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https://www.readbyqxmd.com/read/27933092/effects-of-purified-anthocyanin-supplementation-on-platelet-chemokines-in-hypocholesterolemic-individuals-a-randomized-controlled-trial
#1
Xiandan Zhang, Yanna Zhu, Fenglin Song, Yanling Yao, Fuli Ya, Dan Li, Wenhua Ling, Yan Yang
BACKGROUND: It is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels. METHODS: A total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins (n = 73) or a placebo (n = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27929130/identification-of-a-cd133-cd55-population-functions-as-a-fetal-common-skeletal-progenitor
#2
Lihong Weng, Xingbin Hu, Bijender Kumar, Mayra Garcia, Ivan Todorov, Xiaoman Jung, Guido Marcucci, Stephen J Forman, Ching-Cheng Chen
In this study, we identified a CD105+CD90.1-CD133-CD55- (CD133-CD55-) population in the fetal skeletal element that can generate bone and bone marrow. Besides osteoblasts and chondrocytes, the CD133-CD55- common progenitors can give rise to marrow reticular stromal cells and perivascular mesenchymal progenitors suggesting they function as the fetal common skeletal progenitor. Suppression of CXCL12 and Kitl expression in CD133-CD55- common progenitors severely disrupted the BM niche formation but not bone generation...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924617/cxcl12-sdf-1-dependent-retinal-migration-of-endogenous-bone-marrow-derived-stem-cells-improves-visual-function-after-pharmacologically-induced-retinal-degeneration
#3
Volker Enzmann, Stéphanie Lecaudé, Anna Kruschinski, Axel Vater
Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer...
December 6, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27918748/the-cxcl12-cxcr4-signaling-pathway-a-new-susceptibility-factor-in-human-papillomavirus-pathogenesis
#4
Floriane Meuris, Laetitia Carthagena, Agnieszka Jaracz-Ros, Françoise Gaudin, Pasquale Cutolo, Claire Deback, Yuezhen Xue, Françoise Thierry, John Doorbar, Françoise Bachelerie
The productive human papillomavirus (HPV) life cycle is tightly linked to the differentiation and cycling of keratinocytes. Deregulation of these processes and stimulation of cell proliferation by the action of viral oncoproteins and host cell factors underlies HPV-mediated carcinogenesis. Severe HPV infections characterize the wart, hypogammaglobulinemia, infection, and myelokathexis (WHIM) immunodeficiency syndrome, which is caused by gain-of-function mutations in the CXCR4 receptor for the CXCL12 chemokine, one of which is CXCR41013...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27916896/the-impact-of-cxcr4-blockade-on-the-survival-of-rat-brain-cortical-neurons
#5
José Joaquín Merino, Alba Garcimartín, María Elvira López-Oliva, Juana Benedí, María Pilar González
BACKGROUND: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro)...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914820/cell-therapy-in-critical-limb-ischemia-a-comprehensive-analysis-of-two-cell-therapy-products
#6
Claire Tournois, Bernard Pignon, Marie-Antoinette Sevestre, Rida Al-Rifai, Valerie Creuza, Gaël Poitevin, Caroline François, Philippe Nguyen
BACKGROUND: Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). In spite of the fact that clinical trials found some efficacy, the mechanism of action remains elusive. The objective of this study was to characterize two autologous cell therapy products (CTPs) obtained from patients with advanced peripheral arterial disease. METHODS: Bone marrow (BM-CTPs) (n = 20) and CTPs obtained by non-mobilized cytapheresis (peripheral blood [PB]-CTPs) (n = 20) were compared...
November 30, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27914361/development-of-cxcr4-modulators-by-virtual-hts-of-a-novel-amide-sulfamide-compound-library
#7
Renren Bai, Qi Shi, Zhongxing Liang, Younghyoun Yoon, Yiran Han, Amber Feng, Shuangping Liu, Yoonhyeun Oum, C Chris Yun, Hyunsuk Shim
CXCR4 plays a crucial role in recruitment of inflammatory cells to inflammation sites at the beginning of the disease process. Modulating CXCR4 functions presents a new avenue for anti-inflammatory strategies. However, using CXCR4 antagonists for a long term usage presents potential serious side effect due to their stem cell mobilizing property. We have been developing partial CXCR4 antagonists without such property. A new computer-aided drug design program, the FRESH workflow, was used for anti-CXCR4 lead compound discovery and optimization, which coupled both compound library building and CXCR4 docking screens in one campaign...
November 24, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#8
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913094/hematopoietic-stem-cell-niches-produce-lineage-instructive-signals-to-control-multipotent-progenitor-differentiation
#9
Ana Cordeiro Gomes, Takahiro Hara, Vivian Y Lim, Dietmar Herndler-Brandstetter, Erin Nevius, Tatsuki Sugiyama, Shizue Tani-Ichi, Susan Schlenner, Ellen Richie, Hans-Reimer Rodewald, Richard A Flavell, Takashi Nagasawa, Koichi Ikuta, João Pedro Pereira
Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis...
November 23, 2016: Immunity
https://www.readbyqxmd.com/read/27908965/inf-%C3%AE-encoding-plasmid-administration-triggers-bone-loss-and-disrupts-bone-marrow-microenvironment
#10
Dimitrios Agas, Guilherme Gusmâo Silva, Fulvio Laus, Andrea Marchigiani, Melania Capitani, Cecilia Vullo, Giuseppe Catone, Giovanna Lavava, Antonio Concetti, Luigi Marchetti, Maria Giovanna Sabbieti
IFN-γ is a pleotropic cytokine produced in the bone microenvironment. Although IFN-γ is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN-γ recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN-γ encoding plasmid (pIFN-γ) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis...
December 1, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27905259/regenerative-pharmacology-recent-developments-and-future-perspectives
#11
James Koudy Williams, Karl-Erik Andersson
This review focuses on the current status of research that utilizes the application of pharmacological sciences to accelerate, optimize and characterize the development, maturation and function of bioengineered and regenerating tissues. These regenerative pharmacologic approaches have been applied to diseases of the urogenital tract, the heart, the brain, the musculoskeletal system and diabetes. Approaches have included the use of growth factors (such as VEGF and chemokines (stromal-derived factor - CXCL12) to mobilize cell to the sights of tissue loss or damage...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#12
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#13
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27894110/significant-role-s-of-cxcl12-and-the-sdf-1-3-a-genetic-variant-in-the-pathogenesis-of-multiple-sclerosis
#14
Mojgan Noroozi Karimabad, Soudeh Khanamani Falahati-Pour, Gholamhossein Hassanshahi
Both cellular and molecular components of the immune system are among the substantial factors involved in the pathogenesis of multiple sclerosis (MS). Accumulating evidence confirms that chemokines, as the main members of the immune system, play key roles in the regulation of immune responses. Immune system genetic parameters are believed to influence the onset of immune system-related diseases. Regarding the significant role of the CXCR4/CXCL12 axis in cell differentiation and survival and homing of hematopoietic progenitors to the bone marrow and regulation of neuronal progenitor cell migration in the central nervous system (CNS), genetic factors can cause an increased expression of CXCL12 and induce a vigorous immune response against CNS antigens in MS patients...
November 29, 2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27888760/relationship-between-selected-dna-polymorphisms-and-coronary-artery-disease-complications
#15
Marcin Wirtwein, Olle Melander, Marketa Sjőgren, Michal Hoffmann, Krzysztof Narkiewicz, Marcin Gruchala, Wojciech Sobiczewski
BACKGROUND: Coronary heart disease (CHD) development is complex in origin, with contributions from well-defined lifestyle and not well-determined genetic risk factors. The aim of this study is to report the relationship between certain SNPs and the risk of cardiovascular (CV) complications in patients with CAD confirmed by coronary angiography. METHODS: In the present study, 1345 subjects with CHD were included. The median follow-up period was 8.6years. 19 SNPs were investigated for any association with Major Advanced CV Events (MACE), Acute Coronary Syndromes (ACS) and Revascularizations...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#16
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27886253/cxcr4-cxcl12-axis-counteracts-hematopoietic-stem-cell-exhaustion-through-selective-protection-against-oxidative-stress
#17
Yanyan Zhang, Mallorie Dépond, Liang He, Adlen Foudi, Edward Owusu Kwarteng, Evelyne Lauret, Isabelle Plo, Christophe Desterke, Philippe Dessen, Nobutaka Fujii, Paule Opolon, Olivier Herault, Eric Solary, William Vainchenker, Virginie Joulin, Fawzia Louache, Monika Wittner
Hematopoietic stem cells (HSCs) undergo self-renewal to maintain hematopoietic homeostasis for lifetime, which is regulated by the bone marrow (BM) microenvironment. The chemokine receptor CXCR4 and its ligand CXCL12 are critical factors supporting quiescence and BM retention of HSCs. Here, we report an unknown function of CXCR4/CXCL12 axis in the protection of HSCs against oxidative stress. Disruption of CXCR4 receptor in mice leads to increased endogenous production of reactive oxygen species (ROS), resulting in p38 MAPK activation, increased DNA double-strand breaks and apoptosis leading to marked reduction in HSC repopulating potential...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875312/mutational-analysis-of-atypical-chemokine-receptor-3-ackr3-cxcr7-interaction-with-its-chemokine-ligands-cxcl11-and-cxcl12
#18
Besma Benredjem, Mélanie Girard, David Rhainds, Geneviève St-Onge, Nikolaus Heveker
Atypical chemokine receptors do not mediate chemotaxis or G-protein signalling, but they recruit arrestin. They also efficiently scavenge their chemokine ligands, thereby contributing to gradient maintenance and termination. ACKR3, also known as CXCR7, binds and degrades the constitutive chemokine CXCL12, which also binds the canonical receptor CXCR4, and CXCL11, which also binds CXCR3. Here we report comprehensive mutational analysis of the ACKR3 interaction with its chemokine ligands, using 30 substitution mutants...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27872867/bone-marrow-mesenchymal-stem-cells-enhance-the-differentiation-of-human-switched-memory-b-lymphocytes-into-plasma-cells-in-serum-free-medium
#19
Guillaume Bonnaure, Catherine Gervais-St-Amour, Sonia Néron
The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27872209/depletion-of-neural-crest-derived-cells-leads-to-reduction-in-plasma-noradrenaline-and-alters-b-lymphopoiesis
#20
Naoki Tsunokuma, Toshiyuki Yamane, Chiaki Matsumoto, Motokazu Tsuneto, Kana Isono, Kyoko Imanaka-Yoshida, Hidetoshi Yamazaki
Hematopoietic stem cells and their lymphoid progenitors are supported by the bone marrow (BM) microenvironmental niches composed of various stromal cells and Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells contribute to the development of all the three, their function in BM is not well understood. In this study, NC-derived cells were ablated with diphtheria toxin in double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin receptor with yellow fluorescent protein reporter...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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