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https://www.readbyqxmd.com/read/28440499/effects-of-tanshinone-iia-on-the-regulation-of-renal-proximal-tubular-fibrosis
#1
Luoyuan Cao, Baoying Huang, Xianguo Fu, Jing Yang, Yinghua Lin, Feng Lin
The development of diabetes mellitus, along with its complications, is a chronic inflammatory response process. Chronic kidney diseases are characterized by renal fibrosis, and fibrosis is an important pathway for end‑stage renal failure. According to previous studies, high glucose (HG) has been demonstrated to be the most important fibrogenesis‑inducing agent. Tanshinone IIA is one of the main components isolated from Danshen (Salvia miltiorrhiza). Although tanshinone IIA has been widely used for the treatment of cardiovascular diseases, the possible role of tanshinone IIA in fibrosis regulation remains to be elucidated and requires investigation...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28434000/apolipoprotein-a1-inhibits-the-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-of-human-coronary-artery-endothelial-cells
#2
Juling Feng, Jingjing Zhang, Ampadu O Jackson, Xiao Zhu, Hainan Chen, Wen Chen, Qingjun Gui, Kai Yin
OBJECTIVE: Transforming growth factor β1 (TGF-β1) is the major cytokine for stimulating endothelial cells (ECs) to transdifferentiate to mesenchymal cells (MCs) in the process known as endothelial-to-mesenchymal transition (EndMT). Recently, TGF-β1-induced EndMT has been implicated in the pathogenesis of atherosclerosis (AS). It has been identified that apolipoprotein A1 (ApoA-I) obstructs TGF-β1-induced endothelial dysfunction, providing a protective effect for ECs and also anti-AS activity...
April 22, 2017: Cardiology
https://www.readbyqxmd.com/read/28428963/quercetin-inhibits-pulmonary-arterial-endothelial-cell-transdifferentiation-possibly-by-akt-and-erk1-2-pathways
#3
Shian Huang, Xiulong Zhu, Wenjun Huang, Yuan He, Lingpin Pang, Xiaozhong Lan, Xiaorong Shui, Yanfang Chen, Can Chen, Wei Lei
This study aimed to investigate the effects and mechanisms of quercetin on pulmonary arterial endothelial cell (PAEC) transdifferentiation into smooth muscle-like cells. TGF-β1-induced PAEC transdifferentiation models were applied to evaluate the pharmacological actions of quercetin. PAEC proliferation was detected with CCK8 method and BurdU immunocytochemistry. Meanwhile, the identification and transdifferentiation of PAECs were determined by FVIII immunofluorescence staining and α-SMA protein expression...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28421197/ginsenoside-rg1-ameliorates-cigarette-smoke-induced-airway-fibrosis-by-suppressing-the-tgf-%C3%AE-1-smad-pathway-in-vivo-and-in-vitro
#4
Sibin Guan, Qian Liu, Fengfeng Han, Wen Gu, Lin Song, Yue Zhang, Xuejun Guo, Weiguo Xu
Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28416697/small-molecule-mediated-inhibition-of-myofibroblast-transdifferentiation-for-the-treatment-of-fibrosis
#5
Michael J Bollong, Baiyuan Yang, Naja Vergani, Brittney A Beyer, Emily N Chin, Claudio Zambaldo, Danling Wang, Arnab K Chatterjee, Luke L Lairson, Peter G Schultz
Fibrosis, a disease in which excessive amounts of connective tissue accumulate in response to physical damage and/or inflammatory insult, affects nearly every tissue in the body and can progress to a state of organ malfunction and death. A hallmark of fibrotic disease is the excessive accumulation of extracellular matrix-secreting activated myofibroblasts (MFBs) in place of functional parenchymal cells. As such, the identification of agents that selectively inhibit the transdifferentiation process leading to the formation of MFBs represents an attractive approach for the treatment of diverse fibrosis-related diseases...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415787/knockdown-of-p4ha1-inhibits-neovascularization-via-targeting-glioma-stem-cell-endothelial-cell-transdifferentiation-and-disrupting-vascular-basement-membrane
#6
Yiqiang Zhou, Guishan Jin, Ruifang Mi, Junwen Zhang, Jin Zhang, Hengzhou Xu, Sen Cheng, Yunsheng Zhang, Wenjie Song, Fusheng Liu
Emerging evidence has demonstrated transdifferentiation process of glioma stem cells (GSCs) into endothelial cells (ECs) in glioma neovascularization. Herein, we focused on screening for genes that were differentially expressed in the transdifferentiation process using microarray analysis. Bioinformatics analysis revealed differential expression of the prolyl 4-hydroxylase subunit alpha-1 (P4HA1) gene. We determined that P4HA1 expression was correlated with histological grade, the level of Ki67 and microvessel density (MVD) in human glioma specimens...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#7
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#8
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, Wh W Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection...
April 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28396837/myostatin-promotes-tenogenic-differentiation-of-c2c12-myoblast-cells-through-smad3
#9
Kazutaka Uemura, Masanori Hayashi, Toshiro Itsubo, Ayumu Oishi, Hiroko Iwakawa, Masatoshi Komatsu, Shigeharu Uchiyama, Hiroyuki Kato
Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in developing and adult skeletal muscle and negatively regulates skeletal muscle growth. Recently, myostatin has been found to be expressed in tendons and increases tendon fibroblast proliferation and the expression of tenocyte markers. C2C12 is a mouse myoblast cell line, which has the ability to transdifferentiate into osteoblast and adipocyte lineages. We hypothesized that myostatin is capable of inducing tenogenic differentiation of C2C12 cells...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28395729/a-novel-perivascular-cell-population-in-the-zebrafish-brain
#10
Marina Venero Galanternik, Daniel Castranova, Aniket V Gore, Nathan H Blewett, Hyun Min Jung, Amber N Stratman, Martha R Kirby, James Iben, Mayumi F Miller, Koichi Kawakami, Richard J Maraia, Brant M Weinstein
The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or 'Mato Cells' in mammals...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28389561/tgf-beta-1-induced-cd44v6-nox4-signaling-in-pathogenesis-of-idiopathic-pulmonary-fibrosis
#11
Shibnath Ghatak, Vincent C Hascall, Roger R Markwald, Carol Feghali-Bostwick, Carol M Artlett, Monika Gooz, Galina S Bogatkevich, Ilia Atanelishvili, Richard M Silver, Jeanette Wood, Victor J Thannickal, Suniti Misra
Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblasts phenotype has prevented the development of targeted therapies for IPF. Our previous study (1) showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44v6 (CD44-variants containing exon-6), which enhances the TGF-beta-1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28386176/derivation-and-characterization-of-sheep-bone-marrow-derived-mesenchymal-stem-cells-induced-with-telomerase-reverse-transcriptase
#12
Xuemin Zhu, Zongzheng Liu, Wen Deng, Ziqiang Zhang, Yumei Liu, Lan Wei, Yuling Zhang, Liutao Zhou, Yuzhu Wang
Bone marrow mesenchymal stem cells (BMSCs) are a type of adult stem cells with a wide range of potential applications. However, BMSCs have a limited life cycle under normal culturing conditions, which has hindered further study and application. Many studies have confirmed that cells modified by telomerase reverse transcriptase (TERT) can maintain the ability to proliferate in vitro over a long period of time. In this study, we constructed a gene expression vector to transfer TERT into sheep BMSCs, and evaluated whether the TERT cell strain was successfully transferred...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28381471/sox17-regulates-conversion-of-human-fibroblasts-into-endothelial-cells-and-erythroblasts-via-de-differentiation-into-cd34-progenitor-cells
#13
Lianghui Zhang, Ankit Jambusaria, Zhigang Hong, Glenn Marsboom, Peter T Toth, Brittney-Shea Herbert, Asrar B Malik, Jalees Rehman
Background -The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28380380/virgin-beta-cells-persist-throughout-life-at-a-neogenic-niche-within-pancreatic-islets
#14
Talitha van der Meulen, Alex M Mawla, Michael R DiGruccio, Michael W Adams, Vera Nies, Sophie Dólleman, Siming Liu, Amanda M Ackermann, Elena Cáceres, Anna E Hunter, Klaus H Kaestner, Cynthia J Donaldson, Mark O Huising
Postnatal maintenance or regeneration of pancreatic beta cells is considered to occur exclusively via the replication of existing beta cells, but clinically meaningful restoration of human beta cell mass by proliferation has never been achieved. We discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or "neogenic niche" at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28378126/global-transcriptomic-analysis-of-induced-cardiomyocytes-predicts-novel-regulators-for-direct-cardiac-reprogramming
#15
Mahmood Talkhabi, Seyed Morteza Razavi, Ali Salari
Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs...
April 4, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28376896/regulation-of-visceral-and-epicardial-adipose-tissue-for-preventing-cardiovascular-injuries-associated-to-obesity-and-diabetes
#16
REVIEW
N González, Z Moreno-Villegas, A González-Bris, J Egido, Ó Lorenzo
Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy...
April 4, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28371543/upregulation-of-matrix-metalloproteinase-triggers-transdifferentiation-of-retinal-pigmented-epithelial-cells-in-xenopus-laevis-a-link-between-inflammatory-response-and-regeneration
#17
Hanako Naitoh, Yukari Suganuma, Yoko Ueda, Takahiko Sato, Yosuke Hiramuki, Atsuko Fujisawa-Sehara, Shigeru Taketani, Masasuke Araki
In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, we examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid...
April 2, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28356547/mechanisms-of-ips-cell-generation-and-beyond
#18
Keisuke Kaji
The generation of induced pluripotent stem cells (iPSCs) achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc, transformed our classical views of the cellular epigenetic landscape and delivered a new concept for cell and tissue engineering. In addition to iPSCs, several other cell types have also been generated by master transcription factor (TF)-mediated transdifferentiation. However, the critical molecular mechanisms amongst diverse cellular identity changes are not well understood. Through the investigation of reprogramming mechanisms, we recently revealed that over-expression of constitutive active Smad3 boosted not only iPSC generation, but also 3 other master TF-mediated conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons...
2017: Keio Journal of Medicine
https://www.readbyqxmd.com/read/28349784/fibroblasts-in-hypoxic-conditions-mimic-laryngotracheal-stenosis
#19
Linda X Yin, Kevin M Motz, Idris Samad, Madhavi Duvvuri, Michael Murphy, Dacheng Ding, Alexander T Hillel
Objective To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS). Study Design (1) Examination of mucosal surface gene expression in human iLTS. (2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions. Setting Tertiary care hospital in a research university (2012-2016). Subjects and Methods Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared...
March 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28341222/the-science-and-ethics-of-cell-based-therapies-for-parkinson-s-disease
#20
REVIEW
C R Towns
Parkinson's Disease (PD) is an age-related, disabling neurodegenerative disorder. Although sufferers usually respond to dopamine agonists for extended periods, the disease remains progressive and adverse drug effects can compromise effective long term treatment. Cell-based therapies have been the subject of much hype and optimism with regard to PD. Proof of principle was provided in the 1980s with fetal tissue transplantation trials demonstrating successful graft survival. Embryonic stem cells and reprogrammed or transdifferentiated somatic cells may provide alternative sources of tissue with the potential to overcome the material shortages and technical difficulties that have hindered fetal neural transplants...
January 2017: Parkinsonism & related Disorders
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