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https://www.readbyqxmd.com/read/29329953/canine-macrophages-can-like-human-macrophages-be-in-vitro-activated-toward-the-m2a-subtype-relevant-in-allergy
#1
Ina Herrmann, Jelena Gotovina, Judit Fazekas-Singer, Michael B Fischer, Karin Hufnagl, Rodolfo Bianchini, Erika Jensen-Jarolim
The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in-vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side-by-side comparison, we compared the canine cells to human MDMs, and the human monocytic cell line U937 activated towards M1-and M2a cells on the cellular and molecular level...
January 9, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29329878/course-dose-and-stage-dependent-toxic-effects-of-prenatal-dexamethasone-exposure-on-fetal-articular-cartilage-development
#2
Ze Chen, Zhe Zhao, Yunzepeng Li, Xingyu Zhang, Bin Li, Liaobin Chen, Hui Wang
Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development...
January 9, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29326173/transcriptional-regulator-zeb2-is-essential-for-bergmann-glia-development
#3
Li He, Kun Yu, Fanghui Lu, Jiajia Wang, Laiman N Wu, Chuntao Zhao, Qianmei Li, Xianyao Zhou, Hanmin Liu, Dezhi Mu, Mei Xin, Mengsheng Qiu, Q Richard Lu
Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson-syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical lamination dysgenesis and locomotion defects...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29321644/cox-2-induces-oncogenic-micro-rna-mir655-in-human-breast-cancer
#4
Mousumi Majumder, Leanna Dunn, Ling Liu, Asma Hasan, Krista Vincent, Muriel Brackstone, David Hess, Peeyush K Lala
We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA miR655 in human breast cancer cells by activation of EP4. MiR655 expression positively correlated with COX-2 in genetically disparate breast cancer cell lines and increased in all cell lines when grown as spheroids, implicating its link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid formation and Epithelial to Masenchymal transition (EMT)...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320969/differential-expression-of-tgf%C3%AE-isoforms-in-breast-cancer-highlights-different-roles-during-breast-cancer-progression
#5
Mahmood Y Hachim, Ibrahim Y Hachim, Meiou Dai, Suhad Ali, Jean-Jacques Lebrun
While TGFβ plays a critical role in tumor formation and progression, the role and contribution of its three different isoforms remain unclear. In this study, we aimed at elucidating the prognostic value of the TGFβ isoforms and assessed their expression levels in breast cancer patients at different stages of the disease. We found higher levels of TGFβ1 and TGFβ3 in cancer patients compared to normal tissues, with no significant changes in TGFβ2 expression. Similarly, TGFβ1 and TGFβ3, but not TGFβ2, showed higher expression levels in advanced lymph node-positive and metastatic tumors, suggesting different roles for the different isoforms in tumor progression and the metastatic process, while in the least aggressive molecular subtype (luminal A), expression of the three TGFβ isoforms significantly correlated with expression of both TGFβ receptors, such correlation only occurred between TGFβ1 and TGFβ3 and the TGFβ type II receptor (TβRII) in the highly aggressive basal-like subtype...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29318884/inhibition-of-epithelial-mesenchymal-transition-and-tissue-regeneration-by-waterborne-titanium-dioxide-nanoparticles
#6
Xiaojiao Li, Lele Song, Xingjie Hu, Chang Liu, Jiye Shi, Hui Wang, Lixing Zhan, Haiyun Song
Titanium dioxide nanoparticles (TiO2NPs) are among the most widely manufactured nanomaterials with broad applications in food industry, cosmetics and medicine. Whereas the toxicity of TiO2NPs at high doses has been extensively explored, potential health risks of TiO2NPs exposure at non-toxic concentrations remain poorly understood. Epithelial-mesenchymal transition (EMT) plays pivotal roles in a diversity of physiological and pathological processes including tissue regeneration and cancer metastasis. In this study, we find that cellular uptake of TiO2NPs inhibits EMT-mediated cell remodeling and cell migration without exhibiting cytotoxicity...
January 10, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29317486/mutual-dependence-of-the-mrtf-srf-and-yap-tead-pathways-in-cancer-associated-fibroblasts-is-indirect-and-mediated-by-cytoskeletal-dynamics
#7
Charles T Foster, Francesco Gualdrini, Richard Treisman
Both the MRTF-SRF and the YAP-TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF-SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF-SRF and YAP-TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF-SRF genomic targets is also dependent on YAP-TEAD activity, and, conversely, YAP-TEAD target gene expression is also dependent on MRTF-SRF signaling...
January 9, 2018: Genes & Development
https://www.readbyqxmd.com/read/29311148/protein-kinases-g-are-essential-downstream-mediators-of-the-antifibrotic-effects-of-sgc-stimulators
#8
Alexandru-Emil Matei, Christian Beyer, Andrea-Hermina Györfi, Alina Soare, Chih-Wei Chen, Clara Dees, Christina Bergmann, Andreas Ramming, Andreas Friebe, Franz Hofmann, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Stimulators of soluble guanylate cyclase (sGC) are currently investigated in clinical trials for the treatment of fibrosis in systemic sclerosis (SSc). In this study, we aim to investigate the role of protein kinases G (PKG) as downstream mediators of sGC-cyclic guanosine monophosphate (cGMP) in SSc. METHODS: Mice with combined knockout of PKG1 and 2 were challenged with bleomycin and treated with the sGC stimulator BAY 41-2272. Fibroblasts were treated with BAY 41-2272 and with the PKG inhibitor KT 5823...
January 8, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29302747/cytokine-chemokine-and-bdnf-levels-in-medication-free-pediatric-patients-with-obsessive-compulsive-disorder
#9
Rukiye Çolak Sivri, Ayhan Bilgiç, İbrahim Kılınç
The aim of this study was to investigate whether the serum levels of IL-12, IL-17, TGFβ, TNF-alpha, sTNFR1, sTNFR2, IL-1β, CCL3, CCL24, CXCL8, and BDNF are associated with obsessive-compulsive disorder (OCD) in medication-free children. A total of 44 (22 boys/22 girls) medication-free children with OCD and 40 (23 boys/17 girls) healthy controls were included in this study. The severity of the OCD symptoms were assessed by the Children's Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory...
January 4, 2018: European Child & Adolescent Psychiatry
https://www.readbyqxmd.com/read/29299138/new-role-of-id3-in-melanoma-adaptive-drug-resistance
#10
Sachindra, Lionel Larribère, Daniel Novak, Huizi Wu, Laura Hüser, Karol Granados, Elias Orouji, Jochen Utikal
Adaptive resistance to targeted therapy such as BRAF inhibitors represents in melanoma a major drawback to this otherwise powerful treatment. Some of the underlying molecular mechanisms have recently been described: hyperactivation of the BRAF-MAPK pathway, of the AKT pathway, of the TGFβ/EGFR/PDGFRB pathway, or the low MITF/AXL ratio. Nevertheless, the phenomenon of early resistance is still not clearly understood. In this report, we show that knockdown of neural crest-associated gene ID3 increases the melanoma sensitivity to vemurafenib short-term treatment...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298864/targeting-extracellular-matrix-stiffness-to-attenuate-disease-from-molecular-mechanisms-to-clinical-trials
#11
REVIEW
Marsha C Lampi, Cynthia A Reinhart-King
Tissues stiffen during aging and during the pathological progression of cancer, fibrosis, and cardiovascular disease. Extracellular matrix stiffness is emerging as a prominent mechanical cue that precedes disease and drives its progression by altering cellular behaviors. Targeting extracellular matrix mechanics, by preventing or reversing tissue stiffening or interrupting the cellular response, is a therapeutic approach with clinical potential. Major drivers of changes to the mechanical properties of the extracellular matrix include phenotypically converted myofibroblasts, transforming growth factor β (TGFβ), and matrix cross-linking...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29297981/primary-biliary-cholangitis-in-british-columbia-first-nations-clinical-features-and-discovery-of-novel-genetic-susceptibility-loci
#12
Sirisha Asuri, Sarah McIntosh, Valerie Taylor, Andrew Rokeby, James Kelly, Karey Shumansky, L Leigh Field, Eric M Yoshida, Laura Arbour
BACKGROUND AND AIMS: Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by destruction of intrahepatic bile ducts, portal inflammation, and cirrhosis. Although rare in most populations, it is prevalent and often familial in British Columbia First Nations. We hypothesized that major genetic factors increased the risk in First Nations. METHODS: 44 individuals with PBC and 61 unaffected relatives from 32 First Nations families participated...
January 3, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29297621/amnion-epithelial-cell-derived-exosomes-restrict-lung-injury-and-enhance-endogenous-lung-repair
#13
Jean L Tan, Sin N Lau, Bryan Leaw, Hong P T Nguyen, Lois A Salamonsen, Mohamed I Saad, Siow T Chan, Dandan Zhu, Mirja Krause, Carla Kim, William Sievert, Euan M Wallace, Rebecca Lim
Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo...
January 3, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29287776/activin-a-causes-hepatic-stellate-cell-activation-via-the-induction-of-tnf%C3%AE-%C3%AE%C2%BA%C3%AE-%C3%AE-tgf%C3%AE-in-kupffer-cells
#14
Foteini Kiagiadaki, Marilena Kampa, Argyro Voumvouraki, Elias Castanas, Elias Kouroumalis, George Notas
Background&Aims. TGFβ superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells., where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased...
December 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29286439/isolation-and-characterization-of-primary-rat-valve-interstitial-cells-a-new-model-to-study-aortic-valve-calcification
#15
Cui Lin, Dongxing Zhu, Greg Markby, Brendan M Corcoran, Colin Farquharson, Vicky E Macrae
Calcific aortic valve disease (CAVD) is characterized by the progressive thickening of the aortic valve leaflets. It is a condition frequently found in the elderly and end-stage renal disease (ESRD) patients, who commonly suffer from hyperphosphatemia and hypercalcemia. At present, there are no medication therapies that can stop its progression. The mechanisms that underlie this pathological process remain unclear. The aortic valve leaflet is composed of a thin layer of valve endothelial cells (VECs) on the outer surfaces of the aortic cusps, with valve interstitial cells (VICs) sandwiched between the VECs...
November 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285138/curcumin-modulates-covalent-histone-modification-and-timp1-gene-activation-to-protect-against-vascular-injury-in-a-hypertension-rat-model
#16
Jun Hu, Tingting Shen, Jun Xie, Siyang Wang, Yue He, Fu Zhu
Hypertension is a leading risk factor for morbidity and mortality. Previous studies have reported that curcumin has anti-oxidation and anti-aging effects and inhibits histone deacetylase activity. However, it is still unclear whether curcumin could protect against vascular injury induced by hypertension. Thus, the current study examined the therapeutic effects and mechanism of curcumin on vascular injury induced by hypertension in spontaneous hypertensive rats (SHRs). The present study revealed that curcumin may improve vascular structure and attenuate coronary artery pathology...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282520/tgf%C3%AE-counteracts-lyve-1-mediated-induction-of-lymphangiogenesis-by-small-hyaluronan-oligosaccharides
#17
Jochen Bauer, Melanie Rothley, Anja Schmaus, Luca Quagliata, Markus Ehret, Moritz Biskup, Véronique Orian-Rousseau, David G Jackson, Ronald J Pettis, Alfred Harvey, Stefan Bräse, Wilko Thiele, Jonathan P Sleeman
During tissue injury, inflammation, and tumor growth, enhanced production and degradation of the extracellular matrix glycosaminoglycan hyaluronan (HA) can lead to the accumulation of small HA (sHA) oligosaccharides. We have previously reported that accumulation of sHA in colorectal tumors correlates with lymphatic invasion and lymph node metastasis, and therefore, investigated here are the effects of sHA on the lymphatic endothelium. Using cultured primary lymphatic endothelial cells (LECs) and ex vivo and in vivo lymphangiogenesis assays, we found that in contrast to high-molecular-weight HA (HMW-HA), sHA of 4-25 disaccharides in length can promote the proliferation of LECs and lymphangiogenesis in a manner that is dependent on their size and concentration...
December 27, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29281894/adeno-associated-virus-2-aav2-mediated-reintroduction-of-microrna-19b-attenuates-hepatic-fibrosis
#18
Elizabeth Brandon-Warner, Jennifer H Benbow, Jacob H Swet, Nicole A Feilen, Catherine R Culberson, Iain H McKillop, Andrew S deLemos, Mark W Russo, Laura W Schrum
Fibrotic liver injury is a significant healthcare burden in the United States that represents a major cause of morbidity and mortality for which there are no effective FDA approved treatment strategies. Fibrosis is considered a disruption of normal wound healing responses mediated by fibroblastic cells which are triggered and sustained by pro-fibrotic cytokines such as transforming growth factor-beta1 (TGFβ1). TGFβ1-mediated transdifferentiation of hepatic stellate cells (HSCs) from quiescent to activated myofibroblast is a pivotal event in the development of fibrosis...
December 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29281682/overexpression-of-map3k7-activates-sinoatrial-node-like-differentiation-in-mouse-es-derived-cardiomyocytes
#19
Kemar Brown, Stephanie Legros, Francis A Ortega, Yunkai Dai, Michael Xavier Doss, David J Christini, Richard B Robinson, Ann C Foley
In vivo, cardiomyocytes comprise a heterogeneous population of contractile cells defined by unique electrophysiologies, molecular markers and morphologies. The mechanisms directing myocardial cells to specific sub-lineages remain poorly understood. Here we report that overexpression of TGFβ-Activated Kinase (TAK1/Map3k7) in mouse embryonic stem (ES) cells faithfully directs myocardial differentiation of embryoid body (EB)-derived cardiac cells toward the sinoatrial node (SAN) lineage. Most cardiac cells in Map3k7-overexpressing EBs adopt markers, cellular morphologies, and electrophysiological behaviors characteristic of the SAN...
2017: PloS One
https://www.readbyqxmd.com/read/29275310/mmp7-modulation-by-short-and-long-term-radiotherapy-in-patients-with-rectal-cancer
#20
Christina Stene, Andrea Polistena, Alexander Gaber, Björn Nodin, Bianca Ottochian, Diya Adawi, Nicola Avenia, Karin Jirström, Louis Banka Johnson
BACKGROUND/AIM: Matrix metalloproteinase 7 (MMP7) expression is highly associated with colorectal cancer and modulates tumour growth and invasion. Radiation injury induces inflammation with increases in MMP7 and in transforming growth factor beta (TGFβ). The aim of this study was to investigate the effect on MMP7 and TGFβ. expression in patients with rectal cancer undergoing different regimens of neoadjuvant radiotherapy (RT). PATIENTS AND METHODS: We studied 53 patients in three RT treatment groups receiving RT of 25 Gy, long-term RT 50 Gy and controls receiving no RT...
January 2018: In Vivo
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