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soluble tyrosine kinase 1

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https://www.readbyqxmd.com/read/29334762/altered-redox-state-modulates-endothelial-kca2-3-and-kca3-1-levels-in-normal-pregnancy-and-preeclampsia
#1
Shinkyu Choi, Ji Aee Kim, Hai-Yan Li, Sae-Jin Lee, Ye Seon Seok, Tae Hun Kim, Ki-Hwan Han, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh
AIMS: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an important role in vasodilation, and KCas levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated KCas expression modulation during NP and PE. RESULTS: Human uterine microvascular endothelial cells were incubated in serum from normal non-pregnant women (n=13) and women with NP (n=24) or PE (n=15), or in VEGF, oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17-containing medium for 24 hours...
January 15, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29324347/design-synthesis-and-biological-evaluation-of-7h-pyrrolo-2-3-d-pyrimidin-4-amine-derivatives-as-selective-btk-inhibitors-with-improved-pharmacokinetic-properties-for-the-treatment-of-rheumatoid-arthritis
#2
Linhong He, Heying Pei, Chufeng Zhang, Mingfeng Shao, Dan Li, Mingli Tang, Taijing Wang, Xiaoxin Chen, Mingli Xiang, Lijuan Chen
Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16...
December 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29311569/hepatic-dysfunction-and-thrombocytopenia-induced-by-excess-sflt1-in-mice-lacking-endothelial-nitric-oxide-synthase
#3
Yuji Oe, Mieko Ko, Tomofumi Fushima, Emiko Sato, S Ananth Karumanchi, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi
Liver dysfunction is a major problem in patients with severe preeclampsia (PE), hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, or in patients receiving anti-vascular endothelial growth factor (VEGF) therapy. Excessive soluble fms-like tyrosine kinase 1 (sFlt1) that antagonizes VEGF has been implicated in the pathogenesis of PE. VEGF increases the expression of endothelial nitric oxide synthase (eNOS) and activates it. eNOS polymorphisms that cause reduced NO production are associated with PE...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29288571/early-second-trimester-maternal-serum-markers-in-prediction-of-gestational-diabetes-mellitus
#4
Baihui Zhao, Xiujun Han, Qing Meng, Qiong Luo
AIMS: To determine whether maternal serum markers in the early-second trimester are useful for prediction of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 876 singleton pregnancies were recruited in the present study. Blood samples were collected during 16-20 gestational weeks. GDM women were diagnosed by OGTT during 24-28 gestational weeks. Fifty-six cases of GDM and 73 healthy cases were selected. Maternal serum concentrations of placental protein 13 (PP13), pentraxin 3 (PTX3), soluble fms-like tyrosine kinase-1 (sFlt-1), myostatin and follistatin (FST) were detected at 16-20 weeks' gestation...
December 29, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29251628/erythrocyte-efferocytosis-modulates-macrophages-towards-recovery-after-intracerebral-hemorrhage
#5
Che-Feng Chang, Brittany A Goods, Michael H Askenase, Matthew D Hammond, Stephen C Renfroe, Arthur F Steinschneider, Margaret J Landreneau, Youxi Ai, Hannah E Beatty, Luís Henrique Angenendt da Costa, Matthias Mack, Kevin N Sheth, David M Greer, Anita Huttner, Daniel Coman, Fahmeed Hyder, Sourav Ghosh, Carla V Rothlin, J Christopher Love, Lauren H Sansing
Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery...
December 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29229743/meta-analysis-and-systematic-review-to-assess-the-role-of-soluble-fms-like-tyrosine-kinase-1-and-placenta-growth-factor-ratio-in-prediction-of-preeclampsia-the-sappphire-study
#6
Swati Agrawal, Ana Sofia Cerdeira, Christopher Redman, Manu Vatish
Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia...
December 11, 2017: Hypertension
https://www.readbyqxmd.com/read/29222938/role-of-angiogenic-factors-in-the-pathogenesis-and-management-of-pre-eclampsia
#7
REVIEW
Nnabuike C Ngene, Jagidesa Moodley
The cause of pre-eclampsia is unknown. Different postulates have been developed to explain its pathogenesis. The two-stage theory and angiogenic imbalance are two notable postulates of the disease. Together, they propose that there is a lack of cytotrophoblastic invasion of the uterine spiral arteries in pre-eclampsia. The lumen of these arteries remains narrow instead of converting to the wide channels seen in normal pregnancy, and result in poor placental perfusion. Coupled with maternal susceptibility, this process leads to the release of mediators, including an excess of anti-angiogenic factors that result in the clinical manifestations of the disease...
December 9, 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/29215518/angiogenic-factor-profiles-in-pregnant-women-with-a-history-of-early-onset-severe-preeclampsia-receiving-low-molecular-weight-heparin-prophylaxis
#8
RANDOMIZED CONTROLLED TRIAL
Edouard Lecarpentier, Jean Christophe Gris, Eva Cochery-Nouvellon, Erick Mercier, Cyril Touboul, Ravi Thadhani, S Ananth Karumanchi, Bassam Haddad
OBJECTIVE: To evaluate whether daily low-molecular-weight (LMW) heparin prophylaxis during pregnancy alters profile of circulating angiogenic factors that have been linked with the pathogenesis of preeclampsia and fetal growth restriction. METHODS: This is a planned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive LMW heparin or aspirin alone...
January 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29214752/evaluation-of-sflt-1-plgf-ratio-for-predicting-and-improving-clinical-management-of-pre-eclampsia-experience-in-a-specialized-perinatal-care-center
#9
Hélène Caillon, Cécile Tardif, Erwan Dumontet, Norbert Winer, Damien Masson
BACKGROUND: Management of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE...
March 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29208243/resveratrol-mitigates-trophoblast-and-endothelial-dysfunction-partly-via-activation-of-nuclear-factor-erythroid-2-related-factor-2
#10
Seshini Gurusinghe, Annie G Cox, Rahana Rahman, Siow T Chan, Ruth Muljadi, Harmeet Singh, Bryan Leaw, Joanne C Mockler, Sarah A Marshall, Padma Murthi, Rebecca Lim, Euan M Wallace
INTRODUCTION: Maternal endothelial dysfunction underlying preeclampsia arises from excessive placental release of anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and activin A. Resveratrol, an activator of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, mediates the gene expression of antioxidant and vasoprotective factors that may counter the endothelial damage imposed by these anti-angiogenic factors. The objective of this study was to assess whether resveratrol could reduce placental oxidative stress and production of anti-angiogenic factors in vitro and/or improve in vitro markers of endothelial dysfunction via Nrf2 activation...
December 2017: Placenta
https://www.readbyqxmd.com/read/29205570/brain-angiogenic-gene-expression-in-congenital-heart-disease
#11
Olga Sánchez, Aina Ruiz-Romero, Carmen Domínguez, Queralt Ferrer, Irene Ribera, Víctor Rodríguez-Sureda, Jaume Alijotas, Sílvia Arévalo, Elena Carreras, Lluís Cabero, Elisa Llurba
OBJECTIVES: To analyze potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue from euploid fetuses with congenital heart disease (CHD) and control fetuses. METHODS: Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses undergoing termination of pregnancy. Expression profiles of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and genes associated with chronic hypoxia were determined by real-time PCR in tissue from the frontal cortex and from basal ganglia-hypothalamus...
December 5, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29194956/at-the-mercy-of-platelet-primers
#12
Judith M E M Cosemans
In this issue of the Journal of Thrombosis and Haemostasis, Branchford et al. [1] present novel data on the role of Mer tyrosine kinase in platelet function and thrombosis. Mer forms, together with Axl and Tyro3, the TAM receptor family of Growth arrest-specific (Gas6) receptors. The vitamin-K dependent protein Gas6 is regarded as a platelet primer, next to other molecules such as epinephrin, insulin-like growth factor-1 and 2, matrix metalloproteinase-1 and 2, oxided low-density lipoprotein, prostaglandin E2, soluble CD40 ligand and thrombopoeitin [2]...
December 1, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29193681/angiogenic-factors-potential-to-change-clinical-practice-in-preeclampsia
#13
REVIEW
Ana Sofia Cerdeira, Swati Agrawal, Anne Cathrine Staff, Christopher W Redman, Manu Vatish
Preeclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. The field is rapidly evolving with the definition of preeclampsia being challenged by some organizations with proteinuria no longer being essential in the presence of other features. In the last decade angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis of preeclampsia. Here we review the most recent evidence regarding the potential of these factors as biomarkers and therapeutic targets for preeclampsia...
November 29, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/29187870/ectopic-expression-of-snail-and-twist-in-ph-leukemia-cells-upregulates-cd44-expression-and-alters-their-differentiation-potential
#14
Noa Kidan, Hazem Khamaisie, Nili Ruimi, Shay Roitman, Elizabeth Eshel, Najib Dally, Martin Ruthardt, Jamal Mahajna
Philadelphia chromosome-positive (Ph+) leukemia is characterized by reciprocal translocation between chromosomes 9 and 22. The resultant BCR/ABL fusion protein displays constitutive tyrosine kinase activity, leading to the induction of aberrant proliferation and neoplastic transformation. The bone marrow (BM) microenvironment is tumor-promoting, and contributes to disease recurrence in Ph+ leukemia. Activity in the BM microenvironment is mediated by several cellular compartments, extracellular matrix, various soluble factors including transforming growth factor beta 1 (TGF-β1), and the hypoxic conditions in the BM niche...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29173607/clinical-features-and-outcomes-of-acute-coronary-syndrome-in-women-with-previous-pregnancy-complications
#15
Sophie Grand'Maison, Louise Pilote, Kenny Schlosser, Duncan J Stewart, Marisa Okano, Natalie Dayan
BACKGROUND: Women with previous cardiometabolic complications of pregnancy experience double the risk of cardiovascular disease. However, few data exist on the clinical effect of these complications at the time of an acute coronary syndrome (ACS). The objective of this work was to compare risk factors, clinical features, and outcomes among women with premature ACS with or without previous pregnancy complications (gestational diabetes and/or hypertensive disorders of pregnancy). METHODS: Data were obtained from a multicentre cohort of individuals hospitalized with premature ACS...
December 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29172779/the-effect-of-magnesium-sulfate-on-gene-expression-in-maternal-microvascular-endothelial-cells
#16
Dennis K Lee, Anindita Sengupta, Ori Nevo
Preeclampsia is a severe complication of pregnancy associated with maternal and fetal morbidity and mortality. To date, magnesium sulfate remains the preferred method of treatment used to reduce the development of eclampsia. Our aim was to investigate the effects of magnesium sulfate on the expression of genes involved with endothelial function in maternal microvascular endothelial cells from both normal and preeclamptic pregnancies. Primary cells from normal pregnancies treated with 80 mg/L magnesium sulfate for 6 h revealed an overall trend of increased expression of angiogenic and vasopressor-related factors by qPCR analyses...
November 27, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/29168351/complement-5a-mediated-trophoblasts-dysfunction-is-involved-in-the-development-of-pre-eclampsia
#17
Yu Ma, Ling-Ran Kong, Qian Ge, Yuan-Yuan Lu, Mo-Na Hong, Yu Zhang, Cheng-Chao Ruan, Ping-Jin Gao
Pre-eclampsia (PE) is a life-threatening multisystem disorder leading to maternal and neonatal mortality and morbidity. Emerging evidence showed that activation of the complement system is implicated in the pathological processes of PE. However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. In this study, we reported that complement 5a (C5a) plays a pivotal role in aberrant placentation, which is essential for the onset of PE. We detected an elevated C5a deposition in macrophages and C5a receptor (C5aR) expression in trophoblasts of pre-eclamptic placentas...
November 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#18
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29153675/sflt-1-and-soluble-endoglin-concentrations-in-serum-vs-plasma-in-preterm-preeclampsia-are-they-interchangeable-for-biomarker-studies
#19
Fiona Brownfoot, Tu'uhevaha Kaitu'u-Lino, Sally Beard, Stephen Tong, Natalie Hannan
Soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG) are increased in the circulation of women with preeclampsia. We examined whether they differ in concentration between plasma and serum samples. Maternal blood was collected and processed for serum and plasma, from 28 women with preterm preeclampsia and 18 gestation matched controls (<34weeks). Significantly higher sFlt-1 was detected in preeclamptic serum compared to plasma. Significantly higher levels of sENG were identified in serum compared to plasma from control pregnancies...
October 2017: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29075761/corneal-mesenchymal-stromal-cells-are-directly-antiangiogenic-via-pedf-and-sflt-1
#20
Medi Eslani, Ilham Putra, Xiang Shen, Judy Hamouie, Neda Afsharkhamseh, Soroush Besharat, Mark I Rosenblatt, Reza Dana, Peiman Hematti, Ali R Djalilian
Purpose: To evaluate the angiogenic properties of corneal derived mesenchymal stromal cells (Co-MSC). Methods: Co-MSCs were extracted from human cadaver, and wild-type (C57BL/6J) and SERPINF1-/- mice corneas. The MSC secretome was collected in a serum-free medium. Human umbilical vein endothelial cell (HUVEC) tube formation and fibrin gel bead assay (FIBA) sprout formation were used to assess the angiogenic properties of Co-MSC secretome. Complete corneal epithelial debridement was used to induce corneal neovascularization in wild-type mice...
October 1, 2017: Investigative Ophthalmology & Visual Science
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