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https://www.readbyqxmd.com/read/28531216/impact-of-mutations-in-toll-like-receptor-pathway-genes-on-esophageal-carcinogenesis
#1
Daffolyn Rachael Fels Elliott, Juliane Perner, Xiaodun Li, Martyn F Symmons, Brett Verstak, Matthew Eldridge, Lawrence Bower, Maria O'Donovan, Nick J Gay, Rebecca C Fitzgerald
Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR) pathway could disrupt innate immune signaling and promote a microenvironment that favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed that non-synonymous mutations collectively affect the TLR pathway in 25/171 (14...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28531130/comparative-safety-and-efficacy-profile-of-a-novel-oil-in-water-vaccine-adjuvant-comprising-vitamins-a-and-e-and-a-catechin-in-protective-anti-influenza-immunity
#2
Sapna Patel, Yasser Faraj, Debra K Duso, William W Reiley, Erik A Karlsson, Stacey Schultz-Cherry, Michael Vajdy
Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus...
May 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28530643/danger-signals-in-regulating-the-immune-response-to-solid-organ-transplantation
#3
Jamie L Todd, Scott M Palmer
Endogenous danger signals, or damage-associated molecular patterns (DAMPs), are generated in response to cell stress and activate innate immunity to provide a pivotal mechanism by which an organism can respond to damaged self. Accumulating experimental and clinical data have established the importance of DAMPs, which signal through innate pattern recognition receptors (PRRs) or DAMP-specific receptors, in regulating the alloresponse to solid organ transplantation (SOT). Moreover, DAMPs may incite distinct downstream cellular responses that could specifically contribute to the development of allograft fibrosis and chronic graft dysfunction...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#4
Preeti Chhabra, Priya Ranjan, Theresa Cromeans, Suryaprakash Sambhara, Jan Vinjé
Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28530443/association-of-single-nucleotide-polymorphism-in-the-hepcidin-promoter-gene-with-susceptibility-to-extrapulmonary-tuberculosis
#5
Li Liang, Huijuan Liu, Jun Yue, Li-Rong Liu, Min Han, Liu-Lin Luo, Yan-Lin Zhao, Heping Xiao
BACKGROUND: Hepcidin is a 25-amino acid peptide produced by the liver in response to inflammation and iron overload. It is encoded by the hepcidin antimicrobial peptide (HAMP) gene and plays a key role in innate immunity. Previous studies have reported that a -582 A>G polymorphism in the HAMP promoter (HAMP-P) affects hepcidin expression, causing susceptibility to various bacterial and viral pathogens. However, it is not known whether the HAMP-P -582 A>G polymorphism is associated with tuberculosis (TB) susceptibility...
May 22, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28530057/-hansen-s-disease-in-israel
#6
REVIEW
Leon Gilead, Ruth Wexler
Hansen's disease (HD) is an anthropophylic, infectious, chronic disease, caused by Mycobacterium leprae. The systemic disease, affecting both males and females at any age, involves mainly the skin and the peripheral nerves located in the limbs close to the skin. Traditionally the treatment of HD patients was entrusted to dermatologists. Current drug therapy given at an early stage can prevent many of the complications, and enables patients to go on with life. In 95% of the population there is an innate immunity, which following exposure, enables the development of an effective immune response preventing the development of overt clinical disease...
October 2016: Harefuah
https://www.readbyqxmd.com/read/28529938/senescence-inflammatory-regulation-of-reparative-cellular-reprogramming-in-aging-and-cancer
#7
Javier A Menendez, Tomás Alarcón
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28529930/the-central-role-of-ifi204-in-ifn-%C3%AE-release-and-autophagy-activation-during-mycobacterium-bovis-infection
#8
Liu Chunfa, Sun Xin, Li Qiang, Srinand Sreevatsan, Lifeng Yang, Deming Zhao, Xiangmei Zhou
Mycobacterium bovis (M. bovis) is the pathogen of animals and humans that can replicate in the phagosomes of myeloid cells. Cytosolic detection of bacterial products plays a crucial role in initiating the innate immune response, including autophagy activation and interferon-β (IFN-β) release. Although IFN-β release and autophagy activation have been reported during mycobacterium infection, the mechanisms underlying remains poorly defined. Here, we demonstrated that IFN-β release increases in macrophages exposed to M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529904/mini-review-of-conventional-and-hypofractionated-radiation-therapy-combined-with-immunotherapy-for-non-small-cell-lung-cancer
#9
REVIEW
Allison M Campbell, Roy H Decker
A successful antitumoral response requires immunological activation as well as an antigenic pool capable of stimulating both the innate and the adaptive immune system. Recent advances in immunotherapy have been aimed at boosting the activation status of the innate and adaptive immune system, including cytokine administration, monoclonal antibodies engineered to target high yield elements in oncogenic signaling pathways, cancer vaccines, and checkpoint inhibitors. Herein, we examine the ways that radiation therapy induced cell death provides a pool of stimulus antigen, and draw parallels from the immunobiology of autoimmunity to explore how the immunogenicity of antigen derived from radiation-induced cell death might augment the antitumoral response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529900/immunotherapy-and-radiation-therapy-for-operable-early-stage-and-locally-advanced-non-small-cell-lung-cancer
#10
REVIEW
Neil K Taunk, Andreas Rimner, Melissa Culligan, Joseph S Friedberg, Julie Brahmer, Jamie Chaft
Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality. Although a significant proportion of patients can be cured with surgery, with or without adjuvant or neoadjuvant chemotherapy and radiation, a significant proportion of patients will fail, particularly distantly. Over fifty percent of patients present with stage IV disease. There are multiple forms of immunotherapy available including T-cell transfer, cytokine therapy, and oncolytic viruses. Checkpoint inhibitors have shown tremendous activity in NSCLC and are currently under intense study given promising data on response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529512/toll-interacting-protein-in-resolving-and-non-resolving-inflammation
#11
REVIEW
Elizabeth J A Kowalski, Liwu Li
Innate leukocytes manifest dynamic and distinct inflammatory responses upon challenges with rising dosages of pathogen-associated molecular pattern molecules such as lipopolysaccharide (LPS). To differentiate signal strengths, innate leukocytes may utilize distinct intracellular signaling circuitries modulated by adaptor molecules. Toll-interacting protein (Tollip) is one of the critical adaptor molecules potentially playing key roles in modulating the dynamic adaptation of innate leukocytes to varying dosages of external stimulants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28528707/molecular-transcriptional-and-functional-insights-into-duplicated-goose-type-lysozymes-from-sebastes-schlegelii-and-their-potential-immunological-role
#12
Jehanathan Nilojan, S D N K Bathige, Roopasingam Kugapreethan, W S Thulasitha, Bo-Hye Nam, Jehee Lee
Black rockfish (Sebastes schlegelii), an important aquaculture species in Korea, has been affected by bacterial diseases leading to a drastic decline in production. Goose-type lysozyme (LysG) is a key enzyme of the innate immune system to eradicate bacterial infections. In this study, two isoforms of LysG from black rockfish, designated as RfLysG1 and RfLysG2, have been identified and characterized at the molecular, transcriptional, and functional levels. The deduced amino acid sequences had the LysG family characteristics and exhibited conserved properties, including active residues and domains...
May 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28528647/transition-metal-homeostasis-in-streptococcus-pyogenes-and-streptococcus-pneumoniae
#13
Andrew G Turner, Cheryl-Lynn Y Ong, Mark J Walker, Karrera Y Djoko, Alastair G McEwan
Trace metals such as Fe, Mn, Zn and Cu are essential for various biological functions including proper innate immune function. The host immune system has complicated and coordinated mechanisms in place to either starve and/or overload invading pathogens with various metals to combat the infection. Here, we discuss the roles of Fe, Mn and Zn in terms of nutritional immunity, and also the roles of Cu and Zn in metal overload in relation to the physiology and pathogenesis of two human streptococcal species, Streptococcus pneumoniae and Streptococcus pyogenes...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28528521/myeloid-populations-in-systemic-autoimmune-diseases
#14
REVIEW
María Morell, Nieves Varela, Concepción Marañón
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors...
May 20, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28528440/the-human-cmv-ie1-protein-an-offender-of-pml-nuclear-bodies
#15
Myriam Scherer, Eva-Maria Schilling, Thomas Stamminger
PML nuclear bodies (PML-NBs) are SUMOylation-dependent, highly complex protein assemblies that accumulate in the interchromosomal territories of the cell nucleus. Research of the last two decades revealed that many viruses have evolved effector proteins that modify PML-NBs. This correlates with antagonization of individual PML-NB components which act as host cell restriction factors. The multifunctional immediate-early protein IE1 of human cytomegalovirus directly interacts with the PML protein resulting in a disruption of the dot-like structure of PML-NBs...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528439/innate-immune-mechanisms-and-herpes-simplex-virus-infection-and-disease
#16
Evelyn A Kurt-Jones, Megan H Orzalli, David M Knipe
Innate immune responses play a major role in the control of herpes simplex virus (HSV) infections, and a multiplicity of mechanisms have emerged as a result of human evolution to sense and respond to HSV infections. HSV in turn has evolved a number of ways to evade immune detection and to blunt human innate immune responses. In this review, we summarize the major host innate immune mechanisms and the HSV evasion mechanisms that have evolved. We further discuss how disease can result if this equilibrium between virus and host response is disrupted...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528214/nmr-structure-conformational-dynamics-and-biological-activity-of-psdef1-defensin-from-pinus-sylvestris
#17
Bulat I Khairutdinov, Elena A Ermakova, Yuri M Yusypovych, Elena K Bessolicina, Nadezhda B Tarasova, Yana Y Toporkova, Valentina Kovaleva, Yuriy F Zuev, Irina V Nesmelova
Plants have developed a complex defense response system against pests and pathogens. Defensins, produced by plants as part of their innate immune response, form the family of small, basic, cysteine-rich proteins with activity primarily directed against fungal pathogens. In addition, plant defensins can show antibacterial activity and protease and insect amylase inhibitory activities. However, in gymnosperms, only antifungal activity of defensins has been described thus far. Here, we report antibacterial and insect α-amylase inhibition activities for defensin PsDef1 from P...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#18
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28528178/expanding-biological-activities-of-ts19-frag-ii-toxin-insights-into-il-17-production
#19
Felipe Augusto Cerni, Manuela Berto Pucca, Karina Furlani Zoccal, Fabiani Gai Frantz, Lucia Helena Faccioli, Eliane Candiani Arantes
Tityus serrulatus (Ts) venom is composed of a mixture of toxins presenting diverse biological functions. However, although this venom has been studied over the past three decades, omics analysis revealed that most of its toxins are not identified or their biological activities are unknown. Ts19 Frag-II is included is this group, which function is still uncertain. This study aimed to expand the biological activities of Ts19 Frag-II through in vivo investigation. Our results demonstrates that mice challenged with Ts19 Frag-II presented biochemical alterations, increasing serum levels of urea, ALT and β-globulin, besides decreasing γ-globulins...
May 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28527860/biochemical-principles-and-inhibitors-to-interfere-with-viral-capping-pathways
#20
REVIEW
Etienne Decroly, Bruno Canard
Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases ('cap-snatching'). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors...
May 18, 2017: Current Opinion in Virology
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