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mitochondrial immunity

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https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#1
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436451/empirical-modeling-of-physiochemical-immune-response-of-multilayer-zinc-oxide-nanomaterials-under-uv-exposure-to-melanoma-and-foreskin-fibroblasts
#2
Muhammad Fakhar-E-Alam, M Waseem Akram, Seemab Iqbal, K S Alimgeer, M Atif, K Sultana, M Willander, Zhiming M Wang
Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28433458/linking-the-biological-underpinnings-of-depression-role-of-mitochondria-interactions-with-melatonin-inflammation-sirtuins-tryptophan-catabolites-dna-repair-and-oxidative-and-nitrosative-stress-with-consequences-for-classification-and-cognition
#3
REVIEW
George Anderson
The pathophysiological underpinnings of neuroprogressive processes in recurrent major depressive disorder (rMDD) are reviewed. A wide array of biochemical processes underlie MDD presentations and their shift to a recurrent, neuroprogressive course, including: increased immune-inflammation, tryptophan catabolites (TRYCATs), mitochondrial dysfunction, aryl hydrocarbonn receptor activation, and oxidative and nitrosative stress (O&NS), as well as decreased sirtuins and melatonergic pathway activity. These biochemical changes may have their roots in central, systemic and/or peripheral sites, including in the gut, as well as in developmental processes, such as prenatal stressors and breastfeeding consequences...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#4
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28430694/iron-loading-exaggerates-the-inflammatory-response-to-the-toll-like-receptor-4-ligand-lipopolysaccharide-by-altering-mitochondrial-homeostasis
#5
Konrad Hoeft, Donald B Bloch, Jan A Graw, Rajeev Malhotra, Fumito Ichinose, Aranya Bagchi
BACKGROUND: Perioperative and critically ill patients are often exposed to iron (in the form of parenteral-iron administration or blood transfusion) and inflammatory stimuli, but the effects of iron loading on the inflammatory response are unclear. Recent data suggest that mitochondrial reactive oxygen species have an important role in the innate immune response and that increased mitochondrial reactive oxygen species production is a result of dysfunctional mitochondria. We tested the hypothesis that increased intracellular iron potentiates lipopolysaccharide-induced inflammation by increasing mitochondrial reactive oxygen species levels...
April 21, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#6
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#7
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418037/mitochondrial-c11orf83-is-a-potent-antiviral-protein-independent-of-interferon-production
#8
Yun Yang, Shaoquan Xiong, Bei Cai, Hui Luo, E Dong, Qiqi Li, Gaili Ji, Chengjian Zhao, Yanjun Wen, Yuquan Wei, Hanshuo Yang
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414327/a-novel-antibody-against-cancer-stem-cell-biomarker-dclk1-s-is-potentially-useful-for-assessing-colon-cancer-risk-after-screening-colonoscopy
#9
Shubhashish Sarkar, Vsevolod L Popov, Malaney R O'Connell, Heather L Stevenson, Brian S Lee, Robert A Obeid, Gurinder K Luthra, Pomila Singh
DCLK1 expression is critically required for maintaining growth of human colon cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel short isoform of DCLK1 (DCLK1-S; isoform 2) from β-promoter of hDCLK1 gene, while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, we succeeded in generating a monospecific DCLK1-S-Antibody (PS41014), which does not cross-react with DCLK1-L, and specifically detects CSCs...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28410195/antagonistic-effects-of-selenium-on-lead-induced-autophagy-by-influencing-mitochondrial-dynamics-in-the-spleen-of-chickens
#10
Yujing Han, Chunqiu Li, Mingjun Su, Zhihui Wang, Ning Jiang, Dongbo Sun
Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406958/molecular-analysis-of-culex-quinquefasciatus-larvae-responses-to-lysinibacillus-sphaericus-bin-toxin
#11
Chontida Tangsongcharoen, Natapong Jupatanakul, Boonhiang Promdonkoy, George Dimopoulos, Panadda Boonserm
Lysinibacillus sphaericus produces the mosquito larvicidal binary toxin consisting of BinA and BinB, which are both required for toxicity against Culex and Anopheles larvae. The molecular mechanisms behind Bin toxin-induced damage remain unexplored. We used whole-genome microarray-based transcriptome analysis to better understand how Culex larvae respond to Bin toxin treatment at the molecular level. Our analyses of Culex quinquefasciatus larvae transcriptome changes at 6, 12, and 18 h after Bin toxin treatment revealed a wide range of transcript signatures, including genes linked to the cytoskeleton, metabolism, immunity, and cellular stress, with a greater number of down-regulated genes than up-regulated genes...
2017: PloS One
https://www.readbyqxmd.com/read/28405612/microrna-125a-and-b-inhibit-a20-and-mavs-to-promote-inflammation-and-impair-antiviral-response-in-copd
#12
Alan C-Y Hsu, Kamal Dua, Malcolm R Starkey, Tatt-Jhong Haw, Prema M Nair, Kristy Nichol, Nathan Zammit, Shane T Grey, Katherine J Baines, Paul S Foster, Philip M Hansbro, Peter A Wark
Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28403066/non-hemodynamic-effects-of-catecholamines
#13
Clair Hartmann, Peter Radermacher, Martin Wepler, Benedikt Nubaum
Circulatory shock is defined as an imbalance between tissue oxygen supply and demand, and mostly results from a loss of blood volume, cardiac pump failure and/or reduction of vasomotor tone. The clinical hallmarks of circulatory shock are arterial hypotension and lactate acidosis. Since the degree and duration of hypotension are major determinants of outcome, vasopressor administration represents a cornerstone therapy to treat these patients. Current guidelines recommend the use of catecholamines as the drug of first choice...
April 11, 2017: Shock
https://www.readbyqxmd.com/read/28399645/prohibitin-at-the-crossroads-of-obesity-linked-diabetes-and-cancer
#14
Suresh Mishra, Bl Grégoire Nyomba
The promoter of a gene that is selectively expressed in just a few cell types provides unique opportunities to study: (1) the pleiotropic function of a protein in two different cell types including the cell compartment specific function, and (2) the crosstalk between two cell/tissue types at the systemic level. This is not possible with a ubiquitous or a highly specific gene promoter. The adipocyte protein-2 ( aP2) is one such gene. It is primarily expressed in adipocytes, but also selectively in monocytic macrophages and dendritic cells, among various immune cell types...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28399409/direct-pharmacological-targeting-of-a-mitochondrial-ion-channel-selectively-kills-tumor-cells-in%C3%A2-vivo
#15
Luigi Leanza, Matteo Romio, Katrin Anne Becker, Michele Azzolini, Livio Trentin, Antonella Managò, Elisa Venturini, Angela Zaccagnino, Andrea Mattarei, Luca Carraretto, Andrea Urbani, Stephanie Kadow, Lucia Biasutto, Veronica Martini, Filippo Severin, Roberta Peruzzo, Valentina Trimarco, Jan-Hendrik Egberts, Charlotte Hauser, Andrea Visentin, Gianpietro Semenzato, Holger Kalthoff, Mario Zoratti, Erich Gulbins, Cristina Paradisi, Ildiko Szabo
The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28395431/-nix-mediated-mitochondrial-autophagy-in-pathogenesis-of-myelodysplastic-syndrome-anemia
#16
L Y Yang, N B Cui, H Q Wang, R Fu, W Qu, E B Ruan, X M Wang, G J Wang, Y H Wu, H Liu, J Song, J Guan, L M Xing, L J Li, H J Jiang, H Liu, Y H Wang, C Y Liu, W Zhang, Z H Shao
Objective: To investigate the change of NIX level of bone marrow nucleated red blood cells in anemia patients with myelodysplastic syndromes (MDS), to explore the significance of NIX-mediated mitochondrial autophagy in the pathogenesis of MDS anemia. Methods: A total of 54 patients with MDS diagnosed in the Department of Hematology of General Hospital, Tianjin Medical University from July 2015 to July 2016 were enrolled into the MDS group, 33 cases of immune thrombocytopenia or idiopathic leukopenia as controls...
April 11, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#17
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28393922/mitochondrial-dna-in-innate-immune-responses-and-inflammatory-pathology
#18
REVIEW
A Phillip West, Gerald S Shadel
Mitochondrial DNA (mtDNA) - which is well known for its role in oxidative phosphorylation and maternally inherited mitochondrial diseases - is increasingly recognized as an agonist of the innate immune system that influences antimicrobial responses and inflammatory pathology. On entering the cytoplasm, extracellular space or circulation, mtDNA can engage multiple pattern-recognition receptors in cell-type- and context-dependent manners to trigger pro-inflammatory and type I interferon responses. Here, we review the expanding research field of mtDNA in innate immune responses to highlight new mechanistic insights and discuss the physiological and pathological relevance of this exciting area of mitochondrial biology...
April 10, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28388439/celastrol-induced-nur77-interaction-with-traf2-alleviates-inflammation-by-promoting-mitochondrial-ubiquitination-and-autophagy
#19
Mengjie Hu, Qiang Luo, Gulimiran Alitongbieke, Shuyi Chong, Chenting Xu, Lei Xie, Xiaohui Chen, Duo Zhang, Yuqi Zhou, Zhaokai Wang, Xiaohong Ye, Lijun Cai, Fang Zhang, Huibin Chen, Fuquan Jiang, Hui Fang, Shanjun Yang, Jie Liu, Maria T Diaz-Meco, Ying Su, Hu Zhou, Jorge Moscat, Xiangzhi Lin, Xiao-Kun Zhang
Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28386997/the-transformation-in-biomarker-detection-and-management-of-drug-induced-liver-injury
#20
REVIEW
Rachel J Church, Paul B Watkins
Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Studies in rodents indicate that the ratio of the caspase cleaved fragment of cytokeratin 18 to total K18 in serum (termed the "apoptotic index") estimates the relative proportions of apoptosis vs necrosis during drug-induced liver injury...
April 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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