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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/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#2
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/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#3
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
#4
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/28222760/tlr4-rs41426344-increases-susceptibility-of-rheumatoid-arthritis-ra-and-juvenile-idiopathic-arthritis-jia-in-a-central-south-chinese-han-population
#5
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/28222448/acute-effects-of-viral-exposure-on-p-glyco-protein-function-in-the-mouse-fetal-blood-brain-barrier
#6
Enrrico Bloise, Sophie Petropoulos, Majid Iqbal, Alisa Kostaki, Tania Maria Ortiga-Carvalho, William Gibb, Stephen G Matthews
BACKGROUND/AIMS: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB). As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation...
February 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28219988/sex-differences-in-microglia-activity-within-the-periaqueductal-gray-of-the-rat-a-potential-mechanism-driving-the-dimorphic-effects-of-morphine
#7
H H Doyle, L N Eidson, D M Sinkiewicz, A Z Murphy
Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require 2-3 times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal μ opioid receptor (MOR), morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28219695/inhibitory-effects-of-dynorphin-3-14-on-the-lipopolysaccharide-induced-toll-like-receptor-4-signalling-pathway
#8
Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells...
February 17, 2017: Peptides
https://www.readbyqxmd.com/read/28214954/association-of-toll-like-receptor-4-single-nucleotide-polymorphisms-asp299gly-and-thr399ile-with-the-risk-of-primary-open-angle-glaucoma
#9
Jose Navarro-Partida, Abril Bernardette Martinez-Rizo, Pedro Ramirez-Barrera, Jesus Bernardino Velazquez-Fernandez, Veronica A Mondragon-Jaimes, Arturo Santos-Garcia, Veronica Benites-Godinez
PURPOSE: Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands. Previously, non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene were related to primary open angle glaucoma (POAG). This study was undertaken to investigate whether coding TLR4 Asp299Gly (rs4986790 A/G) and Thr399Ile (rs4986791 C/T) are associated with POAG in a Mexican population. METHODS: One hundred and eighty-seven unrelated Mexican patients with POAG (94 men and 95 women; mean age 66...
February 18, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#10
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213041/newly-identified-pctoll4-regulates-antimicrobial-peptide-expression-in-intestine-of-red-swamp-crayfish-procambarus-clarkii
#11
Ying Huang, Tingting Li, Min Jin, Shaowu Yin, Kai-Min Hui, Qian Ren
Tolls or Toll-like receptors (TLRs) have an essential role in initiating innate immune responses against pathogens. In this study, a novel Toll gene, PcToll4, was first identified from the intestinal transcriptome of the freshwater crayfish, Procambarus clarkii. The PcToll4 cDNA is 4849bp long with a 3036bp open reading frame that encodes a 1011-amino acid protein. PcToll4 contains a signal peptide, 13 LRR domains, 3 LRR TYP domains, 2 LRR CT domains, an LRR NT domain, a transmembrane region, and a TIR domain...
February 14, 2017: Gene
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#12
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211536/expression-profiling-of-trim-protein-family-in-thp1-derived-macrophages-following-tlr-stimulation
#13
Mei-Xiu Jiang, Xuan Hong, Bin-Bin Liao, Shui-Zhen Shi, Xiao-Fang Lai, Huai-Yu Zheng, Lin Xie, Yuan Wang, Xiao-Lei Wang, Hong-Bo Xin, Mingui Fu, Ke-Yu Deng
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210837/toll-like-receptor-3-tlr-3-tlr-4-and-cd80-expression-in-peripheral-blood-mononuclear-cells-and-urinary-cd80-levels-in-children-with-idiopathic-nephrotic-syndrome
#14
Om P Mishra, Ravindra Kumar, Gopeshwar Narayan, Pradeep Srivastava, Abhishek Abhinay, Rajniti Prasad, Ankur Singh, Vineeta V Batra
BACKGROUND: The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). METHODS: The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls...
February 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28208028/early-life-wildfire-smoke-exposure-is-associated-with-immune-dysregulation-and-lung-function-decrements-in-adolescence
#15
Carolyn Black, Joan E Gerriets, Justin H Fontaine, Richart W Harper, Nicholas J Kenyon, Fern Tablin, Edward S Schelegle, Lisa A Miller
RATIONALE: The long-term health effects of wildfire smoke exposure in pediatric populations are not known. OBJECTIVE: To determine if early life exposure to wildfire smoke can affect parameters of immunity and airways physiology that are detectable with maturity. METHODS: We studied a mixed gender cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008...
February 16, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28207326/micro-rna-146a-but-not-irak1-is-associated-with-rheumatoid-arthritis-in-the-tunisian-population
#16
Hana Ben Hassine, Asma Boumiza, Rim Sghiri, Khadija Baccouche, Imen Boussaid, Ahlem Atig, Zahid Shakoor, Elyes Bouajina, Ramzi Zemni
BACKGROUND: Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR...
February 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28205610/cr-laao-an-l-amino-acid-oxidase-from-calloselasma-rhodostoma-venom-as-a-potential-tool-for-developing-novel-immunotherapeutic-strategies-against-cancer
#17
Tássia R Costa, Danilo L Menaldo, Karina F Zoccal, Sandra M Burin, Alexandre F Aissa, Fabíola A de Castro, Lúcia H Faccioli, Lusânia M Greggi Antunes, Suely V Sampaio
L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses in vivo, with recruitment of neutrophils and release of IL-6, IL-1β, LTB4 and PGE2. In vitro, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202935/polymorphisms-of-toll-like-receptors-2-and-9-and-severity-and-prognosis-of-bacterial-meningitis-in-chinese-children
#18
Pingping Zhang, Nan Zhang, Linlin Liu, Kai Zheng, Liang Zhu, Junping Zhu, Lina Cao, Yiyuan Jiang, Gang Liu, Qiushui He
Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202909/leukocyte-tlr5-deficiency-inhibits-atherosclerosis-by-reduced-macrophage-recruitment-and-defective-t-cell-responsiveness
#19
Guilielmus H J M Ellenbroek, Gijs H M van Puijvelde, Adam A Anas, Martine Bot, Miriam Asbach, Arjan Schoneveld, Peter J van Santbrink, Amanda C Foks, Leo Timmers, Pieter A Doevendans, Gerard Pasterkamp, Imo E Hoefer, Tom van der Poll, Johan Kuiper, Saskia C A de Jager
Toll-like receptors (TLR) provide a critical link between innate and adaptive immunity, both important players in atherosclerosis. Since evidence for the role of TLR5 is lacking, we aimed to establish this in the immune axis of atherosclerosis. We assessed the effect of the TLR5-specific ligand Flagellin on macrophage maturation and T-cell polarisation. Next, we generated TLR5(-/-)LDLr(-/-) chimeras to study the effect of hematopoietic TLR5 deficiency on atherosclerosis formation. Flagellin stimulation did not influence wildtype or TLR5(-/-) macrophage maturation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28201982/transcriptome-profile-of-rat-genes-in-injured-spinal-cord-at-different-stages-by-rna-sequencing
#20
Ling-Ling Shi, Nan Zhang, Xiu-Mei Xie, Yue-Juan Chen, Rui Wang, Lin Shen, Jian-Sheng Zhou, Jian-Guo Hu, He-Zuo Lü
BACKGROUND: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology. RESULTS: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group)...
February 15, 2017: BMC Genomics
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