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Extracellular Histones

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https://www.readbyqxmd.com/read/28643239/serum-histones-as-biomarkers-of-the-severity-of-heatstroke-in-dogs
#1
Yaron Bruchim, Isaac Ginsburg, Gilad Segev, Ahmad Mreisat, Yochai Avital, Itamar Aroch, Michal Horowitz
Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study...
June 22, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#2
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#3
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28627340/-experimental-study-on-formation-of-neutrophil-extracellular-traps-in-human-peripheral-blood-induced-by-paraquat-in-vitro
#4
Wei Jin, Jian Lu, Hui Xie, Yiqun Jiang, Xiaoxiao Meng, Yong Zhu, Ruilan Wang
OBJECTIVE: To explore whether paraquat (PQ) can induce the formation of neutrophil extracellular traps (NETs) in human peripheral blood. METHODS: Neutrophils were isolated from healthy human peripheral blood, and the cells were identified by hematoxylin-eosin (HE) strain. The cells were treated with different concentrations of PQ [0 (as control), 200, 400, 600, 800, 1 000 and 1 200 μmol/L], and the cell viability was measured by cell proliferation and CCK-8 cytotoxicity detection kit, and the median lethal concentration of PQ was selected...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28615512/hdac10-promotes-angiogenesis-in-endothelial-cells-through-the-ptpn22-erk-axis
#5
Baoyu Duan, Dan Ye, Songcheng Zhu, Wenwen Jia, Chenqi Lu, Guiying Wang, Xudong Guo, Yangyang Yu, Chuanyue Wu, Jiuhong Kang
Angiogenesis is crucially involved in many physiological and pathological processes including tumor growth, but the molecular mechanisms regulating angiogenesis are incompletely understood. In this study, we investigated the functions and mechanism of histone deacetylase 10 (HDAC10), a member of the HDAC II family, in regulation of angiogenesis. HDAC10 overexpression in human umbilical vein endothelial cells (HUVECs) promoted tube formation, whereas depletion of HDAC10 from HUVECs inhibited tube formation in vitro and in vivo...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#6
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28611772/bovine-polymorphonuclear-neutrophils-cast-neutrophil-extracellular-traps-against-the-abortive-parasite-neospora-caninum
#7
Rodolfo Villagra-Blanco, Liliana M R Silva, Tamara Muñoz-Caro, Zhengtao Yang, Jianhua Li, Ulrich Gärtner, Anja Taubert, Xichen Zhang, Carlos Hermosilla
Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. In vitro interactions of bovine PMN with N. caninum were analyzed at different ratios and time spans. Extracellular DNA staining was used to illustrate the typical molecules of NETs [i.e., histones (H3), neutrophil elastase (NE), myeloperoxidase (MPO), pentraxin] via antibody-based immunofluorescence analyses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28586053/hdac6-inhibition-suppresses-chondrosarcoma-by-restoring-the-expression-of-primary-cilia
#8
Wei Xiang, Fengjing Guo, Weiting Cheng, Jiaming Zhang, Junming Huang, Rui Wang, Zhongxi Ma, Kai Xu
Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6...
June 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28584398/tumor-necrosis-factor-%C3%AE-decreases-ec-sod-expression-through-dna-methylation
#9
Shunpei Morisawa, Hiroyuki Yasuda, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD) is a secreted antioxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. EC-SOD expression in cultured cell lines is regulated by various cytokines including tumor necrosis factor-α (TNF-α). TNF-α is a major mediator of pathophysiological conditions and may induce or suppress the generation of various types of mediators. Epigenetics have been defined as mitotically heritable changes in gene expression that do not affect the DNA sequence, and include DNA methylation and histone modifications...
May 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28579250/dna-methylation-of-extracellular-matrix-remodeling-genes-in-children-exposed-to-arsenic
#10
Tania Gonzalez-Cortes, Rogelio Recio-Vega, Robert Clark Lantz, Binh T Chau
Several novel mechanistic findings regarding to arsenic's pathogenesis has been reported and some of them suggest that the etiology of some arsenic induced diseases are due in part to heritable changes to the genome via epigenetic processes such as DNA methylation, histone maintenance, and mRNA expression. Recently, we reported that arsenic exposure during in utero and early life was associated with impairment in the lung function and abnormal receptor for advanced glycation endproducts (RAGE), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) sputum levels...
June 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28576417/low-concentrations-of-neutrophil-extracellular-traps-induce-proliferation-in-human-keratinocytes-via-nf-kb-activation
#11
Stelvio Tonello, Manuela Rizzi, Mario Migliario, Vincenzo Rocchetti, Filippo Renò
INTRODUCTION: Granulocytes play a pivotal role in innate immune response, as pathogen invasion activates neutrophils, a subclass of granulocytes, inducing the production of neutrophil extracellular traps (NETs). In this study, it has been evaluated how NETs could affect human keratinocytes (HaCaT cells) behaviour. MATERIALS AND METHODS: HaCaT cells were treated with increasing NETs concentrations (0.01-200ng/ml) and the effect on cell proliferation was evaluated by MTT assay...
May 23, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28575876/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#12
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28574381/-measurement-of-histones-and-circulating-extracellular-nucleic-acids-in-patients-with-complicated-forms-of-peptic-ulcer
#13
G Yerznkyan, B Kultanov, K Shakeev, Ye Tatina
We studied 135 people (24 people, apparently healthy, 39 uncomplicated peptic ulcer disease, 42 people with complex forms peptic ulcer, 30 and after the treatment of complicated forms of peptic ulcer disease, both sexes (18-45 y.). In all patients, the diagnosis was confirmed fibrogastroduodenoscopy (EGD). Determination of histones and acid soluble fraction (ASF), RNA, DNA, in blood was performed by the method of L. Markusheva. Studies have led to the conclusion that the change in the blood concentration of extracellular nucleic acids in patients with uncomplicated disease and complex shapes can be caused by oxidative stress products and can be a signal for elimination of nucleic acids from cells...
April 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28555513/high-mobility-group-box-protein-1-expression-in-inflammatory-diseases-of-the-middle-ear
#14
Luisa Maria Bellussi, Carla Vindigni, Serena Cocca, Marie Aimee Gloria Munezero Butorano, Walter Livi, Giulia Corallo, Desiderio Passali
High-mobility group box 1 (HMGB1) is a nuclear non-histone protein, playing a critical role as a mediator between innate and acquired immunity; when released extracellularly, it coordinates the cellular stress response (under necrosis, bacterial lipopolysaccharide stimulation) and acts as an inflammatory marker and cytokine. The aim of the study was to demonstrate whether HMGB1 is over-expressed in chronic middle-ear pathologies and whether the entity of expression and the localization are correlated with the degree of the inflammatory reaction, thus suggesting that HMGB1 may play a crucial role in chronic inflammatory disorders of the middle ear, as already demonstrated in other airway diseases...
March 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28545587/type-2-diabetes-and-obesity-induce-similar-transcriptional-reprogramming-in-human-myocytes
#15
Leif Väremo, Tora Ida Henriksen, Camilla Scheele, Christa Broholm, Maria Pedersen, Mathias Uhlén, Bente Klarlund Pedersen, Jens Nielsen
BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor on genome-wide transcription...
May 25, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#16
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28538085/circulating-heparan-sulfate-fragments-attenuate-histone-induced-lung-injury-independently-of-histone-binding
#17
Yanlin Zhang, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Joshay A Ford, Eric P Schmidt
Extracellular histones are cationic damage-associated molecular pattern molecules capable of directly inducing cellular injury via charge-mediated interactions with plasma membranes. Accordingly, histones released into the plasma during critical illness are known to contribute to the onset and propagation of lung injury. Vascular injury (with consequent degradation of the endothelial glycocalyx) simultaneously releases anionic heparan sulfate fragments (hexa- to octasaccharides in size) into the plasma. It is unknown whether this endogenous release of heparan sulfate fragments modulates charge-dependent histone cytotoxicity, or if exogenous heparan sulfate fragments could therapeutically attenuate histone-induced lung injury...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#18
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#19
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#20
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
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