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https://www.readbyqxmd.com/read/29679546/lithium-chloride-licl-induced-autophagy-and-downregulated-expression-of-transforming-growth-factor-%C3%AE-induced-protein-tgfbi-in-granular-corneal-dystrophy
#1
Danyao Nie, Yun Peng, Ming Li, Xinhua Liu, Meilan Zhu, Lin Ye
This study evaluated whether lithium chloride (LiCl) prevents cytoplasmic accumulation of mutant-transforming growth factor β-induced protein (Mut-TGFBI) in granular corneal dystrophy (GCD) via activation of the autophagy pathway. Levels of TGFBI and microtubule-associated protein 1A/1B-light chain 3 (LC3) in 3 GCD patients and healthy controls were analyzed by immunohistochemistry (IHC) staining and Western blot. Primary corneal fibroblasts were isolated and transfected with wild type or mutant type TGFBI over-expressed vectors, and then treated with LiCl and/or autophagy inhibitor 3-methyladenine (3-MA)...
April 18, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29678906/rnai-screening-identifies-a-mechanosensitive-rock-jak2-stat3-network-central-to-myofibroblast-activation
#2
Raymond S Oh, Andrew J Haak, Karry M J Smith, Giovanni Ligresti, Kyoung Moo Choi, Tiao Xie, Shaohua Wang, Paula R Walters, Michael A Thompson, Michelle R Freeman, Logan J Manlove, Vivian M Chu, Carol Feghali-Bostwick, Anja C Roden, Jürgen Schymeinsky, Christina M Pabelick, Y S Prakash, Robert Vassallo, Daniel J Tschumperlin
Myofibroblasts play key roles in wound healing and pathologic fibrosis. Here we undertook an RNAi screen to characterize myofibroblast regulatory genes, using a high-content imaging approach to quantify alpha-smooth muscle actin stress fibers in cultured human fibroblasts. Screen hits were validated on physiological compliance hydrogels, and selected hits tested in primary fibroblasts from patients with idiopathic pulmonary fibrosis. Our RNAi screen led to the identification of STAT3 as an essential mediator of myofibroblast activation and function...
April 20, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29674751/characterization-of-the-most-frequent-atp7b-mutation-causing-wilson-disease-in-hepatocytes-from-patient-induced-pluripotent-stem-cells
#3
Silvia Parisi, Elena V Polishchuk, Simona Allocca, Michela Ciano, Anna Musto, Maria Gallo, Lucia Perone, Giusy Ranucci, Raffaele Iorio, Roman S Polishchuk, Stefano Bonatti
H1069Q substitution represents the most frequent mutation of the copper transporter ATP7B causing Wilson disease in Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes but moves in response to copper overload to the endo-lysosomal compartment to support copper excretion via bile canaliculi. In heterologous or hepatoma-derived cell lines, overexpressed ATP7B-H1069Q is strongly retained in the ER and fails to move to the post-Golgi sites, resulting in toxic copper accumulation. However, this pathogenic mechanism has never been tested in patients' hepatocytes, while animal models recapitulating this form of WD are still lacking...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29673841/electrospun-silk-fibroin-fibers-for-storage-and-controlled-release-of-human-platelet-lysate
#4
Cataldo Pignatelli, Giovanni Perotto, Marta Nardini, Ranieri Cancedda, Maddalena Mastrogiacomo, Athanassia Athanassiou
Human platelet lysate (hPL) is a pool of growth factors and cytokines able to induce regeneration of different tissues. Despite its good potentiality as therapeutic tool for regenerative medicine applications, hPL has been only moderately exploited in this field. A more widespread adoption has been limited because of its rapid degradation at room temperature that decreases its functionality. Another limiting factor for its extensive use is the difficulty of handling the hPL gels. In this work, silk fibroin-based patches were developed to address several points: improving the handling of hPL, enabling their delivery in a controlled manner and facilitating their storage by creating a device ready to use with expanded shelf life...
April 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29673351/fk506-binding-protein-10-fkbp10-regulates-lung-fibroblast-migration-via-collagen-vi-synthesis
#5
Larissa Knüppel, Katharina Heinzelmann, Michael Lindner, Rudolf Hatz, Jürgen Behr, Oliver Eickelberg, Claudia A Staab-Weijnitz
BACKGROUND: In idiopathic pulmonary fibrosis (IPF), fibroblasts gain a more migratory phenotype and excessively secrete extracellular matrix (ECM), ultimately leading to alveolar scarring and progressive dyspnea. Here, we analyzed the effects of deficiency of FK506-binding protein 10 (FKBP10), a potential IPF drug target, on primary human lung fibroblast (phLF) adhesion and migration. METHODS: Using siRNA, FKBP10 expression was inhibited in phLF in absence or presence of 2ng/ml transforming growth factor-β1 (TGF-β1) and 0...
April 19, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29673279/advanced-development-of-primary-pancreatic-organoid-tumor-models-for-high-throughput-phenotypic-drug-screening
#6
Shurong Hou, Hervé Tiriac, Banu Priya Sridharan, Louis Scampavia, Franck Madoux, Jan Seldin, Glauco R Souza, Donald Watson, David Tuveson, Timothy P Spicer
Traditional high-throughput drug screening in oncology routinely relies on two-dimensional (2D) cell models, which inadequately recapitulate the physiologic context of cancer. Three-dimensional (3D) cell models are thought to better mimic the complexity of in vivo tumors. Numerous methods to culture 3D organoids have been described, but most are nonhomogeneous and expensive, and hence impractical for high-throughput screening (HTS) purposes. Here we describe an HTS-compatible method that enables the consistent production of organoids in standard flat-bottom 384- and 1536-well plates by combining the use of a cell-repellent surface with a bioprinting technology incorporating magnetic force...
April 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29672321/metabolic-plasticity-enables-circadian-adaptation-to-acute-hypoxia-in-zebrafish-cells
#7
Adolf M Sandbichler, Bianca Jansen, Bettina A Peer, Monika Paulitsch, Bernd Pelster, Margit Egg
BACKGROUND/AIMS: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. METHODS: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts...
April 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29672221/glucocorticoid-receptor-isoform-specific-regulation-of-development-circadian-rhythm-and-inflammation-in-mice
#8
Robert H Oakley, Sivapriya Ramamoorthy, Julie F Foley, Jonathan T Busada, Nick Z Lu, John A Cidlowski
Glucocorticoids are primary stress hormones, and their synthetic derivatives are widely used clinically. The therapeutic efficacy of these steroids is limited by side effects and glucocorticoid resistance. Multiple glucocorticoid receptor (GR) isoforms are produced from a single gene by alternative translation initiation; however, the role individual isoforms play in tissue-specific responses to glucocorticoids is unknown. We have generated knockin mice that exclusively express the most active receptor isoform, GR-C3...
April 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29672023/chitosan-based-peptidopolysaccharides-as-cationic-antimicrobial-agents-and-antibacterial-coatings
#9
Dicky Pranantyo, Li Qun Xu, En-Tang Kang, Mary B Chan-Park
The rapid spread of multidrug resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide 'click' conjugation, utilizing the maleimidohexanoic linkers...
April 19, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29670467/trail-dependent-resolution-of-pulmonary-fibrosis
#10
David M Habiel, Ana Paula Moreira, Ugur B Ismailoglu, Michael P Dunleavy, Karen A Cavassani, Nico van Rooijen, Ana Lucia Coelho, Cory M Hogaboam
Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+ TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29669938/canagliflozin-triggers-the-fgf23-1-25-dihydroxyvitamin-d-pth-axis-in-healthy-volunteers-in-a-randomized-crossover-study
#11
Jenny E Blau, Viviana Bauman, Ellen M Conway, Paolo Piaggi, Mary F Walter, Elizabeth C Wright, Shanna Bernstein, Amber B Courville, Michael T Collins, Kristina I Rother, Simeon I Taylor
BACKGROUND: Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29668038/photodynamic-therapy-induces-antifibrotic-alterations-in-primary-human-vocal-fold-fibroblasts
#12
Chi Zhang, Jiajia Wang, Adriana Chou, Ting Gong, Erin E Devine, Jack J Jiang
OBJECTIVES/HYPOTHESIS: Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. STUDY DESIGN: In vitro analysis from one human donor. METHODS: Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method...
April 18, 2018: Laryngoscope
https://www.readbyqxmd.com/read/29665018/differential-response-of-human-dermal-fibroblast-subpopulations-to-visible-and-near-infrared-light-potential-of-photobiomodulation-for-addressing-cutaneous-conditions
#13
Charles Mignon, Natallia E Uzunbajakava, Irene Castellano-Pellicena, Natalia V Botchkareva, Desmond J Tobin
BACKGROUND OBJECTIVES: The past decade has witnessed a rapid expansion of photobiomodulation (PBM), demonstrating encouraging results for the treatment of cutaneous disorders. Confidence in this approach, however, is impaired not only by a lack of understanding of the light-triggered molecular cascades but also by the significant inconsistency in published experimental outcomes, design of the studies and applied optical parameters. This study aimed at characterizing the response of human dermal fibroblast subpopulations to visible and near-infrared (NIR) light in an attempt to identify the optical treatment parameters with high potential to address deficits in aging skin and non-healing chronic wounds...
April 17, 2018: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29663541/eccentric-exercise-increases-circulating-fibroblast-activation-protein-but-not-bioactive-fibroblast-growth-factor-21-in-healthy-humans
#14
Biraj Parmar, Jo E Lewis, Ricardo J Samms, Francis J P Ebling, Christine C Cheng, Andrew C Adams, Joanne Mallinson, Scott Cooper, Tariq Taylor, Reza Ghasemi, Francis B Stephens, Kostas Tsintzas
NEW FINDINGS: What is the central question of this study? The role of FGF21 as an exercise-induced myokine remains controversial. The aim of this study was to determine whether eccentric exercise would augment the release of FGF21 and/or its regulatory enzyme Fibroblast Activation Protein (FAP) from skeletal muscle tissue into the systemic circulation of healthy human volunteers. What is the main finding and its importance? Eccentric exercise does not release total or bioactive FGF21 from human skeletal muscle...
April 16, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29663481/the-ampk-v-atpase-ph-axis-a-key-regulator-of-the-pro-fibrogenic-phenotype-of-human-hepatic-stellate-cells
#15
Giusi Marrone, Francesco De Chiara, Katrin Böttcher, Ana Levi, Dipok Dhar, Lisa Longato, Giuseppe Mazza, Zhenzhen Zhang, Martina Marrali, Anabel Fernández- Iglesias, Andrew Hall, Tu Vinh Luong, Benoit Viollet, Massimo Pinzani, Krista Rombouts
Liver fibrosis and cirrhosis are characterized by activation of hepatic stellate cells (HSC) which is associated with higher intracellular pH (pHi). The vacuolar H+ adenosine-tri-phosphatase (v-ATPase) multi-subunit complex is a key regulator of intracellular pH homeostasis. The present work was aimed at investigating the functional role of v-ATPase in primary human HSC (hHSC) activation and its modulation by specific AMPK subunits. Here, we demonstrated that the expression of different v-ATPase subunits was increased in in vivo and in vitro activated hHSC, compared to non-activated hHSC...
April 17, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29661188/molecular-and-clinical-analyses-of-helicobacter-pylori-colonization-in-inflamed-dental-pulp
#16
Ryota Nomura, Yuko Ogaya, Saaya Matayoshi, Yumiko Morita, Kazuhiko Nakano
BACKGROUND: Recently, dental pulp has been considered a possible source of infection of Helicobacter pylori (H. pylori) in children. We previously developed a novel PCR system for H. pylori detection with high specificity and sensitivity using primer sets constructed based on the complete genome information for 48 H. pylori strains. This PCR system showed high sensitivity with a detection limit of 1-10 cells when serial dilutions of H. pylori genomic DNA were used as templates. However, the detection limit was lower (102 -103 cells) when H...
April 16, 2018: BMC Oral Health
https://www.readbyqxmd.com/read/29659691/perspective-cardiovascular-responses-to-sugar-sweetened-beverages-in-humans-a-narrative-review-with-potential-hemodynamic-mechanisms
#17
Cathriona R Monnard, Erik Konrad Grasser
Cardiovascular diseases are still the primary cause of mortality worldwide, with high blood pressure and type 2 diabetes as major promoters. Over the past 3 decades, almost in parallel with the rise in cardiovascular disease incidence, the consumption of sugar-sweetened beverages (SSBs) has increased. In this context, SSBs are potential contributors to weight gain and increase the risk for elevations in blood pressure, type 2 diabetes, coronary heart disease, and stroke. Nevertheless, the mechanisms underlying the cardiovascular and metabolic responses to SSBs, in particular on blood pressure, are poorly understood...
March 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29658916/microdissection-of-primary-renal-tissue-segments-and-incorporation-with-novel-scaffold-free-construct-technology
#18
Chase A Arbra, Satish N Nadig, Sarah Grace Dennis, Sanket Pattanaik, Heather A Bainbridge, J Matthew Rhett, Stephen A Fann, Carl Atkinson, Michael J Yost
Kidney transplantation is now a mainstream therapy for end-stage renal disease. However, with approximately 96,000 people on the waiting list and only one-fourth of these patients achieving transplantation, there is a dire need for alternatives for those with failing organs. In order to decrease the harmful consequences of dialysis along with the overall healthcare costs it incurs, active investigation is ongoing in search of alternative solutions to organ transplantation. Implantable tissue-engineered renal cellular constructs are one such feasible approach to replacing lost renal functionality...
March 27, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29655920/suppressing-ku70-ku80-expression-elevates-homology-directed-repair-efficiency-in-primary-fibroblasts
#19
Guoling Li, Dewu Liu, Xianwei Zhang, Rong Quan, Cuili Zhong, Jianxin Mo, Yaoqiang Huang, Haoqiang Wang, Xiaofang Ruan, Zheng Xu, Enqin Zheng, Ting Gu, Linjun Hong, Zicong Li, Zhenfang Wu, Huaqiang Yang
The main DNA repair pathways, nonhomologous end joining (NHEJ) and homology-directed repair (HDR), are complementary to each other; hence, interruptions of the NHEJ pathway can favor HDR. Improving HDR efficiency in animal primary fibroblasts can facilitate the generation of gene knock-in animals with agricultural and biomedical values by somatic cell nuclear transfer. In this study, we used siRNA to suppress the expression of Ku70 and Ku80, which are the key factors in NHEJ pathway, to investigate the effect of Ku silencing on the HDR efficiency in pig fetal fibroblasts...
April 12, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29653105/cst3-and-gdf15-ameliorate-renal-fibrosis-by-inhibiting-fibroblast-growth-and-activation
#20
Young-Im Kim, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
The final strategies to care patients with end-stage renal fibrosis rely on dialysis and kidney transplantation. Because such treatments are invasive and cause health problems eventually, it is necessary to develop new therapeutic strategies for delaying the disease progress. We here searched for cytokines showing an anti-fibrotic activity in cell-based experiments. Cystatin C (CST3) and Growth differentiation factor 15 (GDF15) were identified to have anti-fibrotic activities in a cytokine array screening. In primary fibroblasts isolated from the mouse kidneys subjected to ureteral obstruction-induced fibrosis, each cytokine induced apoptotic cell death and reduced collagen production...
April 13, 2018: Biochemical and Biophysical Research Communications
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