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https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#1
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28079986/establishment-of-an-in-vitro-3-d-model-for-cartilage-damage-in-rheumatoid-arthritis-ra
#2
Yvonne Peck, Li Ting Leom, Pei Fen Patricia Low, Dong-An Wang
Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint destruction. To further understand the process of rheumatoid cartilage damage, an in vitro model consisting of an interactive tri-culture of synovial fibroblasts (SFs), LPS-stimulated macrophages and a primary chondrocyte-based tissue engineered construct was established. The tissue engineered construct has a similar composition to human cartilage, which are rich in collagen type II and proteoglycans. Data generated from this model revealed that healthy chondrocytes were activated in the presence of SFs and macrophages...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28079506/response-of-human-rheumatoid-arthritis-osteoblasts-and-osteoclasts-to-adiponectin
#3
Grit Krumbholz, Susann Junker, Florian M P Meier, Markus Rickert, Jürgen Steinmeyer, Stefan Rehart, Uwe Lange, Klaus W Frommer, Georg Schett, Ulf Müller-Ladner, Elena Neumann
OBJECTIVES: Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. METHODS: Adiponectin and its receptors were examined in bone tissue...
January 5, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28078780/in-vitro-anti-tubulin-effects-of-mebendazole-and-fenbendazole-on-canine-glioma-cells
#4
S R Lai, S A Castello, A C Robinson, J W Koehler
Benzimidazole anthelmintics have reported anti-neoplastic effects both in vitro and in vivo. The purpose of this study was to evaluate the in vitro chemosensitivity of three canine glioma cell lines to mebendazole and fenbendazole. The mean inhibitory concentration (IC50 ) (±SD) obtained from performing the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay after treating J3T, G06-A, and SDT-3G cells for 72 h with mebendazole were 0.030 ± 0.003, 0.080 ± 0.015 and 0.030 ± 0...
January 12, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28077620/mitogen-induced-distinct-epi-alleles-are-phosphorylated-at-either-h3s10-or-h3s28-depending-on-h3k27-acetylation
#5
Dilshad H Khan, Shannon Healy, Shihua He, Daniel Lichtensztejn, Ludger Klewes, Kiran L Sharma, Veronica Lau, Sabine Mai, Geneviève P Delcuve, James R Davie
Stimulation of the MAPK pathway results in mitogen- and stress-activated protein kinase 1/2 (MSK1/2)-catalyzed phosphorylation of histone H3 at serine 10 or 28 and expression of immediate-early (IE) genes. In 10T1/2 mouse fibroblasts, phosphorylation of H3S10 and H3S28 occurs on different H3 molecules and in different nuclear regions. Likewise, we show that mitogen-induced H3S10 and H3S28 phosphorylation occurs in separate pools in human primary fibroblasts. High-resolution imaging studies on both cell types have revealed that H3S10 and H3S28 phosphorylation events can be induced in a single cell but on different alleles, giving rise to H3S10ph and H3S28ph epi-alleles...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077619/relative-importance-of-%C3%AE-cyto-and-%C3%AE-cyto-actin-in-primary-mouse-embryonic-fibroblasts
#6
Xiaobai Patrinostro, Allison R O'Rourke, Christopher M Chamberlain, Branden S Moriarity, Benjamin J Perrin, James M Ervasti
The highly homologous beta (βcyto) and gamma (γcyto) cytoplasmic actins are hypothesized to carry out both redundant and unique essential functions, but studies using targeted gene knockout and siRNA mediated transcript knockdown to examine βcyto- and γcyto-isoform specific functions in various cell types have yielded conflicting data. Here, we quantitatively characterized actin transcript and protein levels as well as cellular phenotypes in both gene- and transcript-targeted primary mouse embryonic fibroblasts...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#7
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28077425/metastasis-suppressor-nm23-limits-oxidative-stress-in-mammals-by-preventing-activation-of-stress-activated-protein-kinases-jnks-through-its-nucleoside-diphosphate-kinase-activity
#8
Evelyne Peuchant, Marie-Lise Bats, Isabelle Moranvillier, Michel Lepoivre, Jérôme Guitton, Dominique Wendum, Marie-Lise Lacombe, François Moreau-Gaudry, Mathieu Boissan, Sandrine Dabernat
NME1 (nonmetastatic expressed 1) gene, which encodes nucleoside diphosphate kinase (NDPK) A [also known as nonmetastatic clone 23 (NM23)-H1 in human and NM23-M1 in mouse], is a suppressor of metastasis, but several lines of evidence-mostly from plants-also implicate it in the regulation of the oxidative stress response. Here, our aim was to investigate the physiologic relevance of NDPK A with respect to the oxidative stress response in mammals and to study its molecular basis. NME1 knockout mice died sooner, suffered greater hepatocyte injury, and had lower superoxide dismutase activity than did wild-type (WT) mice in response to paraquat-induced acute oxidative stress...
January 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28076385/the-effect-of-a-novel-c-820c-t-arg274trp-mutation-in-the-mitofusin-2-gene-on-fibroblast-metabolism-and-clinical-manifestation-in-a-patient
#9
Małgorzata Beręsewicz, Anna Boratyńska-Jasińska, Łukasz Charzewski, Maria Kawalec, Dagmara Kabzińska, Andrzej Kochański, Krystiana A Krzyśko, Barbara Zabłocka
Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction...
2017: PloS One
https://www.readbyqxmd.com/read/28074631/transdifferentiation-of-human-dermal-fibroblasts-to-smooth-muscle-like-cells-to-study-the-effect-of-myh11-and-acta2-mutations-in-aortic-aneurysms
#10
Kak K Yeung, Natalija Bogunovic, Niels Keekstra, Adriaan A M Beunders, Jorrit Pals, Kim van der Kuij, Eline Overwater, Willem Wisselink, Jan D Blankensteijn, Victor W M van Hinsbergh, Rene J P Musters, Gerard Pals, Dimitra Micha, Behrouz Zandieh-Doulabi
Mutations in genes encoding proteins of the smooth muscle cell (SMC) contractile apparatus contribute to familial aortic aneurysms. To investigate the pathogenicity of these mutations, SMC are required. We demonstrate a novel method to generate SMC-like cells from human dermal fibroblasts by transdifferentiation to study the effect of variants in genes encoding proteins of the SMC contractile apparatus (ACTA2 and MYH11) in patients with aortic aneurysms. Dermal fibroblasts from 7 healthy donors and cells from 7 patients with MYH11 or ACTA2 variants were transdifferentiated into SMC-like cells within a 2 week duration using 5ng/mL TGFβ1 on a scaffold containing collagen and elastin...
January 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/28073290/intra-and-interorgan-communication-in-the-cardiovascular-system-a-special-view-on-redox-regulation
#11
Axel Gödecke, Judith Haendeler
Intraorgan communication in the cardiovascular system is exerted by direct cell-cell contacts, but also by locally released factors, which modulate neighboring cells by paracrine signals (e.g. NO, vascular endothelial growth factor, adenosine, reactive oxygen species (ROS)). Moreover, cells in close proximity to the typical cardiovascular cells such as fibroblasts, red blood cells, as well as resident and invading immune cells must be considered in attempts to understand cardiovascular function in physiology and pathology...
January 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28070045/-effect-of-calcium-channel-blockers-on-primary-cultured-human-urethra-scar-fibroblasts
#12
Mingqiang Zeng, Junjie Chen, Liang Huang, Ruizhi Xue, Xuyu Xiang, Fanchang Zeng, Guilin Wang, Zhengyan Tang
To investigate effects of verapamil on primary cultured human urethral scar fibroblasts (USFs) and to provide basis for protecting the formation of urethra scar.
 Methods: The cell proliferation was evaluated with the cell counting kit (CCK)-8 method after USFs were incubated various verapamil concentrations (50, 100, 150, 200, or 250 μmol/L) or solvent for 12, 24, or 48 h. The protein level of matrix metalloproteinase (MMP) was evaluated with ELISA after cells were incubated with verapamil (100 μmol/L) or solvent (control cells) for 24 h...
December 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28068976/il-1%C3%AE-induced-modulation-of-gene-expression-profile-in-human-dermal-fibroblasts-the-effects-of-thai-herbal-sahatsatara-formula-piperine-and-gallic-acid-possessing-antioxidant-properties
#13
Onusa Thamsermsang, Pravit Akarasereenont, Tawee Laohapand, Uraiwan Panich
BACKGROUND: Pain is the main symptom of most musculoskeletal disorders and can be caused by inflammation in association with oxidative stress. Thai herbal Sahatsatara formula (STF), a polyherbal formula, has been traditionally used for relieving muscle pain and limb numbness. This study aimed to investigate biologically active compounds of STF and its pharmacological effects related to antioxidant and anti-inflammatory activities. METHODS: The identification of possibly active compounds of STF was performed by high performance liquid chromatography (HPLC)...
January 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28068631/microrna-202-3p-regulates-scleroderma-fibrosis-by-targeting-matrix-metalloproteinase-1
#14
Bin Zhou, Honglin Zhu, Hui Luo, Siming Gao, Xiaodan Dai, Yisha Li, Xiaoxia Zuo
The leading cause of death in systemic sclerosis (SSc) is the uncontrolled fibrosis in multiple organs. The exact mechanism of fibrosis is not fully clear. Our previous studies using miRNA array analysis indicated that miR-202-3p was increased in SSc lesion skin tissues. Bioinformatics analysis suggested matrix metallopeptidase (MMP) 1 is the target gene of miR-202-3p. Here we confirmed that miR-202-3p was upregulated, and the mRNA and protein expression of MMP1 were significantly decreased in SSc skin tissues and primary fibroblast compared with normal skin...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28061443/mhy1485-ameliorates-uv-induced-skin-cell-damages-via-activating-mtor-nrf2-signaling
#15
Bo Yang, Qiu-Yun Xu, Chun-Yan Guo, Jin-Wen Huang, Shu-Mei Wang, Yong-Mei Li, Ying Tu, Li He, Zhi-Gang Bi, Chao Ji, Bo Cheng
Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060543/inhibition-of-the-kca3-1-channel-alleviates-established-pulmonary-fibrosis-in-a-large-animal-model
#16
Louise Organ, Barbara Bacci, Emmanuel Koumoundouros, Wayne G Kimpton, Chrishan S Samuel, Cameron J Nowell, Peter Bradding, Katy M Roach, Glen Westall, Jade Jaffar, Ken J Snibson
Idiopathic pulmonary fibrosis is a chronic progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca2+-activated KCa3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-βand bFGF-dependent profibrotic responses. In the current study, we investigated whether blockade of the KCa3...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28060310/induced-pluripotent-stem-cell-generation-from-blood-cells-using-sendai-virus-and-centrifugation
#17
Yeri Alice Rim, Yoojun Nam, Ji Hyeon Ju
The recent development of human induced pluripotent stem cells (hiPSCs) proved that mature somatic cells can return to an undifferentiated, pluripotent state. Now, reprogramming is done with various types of adult somatic cells: keratinocytes, urine cells, fibroblasts, etc. Early experiments were usually done with dermal fibroblasts. However, this required an invasive surgical procedure to obtain fibroblasts from the patients. Therefore, suspension cells, such as blood and urine cells, were considered ideal for reprogramming because of the convenience of obtaining the primary cells...
December 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059467/muty-dna-glycosylase-protects-cells-from-tumor-necrosis-factor-alpha-induced-necroptosis
#18
An Hue Vy Tran, Se Hee Han, Joon Kim, Francesca Grasso, Ye Sun Han
Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28057872/a-phase-3-multicentre-randomized-double-blind-placebo-controlled-parallel-group-study-to-evaluate-the-efficacy-and-safety-of-etelcalcetide-ono-5163-amg-416-a-novel-intravenous-calcimimetic-for-secondary-hyperparathyroidism-in-japanese-haemodialysis-patients
#19
Masafumi Fukagawa, Keitaro Yokoyama, Takashi Shigematsu, Takashi Akiba, Akifumi Fujii, Takuto Kuramoto, Motoi Odani, Tadao Akizawa
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. METHODS: In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2...
January 5, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28055991/role-of-mir-24-furin-and-transforming-growth-factor-%C3%AE-1-signal-pathway-in-fibrosis-after-cardiac-infarction
#20
Zhufeng Chen, Sumei Lu, Miao Xu, Peng Liu, Rui Ren, Wanshan Ma
BACKGROUND Cardiac fibrosis after primary infarction is a type of pathological phenomena as shown by increased collagen in myocardial cells. Transforming growth factor (TGF)-β1 is a critical factor participating in myocardial fibrosis. A previous study has shown the inhibitory role on TGF-β1 by microRNA-24 (miR-24) via targeting Furin. This study thus investigated the role of miR-24 and Furin/TGF-β1 in rat myocardial fibrosis. MATERIAL AND METHODS A total of 40 adult SD rats (both males and females) were prepared for myocardial infarction model by ligating the descending branch of left coronary artery after anesthesia...
January 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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