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John D Koerner, Dessislava Z Markova, Greg D Schroeder, Brian P Calio, Anuj Shah, Corbin W Brooks, Alexander R Vaccaro, D Greg Anderson, Chris K Kepler
BACKGROUND CONTEXT: The systemic response regarding cytokine expression after application of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in a rat spinal fusion model has recently been defined1 , but the local response has not. Defining the local cytokine and growth factor response at the fusion site will help explain the roles of these molecules in the fusion process, as well as that of rhBMP-2. Our hypothesis is that application of rhBMP-2 to the fusion site will alter the local levels of cytokines and growth factors throughout the fusion process, in a manner that is different than the systemic response given the tissue-specific effects of rhBMP-2...
March 14, 2018: Spine Journal: Official Journal of the North American Spine Society
Jin Tang, Lingying Luo
Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF)...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tao Li, Mingzheng Peng, Zezheng Yang, Xiaojun Zhou, Yuan Deng, Chuan Jiang, Ming Xiao, Jinwu Wang
To promote vascularization of tissue-engineered bone, IFN-γ polarizing macrophages to M1 was loaded on 5% calcium silicate/β-tricalcium phosphate (CaSiO3 -β-TCP) scaffolds. IFN-γ and Si released from the scaffold were designed to polarize M1 and M2 macrophages, respectively. β-TCP, CaSiO3 -β-TCP, and IFN-γ@CaSiO3 -β-TCP were fabricated and biocompatibilities were evaluated. Polarizations of macrophages were detected by flow cytometry. Human umbilical vein endothelial cells with GFP were cultured and induced on Matrigel with conditioned culture medium extracted from culture of macrophages loaded on scaffolds for evaluating angiogenesis...
March 13, 2018: Acta Biomaterialia
Lily Wei Chen, Chien-Jung Huang, Wen-Hui Tu, Chia-Ju Lu, Yi-Chen Sun, Szu-Yuan Lin, Wei-Li Chen
PURPOSE: To evaluate whether lyophilized human platelet lysate (HPL) powder can preserve the growth factor concentrations and epitheliotrophic properties of liquid HPL, and potentially be used as a clinically-friendly treatment option. METHODS: Two commercialized liquid HPLs, UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were obtained and converted to lyophilized powder. After redissolution, lyophilized powder HPLs were compared with liquid HPLs, as well as human peripheral serum (HPS) and fetal bovine serum (FBS) in liquid or redissolved lyophilized powder forms...
2018: PloS One
Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells...
March 15, 2018: Journal of Cell Biology
Giulia Ravasi, Sara Pelucchi, Gaia Buoli Comani, Federico Greni, Raffaella Mariani, Irene Pelloni, Silvia Bombelli, Roberto Perego, Donatella Barisani, Alberto Piperno
OBJECTIVE: During hypoxia hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analysed molecular mechanisms underlying hypoxia-induced hepcidin inhibition in an in vivo model of acute hypoxia. METHODS: Mice were kept under normal or hypoxic conditions for 6h and 15h and treated with α-PDGF-BB antibody or PDGF-BB receptor inhibitor. Blood, liver, spleen, and bone marrow were collected to extract RNA and protein or to quantify EPO and PDGF-BB...
March 15, 2018: European Journal of Haematology
Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Haruhiko Tokuda, Gen Kuroyanagi, Takashi Onuma, Yukiko Enomoto, Tomoaki Doi, Hiroki Iida, Takanobu Otsuka, Shinji Ogura, Toru Iwama, Kumi Kojima, Osamu Kozawa
It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group)...
April 2018: Biomedical Reports
Bahareh Nazari, Masoud Soleimani, Somayeh Ebrahimi Barough, Seyed Ehsan Enderami, Mansure Kazemi, Babak Negahdari, Esmaeil Sadroddiny, Jafar Ai
Oligodendrocytes play critical roles in the central nervous system (CNS) thorough producing myelin sheaths around axons. There are a variety of approaches to produce oligodendrocytes in vitro and in vivo which are a subject of interest in many studies. A new approach to induce this differentiation is using microRNA 219 (miR-219). However, this new approach suffers from a lack of studies regarding the effect of miR-219 on differentiating human induced pluripotent stem cells (hiPSCs) to oligodendrocytes. This study aimed to assess the impact of miR-219-overexpression on hiPSCs...
March 9, 2018: Journal of Chemical Neuroanatomy
Pernilla Roswall, Matteo Bocci, Michael Bartoschek, Hong Li, Glen Kristiansen, Sara Jansson, Sophie Lehn, Jonas Sjölund, Steven Reid, Christer Larsson, Pontus Eriksson, Charlotte Anderberg, Eliane Cortez, Lao H Saal, Christina Orsmark-Pietras, Eugenia Cordero, Bengt Kristian Haller, Jari Häkkinen, Ingrid J G Burvenich, Elgene Lim, Akira Orimo, Mattias Höglund, Lisa Rydén, Holger Moch, Andrew M Scott, Ulf Eriksson, Kristian Pietras
Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas...
March 12, 2018: Nature Medicine
Yongchang Lai, Zhijian Zhao, Tao Zeng, Xiongfa Liang, Dong Chen, Xiaolu Duan, Guohua Zeng, Wenqi Wu
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel-Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy...
2018: Cancer Cell International
Åsa Lidén, Tine Veronika Karlsen, Bengt Guss, Rolf K Reed, Kristofer Rubin
NEW FINDINGS: What is the central question of this study? Collagen-binding β1 -integrins function physiologically in cellular control of dermal interstitial fluid pressure (PIF ) in vivo and thereby participate in control of extravascular fluid volume. During anaphylaxis, simulated by injection of Compound 48/80 integrin αV β3 takes over this physiological function. Here we addressed the question whether integrin αV β3 can replace collagen-binding β1 -integrin to maintain a long-term homeostatic PIF ...
March 10, 2018: Experimental Physiology
Sajeesh Kumar Madhurakkat Perikamana, Jinkyu Lee, Taufiq Ahmad, Eun Mi Kim, Hayeon Byun, Sangmin Lee, Heungsoo Shin
Tendon-bone interface tissue is extremely challenging to engineer because it exhibits complex gradients of structure, composition, biologics, and cellular phenotypes. As a step toward engineering these transitional zones, we initially analyzed how different (topographical or biological) cues affect tenogenic differentiation of adipose-derived stem cells (ADSCs). We immobilized platelet-derived growth factor - BB (PDGF-BB) using polydopamine (PD) chemistry on random and aligned nanofibers and investigated ADSC proliferation and tenogenic differentiation...
February 27, 2018: Biomaterials
Rafal P Piprek, Milena Damulewicz, Malgorzata Kloc, Jacek Z Kubiak
Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Sex determination period is followed by sexual differentiation, i.e. appearance of the first testis- and ovary-specific features. In Xenopus laevis W-linked DM-domain gene (DM-W) had been described as a master determinant of the gonadal female sex...
March 2, 2018: Differentiation; Research in Biological Diversity
Qian Ding, Zhen Li, Bin Liu, Liping Ling, Xiangguo Tian, Chunqing Zhang
Propranolol is known to reduce portal pressure by decreasing blood flow to the splanchnic circulation and the liver. However, it is unknown if propranolol improves fibrogenesis and sinusoidal remodeling in the cirrhotic liver. The aim of this study was to investigate the therapeutic effects of propranolol on carbon tetrachloride (CCl4 )-induced liver fibrosis in a mouse model and the intrinsic mechanisms underlying those effects. In this study, a hepatic cirrhosis mouse model was induced by CCl4 administration for 6weeks...
March 4, 2018: Human Pathology
Tanveer S Batth, Moreno Papetti, Anamarija Pfeiffer, Maxim A X Tollenaere, Chiara Francavilla, Jesper V Olsen
Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules...
March 6, 2018: Cell Reports
Hyuek Jong Lee
White adipose tissue (WAT) expansion is associated with angiogenesis. Although, activation of lipolysis by exercise induces adipocyte hypotrophy and reduction of fat mass, it is poorly understood whether exercise regulates angiogenesis by altering angiogenic gene expression in WAT. Therefore, the purpose of this study was to evaluate the effect of 6 weeks voluntary wheel running exercise on angiogenic gene expression in adipose tissues. Male C57BL/6J mice performed voluntary wheel running for 6 weeks. At 24 hr after the last exercise training, tibialis anterior (TA), soleus (Sol), epididymal WAT (eWAT), inguinal WAT (iWAT), and brown adipose tissue (BAT) were isolated and then the expressions of vascular endothelial growth factor A (VEGFA), angiopoietin1 (Ang1), Ang2, platelet-derived growth factor B (PDGF-B) and their corresponding receptors were analyzed by reverse transcription-polymerase chain reaction...
February 2018: Journal of Exercise Rehabilitation
Alexander Bartelt, Friederike Behler-Janbeck, F Timo Beil, Till Koehne, Brigitte Müller, Tobias Schmidt, Markus Heine, Laura Ochs, Tayfun Yilmaz, Martin Dietrich, Jan P Tuckermann, Michael Amling, Joachim Herz, Thorsten Schinke, Joerg Heeren, Andreas Niemeier
Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption...
2018: Bone Research
Feng Wang, Hongyan Li, Ela Markovsky, Ryan Glass, Elisa de Stanchina, Simon N Powell, Gary K Schwartz, Adriana Haimovitz-Friedman
Recent data in our laboratory indicate that engagement of host-derived microenvironmental elements impact tumor response to single high dose radiation therapy (SDRT). In these studies we showed that microvascular endothelial damage plays a critical role in tumor response as regulator of direct lethal damage of SDRT. Using a genetic model of Acid Sphingomyelinase (ASMase)-deficient mice we showed that activation of this enzyme by SDRT-induced damage in the endothelium is mandatory for tumor cure. ASMase activation triggers ceramide-mediated apoptosis, and therein microvascular dysfunction, which increased the vulnerability of tumor cells to lethal damage by radiation...
February 6, 2018: Oncotarget
Lasse Jørgensen Cehofski, Anders Kruse, Sigriður Olga Magnusdottir, Alexander Nørgård Alsing, Svend Kirkeby, Bent Honoré, Henrik Vorum
A dexamethasone intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a dexamethasone (DEX) implant this study combined an experimental model of BRVO with proteomic techniques. In six Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser...
March 2, 2018: Experimental Eye Research
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