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https://www.readbyqxmd.com/read/28926092/key-genes-regulating-the-liposecretion-process-of-mature-adipocytes
#1
Giulia Maurizi, Tiina Petäistö, Angela Maurizi, Lucio Della Guardia
White mature adipocytes (MAs) are plastic cells able to reversibly transdifferentiate toward fibroblast-like cells maintaining stem cell gene signatures. The main morphologic aspect of this transdifferentiation process, called liposecretion, is the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion. There is a considerable interest in the adipocyte plastic properties involving liposecretion process, but the molecular details are incompletely explored. This review analyzes the gene expression of MAs isolated from human subcutaneous fat tissue with respect to bone marrow (BM)-derived mesenchymal stem cells (MSC) focusing on gene regulatory pathways involved into cellular morphology changes, cellular proliferation and transports of molecules through the membrane, suggesting potential ways to guide liposecretion...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#2
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28919455/is-there-a-role-for-il-17-in-the-pathogenesis-of-systemic-sclerosis
#3
REVIEW
Carlo Chizzolini, Aleksandra Maria Dufour, Nicolò Costantino Brembilla
In systemic sclerosis (SSc) immuno-inflammatory events are central to disease development. Amongst other mediators of inflammation, interleukin 17 (IL-17) and Th17 cells have been reported to be increased in the peripheral blood and target organs including involved skin in SSc. They participate and amplify inflammatory responses by inducing the production of cytokines such as IL-6, chemokines such as CCL2 and CXCL8 (IL-8), matrix metalloproteinases-1, -2, -9 and the expression of adhesion molecules in stromal cells including fibroblasts and endothelial cells...
September 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28916494/transflammation-innate-immune-signaling-in-nuclear-reprogramming
#4
Shu Meng, Palas Chanda, Rajarajan A Thandavarayan, John P Cooke
Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed "transflammation" [1]. Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) [2] trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28915325/brown-and-beige-adipose-tissues-in-health-and-disease
#5
Liangyou Rui
Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white-to-brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28913973/bone-marrow-stem-cells-do-not-contribute-to-endometrial-cell-lineages-in-chimeric-mouse-models
#6
Yih Rue Ong, Fiona L Cousins, Xiaoqing Yang, Ahmed Aedh A Al Mushafi, David T Breault, Caroline E Gargett, James A Deane
Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert-GFP or chicken β-actin-GFP reporters. mTert-GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial and immune cells in the endometrium...
September 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/28902664/comparison-of-the-inhibitory-mechanisms-of-diethyl-citrate-sodium-citrate-and-phosphonoformic-acid-on-calcification-induced-by-high-inorganic-phosphate-contents-in-mouse-aortic-smooth-muscle-cells
#7
Jian-Ming Ouyang, Chao-Yang Duan, Chong-Yu Zhang, Xin-Yuan Sun, Bao-Song Gui, Da Guo
OBJECTIVE: This study aimed to investigate the differences and inhibitory effects of diethyl citrate (Et2Cit), sodium citrate (Na3Cit), and phosphonoformic acid (PFA) on calcification induced by high inorganic phosphate (Pi) contents in mouse aortic smooth muscle cells (MOVAS) and to develop drugs that can induce anticoagulation and inhibit vascular calcification (VC). METHODS: Alive and fixed MOVAS were assessed for 14 days in the presence of high Pi with increasing Et2Cit, Na3Cit, and PFA concentrations...
September 11, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28893556/the-ilk-mmp9-mrtf-axis-is-crucial-for-endmt-differentiation-of-endothelial-cells-in-a-tumor-microenvironment
#8
Wojciech M Ciszewski, Katarzyna Sobierajska, Marta E Wawro, Wanda Klopocka, Natasza Chefczyńska, Angelika Muzyczuk, Kamil Siekacz, Agata Wujkowska, Jolanta Niewiarowska
Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). EndMT is mainly promoted by the Transforming Growth Factor-β (TGF-β) family secreted by tumor cells, though the role of particular members in EndMT regulation remains poorly understood...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28892104/synergistic-anti-aml-effects-of-the-lsd1-inhibitor-t-3775440-and-the-nedd8-activating-enzyme-inhibitor-pevonedistat-via-transdifferentiation-and-dna-rereplication
#9
Y Ishikawa, K Nakayama, M Morimoto, A Mizutani, A Nakayama, K Toyoshima, A Hayashi, S Takagi, R Dairiki, H Miyashita, S Matsumoto, K Gamo, T Nomura, K Nakamura
Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 and K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities in a subset of acute myeloid leukemia (AML) cell lines by inducing cell transdifferentiation. The NEDD8-activating enzyme inhibitor pevonedistat (MLN4924, TAK-924) is an investigational drug with antiproliferative activities in AML, and is also reported to induce cell differentiation...
September 11, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28890543/the-altered-pd-1-pd-l1-pathway-delivers-the-one-two-punch-effects-to-promote-the-treg-th17-imbalance-in-pre-eclampsia
#10
Yonghong Zhang, Zhaozhao Liu, Mei Tian, Xiaohui Hu, Liling Wang, Jinlu Ji, Aihua Liao
The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical for normal pregnancy by promoting regulatory T (Treg) cell development and inhibiting the Th17 response. However, the relationship between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance in pre-eclampsia (PE) is an enigma. In this study, decreased PD-1 and PD-L1 expression and a Treg/Th17 imbalance were observed at the maternal-fetal interface in PE. The regulatory effects of the PD-1/PD-L1 pathway on the Treg and Th17 cell quantities were determined in vitro by targeting T-cell proliferation, differentiation and transdifferentiation...
September 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28890368/cyp17a1-independent-production-of-the-neurosteroid-derived-5%C3%AE-pregnan-3%C3%AE-6%C3%AE-diol-20-one-in-androgen-responsive-prostate-cancer-cell-lines-under-serum-starvation-and-inhibition-by-abiraterone
#11
Antonio G Gomes de Mello Martins, Giuseppe Allegretta, Gerhard Unteregger, Jörg Haupenthal, Jens Eberhard, Michael Hoffmann, Jill A van der Zee, Kerstin Junker, Michael Stöckle, Rolf Müller, Rolf W Hartmann, Carsten-H Ohlmann
CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone...
September 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28889951/pancreatic-%C3%AE-cell-regeneration-as-a-possible-therapy-for-diabetes
#12
REVIEW
Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis)...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28874841/epiphyseal-bone-formation-occurs-via-thyroid-hormone-regulation-of-chondrocyte-to-osteoblast-transdifferentiation
#13
Patrick Aghajanian, Weirong Xing, Shaohong Cheng, Subburaman Mohan
Endochondral ossification in the diaphysis of long bones has been studied in-depth during fetal development but not postnatally in the epiphysis. Immunohistochemical studies revealed that Sox9 and Col2 expressing immature chondrocytes in the epiphysis transition into prehypertrophic and hypetrophic chondrocytes and finally into osteoblasts expressing Col1 and BSP during postnatal day 7-10, when serum levels of thyroid hormone (TH) rise. Lineage tracing using Rosa-td tomato (Col2-Cre-ERT2) mice treated with tamoxifen indicated that the same Col2 expressing chondrocytes expressed prehypertrophic, hypertrophic, and subsequently bone formation markers in a sequential manner in euthyroid but not hypothyroid mice, thus providing evidence that chondrocyte to osteoblast transdifferentiation is TH-dependent...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869484/efficient-skipping-of-single-exon-duplications-in-dmd-patient-derived-cell-lines-using-an-antisense-oligonucleotide-approach
#14
Nicolas Wein, Adeline Vulin, Andrew R Findlay, Felecia Gumienny, Nianyuan Huang, Steve D Wilton, Kevin M Flanigan
BACKGROUND: Exon skipping strategies in Duchenne muscular dystrophy (DMD) have largely been directed toward altering splicing of exons flanking out-of-frame deletions, with the goal of restoring an open mRNA reading frame that leads to production of an internally deleted but partially functional dystrophin protein. OBJECTIVE: We sought to apply exon skipping to duplication mutations, assuming that the inherently limited efficiency of antisense oligonucleotide-induced exon skipping would more frequently skip a single copy of a duplicated exon, rather than both and result in significant amounts of wild-type DMD mRNA...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28861413/paying-the-toll-in-nuclear-reprogramming
#15
REVIEW
Chun Liu, Farhan Himmati, Nazish Sayed
The ability to reverse lineage-committed cells toward pluripotent stem cells or to another cell type is one of the ultimate goals in regenerative medicine. We recently discovered that activation of innate immunity, through Toll-like receptor 3, is required during this conversion of cell fate by causing global changes in the expression and activity of epigenetic modifiers. Here we discuss, in a comprehensive manner, the recent studies on the role of innate immunity in nuclear reprogramming and transdifferentiation, the underlying mechanisms, and its role in regenerative medicine...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28859546/microrna-34a-induces-transdifferentiation-of-glioma-stem-cells-into-vascular-endothelial-cells-by-targeting-notch-pathway
#16
Zaishun Jin, Tao Zhan, Jing Tao, Biao Xu, Huizhe Zheng, Yongxia Cheng, Bin Yan, Hongwei Wang, Guoqiang Lu, Ying Lin, Sufen Guo
The function of microRNA-34a (miR-34a) in transdifferentiation of glioma stem cells (GSCs) into vascular endothelial cells (VECs) was explored by focusing on Notch ligand Delta-like 1 (Dll1). MiR-34a mimics was transfected into CD133 + glioma cell U251. The angiogenesis feature of miR-34a transfected U251 cells was investigated and the expressions of CD31, CD34, Vwf, Notch 1, and Dll1 were quantified. Length of branching vessel-like structures in the miR-34a transfected U251 cells was significantly higher than control cells...
September 1, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28853082/reprogramming-of-human-retinal-pigment-epithelial-cells-under-the-effect-of-bfgf-in-vitro
#17
E V Shafei, A M Kurinov, A V Kuznetsova, M A Aleksandrova
We studied the effect of bFGF on human retinal pigment epithelial cells in vitro In ARPE-19 cells, enhanced expression of KLF4 mRNA and reduced expression of PAX6, MITF, and OTX2 mRNA specific for retinal pigment epithelium were observed after bFGF application. The expression of KLF4 mRNA peaked in 72 h after bFGF application and then sharply decreased, which was accompanied by a 3-fold increase in TUBB3 mRNA expression (neuronal marker). Immunocytochemical analysis showed that in the presence of bFGF, some cells retained epithelial properties and showed positive staining for connexin-43, while others had long axon-like processes and demonstrated positive staining for βIII-tubulin, which attests to their neuronal transdifferentiation...
August 29, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28852936/down-regulation-of-pax2-promotes-in-vitro-differentiation-of-podocytes-from-human-cd34-cells
#18
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Podocytes are major kidney cells that help in glomerular filtration and any damage or loss is a major event in the progression of kidney diseases. Understanding podocytes development will help in designing therapeutic strategies against these renal diseases. Therefore, in vitro generation of podocytes from adult hematopoietic CD34(+) stem cells is explored in the present study. Apheretically, isolated human HSCs from peripheral blood showed the presence of CD34 surface glycoprotein through immunocytochemistry (ICC) and flowcytometry...
August 29, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28852100/mechanisms-of-stem-cell-based-cardiac-repair-gap-junctional-signaling-promotes-the-cardiac-lineage-specification-of-mesenchymal-stem-cells
#19
Heiko Lemcke, Ralf Gaebel, Anna Skorska, Natalia Voronina, Cornelia Aquilina Lux, Janine Petters, Sarah Sasse, Nicole Zarniko, Gustav Steinhoff, Robert David
Different subtypes of bone marrow-derived stem cells are characterized by varying functionality and activity after transplantation into the infarcted heart. Improvement of stem cell therapeutics requires deep knowledge about the mechanisms that mediate the benefits of stem cell treatment. Here, we demonstrated that co-transplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) led to enhanced synergistic effects on cardiac remodeling. While HSCs were associated with blood vessel formation, MSCs were found to possess transdifferentiation capacity...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28841613/dedifferentiated-adipocytes-promote-adipose-tissue-generation-within-an-external-suspension-device
#20
Jingjing Ma, Yao Yao, Jing Wang, Ziqing Dong, Tao Zhou, Feng Lu, Yunjun Liao, Jianhua Gao
BACKGROUND: Mature adipocytes can dedifferentiate into fibroblast-like cells in vitro and acquire proliferation and redifferentiation/transdifferentiation abilities. A soft-tissue expander can induce adipocyte dedifferentiation in vivo. This study combined a tissue expander and an external suspension device to generate a large volume of adipose tissue. METHODS: A soft-tissue expander was implanted beneath the dorsal adipose flaps of rabbits. After 7 days of expansion, the expander was removed and an external suspension device was applied...
September 2017: Plastic and Reconstructive Surgery
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