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https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#1
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28058013/aging-related-methylation-influences-the-gene-expression-of-key-control-genes-in-colorectal-cancer-and-adenoma
#2
Orsolya Galamb, Alexandra Kalmár, Barbara Kinga Barták, Árpád V Patai, Katalin Leiszter, Bálint Péterfia, Barnabás Wichmann, Gábor Valcz, Gábor Veres, Zsolt Tulassay, Béla Molnár
AIM: To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS: In silico DNA methylation analysis of 353 epigenetic clock CpG sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer (CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated age-related genes, secreted frizzled related protein 1 (SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting (MS-HRM) analysis...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28049648/vitamin-k-dependent-carboxylation-of-matrix-gla-protein-influences-the-risk-of-calciphylaxis
#3
Sagar U Nigwekar, Donald B Bloch, Rosalynn M Nazarian, Cees Vermeer, Sarah L Booth, Dihua Xu, Ravi I Thadhani, Rajeev Malhotra
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use...
January 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28045981/hpv-genotyping-of-modified-general-primer-amplicons-is-more-analytically-sensitive-and-specific-by-sequencing-than-by-hybridization
#4
Roger Meisal, Trine Ballestad Rounge, Irene Kraus Christiansen, Alexander Kirkeby Eieland, Merete Molton Worren, Tor Faksvaag Molden, Øyvind Kommedal, Eivind Hovig, Truls Michael Leegaard, Ole Herman Ambur
Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay...
2017: PloS One
https://www.readbyqxmd.com/read/28012893/matrix-gla-protein-an-extracellular-matrix-protein-regulates-myostatin-expression-in-the-muscle-developmental-program
#5
Sarafraz Ahmad, Arif Tasleem Jan, Mohammad Hassan Baig, Eun Ju Lee, Inho Choi
AIM: Skeletal muscle development involves interactions between intracellular and extracellular factors that act in concert to regulate the myogenic process. Matrix gla protein (MGP), a well-known inhibitor of calcification in soft tissues, has been reported to be highly up-regulated during myogenesis. Our interest in the regulation of muscle satellite cells (MSCs) by extracellular matrix (ECM) genes led us to investigate the effects of MGP during the progression of myogenesis. METHODOLOGY: Participation of MGP in the myogenic process was investigated in vitro using C2C12 cells, and knockdown of its gene was performed to determine its effects on the expression of myogenic regulatory factors (MRFs) and other ECM genes...
December 21, 2016: Life Sciences
https://www.readbyqxmd.com/read/28004064/-secondary-hyperuricemia-in-chronic-renal-failure-promotes-vascular-calcification-in-rats
#6
Zhe Song, Yang Zhao, Xian Wang, Ming-Jiang Xu
The present study was aimed to explore the effects of hyperuricemia on vascular calcification in chronic renal failure (CRF) and the mechanisms. Adenine diet-induced CRF rat model was used. Twenty-three male 8-week-old Wistar rats were randomly divided into control group (Ctr, n = 5), CRF group (n = 8) and CRF plus allopurinol group (CRF + ALL, n = 10), and the rats were given standard diet plus standard drinking water, adenine diet plus standard drinking water and adenine diet plus allopurinol drinking for 6 weeks, respectively...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27951533/correlations-of-plasma-desphosphorylated-uncarboxylated-matrix-gla-protein-with-vascular-calcification-and-vascular-stiffness-in-chronic-kidney-disease
#7
Sipanan Thamratnopkoon, Paweena Susantitaphong, Monravee Tumkosit, Pisut Katavetin, Khajohn Tiranathanagul, Kearkiat Praditpornsilpa, Somchai Eiam-Ong
BACKGROUND: Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification and needs vitamin K-dependent carboxylation for its activity. High levels of desphosphorylated uncarboxylated MGP (dp-ucMGP) were significantly associated with vitamin K deficiency and vascular calcification. This study was conducted to explore the correlations of plasma dp-ucMGP with vascular calcification and vascular stiffness in chronic kidney disease (CKD) patients. METHODS: This cross-sectional study enrolled 83 CKD stages 3-5 patients...
December 13, 2016: Nephron
https://www.readbyqxmd.com/read/27927630/inactive-matrix-gla-protein-and-arterial-stiffness-in-type-2-diabetes-mellitus
#8
Mayank Sardana, Izzah Vasim, Swapna Varakantam, Uzma Kewan, Ali Tariq, Maheshwara R Koppula, Amer Ahmed Syed, Melissa Beraun, Nadja E A Drummen, Cees Vermeer, Scott R Akers, Julio A Chirinos
BACKGROUND: Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes...
December 7, 2016: American Journal of Hypertension
https://www.readbyqxmd.com/read/27918257/widespread-usutu-virus-outbreak-in-birds-in-the-netherlands-2016
#9
J M Rijks, M L Kik, R Slaterus, Rpb Foppen, A Stroo, J IJzer, J Stahl, A Gröne, Mgp Koopmans, H P van der Jeugd, Cbem Reusken
We report a widespread Usutu virus outbreak in birds in the Netherlands. Viral presence had been detected through targeted surveillance as early as April 2016 and increased mortality in common blackbirds and captive great grey owls was noticed from August 2016 onwards. Usutu virus infection was confirmed by post-mortem examination and RT-PCR. Extensive Usutu virus activity in the Netherlands in 2016 underlines the need to monitor mosquito activity and mosquito-borne infections in 2017 and beyond.
November 10, 2016: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/27917442/polymorphisms-in-ten-candidate-genes-are-associated-with-conformational-and-locomotive-traits-in-spanish-purebred-horses
#10
Natalia Sevane, Susana Dunner, Ana Boado, Javier Cañon
The Spanish Purebred horses, also known as Andalusian horses, compete to the highest standards in international dressage events. Gait and conformation could be used as early selection criteria to detect young horses with promising dressage ability. Although the genetic background of equine size variation has been recently uncovered, the genetic basis of horse conformational and locomotive traits is not known, hampered by the complex genetic architecture underlying quantitative traits and the lack of phenotypic data...
December 5, 2016: Journal of Applied Genetics
https://www.readbyqxmd.com/read/27886638/preliminary-evidence-that-negative-symptom-severity-relates-to-multilocus-genetic-profile-for-dopamine-signaling-capacity-and-d2-receptor-binding-in-healthy-controls-and-in-schizophrenia
#11
Sarah A Eisenstein, Ryan Bogdan, Ling Chen, Stephen M Moerlein, Kevin J Black, Joel S Perlmutter, Tamara Hershey, Deanna M Barch
Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ)...
November 17, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27861603/functional-response-fr-and-relative-growth-rate-rgr-do-not-show-the-known-invasiveness-of-lemna-minuta-kunth
#12
Wout Van Echelpoel, Pieter Boets, Peter L M Goethals
Growing travel and trade threatens biodiversity as it increases the rate of biological invasions globally, either by accidental or intentional introduction. Therefore, avoiding these impacts by forecasting invasions and impeding further spread is of utmost importance. In this study, three forecasting approaches were tested and combined to predict the invasive behaviour of the alien macrophyte Lemna minuta in comparison with the native Lemna minor: the functional response (FR) and relative growth rate (RGR), supplemented with a combined biomass-based nutrient removal (BBNR)...
2016: PloS One
https://www.readbyqxmd.com/read/27823565/an-improved-comparative-docking-approach-for-developing-specific-glycogen-phosphorylase-inhibitors-using-pentacyclic-triterpenes
#13
V Badireenath Konkimalla
Mitigation of unwanted effects is a major issue to be addressed in drug discovery. The human genome shares a considerable degree of sequence identity and structural homology whereby multiple binding pockets of similar composition is seen across different family of proteins. This distribution of similar binding pockets in different proteins is a major reason for cross reactivity upon ligand binding. Therefore, identifying such off-targets on a case-to-case basis in the early stages of drug discovery pipeline is very much essential...
November 4, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27819733/research-article-molecular-cloning-and-expression-analysis-of-a-matrix-gla-protein-gene-in-the-spinyhead-croaker-collichthys-lucidus
#14
W Song, M D Zhao, K J Jiang, F Y Zhang, M Zhao, Y Y Meng, L B Ma
The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics...
November 3, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27782369/the-structure-of-brain-glycogen-phosphorylase-from-allosteric-regulation-mechanisms-to-clinical-perspectives
#15
REVIEW
Cécile Mathieu, Jean-Marie Dupret, Fernando Rodrigues Lima
Glycogen phosphorylase (GP) is the key enzyme that regulates glycogen mobilization in cells. GP is a complex allosteric enzyme that comprises a family of three isozymes: muscle GP (mGP), liver GP (lGP), and brain GP (bGP). Although the three isozymes display high similarity and catalyze the same reaction, they differ in their sensitivity to the allosteric activator adenosine monophosphate (AMP). Moreover, inactivating mutations in mGP and lGP have been known to be associated with glycogen storage diseases (McArdle and Hers disease, respectively)...
October 26, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27777791/intravitreal-conbercept-injection-with-and-without-grid-laser-photocoagulation-in-the-treatment-of-diffuse-diabetic-macular-edema-in-real-life-clinical-practice
#16
Yule Xu, Ao Rong, Yanlong Bi, Wei Xu
Purpose. To evaluate the efficacy of intravitreal conbercept (IVC) plus modified grid laser photocoagulation (MGP) versus IVC alone for treatment of diffuse diabetic macular edema (DDME). Methods. In this retrospective study, 51 DDME patients were treated with either IVC alone (IVC group) or IVC plus MGP (combined group) with 12 months of follow-up. The clinical records of those patients were reviewed. Results. 26 patients (31 eyes) received IVC alone and 25 patients (30 eyes) received combined therapy. At month 12, the mean best-corrected visual acuity (BCVA) letter score improvement was 9...
2016: Journal of Ophthalmology
https://www.readbyqxmd.com/read/27774543/cooperative-supramolecular-helical-assembly-of-a-pyridinium-tailored-methyl-glycyrrhetate
#17
Yuxia Gao, Jie Hao, Jindan Wu, Ying Li, Yuan Lin, Jun Hu, Yong Ju
Taking a natural triterpenoid as the building block, we have regulated a pyridinium-functionalized methyl glycyrrhetate (C4-MGP) into P-type helices in water primarily driven by hydrophobic forces. By analysing their temperature-dependent CD and UV-Vis spectra, these hierarchical chiral assemblies were found to be formed in a cooperative supramolecular polymerization manner.
October 24, 2016: Soft Matter
https://www.readbyqxmd.com/read/27764795/a-novel-3d-mesenchymal-stem-cell-model-of-the-multiple-myeloma-bone-marrow-niche-biologic-and-clinical-applications
#18
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27752480/vitamin-k-dependent-protection-of-the-renal-microvasculature-histopathological-studies-in-normal-and-diseased-kidneys
#19
Fang-Fei Wei, Nadja E A Drummen, Lutgarde Thijs, Lotte Jacobs, Marjolein Herfs, Cynthia Van't Hoofd, Cees Vermeer, Jan A Staessen
Vitamin-K-dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. We recently reported in a multiethnic population study that the estimated glomerular filtration rate, a microvascular trait, decreased and the risk of chronic kidney disease increased with higher circulating levels of inactive dephospho-uncarboxylated MGP, a marker of vitamin K deficiency. These findings highlighted the possibility that vitamin K might have a beneficial effect on the renal microcirculation...
September 2016: Pulse (Basel, Switzerland)
https://www.readbyqxmd.com/read/27751997/vkorc1-gene-vitamin-k-epoxide-reductase-polymorphisms-are-associated-with-cardiovascular-disease-in-chronic-kidney-disease-patients-on-hemodialysis
#20
Noha A Osman, Nevine El-Abd, Mohamed Nasrallah
Vitamin K is necessary for the carboxylation of clotting factors and matrix Gla protein (MGP). Vitamin K epoxide reductase (VKOR) is the enzyme responsible for recirculation of Vitamin K increasing its tissue availability. Polymorphisms of VKOR may alter the function of MGP, thereby influencing vascular calcification. We conducted this study to investigate the relationship of VKORC1 gene single nucleotide polymorphisms (SNP's) to vascular calcification and clinically overt cardiovascular disease in chronic kidney disease (CKD) patients on hemodialysis (HD)...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
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