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Yuhao Zhang, Cristian Coarfa, Xiaoyu Dong, Weiwu Jiang, Brielle Hayward-Piatkovskyi, Jason P Gleghorn, Krithika Lingappan
Premature male neonates are at a greater risk of developing bronchopulmonary dysplasia (BPD). The reasons underlying sexually dimorphic outcomes in premature neonates are not known. The role of miRNAs in mediating sex biases in BPD is understudied. Analysis of the pulmonary transcriptome revealed that a large percentage of angiogenesis-related differentially expressed genes are miR-30a targets. We tested the hypothesis that there is differential expression of miR-30a in vivo and in vitro in neonatal human pulmonary vascular endothelial cells (HPMEC) upon exposure to hyperoxia...
November 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
F Xia, Y J Wu, Z Z Lu, K L Xu, B Pan
Objective: To explore the levels of IL-22 in thymus damaged by γ-ray total body irradiation (TBI), and to study the role of IL-22 in T cell reconstitution after thymic injury induced by TBI. Methods: To induce thymic injury, mice were treated by sub-lethal TBI. Levels of intra-thymic and circulatory IL-22 were detected by using ELISA assay. Untreated mice were used as control. After receiving sub-lethal TBI, mice were intraperitoneally injected with PBS or recombinant mouse IL-22, which were marked as TBI+PBS or TBI+IL-22, respectively...
September 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
R C H Driessen, O M J A Stassen, M Sjöqvist, F Suarez Rodriguez, J Grolleman, C V C Bouten, C M Sahlgren
Notch signaling and blood flow regulate vascular formation and maturation, but how shear stress affects the different components of the Notch pathway in endothelial cells is poorly understood. We show that laminar shear stress results in a ligand specific gene expression profile in endothelial cells (HUVEC). JAG1 expression increases while DLL4 expression decreases. Jagged1 shows a unique response by clustering intracellularly six to nine hours after the onset of flow. The formation of the Jagged1 clusters requires protein production, ER export and endocytosis...
November 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Xueying Zhang, Ying Xu, Lulu Fu, Dandan Li, Xiaowei Dai, Lianlian Liu, Jingshun Zhang, Lianwen Zheng, Manhua Cui
BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder in women of reproductive age and is commonly complicated by adverse endometrial outcomes. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding transcripts that are more than 200 nucleotides in length. Accumulating evidence indicates that lncRNAs are involved in the development of various human diseases. Among these lncRNAs, lncRNA CD36-005 (CD36-005) is indicated to be associated with the pathogenesis of PCOS...
October 15, 2018: Reproductive Biology and Endocrinology: RB&E
Jianbin Ye, Junjie Wen, Yunshan Ning, Yan Li
BACKGROUND: At present, pancreatic ductal adenocarcinoma (PDAC) is a fetal disease lack of effective prognostic and therapeutic methods resulting in high mortality. The Notch signaling has been demonstrated being up- or down-regulated in many cancers, but the effects in pancreatic ductal adenocarcinoma are still controversial. Moreover, the available cases in an individual study are of small samples. Therefore, it is essential to define the effect of Notch signaling in pancreatic ductal adenocarcinoma with larger samples...
October 1, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Minghua Zhu, Minjie Wang, Yinfang Jiang, Hao Wu, Guirong Lu, Wei Shi, Degang Cong, Shaohui Song, Keyuan Liu, Hao Wang
BACKGROUND Activation of Notch signaling was found to be associated with cancer. Gambogic acid (GA) was reported to be an anti-cancer agent. This study investigated the anti-cancer effect of GA on human non-small cell lung cancer (NSCLC) cells. Involvement of the Notch pathway was also studied. MATERIAL AND METHODS GA at 0, 0.5, 0.75, and 1.0 μmol/l was used to incubate A549 and SPC-A1 cells. MTT assay was used to determine the cell viability. TUNEL assay was used to detect the apoptosis. Western blotting was used to evaluate protein expression levels, protein phosphorylation levels, and nuclear translocation levels...
October 7, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Mayank Verma, Yoko Asakura, Bhavani Sai Rohit Murakonda, Thomas Pengo, Claire Latroche, Benedicte Chazaud, Linda K McLoon, Atsushi Asakura
Skeletal muscle is a complex tissue containing tissue resident muscle stem cells (satellite cells) (MuSCs) important for postnatal muscle growth and regeneration. Quantitative analysis of the biological function of MuSCs and the molecular pathways responsible for a potential juxtavascular niche for MuSCs is currently lacking. We utilized fluorescent reporter mice and muscle tissue clearing to investigate the proximity of MuSCs to capillaries in 3 dimensions. We show that MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro, whereas blocking VEGFA using both a vascular endothelial growth factor (VEGF) inhibitor and MuSC-specific VEGFA gene deletion reduces the proximity of MuSCs to capillaries...
October 4, 2018: Cell Stem Cell
Lena Tveriakhina, Karin Schuster-Gossler, Sanchez M Jarrett, Marie B Andrawes, Meike Rohrbach, Stephen C Blacklow, Achim Gossler
DLL1 and DLL4 are Notch ligands with high structural similarity but context-dependent functional differences. Here, we analyze their functional divergence using cellular co-culture assays, biochemical studies, and in vivo experiments. DLL1 and DLL4 activate NOTCH1 and NOTCH2 differently in cell-based assays and this discriminating potential lies in the region between the N-terminus and EGF repeat three. Mice expressing chimeric ligands indicate that the ectodomains dictate ligand function during somitogenesis, and that during myogenesis even regions C-terminal to EGF3 are interchangeable...
October 5, 2018: ELife
Qiansong He, Shirong Li, Lailai Li, Feiran Hu, Ning Weng, Xiaodi Fan, Shixiang Kuang
Previous studies have demonstrated that total flavonoid extracts from Caragana sinica (TFC) exert multiple therapeutic effects, promote blood flow, and exhibit anti-inflammatory and antioxidant properties. The present study aimed to investigate whether TFC promotes angiogenesis and exerts neuroprotective effects in a rat model of transient middle cerebral artery occlusion (tMCAO). Male Wistar rats were subjected to tMCAO for 1.5 h, followed by 24 h of reperfusion. TFC (15, 30, 60 mg/kg) was administered for 14 days...
2018: Frontiers in Neuroscience
Justyna Niderla-Bielińska, Krzysztof Bartkowiak, Bogdan Ciszek, Ewa Jankowska-Steifer, Alicja Krejner, Anna Ratajska
Sulodexide (SDX) is a mixed drug containing low-molecular-weight heparin sulfate and dermatan sulfate. It exerts mild anticoagulant action but can also affect leukocytes, macrophages, and cell-cell adhesion and may interact with growth factors although its direct influence on endothelial cells is not well described. Clinically, SDX is used for the treatment of cardiovascular diseases, where it exerts anti-inflammatory and endothelial protective effects. The aim of this study was to determine the influence of SDX on tubule formation and angiogenesis-related proteins' mRNA expression in endothelial cell line C166 and mouse proepicardial explants...
September 24, 2018: Fundamental & Clinical Pharmacology
Jordan Darden, Laura Beth Payne, Huaning Zhao, John C Chappell
Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations...
September 20, 2018: Angiogenesis
Antonio Jimeno, Kathleen N Moore, Michael Gordon, Rashmi Chugh, Jennifer R Diamond, Raid Aljumaily, David Mendelson, Ann M Kapoun, Lu Xu, Robert Stagg, David C Smith
Purpose Navicixizumab (OMP-305B83) is a bispecific antibody that inhibits delta-like ligand 4 and vascular endothelial growth factor. This Phase 1a trial assessed escalating doses of navicixizumab in refractory solid tumors patients. Design A 3 + 3 dose escalation design was used followed by the treatment of additional patients in an expansion cohort. Study objectives were determination of the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy. Results Sixty-six patients were treated once every 3 weeks in 8 dose-escalation cohorts (0...
September 19, 2018: Investigational New Drugs
Areerat Kunanopparat, Jiraphorn Issara-Amphorn, Asada Leelahavanichkul, Anapat Sanpavat, Suthiluk Patumraj, Pisit Tangkijvanich, Tanapat Palaga, Nattiya Hirankarn
AIM: To investigate the role of Delta-like ligand 4 (DLL4) on tumour growth in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) in vivo . METHODS: We suppressed DLL4 expression in an HBV expressing HCC cell line, HepG2.2.15 and analysed the growth ability of cells as subcutaneous tumours in nude mice. The expression of tumour angiogenesis regulators, VEGF-A and VEGF-R2 in tumour xenografts were examined by western blotting. The tumour proliferation and neovasculature were examined by immunohistochemistry...
September 14, 2018: World Journal of Gastroenterology: WJG
Hongzhou Liu, Jie Peng, Meizhen Zhao, Pei Ma, Jun Zhong, Shuang Li, Zhongxin Lu
Delta-like 4 (DLL4) is a membrane‑bound ligand, which belongs to the Notch signaling pathway and plays important roles in angiogenesis and vascular development. The expression of DLL4 in non‑small cell lung cancer (NSCLC) remains unclear. Therefore, DLL4 expression was detected in clinical specimens using quantum dots (QDs)‑immunohistochemistry (IHC) and lung cancer cell lines by quantitative real‑time polymerase chain reaction. The protein levels of DLL4 were decreased in the tumor tissues of NSCLC patients and lung cancer cell lines...
November 2018: Oncology Reports
Haiqin Wu, Lulu Ye, Xiaoxi Lu, Shuang Xie, Qian Yang, Qinghua Yu
SCOPE: The intestinal mucosal barrier, including the mucus layer, protects against invasion of enteropathogens, thereby inhibiting infection. In this study, the protective effect of Lactobacillus on the intestinal barrier against Salmonella infection is investigated. The underlying mechanism of its effect, specifically on the regulation of goblet cells through the Notch pathway, is also elucidated. METHODS AND RESULTS: Here, the protective effect of Lactobacillus on alleviating changes in the intestinal barrier caused by Salmonella infection is explored...
September 10, 2018: Molecular Nutrition & Food Research
E Canalis
Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling...
September 7, 2018: Osteoporosis International
Rasoul Baharlou, Nader Tajik, Mahdi Behdani, Mohammad Ali Shokrgozar, Vajiheh Tavana, Fatemeh Kazemi-Lomedasht, Fatemeh Faraji, Mahdi Habibi-Anbouhi
OBJECTIVES: Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor. MATERIALS AND METHODS: In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays...
September 5, 2018: Immunopharmacology and Immunotoxicology
Vedran Radojcic, Katelyn Paz, Jooho Chung, Jing Du, Eric T Perkey, Ryan Flynn, Sanja Ivcevic, Michael Zaiken, Ann Friedman, Minhong Yan, Maria A Pletneva, Stefanie Sarantopoulos, Christian W Siebel, Bruce R Blazar, Ivan Maillard
Chronic GVHD (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) and remains an area of unmet clinical need with few treatment options available. Notch blockade prevents acute GVHD in multiple mouse models, but the impact of Notch signaling on cGVHD remains unknown. Using genetic and antibody-mediated strategies of Notch inhibition, we investigated the role of Notch signaling in complementary mouse cGVHD models that mimic several aspects of human cGVHD in search of candidate therapeutics...
September 4, 2018: Blood
Aleksandra Kostina, Hanna Bjork, Elena Ignatieva, Olga Irtyuga, Vladimir Uspensky, Daria Semenova, Shohreh Maleki, Alexey Tomilin, Olga Moiseeva, Anders Franco-Cereceda, Mikhail Gordeev, Giuseppe Faggian, Anna Kostareva, Per Eriksson, Anna Malashicheva
Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm...
September 2018: Atherosclerosis. Supplements
Sanchita Basu, Iulia Barbur, Alexander Calderon, Suhanti Banerjee, Aaron Proweller
Functional interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) in the arterial wall are necessary for controlling vasoreactivity that underlies vascular resistance and tone. Key signaling pathways converge on the phosphorylation of myosin light chain (P-MLC), the molecular signature of force production in SMCs, through coordinating the relative activities of myosin light chain kinase (MLCK) and myosin phosphatase (MP). Notch signaling in the vessel wall serves critical roles in arterial formation and maturation and has been implicated in arterial vasoregulation...
August 31, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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