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Collagen VI

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https://www.readbyqxmd.com/read/28523478/anti-gpvi-fab-sar264565-effectively-blocks-gpvi-function-in-ex-vivo-human-platelets-under-arterial-shear-in-a-perfusion-chamber
#1
Peter Florian, Peter Wonerow, Sebastian Harder, Karina Kuczka, Michel Dubar, Jochen Graff
INTRODUCTION: Glycoprotein VI (GPVI) is the major platelet receptor for collagen-mediated platelet adhesion and activation. SAR264565 is an anti-GPVI-Fab, binds to GPVI with high affinity, and blocks GPVI function in human platelets in vitro. METHODS: The effect of SAR26456 on platelet responsiveness in the blood of 21 healthy male subjects was investigated using Sakariassen's ex vivo thrombogenesis perfusion chamber model on a collagen-coated surface under conditions mimicking arterial flow...
May 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28481042/misbalance-in-type-iii-collagen-formation-degradation-as-a-novel-serological-biomarker-for-penetrating-montreal-b3-crohn-s-disease
#2
W T van Haaften, J H Mortensen, M A Karsdal, A C Bay-Jensen, G Dijkstra, P Olinga
BACKGROUND: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. AIM: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. METHODS: Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro-C3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls...
May 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28474537/physioxia-promotes-the-articular-chondrocyte-like-phenotype-in-human-chondroprogenitor-derived-self-organized-tissue
#3
Devon E Anderson, Brandon Markway, Kenneth J Weekes, Helen E McCarthy, Brian Johnstone
INTRODUCTION: Biomaterial-based tissue engineering has not successfully reproduced the structural architecture or functional mechanical properties of native articular cartilage. In scaffold-free tissue engineering systems, cells secrete and organize the entire extracellular matrix over time in response to environmental signals, such as oxygen level. In this study, we investigated the effect of oxygen on the formation of neocartilage from human-derived chondrogenic cells. METHODS: Articular chondrocytes (ACs) and articular cartilage progenitor cells (ACPs) derived from healthy human adults were guided toward cell condensation by centrifugation onto plate inserts that were uncoated or coated with either agarose or fibronectin...
May 5, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28450113/a-co-releasing-molecule-prevents-annexin-a2-down-regulation-and-associated-disorders-in-lps-administered-rat-lung
#4
Kana Unuma, Toshihiko Aki, Kanako Noritake, Takeshi Funakoshi, Koichi Uemura
To investigate septic lung injuries and the possible relief from injury by carbon monoxide (CO), rats were intraperitoneally (i.p.) administered water or the water-soluble CO-releasing molecule CORM (30 mg/kg body weight), followed by the successive administration of PBS or lipopolysaccharide (LPS, 15 mg/kg body weight, 6 h). The results in four experimental groups (control, LPS, LPS + CORM, CORM, n = 3 or 4 in each groups) were examined. Histological examination revealed the intravascular aggregation of erythrocytes in the lungs of the LPS group, and serological analysis showed a significant increase in D-dimer in the LPS group...
April 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28448563/corticosteroids-effects-on-lps-induced-rat-inflammatory-keratocyte-cell-model
#5
Huize Yan, Yingwei Wang, Shuhao Shen, Zheng Wu, Pengxia Wan
PURPOSE: Corticosteroids are efficient anti-inflammation treatments. However, there are still arguments on whether it should be used in keratitis. This study was to observe the effect of corticosteroids on keratocytes both in normal condition and inflammation status in vitro. METHODS: Rat keratocytes were cultured and used for examination. 10 μg/ml lipopolysaccharide (LPS) was used to establish the inflammatory keratocyte cell model, and prednisolone acetate (PA), dexamethasone (Dex) and fluorometholone (Flu) were used as corticosteroids treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28444133/increased-collagen-within-the-transverse-tubules-in-human-heart-failure
#6
David J Crossman, Xin Shen, Mia Jüllig, Michelle Munro, Yufeng Hou, Martin Middleditch, Darshan Shrestha, Amy Li, Sean Lal, Cristobal G Dos Remedios, David Baddeley, Peter N Ruygrok, Christian Soeller
Aims: In heart failure transverse-tubule (t-tubule) remodelling disrupts calcium release, and contraction. T-tubules in human failing hearts exhibit increased labelling by wheat germ agglutinin (WGA), a lectin that binds to the dystrophin-associated glycoprotein complex. We hypothesized changes in this complex may explain the increased WGA labelling and contribute to t-tubule remodelling in the failing human heart. In this study we sought to identify the molecules responsible for this increased WGA labelling...
April 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28436002/characterization-of-the-chondrocyte-secretome-in-photoclickable-poly-ethylene-glycol-hydrogels
#7
Margaret C Schneider, Christopher A Barnes, Stephanie J Bryant
Poly(ethylene glycol) (PEG) hydrogels are highly tunable platforms that are promising cell delivery vehicles for chondrocytes and cartilage tissue engineering. In addition to characterizing the type of extracellular matrix (ECM) that forms, understanding the types of proteins that are secreted by encapsulated cells may be important. Thus, the objectives for this study were to characterize the secretome of chondrocytes encapsulated in PEG hydrogels and determine whether the secretome varies as a function of hydrogel stiffness and culture condition...
April 24, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28430784/non-invasive-quantification-of-collagen-turnover-in-renal-transplant-recipients
#8
Elisabeth G D Stribos, Signe Holm Nielsen, Susanne Brix, Morten Asser Karsdal, Marc A Seelen, Harry van Goor, Stephan J L Bakker, Peter Olinga, Henricus A M Mutsaers, Federica Genovese
Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage in RTR. Seventy-eight patients who attended the University Medical Center Groningen for a routine check-up after kidney transplantation were enrolled in the study. Plasma and/or 24h-urine samples were collected and specific matrix-metalloproteinase-generated neo-epitope fragments of collagens were measured by enzyme-linked immunosorbent assay...
2017: PloS One
https://www.readbyqxmd.com/read/28424332/improving-genetic-diagnosis-in-mendelian-disease-with-transcriptome-sequencing
#9
Beryl B Cummings, Jamie L Marshall, Taru Tukiainen, Monkol Lek, Sandra Donkervoort, A Reghan Foley, Veronique Bolduc, Leigh B Waddell, Sarah A Sandaradura, Gina L O'Grady, Elicia Estrella, Hemakumar M Reddy, Fengmei Zhao, Ben Weisburd, Konrad J Karczewski, Anne H O'Donnell-Luria, Daniel Birnbaum, Anna Sarkozy, Ying Hu, Hernan Gonorazky, Kristl Claeys, Himanshu Joshi, Adam Bournazos, Emily C Oates, Roula Ghaoui, Mark R Davis, Nigel G Laing, Ana Topf, Peter B Kang, Alan H Beggs, Kathryn N North, Volker Straub, James J Dowling, Francesco Muntoni, Nigel F Clarke, Sandra T Cooper, Carsten G Bönnemann, Daniel G MacArthur
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404545/doxepin-inhibits-gpvi-dependent-platelet-ca-2-signaling-and-collagen-dependent-thrombus-formation
#10
Sascha Geue, Britta Walker-Allgaier, Daniela Eißler, Roland Tegtmeyer, Malte Schaub, Florian Lang, Meinrad Gawaz, Oliver Borst, Patrick Münzer
Platelet adhesion, activation and aggregation are essential for primary haemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glyocoprotein VI (GPVI) leads to PLCγ-dependent IP3 production with subsequent platelet activation, due to increased intracellular calcium concentration ([Ca(2+)]i). Although it has been described that tricyclic antidepressants potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca(2+) signaling and thrombus formation...
April 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28403201/serum-endotrophin-a-type-vi-collagen-cleavage-product-is-associated-with-increased-mortality-in-chronic-kidney-disease
#11
Anthony Fenton, Mark D Jesky, Charles J Ferro, Jacob Sørensen, Morten A Karsdal, Paul Cockwell, Federica Genovese
BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and renal fibrosis. We assessed the relationship between endotrophin (ETP), a marker of collagen type VI formation, and adverse outcomes in a cohort of patients with CKD. METHODS: We measured serum ETP levels in 500 patients from the Renal Impairment in Secondary Care (RIISC) study, a prospective observational study of patients with high-risk CKD...
2017: PloS One
https://www.readbyqxmd.com/read/28398656/a-biomimetic-hydrogel-functionalized-with-adipose-ecm-components-as-a-microenvironment-for-the-3d-culture-of-human-and-murine-adipocytes
#12
Fiona Louis, Pauline Pannetier, Zied Souguir, Didier Le Cerf, Philippe Valet, Jean-Pierre Vannier, Guillaume Vidal, Elise Demange
The lack of relevant in vitro models for adipose tissue makes necessary the development of a more physiological environment providing spatial and chemical cues for the effective maturation of adipocytes. We developed a biofunctionalized hydrogel with components of adipose extracellular matrix: collagen I, collagen VI and the cell binding domain of fibronectin and we compared it to usual 2D cultures on plastic plates. This scaffold allowed 3D culture of mature adipocytes from the preadipocytes cell lines 3T3-L1 and 3T3-F442A, as well as primary Human White Preadipocytes (HWP), acquiring in vivo-like organization, with spheroid shaped adipocytes forming multicellular aggregates...
April 11, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28388509/nodular-lesions-in-diabetic-nephropathy-collagen-staining-and-renal-prognosis
#13
Koki Mise, Toshiharu Ueno, Junichi Hoshino, Ryo Hazue, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Jun Wada, Hirofumi Makino, Kenmei Takaichi, Kenichi Ohashi, Yoshifumi Ubara
AIMS: Nodular lesions are one of the most characteristic pathological changes of advanced diabetic nephropathy (DN). Previous studies have demonstrated that the pattern of both routine and collagen staining of nodular lesions changes during their development. However, the association between such changes of staining and the renal prognosis remains unclear. METHODS: Among 252 patients with biopsy-proven DN, 67 met the selection criteria and were enrolled to investigate this relationship...
March 22, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28382686/methylparaben-induced-decrease-in-collagen-production-and-viability-of-cultured-human-dermal-fibroblasts
#14
Natalia Majewska, Ilona Zaręba, Arkadiusz Surażyński, Anna Galicka
Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline...
April 6, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28364042/kinetic-based-trapping-by-intervening-sequence-variants-of-the-active-sites-of-protein-disulfide-isomerase-identifies-platelet-protein-substrates
#15
Jack D Stopa, Katherine M Baker, Steven P Grover, Robert Flaumenhaft, Bruce Furie
Thiol isomerases such as protein disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging since PDI catalyzes conformational changes that cannot be easily monitored (e.g., compared with proteolytic cleavage or amino acid phosphorylation), PDI has multiple substrates, and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28340694/composition-and-organization-of-the-pancreatic-extracellular-matrix-by-combined-methods-of-immunohistochemistry-proteomics-and-scanning-electron-microscopy
#16
S Vigier, H Gagnon, K Bourgade, K Klarskov, T Fülöp, P Vermette
The epidemic expansion of diabetes is a major concern of public health. A promising treatment is the transplantation of islets of Langerhans isolated from the whole pancreas but the yields of islets isolation and the rates of successful engraftments still have to be improved to make this therapy effective. The extracellular matrix (ECM) of the pancreatic tissue is partially lost during the isolation process and a comprehensive knowledge of the pancreatic ECM composition and organization could identify targets to improve islets isolation and transplantation or highlight new therapeutics for pancreatic diseases...
January 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28337278/synthesis-of-huaicarbon-a-b-and-their-activating-effects-on-platelet-glycoprotein-vi-receptor-to-mediate-collagen-induced-platelet-aggregation
#17
Hongli Yu, Yeqing Chen, Hao Wu, Kuilong Wang, Liping Liu, Xingde Zhang
Quercetin and rhamnose were efficiently converted into huaicarbon A/B by heating at 250°C for 10-15 min or at 200°C for 25-30 min. With the optimum molar ratio of quercetin/rhamnose (1:3), huaicarbon A and B yields reached 25% and 16% respectively after heating at 250°C, with 55% quercetin conversion. Huaicarbon A/B both promoted washed platelet aggregation dose-dependently, which was antagonized by an inhibitor of glycoprotein VI (GPVI) receptor. Similarly, they both promoted collagen-induced platelet aggregation in platelet-rich plasma in dose-dependent manners...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336561/mice-lacking-the-inhibitory-collagen-receptor-lair-1-exhibit-a-mild-thrombocytosis-and-hyperactive-platelets
#18
Christopher W Smith, Steven G Thomas, Zaher Raslan, Pushpa Patel, Maxwell Byrne, Marie Lordkipanidzé, Danai Bem, Linde Meyaard, Yotis A Senis, Steve P Watson, Alexandra Mazharian
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28300459/mildly-elevated-unconjugated-bilirubin-is-associated-with-reduced-platelet-activation-related-thrombogenesis-and-inflammation-in-gilbert-s-syndrome
#19
Avinash R Kundur, Abishek B Santhakumar, Andrew C Bulmer, Indu Singh
Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelets) and CD62P (marker for P-selectin released from activated degranulated platelets) was assessed in adenosine diphosphate (ADP)-stimulated platelets using flow cytometry...
March 16, 2017: Platelets
https://www.readbyqxmd.com/read/28288584/adipose-tissue-fibrosis-in-human-cancer-cachexia-the-role-of-tgf%C3%AE-pathway
#20
Michele Joana Alves, Raquel Galvão Figuerêdo, Flavia Figueiredo Azevedo, Diego Alexandre Cavallaro, Nelson Inácio Pinto Neto, Joanna Darck Carola Lima, Emidio Matos-Neto, Katrin Radloff, Daniela Mendes Riccardi, Rodolfo Gonzalez Camargo, Paulo Sérgio Martins De Alcântara, José Pinhata Otoch, Miguel Luiz Batista Junior, Marília Seelaender
BACKGROUND: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood...
March 14, 2017: BMC Cancer
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