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Katrin Feldbauer, Jan Schlegel, Juliane Weissbecker, Frank Sauer, Phillip G Wood, Ernst Bamberg, Ulrich Terpitz
An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs) by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C), CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas...
2016: PloS One
Julio Ramírez, José Iniciarte-Mundo, Andrea Cuervo, Virginia Ruiz-Esquide, M Victoria Hernández, Raimón Sanmartí, Juan D Cañete
OBJECTIVES: To analyse clinical, serological and sonographic differences between rheumatoid arthritis (RA) and polyarticular psoriatic arthritis (PsA) patients on anti-TNF therapy in clinical remission. METHODS: Angiogenic and proinflammatory cytokine serum levels were determined by multiplex ELISA in patients with RA and PsA in clinical remission (DAS28-ESR<2.6), clinically-active RA patients (DAS28>3.2) and healthy controls. Ultrasound (US) scans were made of both wrists and hands...
October 7, 2016: Clinical and Experimental Rheumatology
Serra Ucer, Srividhya Iyer, Ha-Neui Kim, Li Han, Christine Rutlen, Kelly Allison, Jeff D Thostenson, Rafael de Cabo, Robert L Jilka, Charles O'Brien, Maria Almeida, Stavros C Manolagas
Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age - a time by which the age-dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice - these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria-targeted catalase - a potent H2 O2 inactivating enzyme - in cells of the myeloid lineage (mitoCAT;LysM-Cre mice), were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Jine Yang, Yang Lu, Ying-Ying Lin, Zhi-Yuan Zheng, Jian-Hong Fang, Shuai He, Shi-Mei Zhuang
Vascular mimicry (VM) describes the phenomenon that tumor cells but not endothelial cells form vascular-like channels, which provide blood perfusion for tumor tissues. VM is associated with tumor growth, metastasis and worse survival of different cancers. The mechanisms of VM formation remain largely unknown. We showed that the conditioned medium of cancer-associated fibroblast (CM-CAF) promoted tumor cells to form capillary-like structure in vitro. Consistently, co-implantation of CAFs with tumor cells significantly enhanced VM formation in mouse xenografts, and higher amount of CAFs was found in VM(+) human HCC tissues compared to VM(-) ones...
September 28, 2016: Cancer Letters
S Lefort, A Thuleau, Y Kieffer, P Sirven, I Bieche, E Marangoni, A Vincent-Salomon, F Mechta-Grigoriou
The CXCR4 receptor and its ligand CXCL12 (also named stromal cell-derived factor 1, SDF1) have a critical role in chemotaxis and homing, key steps in cancer metastasis. Although myofibroblasts expressing CXCL12 are associated with the presence of axillary metastases in HER2 breast cancers (BC), the therapeutic interest of targeting CXCR4/CXCL12 axis in the different BC subtypes remains unclear. Here, we investigate this question by testing antitumor activity of CXCR4 inhibitors in patient-derived xenografts (PDX), which faithfully reproduce human tumor properties...
September 26, 2016: Oncogene
Dominik Rath, Elke Schaeffeler, Stefan Winter, Jens Hewer, Karin Müller, Michal Droppa, Fabian Stimpfle, Meinrad Gawaz, Matthias Schwab, Tobias Geisler
BACKGROUND: SDF1 and its cognate receptors CXCR4 and CXCR7 are involved in myocardial repair and are associated with outcome in cardiovascular patients. Hence, we aimed to investigate clinically significant SDF1 SNPs for their prognostic impact in patients with cardiovascular disease. METHODS AND RESULTS: Genotyping for selected SDF1 variants (rs1065297, rs2839693, rs1801157, rs266087, rs266085 and rs266089 was performed in patients (n = 872) who underwent percutaneous coronary intervention...
2016: PloS One
Petr Dmitriev, Ekaterina Kiseleva, Olga Kharchenko, Evgeny Ivashkin, Andrei Pichugin, Philippe Dessen, Thomas Robert, Frédérique Coppée, Alexandra Belayew, Gilles Carnac, Dalila Laoudj-Chenivesse, Marc Lipinski, Andrei Vasiliev, Yegor S Vassetzky
We performed transcriptome profiling of human immortalized myoblasts (MB) transiently expressing double homeobox transcription factor 4 (DUX4) and double homeobox transcription factor 4 centromeric (DUX4c) and identified 114 and 70 genes differentially expressed in DUX4- and DUX4c-transfected myoblasts, respectively. A significant number of differentially expressed genes were involved in inflammation, cellular migration and chemotaxis suggesting a role for DUX4 and DUX4c in these processes. DUX4 but not DUX4c overexpression resulted in upregulation of the CXCR4 (C-X-C motif Receptor 4) and CXCL12 (C-X-C motif ligand 12 also known as SDF1) expression in human immortalized myoblasts...
August 18, 2016: Oncotarget
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Jingwen Wang, Yuhong Huang, Jun Zhang, Yuanyi Wei, Salma Mahoud, Ahmed Musa Hago Bakheet, Li Wang, Shuting Zhou, Jianwu Tang
Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system...
October 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Umadevi V Wesley, James F Hatcher, Emine R Ayvaci, Abby Klemp, Robert J Dempsey
Cerebral ischemia evokes abnormal release of proteases in the brain microenvironment that spatiotemporally impact angio-neurogenesis. Dipeptidyl peptidase IV (DPPIV), a cell surface and secreted protease, has been implicated in extracellular matrix remodeling by regulating cell adhesion, migration, and angiogenesis through modifying the functions of the major chemokine stromal-derived factor, SDF1. To elucidate the possible association of DPPIV in ischemic brain, we examined the expression of DPPIV in the post-stroke rat brain and under in vitro ischemia by oxygen glucose deprivation (OGD)...
August 15, 2016: Molecular Neurobiology
Barbara Grünwald, Veronika Harant, Susanne Schaten, Monika Frühschütz, Ria Spallek, Bastian Höchst, Katharina Stutzer, Sonja Berchtold, Mert Erkan, Olga Prokopchuk, Marc Martignoni, Irene Esposito, Mathias Heikenwalder, Aayush Gupta, Jens Siveke, Paul Saftig, Percy Knolle, Dirk Wohlleber, Achim Krüger
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) metastasizes to liver at early stages, making this disease highly lethal. Tissue inhibitor of metalloproteinases-1 (TIMP1) creates a metastasis-susceptible environment in the liver. We investigated the role of TIMP1 and its receptor CD63 in metastasis of early-stage pancreatic tumors using mice and human cell lines and tissue samples. METHODS: We obtained liver and plasma samples from patients in Germany with chronic pancreatitis, pancreatic intra-epithelial neoplasia, or PDAC, as well as hepatic stellate cells (HSCs)...
August 6, 2016: Gastroenterology
Jean-Loup Duband, Sophie Escot, Claire Fournier-Thibault
The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial syndrome, is a congenital disease causing numerous structural and behavioral disorders, including cardiac outflow tract anomalies, craniofacial dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It results from a unique chromosomal microdeletion on the 22q11.2 region in which the transcriptional activator TBX1 is decisive for the occurrence of the disease. During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving rise to structures of the face, neck and chest...
2016: Rare Diseases
Hong-Sheng Zhou, Bing Z Carter, Michael Andreeff
Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy...
June 2016: Cancer Biology & Medicine
Mary C Zuniga, Thuy B Tran, Brittanie D Baughman, Gayatri Raghuraman, Elizabeth Hitchner, Allyson Rosen, Wei Zhou
OBJECTIVE: To determine factors affecting cognition and identify predictors of long-term cognitive impairment following carotid revascularization procedures. BACKGROUND: Cognitive impairment is common in older patients with carotid occlusive diseases. METHODS: Patients undergoing carotid intervention for severe occlusive diseases were prospectively recruited. Patients received neurocognitive testing before, 1, and 6 months after carotid interventions...
October 2016: Annals of Surgery
Matthias S Leisegang, Andrea Babelova, Michael Sze Ka Wong, Valeska Helfinger, Norbert Weißmann, Ralf P Brandes, Katrin Schröder
BACKGROUND: 1,25-dihydroxy-vitamin D3 (1,25D) exerts protective effects in the vascular system and promotes myeloid cell differentiation, which are important sources of reactive oxygen species (ROS). Given that myeloid cell ROS derives from Nox-family NADPH oxidases, we hypothesized that this enzyme family contributes to the beneficial effects of 1,25D on vascular regeneration. METHODS AND RESULTS: The function of Nox enzymes in this context was studied in the murine carotid artery electric injury regeneration model...
July 11, 2016: Endocrinology
Juanli Qiao, Zhaojun Liu, Chen Yang, Liankun Gu, Dajun Deng
It has been suggested that the overexpression of serum response factor (SRF) in cancer cells may promote cancer metastasis. However, the exact pathway by which SRF promotes metastasis has not been clarified. Here we showed that SRF promotes gastric cancer (GC) metastasis through stromal fibroblasts in an SDF1-CXCR4-dependent manner. SRF expression was significantly increased in metastatic GCs compared with the non-metastatic GCs (n=50, p=0.013). Immuno-staining indicated that SRF was primarily expressed in a-smooth muscle actin (αSMA)-expressing periglandular fibroblasts in GCs...
June 14, 2016: Oncotarget
Jeffrey Boden, Roberta Marques Lassance-Soares, Huilan Wang, Yuntao Wei, Maria-Grazia Spiga, Jennipher Adi, Hans Layman, Hong Yu, Roberto I Vazquez-Padron, Fotios Andreopoulos, Keith A Webster
BACKGROUND: Critical limb ischemia (CLI) is the extreme manifestation of peripheral artery disease, a major unmet clinical need for which lower limb amputation is the only option for many patients. After 2 decades in development, therapeutic angiogenesis has been tested clinically via intramuscular delivery of proangiogenic proteins, genes, and stem cells. Efficacy has been modest to absent, and the largest phase 3 trial of gene therapy for CLI reported a worsening trend of plasmid fibroblast growth factor...
June 2016: Journal of the American Heart Association
Inna Rabinovich-Nikitin, Assaf Ezra, Beka Barbiro, Polina Rabinovich-Toidman, Beka Solomon
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease, involving both upper and lower motor neurons. The disease is induced by multifactorial pathologies, and as such, it requires a multifaceted therapeutic approach. CXCR4, a chemokine receptor widely expressed in neurons and glial cells and its ligand, CXCL12, also known as stromal-cell-derived factor (SDF1), modulate both neuronal function and apoptosis by glutamate release signaling as well as hematopoietic stem and progenitor cells (HSPCs) migration into the blood and their homing towards injured sites...
2016: Journal of Neuroinflammation
G B Martinelli, D Olivari, A D Re Cecconi, L Talamini, L Ottoboni, S H Lecker, C Stretch, V E Baracos, O F Bathe, A Resovi, R Giavazzi, L Cervo, R Piccirillo
Cancer cachexia is a life-threatening syndrome that affects most patients with advanced cancers and causes severe body weight loss, with rapid depletion of skeletal muscle. No treatment is available. We analyzed microarray data sets to identify a subset of genes whose expression is specifically altered in cachectic muscles of Yoshida hepatoma-bearing rodents but not in those with diabetes, disuse, uremia or fasting. Ingenuity Pathways Analysis indicated that three genes belonging to the C-X-C motif chemokine receptor 4 (CXCR4) pathway were downregulated only in muscles atrophying because of cancer: stromal cell-derived factor 1 (SDF1), adenylate cyclase 7 (ADCY7), and p21 protein-activated kinase 1 (PAK1)...
May 23, 2016: Oncogene
Hideshi Fujinaga, Hiroko Fujinaga, Nobuyuki Watanabe, Tomoko Kato, Moe Tamano, Miho Terao, Shuji Takada, Yushi Ito, Akihiro Umezawa, Masahiko Kuroda
Vascular growth is necessary for normal lung development. Although endothelial progenitor cells (EPCs) play an important role in vascularization, little is known about EPC function in congenital diaphragmatic hernia (CDH), a severe neonatal condition that is associated with pulmonary hypoplasia. We hypothesized that the function of endothelial colony-forming cells (ECFCs), a type of EPC, is impaired in CDH. Cord blood (CB) was collected from full-term CDH patients and healthy controls. We assessed CB progenitor cell populations as well as plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1α (SDF1α) levels...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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