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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28228598/beware-are-bacteria-raising-your-oxidative-stress
#2
Purna Kashyap
Peptostreptococcus anaerobius, enriched in patients with colon cancer, induces cellular proliferation and dysplasia by toll-like receptor (TLR) 2- and TLR4-dependent increase in oxidative stress and cholesterol biosynthesis.
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28228587/prophylactic-herpes-simplex-virus-2-hsv-2-vaccines-adjuvanted-with-stable-emulsion-and-toll-like-receptor-9-agonist-induce-a-robust-hsv-2-specific-cell-mediated-immune-response-protect-against-symptomatic-disease-and-reduce-the-latent-viral-reservoir
#3
Michael T Hensel, Jason D Marshall, Michael R Dorwart, Darren S Heeke, Eileen Rao, Padmaja Tummala, Li Yu, Gary H Cohen, Roselyn J Eisenberg, Derek D Sloan
Several prophylactic vaccines targeting HSV-2 have failed in the clinic to demonstrate a sustained depression in viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies, their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the neutralizing antibody (nAb) targets gD and gB, the novel T cell antigen and tegument protein UL40, and we compared this to a whole-inactivated virus vaccine (FI-HSV-2)...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228554/association-of-lyn-kinase-with-membrane-rafts-determines-its-negative-influence-on-lps-induced-signaling
#4
Kinga Borzęcka-Solarz, Justyna Dembińska, Aneta Hromada-Judycka, Gabriela Traczyk, Anna Ciesielska, Ewelina Ziemlińska, Anna Świątkowska, Katarzyna Kwiatkowska
Lipopolysaccharide (LPS) is the component of Gram-negative bacteria which activates Toll-like receptor 4 (TLR4) to trigger pro-inflammatory responses. We examined the involvement of Lyn tyrosine kinase in TLR4 signaling of macrophages, distinguishing its catalytic activity and intermolecular interactions. For this, a series of Lyn-GFP constructs bearing point mutations in particular domains of Lyn were overexpressed in RAW264 macrophage-like cells or murine peritoneal macrophages, and their influence on LPS-induced responses was analyzed...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228357/activation-of-mtor-i%C3%AE%C2%BAb-%C3%AE-nf-%C3%AE%C2%BAb-pathway-contributes-to-lps-induced-hypotension-and-inflammation-in-rats
#5
Meryem Temiz-Resitoglu, Sefika Pinar Kucukkavruk, Demet Sinem Guden, Pelin Cecen, Ayse Nihal Sari, Bahar Tunctan, Aysegul Gorur, Lulufer Tamer-Gumus, Cuneyt Kemal Buharalioglu, Kafait U Malik, Seyhan Sahan-Firat
Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll-like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)-induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor-κB (NF-κB) p65, inhibitor κB (IκB)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)-α and activity of myeloperoxidase (MPO), which results in hypotension and inflammation...
February 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28228119/genetic-variation-of-the-toll-like-receptors-in-a-swedish-allergic-rhinitis-case-population
#6
V Henmyr, D Carlberg, E Manderstedt, C Lind-Halldén, T Säll, L O Cardell, C Halldén
BACKGROUND: Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF ≤ 1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients. METHODS: Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data...
February 23, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28225489/immunoregulation-effects-of-different-%C3%AE-%C3%AE-t-cells-and-toll-like-receptor-signaling-pathways-in-neonatal-necrotizing-enterocolitis
#7
Lei Hui, Yi Dai, Zhi Guo, Jiahui Zhang, Fang Zheng, Xiangli Bian, Zhimin Wu, Qin Jiang, Miaomiao Guo, Ke Ma, Jinping Zhang
The aim of the study was to observe cytokine and T-cell-related toll-like-receptor (TLR) changes in intestinal samples of neonatal necrotizing enterocolitis patients.Four necrotic bowels were collected from neonatal NEC patients with gestational ages of 28 to 29 weeks in our hospital, whereas 4 neonatal patients who underwent intestinal atresia surgery served as the controls. Intestinal flora was examined and IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and IL-17 expressions in resected intestine samples, as well as in isolated gamma delta T (γδT) cells, were analyzed immunohistochemically and via quantitative RT-PCR...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28225132/an-unexpected-use-of-ferrocene-a-scanning-electrochemical-microscopy-study-of-a-toll-like-receptor-array-and-its-interaction-with-e-coli
#8
Zhe She, Kristin Topping, Bin Dong, Mohtashim H Shamsi, Heinz-Bernhard Kraatz
Imaging of toll-like receptor microarrays was achieved using scanning electrochemical microscopy with the successful integration of two ferrocene derivatives in order to enhance the background contrast. This investigation has resulted in the novel fabrication of a tuneable, multiplex, broad-spectrum bacterial sensor for the interrogation of conserved microbial stimuli.
February 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#9
Trudy McGarry, Monika Biniecka, Wei Gao, Deborah Cluxton, Mary Canavan, Siobhan Wade, Sarah Wade, Lorna Gallagher, Carl Orr, Douglas J Veale, Ursula Fearon
During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in a manner similar to that observed in tumour cells. While TLRs have been implicated in the pathogenesis of rheumatoid arthritis (RA), their role in regulating cellular metabolism in synovial cells, however, is still unknown. In this study, we investigated the effect of TLR2-activation on mitochondrial function and bioenergetics in primary RA-synovial fibroblast cells (RASFC), and further determined the role of glycolytic blockade on TLR2-induced inflammation in RASFC using glycolytic inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO)...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225045/membrane-targeting-of-tirap-is-negatively-regulated-by-phosphorylation-in-its-phosphoinositide-binding-motif
#10
Xiaolin Zhao, Wen Xiong, Shuyan Xiao, Tuo-Xian Tang, Jeffrey F Ellena, Geoffrey S Armstrong, Carla V Finkielstein, Daniel G S Capelluto
Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225018/choline-ameliorates-cardiovascular-damage-by-improving-vagal-activity-and-inhibiting-the-inflammatory-response-in-spontaneously-hypertensive-rats
#11
Longzhu Liu, Yi Lu, Xueyuan Bi, Man Xu, Xiaojiang Yu, Runqing Xue, Xi He, Weijin Zang
Autonomic dysfunction and abnormal immunity lead to systemic inflammatory responses, which result in cardiovascular damage in hypertension. The aim of this report was to investigate the effects of choline on cardiovascular damage in hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were intraperitoneally injected with choline or vehicle (8 mg/kg/day). After 8 weeks, choline restored the cardiac function of the SHRs, as evidenced by decreased heart rate, systolic blood pressure, left ventricle systolic pressure, and ±dp/dtmax and increased ejection fraction and fractional shortening...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224333/anti-neuroinflammatory-effects-of-grossamide-from-hemp-seed-via-suppression-of-tlr-4-mediated-nf-%C3%AE%C2%BAb-signaling-pathways-in-lipopolysaccharide-stimulated-bv2-microglia-cells
#12
Qian Luo, Xiaoli Yan, Larisa Bobrovskaya, Mei Ji, Huiqing Yuan, Hongxiang Lou, Peihong Fan
Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation...
February 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#13
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223925/effects-of-intermittent-alcohol-exposure-on-emotion-and-cognition-a-potential-role-for-the-endogenous-cannabinoid-system-and-neuroinflammation
#14
Laura Sanchez-Marin, Francisco J Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodriguez de Fonseca, Antonia Serrano
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28223830/two-snps-in-the-promoter-region-of-toll-like-receptor-4-gene-are-not-associated-with-smoking-in-saudi-arabia
#15
Muhammad Kohailan, Mohammad Alanazi, Mahmoud Rouabhia, Abdullah Al Amri, Narasimha Reddy Parine, Abdelhabib Semlali
Defects in the innate immune system, particularly in Toll-like receptors (TLRs), have been reported in several cigarette smoke-promoted diseases. The aim of this study was to examine the impact of tobacco smoke on allelic frequencies of TLR4 single-nucleotide polymorphisms (SNPs) and to compare the genotypic distribution of these SNPs in a Saudi Arabian population with that in previously studied populations. DNA was extracted from 303 saliva samples collected from smokers and nonsmokers. Two transitional SNPs in the promoter region of TLR4 were selected, rs2770150 (T/C) and rs10759931 (G/A)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223539/thymol-mitigates-lipopolysaccharide-induced-endometritis-by-regulating-the-tlr4-and-ros-mediated-nf-%C3%AE%C2%BAb-signaling-pathways
#16
Haichong Wu, Kangfeng Jiang, Nannan Yin, Xiaofei Ma, Gan Zhao, Changwei Qiu, Ganzhen Deng
The purpose of this study was to investigate the effects of thymol on lipopolysaccharide (LPS)-induced inflammatory responses and to clarify the potential mechanism of these effects. LPS-induced mouse endometritis was used to confirm the anti-inflammatory action of thymol in vivo. RAW264.7 cells were used to examine the molecular mechanism and targets of thymol in vitro. In vivo, thymol markedly alleviated LPS-induced pathological injury, myeloperoxidase (MPO) activity, and the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223111/expression-analysis-of-nine-toll-like-receptors-in-yellow-catfish-pelteobagrus-fulvidraco-responding-to-aeromonas-hydrophila-challenge
#17
Xiao-Ting Zhang, Gui-Rong Zhang, Ze-Chao Shi, Yu-Jie Yuan, Huan Zheng, Li Lin, Kai-Jian Wei, Wei Ji
Toll-like receptors (TLRs) are important components of pattern recognition receptors (PRRs), which play significant roles in innate immunity to defense against pathogen invasion. Many TLRs have been found in teleosts, but there are no reports about cloning and expression of TLR genes in yellow catfish (Pelteobagrus fulvidraco). In this study, we analyzed the sequence characters and the relative mRNA expression levels of nine TLRs (TLR1, TLR2, TLR3, TLR4-1, TLR5, TLR7, TLR8-2, TLR9 and TLR22) in different tissues of yellow catfish...
February 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28222998/dynamics-of-apc-recruitment-at-the-site-of-injection-following-injection-of-vaccine-adjuvants
#18
Susan van Aalst, Irene Stephanie Ludwig, Peter Johannes Sylvester van Kooten, Ruurd van der Zee, Willem van Eden, Femke Broere
Vaccines often contain adjuvants to strengthen the response to the vaccine antigen. However, their modes of action at the site of injection (SOI) are poorly understood. Therefore, we assessed the local effects of adjuvant on the innate immune system in mice. We investigated the safe, widely used adjuvants MF59 and aluminum hydroxide (alum), as well as trehalose-6,6'-dibehenate (TDB), Complete Freund's Adjuvant (CFA) and the Toll-Like-Receptor-ligands lipopolysaccharide (LPS) and Pam3CysSerLys4 (Pam3CSK4). We assessed muscle immune cell infiltration after adjuvant injection and observed 16h post immunization (hpi) an increased influx with CFA, MF59 and TDB, but not with alum, LPS or Pam3CSK4...
February 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28222760/tlr4-rs41426344-increases-susceptibility-of-rheumatoid-arthritis-ra-and-juvenile-idiopathic-arthritis-jia-in-a-central-south-chinese-han-population
#19
Yan Wang, Lianghui Chen, Fang Li, Meihua Bao, Jie Zeng, Ju Xiang, Huaiqing Luo, Jianming Li, Liang Tang
BACKGROUND: The aim of the study was to determine whether polymorphisms in toll-like receptor 4 (TLR4) confer susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population. METHODS: Genotyping for six well studied polymorphisms (rs4986790, rs4986791, rs10759932, rs41426344, rs11536889 and rs7873784) in TLR4 gene were conducted in 1074 unrelated patients with RA and 1692 healthy control subjects, as well as in 217 unrelated patients with JIA and 378 healthy control subjects using direct sequencing technique...
February 21, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28222752/dendritic-cells-macrophages-nk-and-cd8-t-lymphocytes-play-pivotal-roles-in-controlling-hsv-1-in-the-trigeminal-ganglia-by-producing-il1-beta-inos-and-granzyme-b
#20
Natália Lucinda, Maria Marta Figueiredo, Natália Lima Pessoa, Beatriz Senra Álvares da Silva Santos, Graciela Kunrath Lima, Arthur Molinari Freitas, Alexandre Magalhães Vieira Machado, Erna Geessien Kroon, Lis Ribeiro do Valle Antonelli, Marco Antônio Campos
BACKGROUND: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1β) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1β production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1...
February 21, 2017: Virology Journal
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