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https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#1
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#2
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219766/mitochondrial-and-endoplasmic-reticulum-dysfunction-and-related-defense-mechanisms-in-critical-illness-induced-multiple-organ-failure
#3
REVIEW
Steven E Thiessen, Greet Van den Berghe, Ilse Vanhorebeek
Patients with critical illness-induced multiple organ failure suffer from a very high morbidity and mortality, despite major progress in intensive care. The pathogenesis of this condition is complex and incompletely understood. Inadequate tissue perfusion and an overwhelming inflammatory response with pronounced cellular damage have been suggested to play an important role, but interventions targeting these disturbances largely failed to improve patient outcome. Hence, new therapeutic perspectives are urgently needed...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28219650/dendritic-cells-death-induced-by-contact-sensitizers-is-controlled-by-nrf2-and-depends-on-glutathione-levels
#4
Zeina El Ali, Claudine Deloménie, Jérémie Botton, Marc Pallardy, Saadia Kerdine-Römer
Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action...
February 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28219337/chronic-nicotine-differentially-affects-murine-transcriptome-profiling-in-isolated-cortical-interneurons-and-pyramidal-neurons
#5
Jie Yang, Ai-Yi Liu, Bo Tang, Dong Luo, Yu-Jie Lai, Bing-Lin Zhu, Xue-Feng Wang, Zhen Yan, Guo-Jun Chen
BACKGROUND: Nicotine is known to differentially regulate cortical interneuron and pyramidal neuron activities in the neocortex, while the underlying molecular mechanisms have not been well studied. In this study, RNA-sequencing was performed in acutely isolated cortical somatostatin (Sst)- positive interneurons and pyramidal neurons (Thy1) from mice treated with systemic nicotine for 14 days. We assessed the differentially expressed genes (DEGs) by nicotine in Sst- or Thy1- neurons, respectively, and then compared DEGs between Sst- and Thy1- neurons in the absence and presence of nicotine...
February 20, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28219335/stress-responsive-pathways-and-small-rna-changes-distinguish-variable-developmental-phenotypes-caused-by-msh1-loss
#6
Mon-Ray Shao, Sunil Kumar Kenchanmane Raju, John D Laurie, Robersy Sanchez, Sally A Mackenzie
BACKGROUND: Proper regulation of nuclear-encoded, organelle-targeted genes is crucial for plastid and mitochondrial function. Among these genes, MutS Homolog 1 (MSH1) is notable for generating an assortment of mutant phenotypes with varying degrees of penetrance and pleiotropy. Stronger phenotypes have been connected to stress tolerance and epigenetic changes, and in Arabidopsis T-DNA mutants, two generations of homozygosity with the msh1 insertion are required before severe phenotypes begin to emerge...
February 20, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#7
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#8
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#9
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#10
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28209603/deoxyribonuclease-partially-ameliorates-thioacetamide-induced-hepatorenal-injury
#11
Lenka Vokálová, Lucia Lauková, Jozef Čonka, Veronika Melišková, Veronika Borbélyová, Janka Bábíčková, Ľubomíra Tóthová, Július Hodosy, Barbora Vlková, Peter Celec
Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation exacerbating the liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. In this study the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats were analysed. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#12
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207838/viperin-interaction-with-mitochondrial-antiviral-signaling-protein-mavs-limits-viperin-mediated-inhibition-of-the-interferon-response-in-macrophages
#13
Jia Shee Hee, Peter Cresswell
Viperin is an antiviral protein that is upregulated by interferons and by ligands for a variety of innate immune receptors. It possesses diverse capabilities and functions in an array of viral infections. Studies have shown that it appears to be particularly important in defence against RNA viruses, such as West Nile, Dengue, and Chikungunya viruses, although the specific mechanisms involved are not well understood at the molecular level. Here we identify the mitochondrial antiviral signalling protein MAVS as a novel viperin interaction partner, most likely in mitochondria associated membranes, and characterize a more central, overarching role of viperin as a negative regulator of the interferon response, an ability that can be regulated by the viperin-MAVS interaction...
2017: PloS One
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#14
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#15
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28192238/molecular-networks-related-to-the-immune-system-and-mitochondria-are-targets-for-the-pesticide-dieldrin-in-the-zebrafish-danio-rerio-central-nervous-system
#16
Andrew M Cowie, Kathleena I Sarty, Angella Mercer, Jin Koh, Karen A Kidd, Christopher J Martyniuk
: The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides...
February 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28188297/alternative-splicing-in-the-cytochrome-p450-superfamily-expands-protein-diversity-to-augment-gene-function-and-redirect-human-drug-metabolism
#17
Andrew J Annalora, Craig B Marcus, Patrick L Iversen
The human genome encodes 57 cytochrome P450 (CYP) genes whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics and unknown numbers of endogenous compounds including steroids, retinoids and icosinoids. Indeed, CYP genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human CYP transcriptome. This review describes a remarkable diversification of the 57 human CYP genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's CYP proteome...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28186866/toward-postgenomics-ophthalmology-a-proteomic-map-of-the-human-choroid-retinal-pigment-epithelium-tissue
#18
Manjunath Dammalli, Krishna R Murthy, Sneha M Pinto, Kalpana Babu Murthy, Raja Sekhar Nirujogi, Anil K Madugundu, Gourav Dey, Bipin Nair, Harsha Gowda, Thottethodi Subrahmanya Keshava Prasad
Ophthalmology and visual health research have received relatively limited attention from the personalized medicine community, but this trend is rapidly changing. Postgenomics technologies such as proteomics are being utilized to establish a baseline biological variation map of the human eye and related tissues. In this context, the choroid is the vascular layer situated between the outer sclera and the inner retina. The choroidal circulation serves the photoreceptors and retinal pigment epithelium (RPE). The RPE is a layer of cuboidal epithelial cells adjacent to the neurosensory retina and maintains the outer limit of the blood-retina barrier...
February 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28183981/a-switch-from-canonical-to-noncanonical-autophagy-shapes-b-cell-responses
#19
Nuria Martinez-Martin, Paula Maldonado, Francesca Gasparrini, Bruno Frederico, Shweta Aggarwal, Mauro Gaya, Carlson Tsui, Marianne Burbage, Selina Jessica Keppler, Beatriz Montaner, Harold B J Jefferies, Usha Nair, Yan G Zhao, Marie-Charlotte Domart, Lucy Collinson, Andreas Bruckbauer, Sharon A Tooze, Facundo D Batista
Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1-dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway. B cell stimulation was sufficient to down-regulate canonical autophagy transiently while triggering noncanonical autophagy...
February 10, 2017: Science
https://www.readbyqxmd.com/read/28181526/no-effect-of-mitochondrial-genotype-on-reproductive-plasticity-following-exposure-to-a-non-infectious-pathogen-challenge-in-female-or-male-drosophila
#20
M Nystrand, E J Cassidy, D K Dowling
Mitochondrial genetic variation shapes the expression of life-history traits associated with reproduction, development and survival, and has also been associated with the prevalence and progression of infectious bacteria and viruses in humans. The breadth of these effects on multifaceted components of health, and their link to disease susceptibility, led us to test whether variation across mitochondrial haplotypes affected reproductive success following an immune challenge in the form of a non-infectious pathogen...
February 9, 2017: Scientific Reports
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