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https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#1
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340249/orthodontic-strain-affects-the-hippo-pathway-effector-yap-concomitant-with-proliferation-in-human-periodontal-ligament-fibroblasts
#2
Diana Huelter-Hassler, Pascal Tomakidi, Thorsten Steinberg, Britta A Jung
Objectives: During orthodontic tooth movement (OTM), human periodontal ligament fibroblasts (hPDLFs) sense, and respond to mechanical forces. Since the molecular constituents involved in these processes are not fully elucidated, the objective of the present study was to identify further key molecules of the cellular strain response. Materials and Methods: Primary hPDLFs were strained with a static equiaxial strain of 2.5 per cent for 15 minutes, 1 hour, 6 hours, and 24 hours...
March 17, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28339837/vitamin-d-treatment-attenuates-cardiac-fgf23-fgfr4-signaling-and-hypertrophy-in-uremic-rats
#3
Maren Leifheit-Nestler, Alexander Grabner, Laura Hermann, Beatrice Richter, Karin Schmitz, Dagmar-Christiane Fischer, Christopher Yanucil, Christian Faul, Dieter Haffner
Background.: Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. Methods...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339804/intra-cardiac-and-peripheral-levels-of-biochemical-markers-of-fibrosis-in-patients-undergoing-catheter-ablation-for-atrial-fibrillation
#4
Gordon A Begg, Rashed Karim, Tobias Oesterlein, Lee N Graham, Andrew J Hogarth, Stephen P Page, Christopher B Pepper, Kawal Rhode, Gregory Y H Lip, Arun V Holden, Sven Plein, Muzahir H Tayebjee
Aims: Measurement of circulating biomarkers of fibrosis may have a role in selecting patients and treatment strategy for catheter ablation. Pro-collagen type III N-terminal pro-peptide (PIIINP), C-telopeptide of type I collagen (ICTP), fibroblast growth factor 23 (FGF-23), and galectin 3 (gal-3) have all been suggested as possible biomarkers for this indication, but studies assessing whether peripheral levels reflect intra-cardiac levels are scarce. Methods and results: We studied 93 patients undergoing ablation for paroxysmal atrial fibrillation (AF) (n = 63) or non-paroxysmal AF (n = 30)...
February 27, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339537/stimulatory-effects-of-fibroblast-growth-factor-2-on-proliferation-and-migration-of-uterine-luminal-epithelial-cells-during-early-pregnancy%C3%A2-%C3%A2
#5
Whasun Lim, Hyocheol Bae, Fuller W Bazer, Gwonhwa Song
Fibroblast growth factor 2 (FGF2) is a mitogen that induces proliferation, differentiation, and migration of cells, as well as angiogenesis and carcinogenesis via autocrine or paracrine actions. Fibroblast growth factor 2 expression is abundant in porcine conceptuses and endometrium during the estrous cycle and peri-implantation period of pregnancy. However, its intracellular actions in uterine epithelial cells have not been reported. The results of this study indicated abundant expression of FGFR1 and FGFR2 predominantly in uterine luminal and glandular epithelia during early pregnancy and that their expression decreased with increasing parity of the sows...
December 20, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/28339479/mouse-newborn-cells-allow-highly-productive-mouse-cytomegalovirus-replication-constituting-a-novel-convenient-primary-cell-culture-system
#6
Vu Thuy Khanh Le-Trilling, Mirko Trilling
Mammalian cell culture is indispensable for most aspects of current biomedical research. Immortalized cell lines are very convenient, but transforming principles (e.g. oncogenic viruses or their oncogenes) can heavily influence the experimental outcome. Primary cells do not share this apparent disadvantage but are more laborious to generate. Certain viruses (e.g. mouse cytomegalovirus) do not replicate efficiently in most transformed cell lines. In the past, such viruses have been routinely propagated on primary mouse embryonic fibroblasts (MEF) established around day 17 (d17) of gestation...
2017: PloS One
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#7
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28335342/innovative-self-cleaning-and-biocompatible-polyester-textiles-nano-decorated-with-fe-n-doped-titanium-dioxide
#8
Ionela Cristina Nica, Miruna Silvia Stan, Anca Dinischiotu, Marcela Popa, Mariana Carmen Chifiriuc, Veronica Lazar, Gratiela G Pircalabioru, Eugenia Bezirtzoglou, Ovidiu G Iordache, Elena Varzaru, Iuliana Dumitrescu, Marcel Feder, Florin Vasiliu, Ionel Mercioniu, Lucian Diamandescu
The development of innovative technologies to modify natural textiles holds an important impact for medical applications, including the prevention of contamination with microorganisms, particularly in the hospital environment. In our study, Fe and N co-doped TiO₂ nanoparticles have been obtained via the hydrothermal route, at moderate temperature, followed by short thermal annealing at 400 °C. These particles were used to impregnate polyester (PES) materials which have been evaluated for their morphology, photocatalytic performance, antimicrobial activity against bacterial reference strains, and in vitro biocompatibility on human skin fibroblasts...
November 15, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335317/cytotoxicity-of-silver-nanoparticle-and-chitin-nanofiber-sheet-composites-caused-by-oxidative-stress
#9
Jun Kinoda, Masayuki Ishihara, Hidemi Hattori, Shingo Nakamura, Koichi Fukuda, Hidetaka Yokoe
Size-controlled spherical silver nanoparticles (<10 nm) and chitin-nanofiber sheet composites (Ag NPs/CNFS) have previously been reported to have strong antimicrobial activity in vitro. Although Ag NPs/CNFS have strong antimicrobial activity, their cytotoxicity has not been investigated. This study was performed to evaluate the effects of Ag NPs/CNFS on cytotoxicity for fibroblasts in vitro and healing delay of wound repair in vivo, focused on oxidative stress. Cytotoxic activities of Ag NPs/CNFS were investigated using a fibroblast cell proliferation assay, nitric oxide/nitrogen dioxide (NO/NO₂) measurement of the cell lysates in vitro, inhibitory effects of Ag NPs/CNFS on healing-impaired wound repair using diabetic mice in vivo, 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunohistochemical staining of the skin sections, and generation of carbonyl protein in the wound was performed to evaluate cytotoxicity with oxidative stress...
October 20, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335035/a-novel-cisd2-mutation-associated-with-a-classical-wolfram-syndrome-phenotype-alters-ca2-homeostasis-and-er-mitochondria-interactions
#10
Cécile Rouzier, David Moore, Cécile Delorme, Sandra Lacas-Gervais, Samira Ait-El-Mkadem, Konstantina Fragaki, Florence Burté, Valérie Serre, Sylvie Bannwarth, Annabelle Chaussenot, Martin Catala, Patrick Yu-Wai-Man, Véronique Paquis-Flucklinger
Wolfram syndrome (WS) is progressive neurodegenerative disease characterized by early-onset optic atrophy and diabetes mellitus, which can be associated with more extensive central nervous system and endocrine complications. The majority of patients harbour pathogenic WFS1 mutations, but recessive mutations in a second gene, CISD2, have been described in a small number of families with Wolfram syndrome type 2 (WFS2). The defining diagnostic criteria for WFS2 also consist of optic atrophy and diabetes mellitus, but unlike WFS1, this phenotypic subgroup has been associated with peptic ulcer disease and an increased bleeding tendency...
March 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334913/tdp-43-mutations-causing-amyotrophic-lateral-sclerosis-are-associated-with-altered-expression-of-rna-binding-protein-hnrnp-k-and-affect-the-nrf2-antioxidant-pathway
#11
Diane Moujalled, Alexandra Grubman, Karla Acevedo, Shu Yang, Yazi D Ke, Donia M Moujalled, Clare Duncan, Aphrodite Caragounis, Nirma D Perera, Bradley J Turner, Mercedes Prudencio, Leonard Petrucelli, Ian Blair, Lars M Ittner, Peter J Crouch, Jeffrey R Liddell, Anthony R White
TAR DNA binding protein 43 (TDP-43) is a major disease-associated protein involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous studies found a direct association between TDP-43 and heterogeneous nuclear ribonucleoprotein K (hnRNP K). In this study, utilizing ALS patient fibroblasts harboring a TDP-43M337V mutation and NSC-34 motor neuronal cell line expressing TDP-43Q331K mutation, we show that hnRNP K expression is impaired in urea soluble extracts from mutant TDP-43 cell models...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334876/pdgfrb-gain-of-function-mutations-in-sporadic-infantile-myofibromatosis
#12
Florence A Arts, Raf Sciot, Bénédicte Brichard, Marleen Renard, Audrey de Rocca Serra, Guillaume Dachy, Laura A Noël, Amélie I Velghe, Christine Galant, Maria Debiec-Rychter, An Van Damme, Miikka Vikkula, Raphaël Helaers, Nisha Limaye, Hélène A Poirel, Jean-Baptiste Demoulin
Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334866/c9orf72-and-rab7l1-regulate-vesicle-trafficking-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#13
Yoshitsugu Aoki, Raquel Manzano, Yi Lee, Ruxandra Dafinca, Misako Aoki, Andrew G L Douglas, Miguel A Varela, Chaitra Sathyaprakash, Jakub Scaber, Paola Barbagallo, Pieter Vader, Imre Mäger, Kariem Ezzat, Martin R Turner, Naoki Ito, Samanta Gasco, Norihiko Ohbayashi, Samir El Andaloussi, Shin'ichi Takeda, Mitsunori Fukuda, Kevin Talbot, Matthew J A Wood
A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#14
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334779/targeted-gene-knock-in-by-homology-directed-genome-editing-using-cas9-ribonucleoprotein-and-aav-donor-delivery
#15
Thomas Gaj, Brett T Staahl, Gonçalo M C Rodrigues, Prajit Limsirichai, Freja K Ekman, Jennifer A Doudna, David V Schaffer
Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#16
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333992/improved-epidermal-barrier-formation-in-human-skin-models-by-chitosan-modulated-dermal-matrices
#17
Arnout Mieremet, Marion Rietveld, Samira Absalah, Jeroen van Smeden, Joke A Bouwstra, Abdoelwaheb El Ghalbzouri
Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan...
2017: PloS One
https://www.readbyqxmd.com/read/28333962/different-regulation-of-limb-development-by-p63-transcript-variants
#18
Manabu Kawata, Yuki Taniguchi, Daisuke Mori, Fumiko Yano, Shinsuke Ohba, Ung-Il Chung, Tomomi Shimogori, Alea A Mills, Sakae Tanaka, Taku Saito
The apical ectodermal ridge (AER), located at the distal end of each limb bud, is a key signaling center which controls outgrowth and patterning of the proximal-distal axis of the limb through secretion of various molecules. Fibroblast growth factors (FGFs), particularly Fgf8 and Fgf4, are representative molecules produced by AER cells, and essential to maintain the AER and cell proliferation in the underlying mesenchyme, meanwhile Jag2-Notch pathway negatively regulates the AER and limb development. p63, a transcription factor of the p53 family, is expressed in the AER and indispensable for limb formation...
2017: PloS One
https://www.readbyqxmd.com/read/28332752/bovine-trophectoderm-cells-induced-from-bovine-fibroblasts-with-induced-pluripotent-stem-cell-reprogramming-factors
#19
Neil C Talbot, Wendy O Sparks, Caitlin Phillips, Alan D Ealy, Anne M Powell, Thomas J Caperna, Wesley M Garrett, David M Donovan, Le Ann Blomberg
Thirteen independent induced bovine trophectroderm (iBT) cell lines were established by reprogramming bovine fetal liver-derived fibroblasts after viral-vector transduction with either 6 or 8 factors, including POU5F1 (OCT4), KLF4, SOX2, MYC, NANOG, LIN28, SV40 large T antigen, and hTERT.. Light- and electron-microscopy analysis showed that the iBT cells had epithelial cell morphology typical of bovine trophectoderm cells. Reverse-transcription-PCR assays indicated that all of the cell lines expressed interferon-tau (IFNT) at passages 1 or 2...
March 23, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#20
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
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