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https://www.readbyqxmd.com/read/27924062/chenodeoxycholic-acid-activates-nlrp3-inflammasome-and-contributes-to-cholestatic-liver-fibrosis
#1
Zizhen Gong, Jiefei Zhou, Shengnan Zhao, Chunyan Tian, Panliang Wang, Congfeng Xu, Yingwei Chen, Wei Cai, Jin Wu
Accumulation of hydrophobic bile acids in the liver contributes to cholestatic liver injury. Inflammation induced by excessive bile acids is believed to play a crucial role, however, the mechanisms of bile acids triggered inflammatory response remain unclear. Recent studies have highlighted the effect of NLRP3 inflammasome in mediating liver inflammation and fibrosis. In this study, we for the first time showed that chenodeoxycholic acid (CDCA), the major hydrophobic primary bile acid involved in cholestatic liver injury, could dose-dependently induce NLRP3 inflammasome activation and secretion of pro-inflammatory cytokine-IL-1β in macrophages by promoting ROS production and K+ efflux...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923877/poison-and-alarm-the-asian-hornet-vespa-velutina-uses-sting-venom-volatiles-as-alarm-pheromone
#2
Ya-Nan Cheng, Ping Wen, Shi-Hao Dong, Ken Tan, James C Nieh
In colonial organisms, alarm pheromones can provide a key fitness advantage by enhancing colony defense and warning of danger. Learning which species use alarm pheromone and the key compounds involved therefore enhances our understanding of how this important signal has evolved. However, our knowledge of alarm pheromones is more limited in the social wasps and hornets as compared to the social bees and ants. Vespa velutina is an economically important and widespread hornet predator that attacks humans and honey bees...
December 6, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27923281/nuclear-factor-erythroid-derived-2-like-2-and-thioredoxin-1-in-atherosclerosis-and-ischemia-reperfusion-injury-in-the-heart
#3
Philipp Jakobs, Vlad Serbulea, Norbert Leitinger, Anna Eckers, Judith Haendeler
Significance Redox signaling is one of the key elements involved in cardiovascular diseases. Two important molecules are the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and the oxidoreductase Thioredoxin-1 (Trx-1). Recent Advances During the last years, a lot of studies investigated Nrf2 and Trx-1 as protective proteins in cardiovascular disorders. Moreover, post-translational modifications of those molecules were identified which play an important role in the cardiovascular system...
December 6, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27914690/c1q-as-an-autocrine-and-paracrine-regulator-of-cellular-functions
#4
REVIEW
Berhane Ghebrehiwet, Kinga H Hosszu, Ellinor I B Peerschke
Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes"...
November 30, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27913514/understanding-red-blood-cell-alloimmunization-triggers
#5
Jeanne E Hendrickson, Christopher A Tormey
Blood group alloimmunization is "triggered" when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to an antigen is necessary for alloimmunization to occur, it is not alone sufficient. Blood group antigens are diverse in structure, function, and immunogenicity. In addition to red blood cells (RBCs), a recipient of an RBC transfusion is exposed to donor plasma, white blood cells, and platelets; the potential contribution of these elements to RBC alloimmunization remains unclear...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#6
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27909688/the-danger-signal-extracellular-atp-is-an-inducer-of-fusobacterium-nucleatum-biofilm-dispersal
#7
Qinfeng Ding, Kai Soo Tan
Plaque biofilm is the primary etiological agent of periodontal disease. Biofilm formation progresses through multiple developmental stages beginning with bacterial attachment to a surface, followed by development of microcolonies and finally detachment and dispersal from a mature biofilm as free planktonic bacteria. Tissue damage arising from inflammatory response to biofilm is one of the hallmark features of periodontal disease. A consequence of tissue damage is the release of ATP from within the cell into the extracellular space...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27893819/salvianolic-acid-b-alleviates-heart-failure-by-inactivating-erk1-2-gata4-signaling-pathway-after-pressure-overload-in-mice
#8
Juan Yu, Renshan Chen, Yafang Tan, Jiashin Wu, Jianyong Qi, Minzhou Zhang, Weiwang Gu
BACKGROUND: Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF. METHODS: We created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg-1•day-1, n = 9)...
2016: PloS One
https://www.readbyqxmd.com/read/27890472/dna-damage-talks-to-inflammation
#9
Idan Cohen
Interleukin-1 alpha (IL-1α) and beta (IL-1β) are pleiotropic cytokines affecting multiple cells and regulating many immune and inflammatory responses. The recent finding that nuclear IL-1α is recruited to sites of DNA damage, and its ability to actively sense and report genotoxic stress to the surrounding tissue, dramatically alters the way we view IL-1 biology. This discovery add a new face to the classical "danger theory" and show that danger signaling is not strictly limited to passive release or dying cells...
November 18, 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/27890235/dermatologic-manifestations-of-monogenic-autoinflammatory-diseases
#10
REVIEW
Kyawt Win Shwin, Chyi-Chia Richard Lee, Raphaela Goldbach-Mansky
Autoinflammatory disorders are sterile inflammatory conditions characterized by episodes of early-onset fever, rash, and disease-specific patterns of organ inflammation. Gain-of-function mutations in innate danger-sensing pathways, including the inflammasomes and the nucleic acid sensing pathways, play critical roles in the pathogenesis of IL-1 and Type-I IFN-mediated disorders and point to an important role of excessive proinflammatory cytokine signaling, including interleukin (IL)-1b , Type-I interferons, IL-18, TNF and others in causing the organ specific immune dysregulation...
January 2017: Dermatologic Clinics
https://www.readbyqxmd.com/read/27886218/revisiting-the-fear-of-snakes-in-children-the-role-of-aposematic-signalling
#11
Jérémie Souchet, Fabien Aubret
Why humans fear snakes is an old, yet unresolved debate. Its innate origin from evolutionary causes is debated against the powerful influence early experience, culture, media and religion may have on people's aversion to snakes. Here we show that the aversion to snakes in human beings may have been mistaken for an aversion to aposematic signals that are commonly displayed by snakes. A total of 635 children were asked to rate single item images as "nice" or "mean". Snakes, pets and smiley emoticon items were not rated as "mean" unless they displayed subtle aposematic signals in the form of triangular (rather than round) shapes...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#12
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27885703/immunological-tolerance-part-i-of-a-report-of-a-workshop-on-foundational-concepts-of-immune-regulation
#13
Colin C Anderson, Peter Bretscher, Alexandre Corthay, Zlatko Dembic, Calliopi Havele, Zoltan A Nagy, Inger Øynebråten
This report, the first of two, arose from a one-week workshop directed at discussing concepts of immune regulation, and focuses on immunological tolerance. We first outline the major ideas we thought sufficiently plausible to provide a context for discussing more controversial issues around tolerance. We then report on our discussion of different experiments that appear paradoxical in terms of the different, contemporary models of CD4 T cell inactivation/activation, and how such observations might be resolved in terms of insights provided by these contemporary models...
November 25, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27884377/danger-signals-inflammasomes-and-the-intricate-intracellular-lives-of-chlamydiae
#14
REVIEW
Matthew A Pettengill, Ali Abdul-Sater, Robson Coutinho-Silva, David M Ojcius
Chlamydiae are obligate intracellular bacterial pathogens, and as such are sensitive to alterations in the cellular physiology of their hosts. Chlamydial infections often cause pathologic consequences due to prolonged localized inflammation. Considerable advances have been made in the last few years regarding our understanding of how two key inflammation-associated signaling pathways influence the biology of Chlamydia infections: inflammation regulating purinergic signaling pathways significantly impact intracellular chlamydial development, and inflammasome activation modulates both chlamydial growth and infection mediated pro-inflammatory cytokine production...
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#15
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27876638/changes-in-acoustic-startle-reflex-in-rats-induced-by-playback-of-22-khz-calls
#16
Hideaki Inagaki, Takahiro Ushida
In aversive or dangerous situations, adult rats emit long characteristic ultrasonic calls, often termed "22-kHz calls," which have been suggested to play the role of alarm calls. Although the playback experiment is one of the most effective ways to investigate the alarming properties of 22-kHz calls, clear behavioral evidence showing the anxiogenic effects of these playback stimuli has not been obtained to date. In this study, we investigated whether playback of 22-kHz calls or synthesized sine tones could change the acoustic startle reflex (ASR), enhancement of which is widely considered to be a reliable index of anxiety-related negative affective states in rats...
November 19, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27870323/inflammasome-activators-induce-fibronectin-expression-and-release-in-macrophages
#17
Hye-Kyoung Jun, Young-Jung Jung, Bong-Kyu Choi
Extracellular fibronectin (Fn) can activate pro-inflammatory pathways and serves as an endogenous danger signalling molecule; thus, it has been suggested as a biomarker for several diseases. In the present study, we found that pathogen-derived activators of the inflammasomes induce the expression and secretion of Fn in macrophages through a mechanism involving adenosine triphosphate (ATP) and caspase-1 activation. We also found that plasma Fn induces caspase-1 activation and cell death in macrophages, epithelial cells, and fibroblasts...
November 21, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27867196/extracellular-adp-facilitates-monocyte-recruitment-in-bacterial-infection-via-erk-signaling
#18
Xiaoyu Zhang, Juliang Qin, Junyan Zou, Zhangsheng Lv, Binghe Tan, Jueping Shi, Yihan Zhao, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4...
November 21, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27849015/sterile-inflammation-as-a-factor-in-human-male-infertility-involvement-of-toll-like-receptor-2-biglycan-and-peritubular-cells
#19
C Mayer, M Adam, L Glashauser, K Dietrich, J U Schwarzer, F-M Köhn, L Strauss, H Welter, M Poutanen, A Mayerhofer
Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27845767/activating-autophagy-to-potentiate-immunogenic-chemotherapy-and-radiation-therapy
#20
REVIEW
Lorenzo Galluzzi, José Manuel Bravo-San Pedro, Sandra Demaria, Silvia Chiara Formenti, Guido Kroemer
Autophagy is fundamental to the maintenance of intracellular homeostasis in virtually all human cells. Accordingly, defective autophagy predisposes healthy cells to undergoing malignant transformation. By contrast, malignant cells are able to harness autophagy to thrive, despite adverse microenvironmental conditions, and to resist therapeutic challenges. Thus, inhibition of autophagy has been proposed as a strategy to kill cancer cells or sensitize them to therapy; however, autophagy is also critical for optimal immune function, and mediates cell-extrinsic homeostatic effects owing to its central role in danger signalling by neoplastic cells responding to immunogenic chemotherapy and/or radiation therapy...
November 15, 2016: Nature Reviews. Clinical Oncology
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