efficacy of the everolimus-eluting stent (EES, XIENCE V/PROMUS Stent) in routine clinical practice at 47 centers. In this study, 1848 lesions (1546 patients) were assessed using quantitative coronary angiography. In these 1546 patients, renal function data were unknown in 26 patients...
July 19, 2017: Cardiovascular Intervention and Therapeutics
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#19
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28715767/non-human-primates-as-a-model-for-understanding-the-mechanism-of-action-of-toll-like-receptor-based-vaccine-adjuvants
#20
REVIEW
Elizabeth A Thompson, Karin Loré
While transgenic mouse models are powerful for understanding how the immune system is manipulated by vaccines, they cannot fully recapitulate the characteristics of the innate immune responses leading to adaptive immunity after vaccination in humans. Outbred non-human primates are far more representative models of human vaccine responses as there is high degree of similarities in immune cell subset distributions, receptor expression (including toll-like receptors; TLRs), and immune cell functions, in addition to modeling doses and injection sites more accurately...
July 14, 2017: Current Opinion in Immunology
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