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https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#1
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
https://www.readbyqxmd.com/read/28817810/tgf-%C3%AE-1-is-involved-in-vitamin-d-induced-chondrogenic-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells-by-regulating-the-erk-jnk-pathway
#2
Xiaorui Jiang, Botao Huang, Huiying Yang, Guishi Li, Chunlei Zhang, Guangshi Yang, Feng Lin, Guodong Lin
BACKGROUND/AIMS: Osteoarthritis (OA) is characterized by degradation of cartilage, sole cell type of which is chondrocytes. Bone marrow-derived mesenchymal stem cells (BMSCs) possess multipotency and can be directionally differentiated into chondrocytes under stimulation. This study was aimed to explore the possible roles of vitamin D and transforming growth factor-β1 (TGF-β1) in the chondrogenic differentiation of BMSCs. METHODS: BMSCs were isolated from femurs and tibias of rats and characterized by flow cytometry...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28817801/a-sensitized-igf1-treatment-restores-corticospinal-axon-dependent-functions
#3
Yuanyuan Liu, Xuhua Wang, Wenlei Li, Qian Zhang, Yi Li, Zicong Zhang, Junjie Zhu, Bo Chen, Philip R Williams, Yiming Zhang, Bin Yu, Xiaosong Gu, Zhigang He
A major hurdle for functional recovery after both spinal cord injury and cortical stroke is the limited regrowth of the axons in the corticospinal tract (CST) that originate in the motor cortex and innervate the spinal cord. Despite recent advances in engaging the intrinsic mechanisms that control CST regrowth, it remains to be tested whether such methods can promote functional recovery in translatable settings. Here we show that post-lesional AAV-assisted co-expression of two soluble proteins, namely insulin-like growth factor 1 (IGF1) and osteopontin (OPN), in cortical neurons leads to robust CST regrowth and the recovery of CST-dependent behavioral performance after both T10 lateral spinal hemisection and a unilateral cortical stroke...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817784/hydrogen-peroxide-regulates-angiogenesis-related-factors-in-tumor-cells
#4
Ana Jerónimo, Gonçalo Rodrigues, Filipe Vilas-Boas, Gabriel G Martins, Ana Bagulho, Carla Real
Tumor angiogenesis is required for tumor development and growth and is regulated by several factors including reactive oxygen species (ROS). Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a ROS with an important role in cell signaling but how H<sub>2</sub>O<sub>2</sub> regulates tumor angiogenesis is still poorly understood. We have xenografted tumor cells with altered levels of H<sub>2</sub>O<sub>2</sub> by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization...
August 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28817611/the-directed-migration-of-gonadal-distal-tip-cells-in-caenorhabditis-elegans-requires-ngat-1-a-%C3%A3-1-4-n-acetylgalactosaminyltransferase-enzyme
#5
Joseph Veyhl, Robert J Dunn, Wendy L Johnston, Alexa Bennett, Lijia W Zhang, James W Dennis, Harry Schachter, Joseph G Culotti
Glycoproteins such as growth factor receptors and extracellular matrix have well-known functions in development and cancer progression, however, the glycans at sites of modification are often heterogeneous molecular populations which makes their functional characterization challenging. Here we provide evidence for a specific, discrete, well-defined glycan modification and regulation of a stage-specific cell migration in Caenorhabditis elegans. We show that a chain-terminating, putative null mutation in the gene encoding a predicted β1,4-N-acetylgalactosaminyltransferase, named ngat-1, causes a maternally rescued temperature sensitive (ts) defect in the second phase of the three phase migration pattern of the posterior, but not the anterior, hermaphrodite Distal Tip Cell (DTC)...
2017: PloS One
https://www.readbyqxmd.com/read/28817576/gestational-diabetes-mellitus-is-associated-with-increased-pro-migratory-activation-of-vascular-endothelial-growth-factor-receptor-2-and-reduced-expression-of-vascular-endothelial-growth-factor-receptor-1
#6
Felipe Troncoso, Jesenia Acurio, Kurt Herlitz, Claudio Aguayo, Patricio Bertoglia, Enrique Guzman-Gutierrez, Marco Loyola, Marcelo Gonzalez, Meriem Rezgaoui, Gernot Desoye, Carlos Escudero
Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18)...
2017: PloS One
https://www.readbyqxmd.com/read/28817575/mck1-is-a-novel-regulator-of-myo-inositol-phosphate-synthase-mips-that-is-required-for-inhibition-of-inositol-synthesis-by-the-mood-stabilizer-valproate
#7
Wenxi Yu, Joshua Daniel, Dhara Mehta, Krishna Rao Maddipati, Miriam L Greenberg
Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS), which catalyzes the rate-limiting step of inositol synthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28817487/inhibiting-protein-tyrosine-phosphatase-1b-to-improve-regenerative-functions-of-endothelial-cells
#8
Yuan Wang, Feng Yan, Wenjing Zhang, Shu Pang, Fan Jiang
Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor- and vascular endothelial growth factor receptor-dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration, and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817455/jak-kinase-3-signaling-in-microgliogenesis-from-the-spinal-nestin-progenitors-in-both-development-and-response-to-injury
#9
Sumit Barua, Jee-In Chung, A Young Kim, Soo-Yeon Lee, Soo Hwan Lee, Eun Joo Baik
During spinal cord development, endogenous progenitors expressing nestin can migrate into the target and differentiate into neurons and other glial cells. Microglial cells can also be derived from nestin progenitor cells, even in the adult brain. Knockdown of Jak kinase 3 (Jak3) signaling can increase neurogenesis with longer neurite outgrowth in cortical progenitor cells. This study investigated the effect of Jak3 signaling on differentiation from nestin progenitor cells using E13.5 spinal progenitor cell cultures...
August 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28817446/bevacizumab-as-an-effective-treatment-for-radiation-necrosis-after-radiotherapy-for-melanoma-brain-metastases
#10
Isabella C Glitza, Nandita Guha-Thakurta, Neil M D'Souza, Rodabe N Amaria, Susan L McGovern, Ganesh Rao, Jing Li
Radiation necrosis (RN) is a potential late complication of radiotherapy for intracranial malignancy, which is often associated with significant neurological morbidity. Prolonged treatment with high-dose corticosteroids or surgical resection has been the standard care for RN, but protracted steroid use can lead to significant side effects and surgical resection is not always feasible. The antivascular endothelial growth factor monoclonal antibody bevacizumab induces clinical and radiographic improvements in RN, with overall good tolerance...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28817390/hypoalbuminemia-is-a-predictive-factor-for-fistula-formation-in-recurrent-cervical-cancer
#11
Lavanya H Palavalli Parsons, Brandon Roane, Dustin B Manders, Debra L Richardson, Siobhan M Kehoe, Matthew Carlson, David S Miller, Jayanthi S Lea
OBJECTIVE: Antivascular endothelial growth factor monoclonal antibodies inhibit tumor angiogenesis, consequently impeding the recruitment of new vasculature to existing and new tumor lesions. We sought to evaluate toxicities in women with recurrent cervical cancer after receiving bevacizumab combination chemotherapy. METHODS: A review was conducted of women with recurrent and metastatic cervical cancer who were treated with salvage chemotherapy with or without bevacizumab between 2005 and 2015...
August 16, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28817384/engineering-the-mechanical-and-biological-properties-of-nanofibrous-vascular-grafts-for-in-situ-vascular-tissue-engineering
#12
Jeffrey J D Henry, Jian Yu, Aijun Wang, Randall Lee, Jun Fang, Song Li
Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts...
August 17, 2017: Biofabrication
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#13
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817370/conko-005-adjuvant-chemotherapy-with-gemcitabine-plus-erlotinib-versus-gemcitabine-alone-in-patients-after-r0-resection-of-pancreatic-cancer-a-multicenter-randomized-phase-iii-trial
#14
Marianne Sinn, Marcus Bahra, Torsten Liersch, Klaus Gellert, Helmut Messmann, Wolf Bechstein, Dirk Waldschmidt, Lutz Jacobasch, Martin Wilhelm, Bettina M Rau, Robert Grützmann, Arndt Weinmann, Georg Maschmeyer, Uwe Pelzer, Jens M Stieler, Jana K Striefler, Michael Ghadimi, Sven Bischoff, Bernd Dörken, Helmut Oettle, Hanno Riess
Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817343/suppression-of-choroidal-neovascularization-in-mice-by-subretinal-delivery-of-multigenic-lentiviral-vectors-encoding-anti-angiogenic-micrornas
#15
Anne Louise Askou, Josephine Natalia Esther Benckendorff, Andreas Holmgaard, Tina Storm, Lars Aagaard, Toke Bek, Jacob Giehm Mikkelsen, Thomas Juhl Corydon
Lentivirus-based vectors have been used for the development of potent gene therapies. Here, application of a multigenic lentiviral vector (LV) producing multiple anti-angiogenic microRNAs following subretinal delivery in a laser-induced choroidal neovascularization (CNV) mouse model is presented. This versatile LV, carrying back-to-back RNApolII-driven expression cassettes, enables combined expression of microRNAs targeting vascular endothelial growth factor A (Vegfa) mRNA and fluorescent reporters. In addition, by including a vitelliform macular dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal pigment epithelial (RPE) cells...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28817329/assessing-years-of-life-lost-versus-number-of-deaths-in-the-united-states-1995-2015
#16
Glen B Taksler, Michael B Rothberg
OBJECTIVES: To assess years of life lost to each cause of death in the United States between 1995 and 2015, and compare it with the number of deaths. METHODS: We used Vital Statistics mortality data and defined "life-years lost" as remaining life expectancy for each decedent's age, sex, and race. We calculated the share of life-years lost to each cause of death in each year, and examined reasons for changes. RESULTS: In 2015, heart disease caused the most deaths, but cancer caused 23% more life-years lost...
August 17, 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28817313/ccr7-mediates-tgf-%C3%AE-1-induced-human-malignant-glioma-invasion-migration-and-epithelial-mesenchymal-transition-by-activating-mmp2-9-through-the-nuclear-factor-kappab-signaling-pathway
#17
Yanyan Zheng, Yiting Miu, Xiaokai Yang, Xiaoguo Yang, Meijia Zhu
Chemokine receptor 7 (CCR7) has emerged as an inducer of invasion, migration, and epithelial-mesenchymal transition (EMT) in cancer. In this research, human malignant glioma cells were stimulated with transforming growth factor beta 1 (TGF-β1) and siCCR7. The data show that CCR7 mediates TGF-β1-induced EMT, migration, and invasion in U251 and U87 cells and that these effects of TGF-β1 were reversed by treatment with siCCR7 or a CCR7 neutralizing antibody. Importantly, the TGF-β1-mediated increase in nuclear factor kappaB (NF-κB) activity in human glioma cells was reduced by treatment with siCCR7 or a CCR7 neutralizing antibody...
August 17, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28817296/patients-views-on-price-shopping-and-price-transparency
#18
Hannah L Semigran, Rebecca Gourevitch, Anna D Sinaiko, David Cowling, Ateev Mehrotra
OBJECTIVES: Driven by the growth of high deductibles and price transparency initiatives, patients are being encouraged to search for prices before seeking care, yet few do so. To understand why this is the case, we interviewed individuals who were offered access to a widely used price transparency website through their employer. STUDY DESIGN: Qualitative interviews. METHODS: We interviewed individuals enrolled in a preferred provider organization product through their health plan about their experience using the price transparency tool (if they had done so), their past medical experiences, and their opinions on shopping for care...
June 1, 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28817220/klk14-interactions-with-hai-1-and-hai-2-serine-protease-inhibitors-a-molecular-dynamics-and-relative-free-energy-calculations-study
#19
Christian Solís-Calero, Hernandes F Carvalho
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28817124/directed-differentiation-and-long-term-maintenance-of-epicardial-cells-derived-from-human-pluripotent-stem-cells-under-fully-defined-conditions
#20
Xiaoping Bao, Xiaojun Lian, Tongcheng Qian, Vijesh J Bhute, Tianxiao Han, Sean P Palecek
Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d...
September 2017: Nature Protocols
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