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mitochondrial immune

Yutaka Ikeda, Yukio Nagasaki
Oxidative stress caused by reactive oxygen species (ROS) occurs as events in which living tissues contact certain materials. These events include cell cultures and implantation of materials. Because of the high reactivity of ROS, they damage cells by oxidizing DNA, lipids, and proteins. Conversely, ROS also act as signaling molecules regulating cellular morphology. In particular, mitochondrial ROS are involved in the regulation of cellular physiology, including differentiation, autophagy, metabolic adaptation, apoptosis, and immunity...
March 16, 2018: Biomedical Materials
Junichiro Kawamura, Fumiaki Sugiura, Yasushi Sukegawa, Yasumasa Yoshioka, Jin-Ichi Hida, Shoichi Hazama, Kiyotaka Okuno
The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy...
April 2018: Oncology Letters
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Jenna Anderson, Thorunn A Olafsdottir, Sven Kratochvil, Paul F McKay, Malin Östensson, Josefine Persson, Robin J Shattock, Ali M Harandi
Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization...
2018: Frontiers in Immunology
Xiaojing Zheng, Catherine M O'Connell, Wujuan Zhong, Uma M Nagarajan, Manoj Tripathy, De'Ashia Lee, Ali N Russell, Harold Wiesenfeld, Sharon Hillier, Toni Darville
Sexually transmitted infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae and rates of pelvic inflammatory disease (PID) in women continue to rise, with reinfection being common because of poor adaptive immunity. Diagnosis remains imprecise, and pathogenesis data are derived primarily from monoinfection of mice with C. trachomatis or N. gonorrhoeae By comparing blood mRNA responses of women with C. trachomatis - and/or N. gonorrhoeae -induced PID and histologic endometritis with those from women with C...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kilmer S McCully
The indoleamine hormone melatonin is synthesized by the pineal gland, controls circadian rhythm, and is dependent upon adenosyl methionine for enzymatic synthesis of melatonin from N-acetyl serotonin. Pineal melatonin secretion declines dramatically with aging and dementia. Elevated plasma homocysteine is a risk factor for atherosclerosis and Alzheimer's disease, and the marked decline in adenosyl methionine with aging leads to dysregulation of methionine metabolism and hyperhomocysteinemia. Thioretinaco ozonide is a disulfonium complex formed from thioretinamide, cobalamin, and ozone, which binds the alpha and gamma-phosphate groups of adenosine triphosphate (ATP) and oxygen in the process of oxidative phosphorylation within mitochondria...
January 2018: Annals of Clinical and Laboratory Science
Peng Zhang, Yu Liu, Min Wang, Miren Dong, Zhaoqun Liu, Zhihao Jia, Weilin Wang, Anguo Zhang, Lingling Wang, Linsheng Song
Iron-sulphur clusters (ISCs), one of the oldest and most versatile cofactors of proteins, are involved in catalysis reactions, electron transport reactions, regulation processes as well as sensing of ambient conditions. Iron-sulphur cluster assembly protein (IscA) is a scaffold protein member of ISC formation system, which plays a significant role in the assembly and maturation process of ISC proteins. In the present study, the cDNA sequence of iron-sulphur cluster assembly protein 2 (designated as EsIscA2) was cloned from Eriocheir sinensis...
March 9, 2018: Developmental and Comparative Immunology
Lu Li, Hai-Dong Fu
Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE). Reactive oxygen species derived from the nicotinamide adenine dinucleotide phosphate oxidase pathway or mitochondrial DNA pathway play a key role in the primary stage of NETs formation. The exposure or delayed degradation of abundant autoantigens, such as double-strand DNA, caused by abnormal activation of neutrophils can induce autoantibody to form immune complexes that deposit in local tissues and then induce the plasmacytoid dendritic cells to secrete the interferon alpha and other inflammatory factors...
March 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Fangjie Cao, Peizhuo Wu, Lan Huang, Hui Li, Le Qian, Sen Pang, Lihong Qiu
Previous study indicated that azoxystrobin had high acute toxicity to zebrafish, and larval zebrafish were more sensitive to azoxystrobin than adult zebrafish. The objective of the present study was to investigate short-term developmental effects and potential mechanisms of azoxystrobin in larval and adult zebrafish. After zebrafish embryos and adults were exposed to 0.01, 0.05 and 0.20 mg/L azoxystrobin (equal to 25, 124 and 496 nM azoxystrobin, respectively) for 8 days, the lethal effect, physiological responses, liver histology, mitochondrial ultrastructure, and expression alteration of genes related to mitochondrial respiration, oxidative stress, cell apoptosis and innate immune response were determined...
March 6, 2018: Aquatic Toxicology
Theodora A M Claushuis, Annelou I P Van Der Veen, Janneke Horn, Marcus J Schultz, Riekelt H Houtkooper, Cornelis Van 't Veer, Tom Van Der Poll
Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression...
March 12, 2018: Platelets
E M Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways)...
April 2018: Medical Hypotheses
Maozhi Hu, Weixin Zhao, Hongying Li, Jie Gu, Qiuxiang Yan, Xiaohui Zhou, Zhiming Pan, Guiyou Cui, Xinan Jiao
BACKGROUND: Enhancing caspase-1 activation in macrophages is helpful for the clearance of intracellular bacteria in mice. Our previous studies have shown that EscI, an inner rod protein of type III system in E. coli can enhance caspase-1 activation. The purpose of this study was to further analyze the prospect of EscI in the vaccine design. RESULTS: A recombinant Salmonella expressing SspH2-EscI fusion protein using the promotor of Salmonella effector SspH2, X4550(pYA3334-P-SspH2-EscI), was constructed...
March 9, 2018: BMC Veterinary Research
Daniele Corridoni, Thomas Chapman, Tim Ambrose, Alison Simmons
Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota...
2018: Frontiers in Medicine
Michelle F Goody, Clarissa A Henry
Skeletal muscle enables posture, breathing, and locomotion. Skeletal muscle also impacts systemic processes such as metabolism, thermoregulation, and immunity. Skeletal muscle is energetically expensive and is a major consumer of glucose and fatty acids. Metabolism of fatty acids and glucose requires NAD+ function as a hydrogen/electron transfer molecule. Therefore, NAD+ plays a vital role in energy production. In addition, NAD+ also functions as a cosubstrate for post-translational modifications such as deacetylation and ADP-ribosylation...
March 7, 2018: Skeletal Muscle
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
Duojiao Wu, Xiangdong Wang, Hongzhi Sun
Mitochondrial malfunction is related to aging and to the onset of many diseases, such as obesity/diabetes, cancer, and cardiovascular and neurodegenerative diseases. The molecular principles of biological and toxicological processes the mitochondria can regulate should be disease-specific, cell type-specific, and drug targetable. Mitochondrial biology and toxicology is evolving and undergoing a revolution through fast-developing biotechnologies garnering increasing attention due to the importance of targeted therapies...
March 6, 2018: Cell Biology and Toxicology
Ignacio Hugo Castro, Alejandro Ferrari, María Georgina Herrera, Martín Ezequiel Noguera, Lorenzo Maso, Monica Benini, Alessandra Rufini, Roberto Testi, Paola Costantini, Javier Santos
Friedreich's ataxia is a disease caused by a decrease in the levels of expression or loss of functionality of the mitochondrial protein frataxin (FXN). The development of an active and stable recombinant variant of FXN is important for protein replacement therapy. Although valuable data about the mature form FXN81-210 has been collected, not enough information is available about the conformation of the frataxin precursor (FXN1-210). We investigated the conformation, stability and function of a recombinant precursor variant (His6-TAT-FXN1-210), which includes a TAT peptide in the N-terminal region to assist with transport across cell membranes...
March 2018: FEBS Open Bio
Ashley V Menk, Nicole E Scharping, Dayana B Rivadeneira, Michael J Calderon, McLane J Watson, Deanna Dunstane, Simon C Watkins, Greg M Delgoffe
Despite remarkable responses to cancer immunotherapy in a subset of patients, many patients remain resistant to these therapies. The tumor microenvironment can impose metabolic restrictions on T cell function, creating a resistance mechanism to immunotherapy. We have previously shown tumor-infiltrating T cells succumb to progressive loss of metabolic sufficiency, characterized by repression of mitochondrial activity that cannot be rescued by PD-1 blockade. 4-1BB, a costimulatory molecule highly expressed on exhausted T cells, has been shown to influence metabolic function...
March 6, 2018: Journal of Experimental Medicine
Sharmila Nair, Jeremy P Huynh, Vicky Lampropoulou, Ekaterina Loginicheva, Ekaterina Esaulova, Anshu P Gounder, Adrianus C M Boon, Elizabeth A Schwarzkopf, Tara R Bradstreet, Brian T Edelson, Maxim N Artyomov, Christina L Stallings, Michael S Diamond
Immune-Responsive Gene 1 (Irg1) is a mitochondrial enzyme that produces itaconate under inflammatory conditions, principally in cells of myeloid lineage. Cell culture studies suggest that itaconate regulates inflammation through its inhibitory effects on cytokine and reactive oxygen species production. To evaluate the functions of Irg1 in vivo, we challenged wild-type (WT) and Irg1 -/- mice with Mycobacterium tuberculosis ( Mtb ) and monitored disease progression. Irg1 -/- , but not WT, mice succumbed rapidly to Mtb , and mortality was associated with increased infection, inflammation, and pathology...
March 6, 2018: Journal of Experimental Medicine
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