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https://www.readbyqxmd.com/read/29774102/targeting-tie-2-angiopoietin-axis-in-experimental-mesothelioma-confers-differential-responses-and-raises-predictive-implications
#1
Sophia Magkouta, Apostolos Pappas, Ioannis S Pateras, Androniki Kollintza, Charalampos Moschos, Maria-Eleni Vazakidou, Vasiliki Karavana, Vassilis G Gorgoulis, Ioannis Kalomenidis
Malignant pleural mesothelioma is resistant to currently used treatment. Angiopoieitn-1 directly promotes mesothelioma cell growth in a Tie-2-dependent fashion. Angiopoietin/Tie-2 axis may thus be valid targets for therapeutic interventions against mesothelioma. We hypothesized that a soluble angiopoietin inhibitor (Murine Tek-deltaFc) would halt mesothelioma progression in vivo by enhancing mesothelioma cell proliferation and inhibiting tumor angiogenesis. Our hypothesis was challenged on two syngeneic mesothelioma in vivo models (AB1 cells-Balb/c mice and AE17 cells-C57BL/6 mice...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29742506/neuregulin-1-promotes-myocardial-angiogenesis-in-the-rat-model-of-diabetic-cardiomyopathy
#2
Chun Gui, Zhi-Yu Zeng, Qi Chen, Ya-Wei Luo, Lang Li, Lin-Lin Chen
BACKGROUND/AIMS: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM). So this study was designed to investigate the effects of Neuregulin-1 (NRG-1) treatment on myocardial angiogenesis and the changes of VEGF/Flk1 and Ang-1/Tie-2 signaling in the rat model of DCM. METHODS: Diabetic rats were induced by a single intraperitoneal injection of Streptozotocin. 12 weeks after the diabetes induction, the rats with NRG-1 treatment were treated with tail vein injection of NRG-1 at the dose of 10µg/kg/d for consecutive 10 days...
May 4, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29692685/itraq-based-quantitative-proteomic-analysis-of-processed-euphorbia-lathyris-l-for-reducing-the-intestinal-toxicity
#3
Yu Zhang, Yingzi Wang, Shaojing Li, Xiuting Zhang, Wenhua Li, Shengxiu Luo, Zhenyang Sun, Ruijie Nie
Background: Euphorbia lathyris L., a Traditional Chinese medicine (TCM), is commonly used for the treatment of hydropsy, ascites, constipation, amenorrhea, and scabies. Semen Euphorbiae Pulveratum, which is another type of Euphorbia lathyris that is commonly used in TCM practice and is obtained by removing the oil from the seed that is called paozhi, has been known to ease diarrhea. Whereas, the mechanisms of reducing intestinal toxicity have not been clearly investigated yet. Methods: In this study, the isobaric tags for relative and absolute quantitation (iTRAQ) in combination with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic method was applied to investigate the effects of Euphorbia lathyris L...
2018: Proteome Science
https://www.readbyqxmd.com/read/29661929/arginase-1-expression-in-myeloid-cells-regulates-s-aureus-planktonic-but-not-biofilm-infection
#4
Kelsey J Yamada, Cortney E Heim, Amy L Aldrich, Casey M Gries, Anna G Staudacher, Tammy Kielian
S. aureus is a leading cause of device-associated biofilm infections, which represent a serious health care concern based on their chronicity and antibiotic resistance. We previously reported that S. aureus biofilms preferentially recruit myeloid-derived suppressor cells (MDSCs), which promote monocyte and macrophage anti-inflammatory properties. This is associated with increased myeloid arginase-1 (Arg-1) expression, which has been linked to anti-inflammatory and pro-fibrotic activity that are observed during S...
April 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29618157/angiopoietin-2-and-survival-in-peripheral-artery-disease-patients
#5
Clemens Höbaus, Gerfried Pesau, Carsten Thilo Herz, Thomas Wrba, Renate Koppensteiner, Gerit-Holger Schernthaner
Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period...
April 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29600169/mechanism-of-retinal-pericyte-migration-through-angiopoietin-tie-2-signaling-pathway-on-diabetic-rats
#6
Nadia Artha Dewi, Aulanni'am Aulanni'am, Hidayat Sujuti, Muhammad Aris Widodo, Djoko Wahono Soeatmadji
AIM: To investigate the mechanism of pericyte migration through Angiopoietin-2 (Ang-2)/Tie-2 signaling pathway. METHODS: We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte: endothelial ratio, and morphology of pericyte migration. Tie-2, ERK1/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29597832/maternal-pufa-omega-3-supplementation-prevents-hyperoxia-induced-pulmonary-hypertension-in-the-offspring
#7
Ying Zhong, Daniel Catheline, Ali Houeijeh, Dyuti Sharma, Li-Zhong Du, Capucine Besengez, Philippe Deruelle, Philippe Legrand, Laurent Storme
Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Polyunsaturated fatty acids ω-3 (PUFA ω-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA ω-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA ω-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH...
March 29, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29593228/chronic-kidney-disease-induces-a-systemic-microangiopathy-tissue-hypoxia-and-dysfunctional-angiogenesis
#8
Hans-Ulrich Prommer, Johannes Maurer, Karoline von Websky, Christian Freise, Kerstin Sommer, Hamoud Nasser, Rudi Samapati, Bettina Reglin, Pedro Guimarães, Axel Radlach Pries, Uwe Querfeld
Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29563833/evolution-of-regorafenib-from-bench-to-bedside-in-colorectal-cancer-is-it-an-attractive-option-or-merely-a-me-too-drug
#9
REVIEW
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem in the United States with an estimated 50,260 deaths in 2017. Over the past two decades, several agents have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic CRC (mCRC). Regorafenib (BAY 73-4506) is a small-molecule multikinase inhibitor that was approved for the treatment of mCRC in 2012. This agent is a novel oral diphenylurea-based multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases (RTKs; VEGFR-1, VEGFR-2, VEGFR-3, TIE-2), oncogenic RTKs (c-KIT, RET), stromal RTKs (PDGFR-B, FGFR-1), and intracellular signaling kinases (c-RAF/RAF-1, BRAF, BRAFV600E )...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29556192/leadop-r-structure-based-lead-optimization-with-synthetic-accessibility
#10
Fang-Yu Lin, Emilio Xavier Esposito, Yufeng J Tseng
We previously described a structure-based fragment hopping for lead optimization using a pre-docked fragment database, "LeadOp," that conceptually replaced "bad" fragments of a ligand with "good" fragments while leaving the core of the ligand intact thus improving the compound's activity. LeadOp was proven to optimize the query molecules and systematically developed improved analogs for each of our example systems. However, even with the fragment-based design from common building blocks, it is still a challenge for synthesis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29548688/differential-regulation-of-angiogenesis-in-the-developing-mouse-brain-in-response-to-exogenous-activation-of-the-hypoxia-inducible-transcription-factor-system
#11
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
https://www.readbyqxmd.com/read/29504156/immunolocalization-of-angiogenic-growth-factors-in-the-ovine-uterus-during-the-oestrus-cycle-and-in-response-to-steroids
#12
T D Tremaine, A A Fouladi-Nashta
The vascular changes associated with endometrial maturation in preparation for embryo implantation depend on numerous growth factors, known to regulate key angiogenic events. Primarily, the vascular endothelial growth factor (VEGF) family promotes vascular growth, whilst the angiopoietins maintain blood vessel integrity. The aim was to analyse protein levels of VEGFA ligand and receptors, Angiopoietin-1 and 2 (ANG1/2) and endothelial cell receptor tyrosine kinase (TIE-2) in the ovine endometrium in the follicular and luteal phases of the oestrus cycle and in response to ovarian steroids...
June 2018: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29462367/expression-of-angiogenic-factors-and-plexiform-lesions-in-the-lungs-of-broiler-and-layer-chickens-a-comparison
#13
X Tan, F-J Shao, G-J Fan, Y-T Ying
Plexiform lesions are characteristic histological changes of pulmonary arteries in human patients with severe pulmonary arterial hypertension (PAH) and are regarded as angiogenic lesions. Meat-type broiler chickens are susceptible to PAH and can develop plexiform lesions spontaneously. Whether the lesion development in broilers is associated with PAH predisposition and lung angiogenic environment remains unclear. Moreover, little is known about the cellular origin of these structures. In this work, plexiform lesions were detected in both layer chickens (a strain known to be resistant to PAH) and broiler chickens aged between 1 and 6 wk with normal pulmonary arterial pressures...
May 1, 2018: Poultry Science
https://www.readbyqxmd.com/read/29442209/capillary-rarefaction-and-altered-renal-development-the-imbalance-between-pro-and-anti-angiogenic-factors-in-response-to-angiotensin-ii-inhibition-in-the-developing-rat-kidney
#14
Kee Hwan Yoo, Hyung Eun Yim, Eun Soo Bae, Young Sook Hong
Proper and timely assembly of the kidney vasculature with their respective nephrons is crucial during normal kidney development. In this study, we investigated the effects of enalapril (angiotensin-converting enzyme inhibitor) on angiogenesis-related gene expression and microvascular endothelium related to glomeular and tubular changes in the neonatal rat kidney. Enalapril-treated rats had higher tubular injury scores and lower glomerular maturity grades than those of untreated rats. In the enalapril-treated group, intrarenal angiopoietin-2, Tie-2, and thrombospondin-1 protein expression increased, whereas intrarenal angiopoietin-1 protein expression decreased...
April 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29432853/neurobehavioral-effects-of-1-2-propanediol-in-zebrafish-danio-rerio
#15
Andrey Massarsky, Ayham Abdel, Lilah Glazer, Edward D Levin, Richard T Di Giulio
The use of electronic cigarettes (e-cigarettes) is increasing despite insufficient information concerning their long-term effects, including the effects of maternal e-cigarette use on pre- and postnatal development. Our previous study demonstrated that developmental exposure to 1,2-propanediol (a principal component of e-cigarette liquid) affected early development of zebrafish, causing reduced growth, deformities, and hyperactive swimming behavior in larvae. The current study extends assessment of the developmental toxicity of 1,2-propanediol by examining additional long-term behavioral effects...
March 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29427772/circulating-angiopoietin-2-and-its-soluble-receptor-tie-2-concentrations-are-related-to-inflammatory-markers-in-the-general-population
#16
Elisabeth A Schuldt, Wolfgang Lieb, Marcus Dörr, Markus M Lerch, Henry Völzke, Matthias Nauck, Nele Friedrich
BACKGROUND: The Angiopoietin/Tie (Tyrosine kinase with Ig and EGF homology domains) signaling axis has crucial influences on angiogenesis and the vasculature's reorganization. Moreover, angiopoietin-2 (Ang2) is discussed as a biomarker for diseases' severity and development. Previous studies reported increased Ang2 levels in patients with inflammatory diseases and associations of Ang2 with inflammation markers in relatively small samples. We aimed to assess the relation of Ang2 and Tie2 with inflammation markers in the general population...
May 2018: Cytokine
https://www.readbyqxmd.com/read/29427463/salivary-levels-of-angiopoietin-2-in-infants-with-infantile-haemangiomas-treated-with-and-without-systemic-propranolol
#17
Alexandra Seamens, Elizabeth Nieman, Kristen Losavio, Bridget Bradley, Kate Nelson, Kuang-Ho Chen, Suephy Chen, Jack Arbiser, Leslie P Lawley
Infantile haemangiomas (IHs) with functional or cosmetic concerns necessitate systemic treatment for which propranolol is the preferred treatment. However, the mechanism of action is unknown. Mouse models suggest the angiopoietin-2 (Ang2)/Tie-2 system is implicated. Ang2 can promote endothelial growth or induce apoptosis depending on the presence of vascular endothelial growth factor. This pilot study investigates the saliva Ang2 levels in infants with IH treated with and without systemic propranolol. Patients with clinically confirmed IHs were recruited from an academic paediatric dermatology centre...
February 10, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29415932/-management-of-cardiovascular-complications-in-cml-patients-treated-with-tyrosine-kinase-inhibitors
#18
Itaru Matsumura
Tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with chronic myeloid leukemia (CML). However, patients with CML need to receive TKI therapy for several years. Hence, the safety of long-term TKI treatment warrants utmost attention. Among various adverse events caused by TKI therapy, cardiovascular events (CVEs), such as acute myocardial infarction, cerebral infarction, and pulmonary hypertension, are the most serious with high mortality. TKIs inhibit various off-target molecules involved in the occurrence of CVEs such as c-Kit, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and Tie-2/Tec...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29402834/endothelial-gpr124-exaggerates-the-pathogenesis-of-atherosclerosis-by-activating-inflammation
#19
Dong-Mei Gong, Yan-Li Zhang, Dan-Yang Chen, Ling-Juan Hong, Feng Han, Qi-Bing Liu, Jian-Jun Jiang, Ying-Mei Lu
BACKGROUND/AIMS: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124), an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. METHODS: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29337583/sudden-death-aversion-avoiding-superior-options-because-they-feel-riskier
#20
Jesse Walker, Jane L Risen, Thomas Gilovich, Richard Thaler
We present evidence of sudden-death aversion (SDA)-the tendency to avoid "fast" strategies that provide a greater chance of success, but include the possibility of immediate defeat, in favor of "slow" strategies that reduce the possibility of losing quickly, but have lower odds of ultimate success. Using a combination of archival analyses and controlled experiments, we explore the psychology behind SDA. First, we provide evidence for SDA and its cost to decision makers by tabulating how often NFL teams send games into overtime by kicking an extra point rather than going for the 2-point conversion (Study 1) and how often NBA teams attempt potentially game-tying 2-point shots rather than potentially game-winning 3-pointers (Study 2)...
January 15, 2018: Journal of Personality and Social Psychology
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