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Shulan Zhang, Ziyan Wu, Wen Zhang, Jiuliang Zhao, Gary L Norman, Xiaofeng Zeng, Fengchun Zhang, Yongzhe Li
BACKGROUND: Increasing evidence has highlighted the role of non-criteria antiphospholipid antibodies (aPLs) as important supplements to the current criteria aPLs for the diagnosis of antiphospholipid syndrome (APS). In this retrospective study, we evaluated the clinical relevance of antibodies to phosphatidylserine/prothrombin (aPS/PT) in Chinese patients with APS. METHODS: A total of 441 subjects were tested, including 101 patients with primary APS (PAPS), 140 patients with secondary APS (SAPS), 161 disease controls (DCs) and 39 healthy controls (HCs)...
March 21, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
Suresh Palanivel, Anastasia Zhurina, Phuong Doan, Jerome G Chandraseelan, Vinoth Kumar Megraj Khandelwal, Fedor I Zubkov, Kamran T Mahmudov, Armando J L Pombeiro, Olli Yli-Harja, Meenakshisundaram Kandhavelu
Arylhydrazones of active methylene compounds (AHAMCs) are potent chemotherapy agents for the cancer treatment. AHAMCs enhance the apoptotic cell death and antiproliferation properties in cancer cells. In this study, a series of AHAMCs, 13 compounds, was assayed for cytotoxicity, apoptosis, externalization of phosphatidylserine, heterogeneity and cellular calcium level changes. The in vitro cytotoxicity study against HEK293T cells suggests that AHAMCs have significant cytotoxic effect over the concentrations...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Caroline J Reddel, Gabrielle J Pennings, Jennifer L Curnow, Vivien M Chen, Leonard Kritharides
Platelets play an important role in diseases such as cardiovascular disease and cancer, especially through their release of extracellular vesicles (EVs) and role in thrombosis. The effects of the anti-inflammatory drug colchicine on platelets are not well understood. We investigated the effect of colchicine on the release of pro-coagulant EVs from platelets under low-level activation. Citrated platelet-rich plasma (PRP) from healthy donors was incubated with 2 mM colchicine or vehicle at 37°C for 30 minutes with gentle rotation...
March 19, 2018: Thrombosis and Haemostasis
Ihosvany Fernández Bello, Víctor Jiménez-Yuste, Raquel de Paz, Mónica Martín Salces, Raul Justo Sanz, Elena Monzón Manzano, Elena G Arias-Salgado, María Teresa Álvarez Román, María Isabel Rivas Pollmar, Isabel Goyanes, Nora V Butta
Etiopathogenesis of myelodysplastic syndrome (MDS) might cause per se an anomalous haemostasis that can be even more deteriorated by thrombocytopaenia. So, evaluation of haemostasis in patients with MDS rises as a necessity.This work aimed to characterize haemostasis in non-bleeder MDS patients with a platelet count similar to healthy controls to establish differences between the two groups not related to thrombocytopaenia.Thromboelastometry in samples from MDS patients suggested the existence of at least two antagonistic processes: one of them giving a hypocoagulable pattern (prolonged clotting time and lower α angle) and another conferring a procoagulant profile (decreased fibrinolysis)...
March 19, 2018: Thrombosis and Haemostasis
Ying Su, Jingli Chen, Zengxiang Dong, Yan Zhang, Ruishuang Ma, Junjie Kou, Feng Wang, Jialan Shi
BACKGROUND/AIMS: The mechanisms for thrombosis in diabetic retinopathy (DR) are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS) exposure on microparticles (MPs) and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA) in DR patients. METHODS: PS-positive MPs and cells from healthy controls (n = 20) and diabetic patients (n = 60) were analyzed by flow cytometry and confocal microscopy...
March 15, 2018: Cellular Physiology and Biochemistry
Eva Pallinger, Zoltan Bognar, Agnes Bogdan, Timea Csabai, Hajnalka Abraham, Julia Szekeres-Bartho
Earlier evidence suggests, that the embryo signals to the maternal immune system. Extracellular vesicles (EVs) are produced by all types of cells, and because they transport different kinds of molecules from one cell to the other, they can be considered as means of intercellular communication. The aim of this work was to test, whether the embryo is able to produce sufficient amounts of EVs to alter the function of peripheral lymphocytes. Embryo-derived EVs were identified by their Annexin V biding capacity, and sensitivity to Triton X dependent lysis, using flow cytometry...
March 16, 2018: Scientific Reports
Galia Spectre, Fariborz Mobarrez, Ragnhild Stålesen, Claes-Göran Östenson, David Varon, Håkan Wallen, Paul Hjemdahl
Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry...
March 16, 2018: Platelets
Lixiu Wang, Yayan Bi, Muxin Yu, Tao Li, Dongxia Tong, Xiaoyan Yang, Cong Zhang, Li Guo, Chunxu Wang, Yan Kou, Zengxiang Dong, Valerie A Novakovic, Ye Tian, Junjie Kou, Masood A Shammas, Jialan Shi
BACKGROUND: The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). METHODS: NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy...
May 1, 2018: International Journal of Cardiology
Hui Zhong, Hidenori Wake, Keyue Liu, Yuan Gao, Kiyoshi Teshigawara, Masakiyo Sakaguchi, Shuji Mori, Masahiro Nishibori
The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells...
November 24, 2017: Journal of Pharmacological Sciences
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Woojin Scott Kim, Eve Jary, Russell Pickford, Ying He, Rebekah M Ahmed, Olivier Piguet, John R Hodges, Glenda M Halliday
Behavioral variant frontotemporal dementia (bvFTD) is the most prevalent form of FTD syndromes. bvFTD is characterized clinically by changes in behavior and cognition and pathologically by focal brain atrophy and concomitant loss of lipids. bvFTD is further characterized by eating abnormalities that result in dyslipidemia. Although dyslipidemia is apparent in bvFTD, very little is known about global lipid changes in bvFTD and lipid dysregulation underlying bvFTD. Here, we undertook a comprehensive lipidomics analysis of blood plasma from patients with bvFTD, patients with Alzheimer's disease (AD) and controls, using liquid chromatography-tandem mass spectrometry, with the aim of understanding lipid dysregulation in bvFTD...
2018: Frontiers in Neurology
Tetsuo Mioka, Konomi Fujimura-Kamada, Nahiro Mizugaki, Takuma Kishimoto, Takamitsu Sano, Hitoshi Nunome, David E Williams, Raymond J Andersen, Kazuma Tanaka
Phospholipid flippase (type 4 P-type ATPase) plays a major role in the generation of phospholipid asymmetry in eukaryotic cell membranes. Loss of Lem3p-Dnf1/2p flippases leads to the exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell surface in yeast, resulting in sensitivity to PS- or PE-binding peptides. We isolated Sfk1p, a conserved membrane protein in the TMEM150/FRAG1/DRAM family, as a multicopy suppressor of this sensitivity. Overexpression of SFK1 decreased PS/PE exposure in lem3 Δ mutant cells...
March 14, 2018: Molecular Biology of the Cell
Aaron Strumwasser, Aditi Bhargava, Gregory P Victorino
INTRODUCTION: Translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the endothelial membrane via phospholipid scramblase-1 (PLSCR1) is an apoptotic signal responsible for the loss of endothelial barrier integrity after ischemia-reperfusion injury. We hypothesized that inhibiting phosphatidylserine expression on endothelial cells would attenuate ischemia-reperfusion (IRI) induced increases in hydraulic permeability (Lp). METHODS: Mesenteric hydraulic permeability (Lp) was measured in rat post-capillary mesenteric venules subjected to IRI via superior mesenteric artery (SMA) occlusion (45 minutes) and release (300 minutes) in conjunction with several inhibitors of phosphatidylserine exposure as follows: 1) inhibition of PLSCR1 translocation (DTE - dithioerythritol, n=3), 2) inhibition of PLSCR1 membrane trafficking (2-BP - 2-bromopalmitate, n=3), and 3) inhibition of ion exchange necessary for PLSCR1 function (DIDS - 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid, n=3)...
March 12, 2018: Journal of Trauma and Acute Care Surgery
Hanaa Safya, Amine Mellouk, Julie Legrand, Sylvain M Le Gall, Mohcine Benbijja, Colette Kanellopoulos-Langevin, Jean M Kanellopoulos, Pierre Bobé
A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5'-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RBlow Tconvs, but not CD45RBhigh Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RBlow Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression...
2018: Frontiers in Immunology
Muneaki Motomura, Hideaki Ichihara, Yoko Matsumoto
Negatively charged phosphatidylserine (PS) and sialic acid-containing glycosphingolipids (GM1) were observed to be over represented on the cell membranes of pancreatic cancer cells (BxPC-3) as opposed to normal pancreatic cells. Cationic liposomes (CL) were also found to selectively accumulate into the negatively charged cell membranes of BxPC-3 cells and inhibited their growth but have no effect on the viability of normal pancreatic cells. CL induced apoptosis in BxPC-3 cells via activation of caspase-3, -8, and -9 and mitochondrial events and inhibited tumor enlargement in xenograft mouse models of pancreatic cancer...
March 5, 2018: Bioorganic & Medicinal Chemistry Letters
Winai Jamjan, Chanwit Suriyachadkun, Somboon Tanasupawat, Kenji Sakai, Yukihiro Tashiro, Yuki Okugawa, Saowanit Tongpim
A novel actinobacterial strain, designated C12CA1T , was isolated from forest soil in the conservation area of Chulabhorn dam, Thailand, and its taxonomic position was determined by using a polyphasic approach. Strain C12CA1T contained meso-2,6 diaminopimelic acid in the cell-wall peptidoglycan, and arabinose and galactose as diagnostic sugars of the whole-cell hydrolysate. On the basis of morphological and chemotaxonomic characteristics, strain C12CA1T was classified in the genus Amycolatopsis. It contained MK-9(H4) as the predominant menaquinone, C16 : 0, iso-C15 : 0 and iso-C16 : 0 as the major cellular fatty acids, and several phospholipids consisting of diphosphotidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, hydroxyphosphatidylethanolamine, phosphatidylinositol mannosides and an unidentified glucosamine-containing phospholipid...
March 13, 2018: International Journal of Systematic and Evolutionary Microbiology
Muxin Yu, Rujuan Xie, Yan Zhang, Hui Liang, Li Hou, Chengyuan Yu, Jinming Zhang, Zengxiang Dong, Ye Tian, Yayan Bi, Junjie Kou, Valerie A Novakovic, Jialan Shi
Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30)...
February 26, 2018: Nephrology, Dialysis, Transplantation
Anna A Rybczynska, Hendrikus H Boersma, Steven de Jong, Jourik A Gietema, Walter Noordzij, Rudi A J O Dierckx, Philip H Elsinga, Aren van Waarde
Successful treatment of cancer patients requires balancing of the dose, timing, and type of therapeutic regimen. Detection of increased cell death may serve as a predictor of the eventual therapeutic success. Imaging of cell death may thus lead to early identification of treatment responders and nonresponders, and to "patient-tailored therapy." Cell death in organs and tissues of the human body can be visualized, using positron emission tomography or single-photon emission computed tomography, although unsolved problems remain concerning target selection, tracer pharmacokinetics, target-to-nontarget ratio, and spatial and temporal resolution of the scans...
March 12, 2018: Medicinal Research Reviews
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
Satya Prakash Shukla, D Gomika Udugamasooriya
We recently identified a peptide-peptoid hybrid, PPS1, which specifically recognized lipid-phosphatidylserine (PS). PPS1 consists of distinct positively charged and hydrophobic residue-containing regions. PPS1 monomer was inactive, but the dimeric form, PPS1D1, displayed strong cytotoxicity for lung cancer cells compared to normal cells in vitro, and reduced the tumor growth in vivo. The minimum pharmacophore of PPS1D1 showed that the first (methionine) and fourth (N-lysine) residues were not important for PPS1D1 cytotoxic activity...
December 1, 2017: MedChemComm
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