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https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#1
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641514/clinically-relevant-biomarkers-in-acute-heart-failure-an-update
#2
Agnibh Mukherji, Uzair Ansari, Martin Borggrefe, Ibrahim Akin, Michael Behnes
Acute heart failure (AHF) has been one of the fields, where owing to difficulties in diagnosis, prognostic stratification and management the associated morbidity and mortality remains unusually high. The advent of novel biomarkers apart from the traditional B-type natriuretic peptide and N-terminal proBNP involved in myocardial injury, neuro-hormonal activation, and ventricular remodeling augurs immense hope in redefining our approach towards AHF. METHODS: Biomarkers like midregional proatrial natriuretic peptide, soluble ST2, highly-sensitive troponin, and midregional proadrenomedullin are some such examples that have passed various stages of substantiation while there is an array of potential biomarkers in nascent stages like osteopontin, CTGF, GDF-15 and TGF beta-1 awaiting further reiteration...
June 22, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28640248/voluntary-distance-running-prevents-tnf-mediated-liver-injury-in-mice-through-alterations-of-the-intrahepatic-immune-milieu
#3
Yvonne Huber, Nadine Gehrke, Jana Biedenbach, Susanne Helmig, Perikles Simon, Beate K Straub, Ina Bergheim, Tobias Huber, Detlef Schuppan, Peter R Galle, Marcus A Wörns, Marcus Schuchmann, Jörn M Schattenberg
Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28638997/follistatin-treatment-suppresses-serca1b-levels-independently-of-other-players-of-calcium-homeostasis-in-c2c12-myotubes
#4
János Fodor, Adrienn Gomba-Tóth, Tamás Oláh, János Almássy, Ernő Zádor, László Csernoch
Follistatin (FS) is a high affinity activin-binding protein, neutralizing the effects of the Transforming Growth Factor-beta (TGF-β) superfamily members, as myostatin (MSTN). Since MSTN emerged as a negative regulator, FS has been considered as a stimulator of skeletal muscle growth and differentiation. Here, we studied the effect of FS administration on the Ca(2+)-homeostasis of differentiating C2C12 skeletal muscle cells. FS-treatment increased the fusion index, the size of terminally differentiated myotubes, and transiently elevated the expression of the calcium-dependent protein phosphatase, calcineurin, at the beginning of differentiation...
June 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28638086/wnt2b-attenuates-hscs-activation-and-liver-fibrosis-through-negative-regulating-tlr4-signaling
#5
Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#6
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28627391/low-molecular-weight-fucoidan-and-its-fractions-inhibit-renal-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-or-fgf-2
#7
Xinpeng Li, Xiaohong Li, Quanbin Zhang, Tingting Zhao
We investigated the renal protective effects of low molecular weight fucoidan (LMWF) and its two fractions (F0.5 and F1.0), which were extracted from Laminaria japonica, on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) in HK-2 human renal proximal tubular cells. Cell morphology and EMT markers (fibronectin and alpha-smooth muscle actin) demonstrated that cells treated with TGF-β1 or FGF-2 developed EMT to a significant extent...
June 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#8
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28622591/targeting-proinflammatory-cytokines-oxidative-stress-tgf-%C3%AE-1-and-stat-3-by-rosuvastatin-and-ubiquinone-to-ameliorate-trastuzumab-cardiotoxicity
#9
Ahmed M Kabel, Abeer A Elkhoely
The aim of this study was to assess the possible modulatory effects of rosuvastatin and/or ubiquinone on trastuzumab (TRZ)-induced cardiotoxicity in mice. One hundred and twenty mice were divided into six equal groups as follows: control group; TRZ group; TRZ+carboxymethyl cellulose group; TRZ+rosuvastatin group; TRZ+Ubiquinone group and TRZ+rosuvastatin+Ubiquinone group. Serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), troponin I and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) were measured...
June 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#10
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620270/flucytosine-and-amphotericin-b-coadministration-induces-dose-related-renal-injury
#11
Alexandra Folk, Cornel Balta, Hildegard Herman, Alexandra Ivan, Oana Maria Boldura, Lucian Paiusan, Aurel Ardelean, Anca Hermenean
Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28620241/tgf-beta-atra-induced-tregs-express-a-selected-set-of-micrornas-involved-in-the-repression-of-transcripts-related-to-th17-differentiation
#12
Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Felipe Saldanha-Araujo, João Baiochi, Amélia Goes Araujo, Priscila Santos Scheucher, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610976/dioscin-suppresses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-and-suppresses-a549-lung-cancer-migration-and-invasion
#13
Won-Chul Lim, Hyunhee Kim, Young-Joo Kim, Kyung-Chul Choi, In Ho Lee, Ki Heon Lee, Mi Kyung Kim, Hyeonseok Ko
Epithelial-to-mesenchymal transition (EMT), an important cellular process, occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Dioscin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as anti-tumor, anti-inflammatory, anti-obesity, anti-fungal, and anti-viral activities. However, the possible role of dioscin in the EMT is unclear. We investigated the suppressive effect of dioscin on the EMT...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28608941/tgf-%C3%AE-stimulates-expression-of-chondroitin-polymerizing-factor-in-nucleus-pulposus-cells-through-the-smad3-rhoa-rock1-and-mapk-signaling-pathways
#14
Bo Hu, Chen Xu, Peng Cao, Ye Tian, Ying Zhang, Changgui Shi, Jun Xu, Wen Yuan, Huajiang Chen
The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF-β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF-β induced ChPF expression and enhanced Smad2/3, RhoA/ ROCK activation, and the JNK, p38 and ERK1/2 MAPK signaling pathways...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28607171/astrocyte-transforming-growth-factor-beta-1-protects-synapses-against-a%C3%AE-oligomers-in-alzheimer-s-disease-model
#15
Luan Pereira Diniz, Vanessa Tortelli, Isadora Matias, Juliana Morgado, Ana Paula Bérgamo Araujo, Helen M Melo, Gisele S Seixas da Silva, Soniza V Alves-Leon, Jorge M de Souza, Sergio T Ferreira, Fernanda G De Felice, Flávia Carvalho Alcantara Gomes
Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity and function, we sought to investigate the impact of AβOs on astrocytes, and to determine if this impact is related to the deleterious actions of AβOs on synapses...
June 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28588674/resveratrol-ameliorates-diabetic-nephropathy-in-rats-through-negative-regulation-of-the-p38-mapk-tgf-%C3%AE-1-pathway
#16
Yuan Qiao, Ke Gao, Yangwei Wang, Xueliang Wang, Bo Cui
Resveratrol (RSV) has been shown to have a renoprotective effect against diabetic nephropathy, but the underlying mechanisms of this have not been fully elucidated. The aim of the current study was to explore the mechanisms responsible for the therapeutic effects of RSV in rat mesangial cells in vitro and in a rat model of diabetic nephropathy. The viability of CRL-2573 rat mesangial cells and their expression levels of p38, phosphorylated (p)-p38, transforming growth factor beta 1 (TGF-β1) and fibronectin were assessed in response to treatment with high glucose, with or without RSV...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28579529/genes-directly-regulated-by-nf-%C3%AE%C2%BAb-in-human-hepatocellular-carcinoma-hepg2
#17
Wei Dai, Jian Wu, Shuyan Zhang, Bingjie Shi, Xinhui Xu, Danyang Wang, Jinke Wang
It has been well-known that over activation of NF-κB has close relationship with hepatitis and hepatocellular carcinoma (HCC). However, the complete and exact underlying molecular pathways and mechanisms still remain not fully understood. By manipulating NF-κB activity with its recognized activator TNFα and using ChIP-seq and RNA-seq techniques, this study identified 699 NF-κB direct target genes (DTGs) in a widely used HCC cell line, HepG2, including 399 activated and 300 repressed genes. In these NF-κB DTGs, 216 genes (126 activated and 90 repressed genes) are among the current HCC gene signature...
June 1, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28578888/comparative-evaluation-of-chemotactic-factor-effect-on-migration-and-differentiation-of-stem-cells-of-the-apical-papilla
#18
Sara Fayazi, Koyo Takimoto, Anibal Diogenes
INTRODUCTION: Cell homing strategies could potentially be used in regenerative endodontic procedures (REPs) to promote the progressive coronal migration of stem cells, including stem cells of the apical papilla (SCAPs), along with formation of a new vascular network without the need for intentional apical trauma and intracanal bleeding. Although many chemotactic factors have been investigated for different mesenchymal stem cells, their effect on SCAP migration and differentiation is not fully understood...
June 1, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28568893/tgf-%C3%AE-signaling-directly-regulates-transcription-and-functional-expression-of-the-electrogenic-sodium-bicarbonate-cotransporter-1-nbce1-slc4a4-via-smad4-in-mouse-astrocytes
#19
Shokoufeh Khakipoor, Christian Ophoven, Magdalena Schrödl-Häußel, Melanie Feuerstein, Bernd Heimrich, Joachim W Deitmer, Eleni Roussa
The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH. Here, we introduce transforming growth factor beta (TGF-β) as a novel regulator of NBCe1 transcription and functional expression. Using hippocampal slices and primary hippocampal and cortical astrocyte cultures, we investigated regulation of NBCe1 and elucidated the underlying signaling pathways by RT-PCR, immunoblotting, immunofluorescence, intracellular H((+) ) recording using the H((+) ) -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, mink lung epithelial cell (MLEC) assay, and chromatin immunoprecipitation...
August 2017: Glia
https://www.readbyqxmd.com/read/28556971/low-level-laser-therapy-780%C3%A2-nm-combined-with-collagen-sponge-scaffold-promotes-repair-of-rat-cranial-critical-size-defects-and-increases-tgf-%C3%AE-fgf-2-opg-rank-and-osteocalcin-expression
#20
Lana Sarita de Souza de Oliveira, Aurigena Antunes de Araújo, Raimundo Fernandes de Araújo Júnior, Carlos Augusto Galvão Barboza, Boniek Castillo Dutra Borges, José Sandro Pereira da Silva
The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm(2) ; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3)...
May 29, 2017: International Journal of Experimental Pathology
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