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https://www.readbyqxmd.com/read/29301200/bombyx-mori-nuclear-polyhedrosis-virus-bmnpv-induces-host-cell-autophagy-to-benefit-infection
#1
La Wang, Qin Xiao, Xiao-Lin Zhou, Yan Zhu, Zhan-Qi Dong, Peng Chen, Min-Hui Pan, Cheng Lu
Bombyx mori nuclear polyhedrosis virus (BmNPV) is an important pathogen of silkworms. Despite extensive studies in recent decades, the interaction between BmNPV and host cells is still not clearly understood. Autophagy is an intrinsic innate immune mechanism and it controls infection autonomously in virus-infected cells. In this study, we found that BmNPV infection could trigger autophagy, as demonstrated by the formation of autophagosomes, fluorescent Autophagy-related gene 8-Green Fluorescent Protein (ATG8-GFP) punctate, and lipidated ATG8...
December 30, 2017: Viruses
https://www.readbyqxmd.com/read/29295631/mitochondrial-reactive-oxygen-species-and-type-1-diabetes
#2
Jing Chen, Scott Edward Stimpson, Gabriel Fernandez Bueno, Clayton Elwood Mathews
SIGNIFICANCE: The complex etiology of Type 1 Diabetes (T1D) is the outcome of failures in regulating immunity in combination with beta-cell perturbations. Mitochondrial dysfunction in beta-cells and immune cells may be involved in T1D pathogenesis. Mitochondrial energy production is essential for the major task of beta cells (the secretion of insulin in response to glucose). Mitochondria are a major site of reactive oxygen species (mtROS) production. Under immune attack, mtROS participate in beta-cell damage...
January 2, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29281259/development-of-arrayed-colonic-organoids-for-screening-of-secretagogues-associated-with-enterotoxins
#3
Dulan B Gunasekara, Matthew Disalvo, Yuli Wang, Daniel Nguyen, Mark I Reed, Jennifer Speer, Christopher E Sims, Scott T Magness, Nancy L Allbritton
Enterotoxins increase intestinal fluid secretion through the modulation of ion channels as well as activating the enteric nervous and immune systems. Colonic organoids, also known as colonoids, are functionally and phenotypically similar to in vivo colonic epithelium, and have been used to study intestinal ion transport and subsequent water flux in physiology and disease models. In conventional cultures, organoids exist as spheroids embedded within a hydrogel patty of extracellular matrix, and form at multiple depths impairing efficient imaging which is necessary to capture data from statistically relevant sample sizes...
December 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29276215/deletion-of-both-p62-and-nrf2-spontaneously-results-in-the-development-of-nonalcoholic-steatohepatitis
#4
Kentaro Akiyama, Eiji Warabi, Kosuke Okada, Toru Yanagawa, Tetsuro Ishii, Katsumi Kose, Katsutoshi Tokushige, Kazunori Ishige, Yuji Mizokami, Kenji Yamagata, Kojiro Onizawa, Shun-Ichi Ariizumi, Masakazu Yamamoto, Junichi Shoda
Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism(s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance...
December 25, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29237840/human-cytomegalovirus-ul111a-and-us27-gene-products-enhance-the-cxcl12-cxcr4-signaling-axis-via-distinct-mechanisms
#5
Carolyn C Tu, Kathleen L Arnolds, Christine M O'Connor, Juliet V Spencer
Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29229698/laccase-ghlac1-modulates-broad-spectrum-biotic-stress-tolerance-via-damp-triggered-immunity
#6
Qin Hu, Ling Min, Xiyan Yang, Shuangxia Jin, Lin Zhang, Yaoyao Li, Yizan Ma, Xuewei Qi, Dongqin Li, Hongbo Liu, Keith Lindsey, Longfu Zhu, Xianlong Zhang
Plants are constantly challenged by a multitude of pathogens and pests, which causes massive yield and quality losses annually. A promising approach to reduce such losses is to enhance the immune system of plants through genetic engineering. Previous work has shown that laccases (p-diphenol:dioxygen oxidoreductase, EC 1.10.3.2) function as lignin polymerization enzymes. Here we demonstrate that transgenic manipulation of the expression of the laccase gene GhLac1 in cotton (Gossypium hirsutum) can confer an enhanced defence response to both pathogens and pests...
December 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29225688/repurposing-drugs-in-oncology-redo-chloroquine-and-hydroxychloroquine-as-anti-cancer-agents
#7
Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis, Gauthier Bouche
Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29216217/the-emerging-role-of-asc-in-dendritic-cell-metabolism-during-chlamydia-infection
#8
Danielle N McKeithen, Yusuf O Omosun, Khamia Ryans, Jing Mu, Zhonglin Xie, Tankya Simoneaux, Uriel Blas-Machado, Francis O Eko, Carolyn M Black, Joseph U Igietseme, Qing He
Chlamydia trachomatis is a bacterial agent that causes sexually transmitted infections worldwide. The regulatory functions of dendritic cells (DCs) play a major role in protective immunity against Chlamydia infections. Here, we investigated the role of ASC in DCs metabolism and the regulation of DCs activation and function during Chlamydia infection. Following Chlamydia stimulation, maturation and antigen presenting functions were impaired in ASC-/- DCs compared to wild type (WT) DCs, in addition, ASC deficiency induced a tolerant phenotype in Chlamydia stimulated DCs...
2017: PloS One
https://www.readbyqxmd.com/read/29186856/zinc-as-a-gatekeeper-of-immune-function
#9
REVIEW
Inga Wessels, Martina Maywald, Lothar Rink
After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc "importers" (ZIP 1-14), zinc "exporters" (ZnT 1-10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear...
November 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29179463/olaquindox-disrupts-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#10
Di Wu, Chun-Jie Huang, Xiao-Fei Jiao, Zhi-Ming Ding, Jia-Yu Zhang, Fan Chen, Yong-Sheng Wang, Xiang Li, Li-Jun Huo
Sertoli cells, by creating an immune-privileged and nutrition supporting environment, maintain mammalian spermatogenesis and thereby holds the heart of male fertility. Olaquindox, an effective feed additive in livestock industry, could potentially expose human into the risk of biological hazards due to its genotoxicity and cytotoxicity, highlighting the significance of determining its bio-safety regarding human reproduction. Herein, we deciphered the detrimental effects of olaquindox on male fertility by mechanistically unraveling how olaquindox intervenes blood-testis barrier in mouse...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29176872/para-hydroxyphenylpyruvate-inhibits-the-pro-inflammatory-stimulation-of-macrophage-preventing-lps-mediated-nitro-oxidative-unbalance-and-immunometabolic-shift
#11
Rosella Scrima, Marta Menga, Consiglia Pacelli, Francesca Agriesti, Olga Cela, Claudia Piccoli, Antonella Cotoia, Alessandra De Gregorio, Julia V Gefter, Gilda Cinnella, Nazzareno Capitanio
Targeting metabolism is emerging as a promising therapeutic strategy for modulation of the immune response in human diseases. In the presented study we used the lipopolysaccharide (LPS)-mediated activation of RAW 264.7 macrophage-like cell line as a model to investigate changes in the metabolic phenotype and to test the effect of p-hydroxyphenylpyruvate (pHPP) on it. pHPP is an intermediate of the PHE/TYR catabolic pathway, selected as analogue of the ethyl pyruvate (EP), which proved to exhibit antioxidant and anti-inflammatory activities...
2017: PloS One
https://www.readbyqxmd.com/read/29176405/lipopeptide-pam3cys4-synergizes-n-formyl-met-leu-phe-fmlp-induced-calcium-transients-in-mouse-neutrophils
#12
Renyu Ding, Ganqiong Xu, Yan Feng, Lin Zou, Wei Chao
N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular calcium ([Ca]i) transient that is important for various neutrophil biological functions, e.g., adhesion, ROS and cytokine productions. Toll-like receptors (TLRs), an essential part of host innate immunity, regulate neutrophil activities, but their role in [Ca]i signaling is less clear. In the current study, we examined the effect of several TLR ligands, including Pam3Cys4 (TLR1/2), lipopolysaccharide (LPS, TLR4), and lipoteichoic acid (LTA, TLR2/6), on calcium signaling and on the fMLP-induced [Ca]i transients in mouse neutrophils loaded with Fura-2/AM...
November 15, 2017: Shock
https://www.readbyqxmd.com/read/29156694/pdac-derived-exosomes-enrich-the-microenvironment-in-mdscs-in-a-smad4-dependent-manner-through-a-new-calcium-related-axis
#13
Daniela Basso, Elisa Gnatta, Andrea Padoan, Paola Fogar, Sara Furlanello, Ada Aita, Dania Bozzato, Carlo-Federico Zambon, Giorgio Arrigoni, Chiara Frasson, Cinzia Franchin, Stefania Moz, Thomas Brefort, Thomas Laufer, Filippo Navaglia, Sergio Pedrazzoli, Giuseppe Basso, Mario Plebani
Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141885/a-role-for-bacterial-urease-in-gut-dysbiosis-and-crohn-s-disease
#14
Josephine Ni, Ting-Chin David Shen, Eric Z Chen, Kyle Bittinger, Aubrey Bailey, Manuela Roggiani, Alexandra Sirota-Madi, Elliot S Friedman, Lillian Chau, Andrew Lin, Ilana Nissim, Justin Scott, Abigail Lauder, Christopher Hoffmann, Gloriany Rivas, Lindsey Albenberg, Robert N Baldassano, Jonathan Braun, Ramnik J Xavier, Clary B Clish, Marc Yudkoff, Hongzhe Li, Mark Goulian, Frederic D Bushman, James D Lewis, Gary D Wu
Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29123952/mevalonate-metabolism-governs-cancer-immune-surveillance
#15
REVIEW
Georg Gruenbacher, Martin Thurnher
The metabolic reprogramming that drives immunity engages the mevalonate pathway for cholesterol biosynthesis and protein prenylation. The importance of tight regulation of this metabolic route is reflected by the fact that too low activity impairs cellular function and survival, whereas hyperactivity can lead to malignant transformation. Here, we first address how mevalonate metabolism drives immunity and then highlight ways of the immune system to respond to both, limited and uncontrolled flux through the mevalonate pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29120360/elemental-ingredients-in-the-macrophage-cocktail-role-of-zip8-in-host-response-to-mycobacterium-tuberculosis
#16
REVIEW
Charlie J Pyle, Abul K Azad, Audrey C Papp, Wolfgang Sadee, Daren L Knoell, Larry S Schlesinger
Tuberculosis (TB) is a global epidemic caused by the infection of human macrophages with the world's most deadly single bacterial pathogen, Mycobacterium tuberculosis (M.tb). M.tb resides in a phagosomal niche within macrophages, where trace element concentrations impact the immune response, bacterial metal metabolism, and bacterial survival. The manipulation of micronutrients is a critical mechanism of host defense against infection. In particular, the human zinc transporter Zrt-/Irt-like protein 8 (ZIP8), one of 14 ZIP family members, is important in the flux of divalent cations, including zinc, into the cytoplasm of macrophages...
November 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29083038/plasmodesmal-regulation-during-plant-pathogen-interactions
#17
REVIEW
Cecilia Cheval, Christine Faulkner
Contents I. II. III. IV. V. VI. VII. References SUMMARY: Plasmodesmata (PD) are plasma membrane-lined pores that connect neighbouring plant cells, bridging the cell wall and establishing cytoplasmic and membrane continuity between cells. PD are dynamic structures regulated by callose deposition in a variety of stress and developmental contexts. This process crudely controls the aperture of the pore and thus the flux of molecules between cells. During pathogen infection, plant cells initiate a range of immune responses and it was recently identified that, following perception of fungal and bacterial pathogens, plant cells initially close their PD...
October 30, 2017: New Phytologist
https://www.readbyqxmd.com/read/29074456/histamine-and-t-helper-cytokine-driven-epithelial-barrier-dysfunction-in-allergic-rhinitis
#18
Brecht Steelant, Sven F Seys, Laura Van Gerven, Matthias Van Woensel, Ricard Farré, Paulina Wawrzyniak, Inge Kortekaas Krohn, Dominique M Bullens, Karel Talavera, Ulrike Raap, Louis Boon, Cezmi A Akdis, Guy Boeckxstaens, Jan L Ceuppens, Peter W Hellings
BACKGROUND: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and TH2 cells might decrease epithelial barrier integrity in AR maintaining a leaky epithelial barrier. OBJECTIVE: We sought to investigate the role of histamine and TH2 cells in driving epithelial barrier dysfunction in AR. METHODS: Air-liquid interface (ALI) cultures of primary nasal epithelial cells (pNECs) were used to measure trans-epithelial electrical resistance, paracellular flux of FITC-dextran 4kDa and mRNA expression of tight junctions...
October 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29073759/bioluminescent-probe-for-tumor-hypoxia-detection-via-cyp450-reductase-in-living-animals
#19
Yuqi Gao, Yuxing Lin, Tingting Liu, Hui Chen, Xiaofeng Yang, Chengsen Tian, Lupei Du, Minyong Li
Hypoxia is a pathogenic characteristic of solid tumors owing to absent or abnormal vasculature in the tumor microenvironment and essential in tumor progression, angiogenesis, metastasis, invasion and resistance to immune system and therapy. In hypoxic environments, CYP450 enzymes are more efficient than in normoxia. Herein, based on the reductive capacity of CYP450 enzymes/NADPH system, we managed to cage aminoluciferin developing a reaction-based bioluminescent probe as well as an imaging method for the hypoxia detection...
November 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29064429/zinc-signals-and-immunity
#20
REVIEW
Martina Maywald, Inga Wessels, Lothar Rink
Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article...
October 24, 2017: International Journal of Molecular Sciences
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