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https://read.qxmd.com/read/30976066/activation-of-a-tlr9-mediated-innate-immune-response-in-preeclampsia
#1
Rachel D Williamson, Fergus P McCarthy, Louise C Kenny, Cathal M McCarthy
Preeclampsia is a multisystemic disorder leading to the development of a placental ischemic microenvironment with a resultant increase in oxidative stress. There is evidence that mitochondrial dysfunction and the innate immune system both play a role in the pathophysiology of this disease. Mitochondrial DAMPs such as mtDNA bind specific pattern recognition receptors such as Toll-like receptor 9 (TLR9) on the endosomal surface of immune cells, in particular neutrophils, subsequently activating them and triggering an innate response...
April 11, 2019: Scientific Reports
https://read.qxmd.com/read/30935979/the-single-intravenous-administration-of-mitochondria-targeted-antioxidant-skqr1-after-traumatic-brain-injury-attenuate-neurological-deficit-in-rats
#2
Elisaveta E Genrikhs, Elena V Stelmashook, Olga P Alexandrova, Svetlana V Novikova, Dmitriy N Voronkov, Yuliya A Glibka, Vladimir P Skulachev, Nickolay K Isaev
The protective effect of SkQR1, a mitochondria-targeted antioxidant, was investigated on the model of focal one-sided traumatic brain injury (TBI) of the sensorimotor cortex region from 1 to 7 days after the injury. TBI caused a reliable disruption of the functions of the limbs contralateral to injury focus. The intravenous single injection of SkQR1 (250 nmol/kg) but not C12R1 (a SkQR1 homologue devoid of the antioxidant group) 30 min after TBI reduced the impairment of the motor functions of the limbs...
March 29, 2019: Brain Research Bulletin
https://read.qxmd.com/read/30930257/metabolomics-profiling-in-a-mouse-model-reveals-protective-effect-of-sancao-granule-on-con-a-induced-liver-injury
#3
Yuxue Yang, Fengyi Li, Shizhang Wei, Xiaoyi Liu, Yingying Wang, Honghong Liu, Jiabo Wang, Haotian Li, Huadan Cai, Yanling Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: Sancao granule (SCG) is a traditional Chinese herb formula, which has been used for autoimmune liver disease for decades. Previous study demonstrated that there was an exactly therapeutic effect of SCG on autoimmune hepatitis (AIH) by improving liver function and alleviating the clinical symptoms. However, studies of the mechanism by which SCG alleviates Con A-induced liver injury (CILI) should be complemented. MATERIALS AND METHODS: An ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach combined with principle component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) were integrated applied to obtain metabolites for clarifying mechanisms of disease...
March 28, 2019: Journal of Ethnopharmacology
https://read.qxmd.com/read/30923050/dmm-prize-2018-winner-wenqing-zhou
#4
EDITORIAL
Monica J Justice
Disease Models & Mechanisms (DMM) is delighted to announce that the winner of the DMM Prize 2018 is Wenqing Zhou, for her paper entitled 'Neutrophil-specific knockout demonstrates a role for mitochondria in regulating neutrophil motility in zebrafish' (Zhou et al., 2018a). The prize of $1000 is awarded to the first author of the paper that is judged by the journal's editors to be the most outstanding contribution to the journal that year. To be considered for the prize, the first author must be a student or a postdoc of no more than 5 years standing...
March 26, 2019: Disease Models & Mechanisms
https://read.qxmd.com/read/30902901/identification-of-residues-critical-for-fpr2-activation-by-the-cryptic-peptide-mitocryptide-2-originating-from-the-mitochondrial-dna-encoded-cytochrome-b
#5
Simon Lind, Michael Gabl, André Holdfeldt, Jonas Mårtensson, Martina Sundqvist, Kodai Nishino, Claes Dahlgren, Hidehito Mukai, Huamei Forsman
Similar to bacteria, synthesis of mitochondrial DNA-encoded proteins requires an N -formylated methionine to initiate translation. Thus, the N -formylated methionine peptides originating from mitochondria should be recognized as danger signals. To date, only one such peptide, denoted as mitocryptide-2 (MCT-2), originating from the N-terminal of the mitochondrial cytochrome b , has been isolated from mammalian tissues. Human neutrophils express FPR1 and FPR2 that detect formyl peptides, and the precise structural determinants for receptor recognition remain to be elucidated...
March 22, 2019: Journal of Immunology
https://read.qxmd.com/read/30847435/mitochondria-released-by-apoptotic-cell-death-initiate-innate-immune-responses
#6
Minghua Zhu, Andrew S Barbas, Liwen Lin, Uwe Scheuermann, Muath Bishawi, Todd V Brennan
In solid organ transplantation, cell death arising from ischemia/reperfusion leads to the release of several damage-associated molecular patterns derived from mitochondria. Mitochondrial damage-associated molecular patterns (mtDAMPs) initiate proinflammatory responses, but it remains unknown whether the mode of cell death affects the inflammatory properties of mitochondria. Murine and human cell lines induced to selectively undergo apoptosis and necroptosis were used to examine the extracellular release of mitochondria during programmed cell death...
December 2018: ImmunoHorizons
https://read.qxmd.com/read/30821872/new-strategies-for-treatment-of-infectious-sepsis
#7
REVIEW
Peter A Ward, Fatemeh Fattahi
In this mini review, we describe the molecular mechanisms in polymicrobial sepsis that lead to a series of adverse events including activation of inflammatory and prothrombotic pathways, a faulty innate immune system, and multiorgan dysfunction. Complement activation is a well-established feature of sepsis, especially involving generation of C5a and C5b-9, along with engagement of relevant receptors for C5a. Activation of neutrophils by C5a leads to extrusion of DNA, forming neutrophil extracellular traps that contain myeloperoxidase and oxidases, along with extracellular histones...
March 1, 2019: Journal of Leukocyte Biology
https://read.qxmd.com/read/30778158/effect-of-iron-overload-from-multi-walled-carbon-nanotubes-on-neutrophil-like-differentiated-hl-60-cells
#8
Yosuke Tabei, Hiroko Fukui, Ayako Nishioka, Yuji Hagiwara, Kei Sato, Tadashi Yoneda, Tamami Koyama, Masanori Horie
Multi walled carbon nanotubes (MWCNTs) are one of the most intensively explored nanomaterials because of their unique physical and chemical properties. Due to the widespread use of MWCNTs, it is important to investigate their effects on human health. The precise mechanism of MWCNT toxicity has not been fully elucidated. The present study was designed to examine the mechanisms of MWCNT toxicity toward human promyelocytic leukemia HL-60 cells. First, we found that MWCNTs decreased the viability of neutrophil-like differentiated HL-60 cells but not undifferentiated HL-60 cells...
February 18, 2019: Scientific Reports
https://read.qxmd.com/read/30738994/ppar-%C3%AE-and-erucic-acid-in-multiple-sclerosis-and-alzheimer-s-disease-likely-benefits-in-terms-of-immunity-and-metabolism
#9
REVIEW
Meric A Altinoz, Aysel Ozpinar
The transcription factor, PPARδ is involved in suppressing inflammation, stimulating oligodendroglial biogenesis and myelination. Furthermore, activation of PPARδ directly protects mitochondria against noxious stimuli and stimulates biogenesis of new mitochondria. PPARδ activation directly inhibits neuronal cell death and reduces both the level and neurotoxicity of Amyloid-β fibers in Alzheimer's Disease (AD) models. Among the important ligands of PPARδ is erucic acid (EA, 22:1 n9), an edible omega-9 fatty acid and a component of Lorenzo's oil, which is used in the treatment of adrenoleukodystrophy (ALD)...
February 8, 2019: International Immunopharmacology
https://read.qxmd.com/read/30736433/a-novel-insight-on-endotyping-heterogeneous-severe-asthma-based-on-endoplasmic-reticulum-stress-beyond-the-type-2-non-type-2-dichotomy
#10
REVIEW
Jae Seok Jeong, So Ri Kim, Seong Ho Cho, Yong Chul Lee
Severe asthma is an extremely heterogeneous clinical syndrome in which diverse cellular and molecular pathobiologic mechanisms exist, namely endotypes. The current system for endotyping severe asthma is largely based on inflammatory cellular profiles and related pathways, namely the dichotomy of type 2 response (resulting in eosinophilic inflammation) and non-type 2 response (reinforcing non-eosinophilic inflammation involving neutrophils or less inflammatory cells), forming the basis of a development strategy for novel therapies...
February 7, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30710579/the-non-transcriptional-activity-of-irf3-modulates-hepatic-immune-cell-populations-in-acute-on-chronic-ethanol-administration-in-mice
#11
Carlos Sanz-Garcia, Kyle L Poulsen, Damien Bellos, Han Wang, Megan R McMullen, Xiaoxia Li, Saurabh Chattopadhyay, Ganes Sen, Laura E Nagy
BACKGROUND & AIMS: Interferon regulatory factor 3 (IRF3) is a transcription factor mediating anti-viral responses, yet recent evidence indicates that IRF3 also has critical non-transcriptional functions, including activating RIG-I-like receptors-induced IRF-3-mediated pathway of apoptosis (RIPA) and restricting activity of NFκB. Using a novel murine model expressing only non-transcriptional IRF3 activity (Irf3S1/S1 ), we tested the hypothesis that non-transcriptional functions of IRF3 modulate innate immune responses in the Gao-binge (acute on chronic) model of alcohol-related liver disease...
January 30, 2019: Journal of Hepatology
https://read.qxmd.com/read/30674551/plant-derived-mitochondria-targeting-cysteine-rich-peptide-modulates-cellular-bioenergetics
#12
Antony Kam, Shining Loo, Bamaprasad Dutta, Siu Kwan Sze, James P Tam
Mitochondria are attractive therapeutic targets for developing agents to delay age-related frailty and diseases. However, few promising leads have identified from natural products. Previously, we identified roseltide rT1, a hyperstable 27-residue cysteine-rich peptide from Hibiscus sabdariffa , as a knottin-type neutrophil elastase inhibitor. Here, we show that roseltide rT1 is also a cell-penetrating, mitochondria-targeting peptide that increases ATP production. Results from flow cytometry, live-cell imaging, pull-down assays, and genetically-modified cell lines supported that roseltide rT1 enters cells via glycosaminoglycan-dependent endocytosis, and enters the mitochondria through TOM20, a mitochondrial protein import receptor...
January 23, 2019: Journal of Biological Chemistry
https://read.qxmd.com/read/30669408/histone-acetylation-promotes-neutrophil-extracellular-trap-formation
#13
Hussein J Hamam, Meraj A Khan, Nades Palaniyar
Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation. However, the importance of other forms of histone modifications in NETosis has not been established. We considered that acetylation of histones would also facilitate NETosis...
January 18, 2019: Biomolecules
https://read.qxmd.com/read/30658161/the-damage-associated-molecular-pattern-hmgb1-is-released-early-after-clinical-hepatic-ischemia-reperfusion
#14
Rowan F van Golen, Megan J Reiniers, Gerben Marsman, Lindy K Alles, Derrick M van Rooyen, Björn Petri, Vincent A Van der Mark, Adriaan A van Beek, Ben Meijer, Martinus A Maas, Sacha Zeerleder, Joanne Verheij, Geoffrey C Farrell, Brenda M Luken, Narci C Teoh, Thomas M van Gulik, Michael P Murphy, Michal Heger
OBJECTIVE AND BACKGROUND: Activation of sterile inflammation after hepatic I/R culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. The aim of the study was to validate this relation in a clinical liver I/R cohort and to limit DAMP release using a mitochondria-targeted antioxidant in I/R-subjected mice...
January 15, 2019: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/30582269/mitochondrial-damage-associated-molecular-patterns-released-by-lung-transplants-are-associated-with-primary-graft-dysfunction
#15
Davide Scozzi, Mohsen Ibrahim, Fuyi Liao, Xue Lin, Hsi-Min Hsiao, Ramsey Hachem, Laneshia Tague, Alberto Ricci, Hrishikesh S Kulkarni, Howard J Huang, Seiichiro Sugimoto, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman
Primary graft dysfunction (PGD) is a major limitation to short and long-term lung transplant survival. Recent work has shown mitochondrial damage associated molecular patterns (Mt-DAMPs) can promote solid organ injury but whether they contribute to PGD severity remains unclear. We quantitated circulating plasma Mt-DNA in 62 patients, prior to lung transplant and shortly after ICU arrival. Although all recipients released Mt-DNA, high levels were associated with severe PGD development. In a mouse orthotopic lung transplant model of PGD we detected airway cell-free damaged mitochondria and Mt-DNA in the peripheral circulation...
December 23, 2018: American Journal of Transplantation
https://read.qxmd.com/read/30562571/protective-effects-of-curcumin-against-ischemia-reperfusion-injury-in-the-liver
#16
REVIEW
Kowsar Bavarsad, Maryam Matbou Riahi, Saeideh Saadat, George Barreto, Stephen L Atkin, Amirhossein Sahebkar
Liver ischemia/reperfusion (I/R) injury is a major complication of hepatic surgery and transplantation. It is one of the leading causes of morbidity and mortality because of post-surgery hepatic dysfunction. Several studies have suggested different mechanisms are involved in the pathogenesis of I/R injury in the liver that includes oxidative stress, inflammation, mitochondria dysfunction, liver Kupffer cells (KCs) activation, vascular cell adhesion molecule overexpression, and facilitation of polymorphonuclear neutrophil injury...
December 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/30428625/furanoid-f-acid-f6-uniquely-induces-netosis-compared-to-c16-and-c18-fatty-acids-in-human-neutrophils
#17
Meraj A Khan, Cecil Pace-Asciak, Jassim M Al-Hassan, Mohammad Afzal, Yuan Fang Liu, Sosamma Oommen, Bincy M Paul, Divya Nair, Nades Palaniyar
Various biomolecules induce neutrophil extracellular trap (NET) formation or NETosis. However, the effect of fatty acids on NETosis has not been clearly established. In this study, we focused on the NETosis-inducing ability of several lipid molecules. We extracted the lipid molecules present in Arabian Gulf catfish ( Arius bilineatus , Val) skin gel, which has multiple therapeutic activities. Gas chromatography⁻mass spectrometry (GC-MS) analysis of the lipid fraction-3 from the gel with NETosis-inducing activity contained fatty acids including a furanoid F-acid (F6; 12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid) and common long-chain fatty acids such as palmitic acid (PA; C16:0), palmitoleic acid (PO; C16:1), stearic acid (SA; C18:0), and oleic acid (OA; C18:1)...
November 13, 2018: Biomolecules
https://read.qxmd.com/read/30391192/mitochondrial-transplantation-prolongs-cold-ischemia-time-in-murine-heart-transplantation
#18
Kamila Moskowitzova, Borami Shin, Kaifeng Liu, Giovanna Ramirez-Barbieri, Alvise Guariento, David Blitzer, Jerusha K Thedsanamoorthy, Rouan Yao, Erin R Snay, James A H Inkster, Arzoo Orfany, David Zurakowski, Douglas B Cowan, Alan B Packard, Gary A Visner, Pedro J Del Nido, James D McCully
BACKGROUND: Cold ischemia time (CIT) causes ischemia‒reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein we investigated the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT. METHODS: Heterotopic heart transplantation was performed in C57BL/6J mice...
September 28, 2018: Journal of Heart and Lung Transplantation
https://read.qxmd.com/read/30326737/mitochondrial-pathway-of-apoptosis-and-necrosis-contribute-to-tenofovir-disoproxil-fumarate-induced-renal-damage-in-rats
#19
H Ramamoorthy, P Abraham, B Isaac, D Selvakumar
Tenofovir disoproxil fumarate (TDF) is currently the only nucleotide analogue reverse-transcriptase inhibitor that is approved by the Food and Drug administration (FDA), USA, for the treatment of human immunodeficiency virus (HIV) infection. In recent days, renal toxicity is becoming common i HIV patients treated with TDF. However, the mechanism of tenofovir nephrotoxicity is not clear. We hypothesized that mitochondrial pathway of apoptosis, poly [ADP-ribose] polymerase (PARP) overactivation and neutrophil infiltration may contribute to tenofovir-induced renal damage...
October 16, 2018: Human & Experimental Toxicology
https://read.qxmd.com/read/30319621/the-mitochondrion-lysosome-axis-in-adaptive-and-innate-immunity-effect-of-lupus-regulator-peptide-p140-on-mitochondria-autophagy-and-netosis
#20
Mykolas Bendorius, Indira Neeli, Fengjuan Wang, Srinivasa Reddy Bonam, Eszter Dombi, Nelly Buron, Annie Borgne-Sanchez, Joanna Poulton, Marko Radic, Sylviane Muller
Mitochondria deserve special attention as sensors of cellular energy homeostasis and metabolic state. Moreover, mitochondria integrate intra- and extra-cellular signals to determine appropriate cellular responses that range from proliferation to cell death. In autoimmunity, as in other inflammatory chronic disorders, the metabolism of immune cells may be extensively remodeled, perturbing sensitive tolerogenic mechanisms. Here, we examine the distribution and effects of the therapeutic 21-mer peptide called P140, which shows remarkable efficacy in modulating immune responses in inflammatory settings...
2018: Frontiers in Immunology
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