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https://www.readbyqxmd.com/read/28933050/toll-like-receptor-4-signaling-mediates-inflammation-and-tissue-injury-in-diabetic-nephropathy
#1
REVIEW
Giacomo Garibotto, Annalisa Carta, Daniela Picciotto, Francesca Viazzi, Daniela Verzola
Toll-like receptors (TLRs) are a class of receptors of the innate immune system which detect pathogen-associated and danger-associated molecular patterns in order to initiate an inflammatory response. TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus. In diabetic nephropathy, TLR4, nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and NLRP3 inflammasome are involved in the production and persistence of inflammation...
September 20, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#2
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28928145/structure-insight-of-gsdmd-reveals-the-basis-of-gsdmd-autoinhibition-in-cell-pyroptosis
#3
Siyun Kuang, Jun Zheng, Hui Yang, Suhua Li, Shuyan Duan, Yanfang Shen, Chaoneng Ji, Jianhua Gan, Xue-Wei Xu, Jixi Li
Recent findings have revealed that the protein gasdermin D (GSDMD) plays key roles in cell pyroptosis. GSDMD binds lipids and forms pore structures to induce pyroptosis upon microbial infection and associated danger signals. However, detailed structural information for GSDMD remains unknown. Here, we report the crystal structure of the C-terminal domain of human GSDMD (GSDMD-C) at 2.64-Å resolution. The first loop on GSDMD-C inserts into the N-terminal domain (GSDMD-N), which helps stabilize the conformation of the full-length GSDMD...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28926539/the-immunology-of-the-allergy-epidemic-and-the-hygiene-hypothesis
#4
Bart N Lambrecht, Hamida Hammad
The immunology of the hygiene hypothesis of allergy is complex and involves the loss of cellular and humoral immunoregulatory pathways as a result of the adoption of a Western lifestyle and the disappearance of chronic infectious diseases. The influence of diet and reduced microbiome diversity now forms the foundation of scientific thinking on how the allergy epidemic occurred, although clear mechanistic insights into the process in humans are still lacking. Here we propose that barrier epithelial cells are heavily influenced by environmental factors and by microbiome-derived danger signals and metabolites, and thus act as important rheostats for immunoregulation, particularly during early postnatal development...
September 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28921464/posttranslational-modification-control-of-inflammatory-signaling
#5
Yibo Si, Yunlu Zhang, Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Dapeng Yan
Inflammation is usually the defensive reaction of the immune system to the invasion of pathogen and the exogenous objects. The activation of inflammation helps our body to eliminate pathogenic microbe, virus, and parasite harming our health, while under many circumstances inflammation is the direct cause of the pathological damage in tissues and dysfunction of organs. The posttranslational modification (PTM) of the inflammatory pathways, such as TLR pathways, RLR pathways, NLR pathway, intracellular DNA sensors, intracellular RNA sensors, and inflammasomes, is crucial in the regulation of these signaling trails...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921463/activation-of-the-innate-immune-receptors-guardians-of-the-micro-galaxy-activation-and-functions-of-the-innate-immune-receptors
#6
Dominic De Nardo
The families of innate immune receptors are the frontline responders to danger. These superheroes of the host immune systems populate innate immune cells, surveying the extracellular environment and the intracellular endolysosomal compartments and cytosol for exogenous and endogenous danger signals. As a collective the innate immune receptors recognise a wide array of stimuli, and in response they initiate specific signalling pathways leading to activation of transcriptional or proteolytic pathways and the production of inflammatory molecules to destroy foreign pathogens and/or resolve tissue injury...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28920945/neutrophils-a-cornerstone-of-liver-ischemia-and-reperfusion-injury
#7
Thiago Henrique Caldeira de Oliveira, Pedro Elias Marques, Paul Proost, Mauro Martins M Teixeira
Ischemia-reperfusion injury (IRI) is the main cause of morbidity and mortality due to graft rejection after liver transplantation. During IRI, an intense inflammatory process occurs in the liver. This hepatic inflammation is initiated by the ischemic period but occurs mainly during the reperfusion phase, and is characterized by a large neutrophil recruitment to the liver. Production of cytokines, chemokines, and danger signals results in activation of resident hepatocytes, leukocytes, and Kupffer cells. The role of neutrophils as the main amplifiers of liver injury in IRI has been recognized in many publications...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28916843/the-implicit-learning-of-metrical-and-non-metrical-rhythms-in-blind-and-sighted-adults
#8
Claudia Carrara-Augustenborg, Benjamin G Schultz
Forming temporal expectancies plays a crucial role in our survival as it allows us to identify the occurrence of temporal deviants that might signal potential dangers. The dynamic attending theory suggests that temporal expectancies are formed more readily for rhythms that imply a beat (i.e., metrical rhythms) compared to those that do not (i.e., nonmetrical rhythms). Moreover, metrical frameworks can be used to detect temporal deviants. Although several studies have demonstrated that congenital or early blindness correlates with modality-specific neural changes that reflect compensatory mechanisms, few have examined whether blind individuals show a learning advantage for auditory rhythms and whether learning can occur unintentionally and without awareness, that is, implicitly...
September 15, 2017: Psychological Research
https://www.readbyqxmd.com/read/28916776/nestlings-reduce-their-predation-risk-by-attending-to-predator-information-encoded-within-conspecific-alarm-calls
#9
Ahmad Barati, Paul G McDonald
Predation is one of the main threats to altricial nestlings, with predators often locating nests via eavesdropping on begging signals. Nestlings may be able to adjust their begging based on the current level of risk by monitoring both intra- and interspecific alarm calls near the nest. We show that noisy miner (Manorina melanocephala) nestlings can differentiate between terrestrial and aerial alarm calls of their own species, as they suppressed begging behaviour for longer in response to terrestrial rather than aerial alarm calls...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900295/an-autocrine-purinergic-signaling-controls-astrocyte-induced-neuronal-excitation
#10
Weida Shen, Ljiljana Nikolic, Claire Meunier, Frank Pfrieger, Etienne Audinat
Astrocyte-derived gliotransmitters glutamate and ATP modulate neuronal activity. It remains unclear, however, how astrocytes control the release and coordinate the actions of these gliotransmitters. Using transgenic expression of the light-sensitive channelrhodopsin 2 (ChR2) in astrocytes, we observed that photostimulation reliably increases action potential firing of hippocampal pyramidal neurons. This excitation relies primarily on a calcium-dependent glutamate release by astrocytes that activates neuronal extra-synaptic NMDA receptors...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888416/toll-like-receptors-in-systemic-sclerosis-an-emerging-target
#11
REVIEW
Steven O'Reilly
Pattern Recognition Receptors are critical receptors that elicit an immune response upon their activation that culminates in activation of NF-KB and cytokine secretion. Key among these receptors are the Toll-Like Receptors (TLRs). These evolutionary conserved receptors form a key part in the defence against various pathogens and comprise a key part of the innate immune system. Systemic sclerosis is an autoimmune disease in which a breach of tolerance has occurred and leads to fulminant autoimmunity, dysregulated cytokines, pro-fibrotic mediators and activation of fibroblasts leading to fibrosis via collagen deposition...
September 6, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28882317/persistent-increase-in-microglial-rage-contributes-to-chronic-stress-induced-priming-of-depressive-like-behavior
#12
Tina C Franklin, Eric S Wohleb, Yi Zhang, Manoela Fogaça, Brendan Hare, Ronald S Duman
BACKGROUND: Chronic stress-induced inflammatory responses occur in part via danger-associated molecular pattern (DAMP) molecules, such as high mobility group box 1 protein (HMGB1), but the receptor(s) underlying DAMP signaling have not been identified. METHODS: Microglia morphology and DAMP signaling in enriched rat hippocampal microglia were examined during the development and expression of chronic unpredictable stress (CUS)-induced behavioral deficits, including long-term, persistent changes after CUS...
July 21, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28879051/targeting-danger-molecules-in-tendinopathy-the-hmgb1-tlr4-axis
#13
Moeed Akbar, Derek S Gilchrist, Susan M Kitson, Briana Nelis, Lindsay A N Crowe, Emma Garcia-Melchor, James H Reilly, Shauna C Kerr, George A C Murrell, Iain B McInnes, Neal L Millar
OBJECTIVES: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. METHODS: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery...
2017: RMD Open
https://www.readbyqxmd.com/read/28872671/wnt7a-induces-a-unique-phenotype-of-monocyte-derived-macrophages-with-lower-phagocytic-capacity-and-differential-expression-of-pro-and-anti-inflammatory-cytokines
#14
Jennillee Wallace, Victoria Lutgen, Sreedevi Avasarala, Brad St Croix, Robert A Winn, Lena Al-Harthi
The variation of macrophage functions suggests the involvement of multiple signaling pathways in fine tuning their differentiation. Macrophages that originate from monocytes in the blood migrate to tissue in response to homeostatic or "danger" signals and undergo substantial morphological and functional modifications to meet the needs of the dominant signals in the microenvironment. Wnts are secreted glycoproteins that play a significant role in organ and cell differentiation, yet their impact on monocyte differentiation is not clear...
September 5, 2017: Immunology
https://www.readbyqxmd.com/read/28867168/the-unfolded-protein-response-in-immunogenic-cell-death-and-cancer-immunotherapy
#15
REVIEW
Nicole Rufo, Abhishek D Garg, Patrizia Agostinis
The unfolded protein response (UPR) is a conserved pathway that is stimulated when endoplasmic reticulum (ER) proteostasis is disturbed or lost. Accumulating evidence indicates that chronic activation of the UPR supports the main hallmarks of cancer by favoring cancer cell-autonomous and nonautonomous processes, which ultimately foster the immunosuppressive and protumorigenic microenvironment. However, certain forms of therapy-induced ER stress can elicit immunogenic cancer cell death (ICD), which enables the release of key immunostimulatory or danger signals, eventually driving efficient antitumor immunity...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28865486/nlrp3-inflammasome-activation-promotes-inflammation-induced-carcinogenesis-in-head-and-neck-squamous-cell-carcinoma
#16
Cong-Fa Huang, Lei Chen, Yi-Cun Li, Lei Wu, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
BACKGROUND: NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. METHODS: In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model...
September 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28861281/comparing-intensities-and-modalities-within-the-sensory-attenuation-paradigm-preliminary-evidence
#17
Dalila Burin, Alvise Battaglini, Lorenzo Pia, Giusy Falvo, Mattia Palombella, Adriana Salatino
It is well-documented that the intensity of a self-generated somatosensory stimulus is perceived to be attenuated in respect to an identical stimulus generated by others. At present, it is not clear whether such a phenomenon, known as somatosensory attenuation, is based not only on feedforward motor signals but also on re-afferences towards the body. To answer this question, in the present pilot investigation on twelve healthy subjects, three types of stimulations (sensory non-nociceptive electrical - ES, nociceptive electrical - NES, and vibrotactile - VTS) and intensities (1 = sensory threshold ∗ 2...
November 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28861073/epithelial-cell-damage-activates-bactericidal-permeability-increasing-protein-bpi-expression-in-intestinal-epithelium
#18
Arjun Balakrishnan, Dipshikha Chakravortty
As the first line of defense against invading pathogen, intestinal epithelium produces various antimicrobial proteins (AMP) that help in clearance of pathogen. Bactericidal/permeability-increasing protein (BPI) is a 55 kDa AMP that is expressed in intestinal epithelium. Dysregulation of BPI in intestinal epithelium is associated with various inflammatory diseases like Crohn's Disease, Ulcerative colitis, and Infectious enteritis's. In this paper, we report a direct correlation between intestinal damage and BPI expression...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28855232/molecular-mechanisms-of-inflammasome-signaling
#19
REVIEW
Anukriti Mathur, Jenni A Hayward, Si Ming Man
The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis...
August 30, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28846643/a-portable-impedance-immunosensing-system-for-rapid-detection-of-salmonella-typhimurium
#20
Tao Wen, Ronghui Wang, America Sotero, Yanbin Li
SalmonellaTyphimurium is one of the most dangerous foodborne pathogens and poses a significant threat to human health. The objective of this study was to develop a portable impedance immunosensing system for rapid and sensitive detection of S. Typhimurium in poultry. The developed portable impedance immunosensing system consisted of a gold interdigitated array microelectrode (IDAM), a signal acquisitive interface and a laptop computer with LabVIEW software. The IDAM was first functionalized with 16-Mercaptohexadecanoic acid, and streptavidin was immobilized onto the electrode surface through covalent bonding...
August 28, 2017: Sensors
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