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https://www.readbyqxmd.com/read/28335437/effect-of-clozapine-on-dna-methylation-in-peripheral-leukocytes-from-patients-with-treatment-resistant-schizophrenia
#1
Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Shinya Watanabe, Hidehiro Umehara, Shinji Shimodera, Takanobu Nakazawa, Masataka Kikuchi, Akihiro Nakaya, Hitoshi Hashimoto, Issei Imoto, Ryota Hashimoto, Tetsuro Ohmori
Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28330896/cell-specific-variation-in-e-selectin-ligand-expression-among-human-peripheral-blood-mononuclear-cells-implications-for-immunosurveillance-and-pathobiology
#2
Mariana Silva, Ronald Kam Fai Fung, Conor Brian Donnelly, Paula Alexandra Videira, Robert Sackstein
Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and Western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28328326/interleukin-12-and-interleukin-23-blockade-in-leukocyte-adhesion-deficiency-type-1
#3
Niki M Moutsopoulos, Christa S Zerbe, Teresa Wild, Nicolas Dutzan, Laurie Brenchley, Giovanni DiPasquale, Gulbu Uzel, Karen C Axelrod, Andrea Lisco, Lucia D Notarangelo, George Hajishengallis, Luigi D Notarangelo, Steven M Holland
A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23-interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23-dependent production of interleukin-17...
March 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#4
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326083/the-small-tellurium-compound-as101-ameliorates-rat-crescentic-glomerulonephritis-association-with-inhibition-of-macrophage-caspase-1-activity-via-very-late-antigen-4-inactivation
#5
Yafit Hachmo, Yona Kalechman, Itai Skornick, Uzi Gafter, Rachel R Caspi, Benjamin Sredni
Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325697/alcam-a-novel-biomarker-in-patients-with-type-2-diabetes-mellitus-complicated-with-diabetic-nephropathy
#6
Alba Sulaj, Stefan Kopf, Elisabeth Gröne, Hermann-Josef Gröne, Sigrid Hoffmann, Erwin Schleicher, Hans-Ulrich Häring, Vedat Schwenger, Stephan Herzig, Thomas Fleming, Peter P Nawroth, Rüdiger von Bauer
BACKGROUND & AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN. METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA...
January 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28322971/effects-and-mechanisms-of-compound-chinese-medicine-and-major-ingredients-on-microcirculatory-dysfunction-and-organ-injury-induced-by-ischemia-reperfusion
#7
REVIEW
Jing-Yan Han, Quan Li, Zhi-Zhong Ma, Jing-Yu Fan
Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for more than 2000 years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322834/anti-human-cd14-monoclonal-antibody-improves-survival-following-sepsis-induced-by-endotoxin-but-not-following-polymicrobial-infection
#8
Masaki Nakamura, Takashi Takeuchi, Kamon Shirakawa, Shoji Furusako
Cluster of differentiation 14 (CD14), a pattern recognition receptor expressed on myeloid cells and a critical component of the innate immune system, mediates local and systemic host responses to gram-negative bacterial products, including lipopolysaccharide (LPS). Therefore, CD14 is an attractive target for development of sepsis therapies, and several monoclonal anti-CD14 antibodies have been reported. In this study, we prepared an anti-human CD14 monoclonal antibody, F1024-1-3, which suppressed LPS-induced upregulation of pro-inflammatory cytokines and an adhesion molecule in human peripheral mononuclear cells and human vascular endothelial cells...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28320610/carbon-monoxide-releasing-molecule-401-suppresses-polymorphonuclear-leukocyte-migratory-potential-by-modulating-f-actin-dynamics
#9
Ken Inoue, Eric K Patterson, Alfredo Capretta, Abdel R Lawendy, Douglas D Fraser, Gediminas Cepinskas
Carbon monoxide-releasing molecules (CORMs) suppress inflammation by reducing polymorphonuclear leukocyte (PMN) recruitment to the affected organs. We investigated modulation of PMN-endothelial cell adhesive interactions by water-soluble CORM-401 using an experimental model of endotoxemia in vitro. Human umbilical vein endothelial cells grown on laminar-flow perfusion channels were stimulated with 1 μg/mL lipopolysaccharide for 6 hours and perfused with 100 μmol/L CORM-401 (or inactive compound iCORM-401)-pretreated PMN for 5 minutes in the presence of 1...
March 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28316167/-influences-of-high-voltage-electrical-burns-on-microcirculation-perfusion-on-serosal-surface-of-small-intestine-of-rats-and-the-interventional-effects-of-pentoxifylline
#10
Q F Zhang, S J Xu, L M Liang, J K Feng, Y F Xu, L L Tu
Objective: To investigate influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline (PTX). Methods: Totally 180 SD rats were divided into sham injury group, simple electrical burn group, and treatment group according to the random number table, with 60 rats in each group. The electrical current was applied to the outside proximal part of left forelimb of rats and exited from the outside proximal part of right hind limb of rats...
March 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28316123/the-msc-adhesion-cascade-insights-into-homing-and-transendothelial-migration
#11
Franziska Nitzsche, Claudia Müller, Barbara Lukomska, Jukka Jolkkonen, Alexander Deten, Johannes Boltze
Mesenchymal stem cells (MSC) are promising candidates for adult cell therapies in regenerative medicine. To fully exert their potential, efficient homing and migration towards lesion sites plays an important role. Local transplantation deposits MSC in spatial proximity to the lesion, but often requires invasive procedures. Systemic administration routes are favored, but require the targeted extravasation of the circulating MSC at the site of injury. Transplanted MSC can indeed leave the blood flow and transmigrate through the endothelial barrier, and reach the lesion site...
March 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28303603/human-il-6-il-17-il-1%C3%AE-and-tnf-%C3%AE-differently-regulate-the-expression-of-pro-inflammatory-related-genes-tissue-factor-and-swine-leukocyte-antigen-class-i-in-porcine-aortic-endothelial-cells
#12
Hanchao Gao, Lu Liu, Yanli Zhao, Hidetaka Hara, Pengfei Chen, Jia Xu, Jia Tang, Ling Wei, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
BACKGROUND: Pro-inflammatory cytokines play important pathological effects in various diseases and allotransplantation; however, their pathological role in xenotransplantation remains elusive. In pig-to-human cell or organ transplantation, whether porcine cells or organs are activated by human cytokines or not as an important question needs to be investigated. METHODS: We investigated the effect of human IL-6, IFN-γ, IL-17, IL-1β, and TNF-α in xenotransplantation using several in vitro models and porcine aortic endothelial cells (PAECs) as target cells...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28301988/the-influence-of-lipid-and-proinflammatory-status-on-maternal-uterine-blood-flow-in-women-with-late-onset-gestational-diabetes
#13
Fernando Bugatto, Rocío Quintero-Prado, Francisco M Visiedo, José M Vilar-Sánchez, Alejandro Figueroa-Quiñones, Cristina López-Tinoco, Rafael Torrejón, José L Bartha
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased proinflammatory cytokines and is also associated with adverse cardiovascular disease (CVD) outcomes later in life. We aim to evaluate the relationships between uterine arteries vascularization and endothelial dysfunction markers, proinflammatory cytokines, and glycemic and lipid profile in women with GDM. METHODS: Fifty pregnant women were recruited at the third trimester of pregnancy for a prospective cohort study...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28298656/a-high-salt-diet-enhances-leukocyte-adhesion-in-association-with-kidney-injury-in-young-dahl-salt-sensitive-rats
#14
Hidenori Takahashi, Suguru Nakagawa, Yaqiong Wu, Yukari Kawabata, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Yoshio Uehara, Makoto Araie
Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope...
March 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28297678/roles-for-cell-cell-adhesion-and-contact-in-obesity-induced-hepatic-myeloid-cell-accumulation-and-glucose-intolerance
#15
Yasutaka Miyachi, Kyoichiro Tsuchiya, Chikara Komiya, Kumiko Shiba, Noriko Shimazu, Shinobu Yamaguchi, Michiyo Deushi, Mizuko Osaka, Kouji Inoue, Yuta Sato, Sayaka Matsumoto, Junichi Kikuta, Kenjiro Wake, Masayuki Yoshida, Masaru Ishii, Yoshihiro Ogawa
Obesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver, but their functions in the development of obesity-associated glucose metabolism remain unclear. Here, we find that LSECs are involved in obesity-associated accumulation of myeloid cells via VLA-4-dependent cell-cell adhesion...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28293857/effect-of-cilostazol-in-treating-diabetes-associated-microvascular-complications
#16
REVIEW
Nicole J Asal, Karolina A Wojciak
PURPOSE: Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus...
March 14, 2017: Endocrine
https://www.readbyqxmd.com/read/28292945/from-leukocyte-recruitment-to-resolution-of-inflammation-the-cardinal-role-of-integrins
#17
REVIEW
Ioannis Kourtzelis, Ioannis Mitroulis, Janusz von Renesse, George Hajishengallis, Triantafyllos Chavakis
Integrins constitute a large group of adhesion receptors that are formed as heterodimers of α and β subunits. Their presence and activation status on the surface of leukocytes modulate a broad spectrum of processes in inflammation and immunity. This mini review critically outlines research advances with regard to the function of leukocyte integrins in regulating and integrating the onset and resolution of acute inflammation. Specifically, we summarize and discuss relevant, current literature that supports the multifunctional role of integrins and their partners...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28290214/computational-study-of-cell-adhesion-and-rolling-in-flow-channel-by-meshfree-method
#18
Liqiang Lin, Xiaowei Zeng
Tethering and rolling of circulating leukocytes on the surface of endothelium are critical steps during an inflammatory response. A soft solid cell model was proposed to study monocytes tethering and rolling behaviors on substrate surface in shear flow. The interactions between monocytes and micro-channel surface were modeled by a coarse-grained molecular adhesive potential. The computational model was implemented in a Lagrange-type meshfree Galerkin formulation to investigate the monocyte tethering and rolling process with different flow rates...
March 14, 2017: Computer Methods in Biomechanics and Biomedical Engineering
https://www.readbyqxmd.com/read/28288918/increased-carbon-dioxide-levels-stimulate-neutrophils-to-produce-microparticles-and-activate-the-nucleotide-binding-domain-like-receptor-3-inflammasome
#19
Stephen R Thom, Veena M Bhopale, JingPing Hu, Ming Yang
We hypothesized that elevations of carbon dioxide (CO2) commonly found in modern buildings will stimulate leukocytes to produce microparticles (MPs) and activate the nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome due to mitochondrial oxidative stress. Human and murine neutrophils generate MPs with high interleukin-1β (IL-1β) content when incubated ex vivo in buffer equilibrated with 0.1-0.4% additional CO2. Enhanced MPs production requires mitochondrial reactive oxygen species production, which is mediated by activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase...
March 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28282455/dynamic-biochemical-tissue-analysis-detects-functional-l-selectin-ligands-on-colon-cancer-tissues
#20
Grady E Carlson, Eric W Martin, Venktesh S Shirure, Ramiro Malgor, Vicente A Resto, Douglas J Goetz, Monica M Burdick
A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions...
2017: PloS One
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