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Eitaro Aihara, Andrea L Matthis, Rebekah A Karns, Kristen A Engevik, Peihua Jiang, Jiang Wang, Bruce R Yacyshyn, Marshall H Montrose
BACKGROUND & AIMS: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. METHODS: Gastric ulcers were induced in mice by serosal topical application of acetic acid...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
Sheng-Chieh Lin, Yu-Ting Chou, Shih-Sheng Jiang, Junn-Liang Chang, Chih-Hung Chung, Yu-Rung Kao, I-Shou Chang, Cheng-Wen Wu
Cell differentiation within stem cell lineages can check proliferative potential but nodal pathways that can limit tumor growth are obscure. Here we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus altering proliferative and invasive capabilities. In lung cancer cells, SOX2 bound the EPCAM promoter to induce EpCAM-p21Cip1-cyclin A2 signaling, encouraging cell proliferation as well as barrier properties...
October 7, 2016: Cancer Research
Elizabeth M Meier, Bin Wu, Aamir Siddiqui, Donna G Tepper, Michael T Longaker, Mai T Lam
: Efforts have been made to engineer knee meniscus tissue for injury repair, yet most attempts have been unsuccessful. Creating a cell source that resembles the complex, heterogeneous phenotype of the meniscus cell remains difficult. Stem cell differentiation has been investigated, mainly using bone marrow mesenchymal cells and biochemical means for differentiation, resulting in no solution. Mechanical stimulation has been investigated to an extent with no conclusion. Here, we explore the potential for and effectiveness of mechanical stimulation to induce the meniscal phenotype in adipose-derived stromal cells...
September 2016: Plastic and Reconstructive Surgery. Global Open
Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62 and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically-induced liver injury...
October 17, 2016: Journal of Cellular Physiology
R D Chavez, G Coricor, J Perez, H-S Seo, R Serra
OBJECTIVE: We previously identified PAPSS2 as a transcriptional target of TGF-β in chondrocytes. PAPSS2 is required for proper sulfation of proteoglycans in cartilage. Defective sulfation in the matrix results in alterations in mechanical properties of the cartilage that would be expected to result in degeneration. The objective of this study was to identify factors that regulate PAPSS2 expression and compare to a known TGF-β responsive gene, PRG4. In this study, TGF-β-mediated regulation of SOX9 was characterized, and the involvement of SOX9 in regulation of PAPSS2 mRNA was investigated...
October 13, 2016: Osteoarthritis and Cartilage
Stefania Pagani, Veronica Borsari, Francesca Veronesi, Andrea Ferrari, Simona Cepollaro, Paola Torricelli, Giuseppe Filardo, Milena Fini
OBJECTIVES: Primarily, to compare the behavior of human mesenchymal stem cells (MSCs) derived from bone marrow (hBMSCs) and adipose tissue (hADSCs) in an osteoarthritic (OA) microenvironment; secondly, to investigate the reaction of these cell types in two alternative in vitro culture systems, obtained by using TNFα and/or IL1β as inflammation mediators, or by using synovial fluid harvested by OA patients (OSF) to simulate the complex inflamed knee microenvironment. METHODS: 3D micromass cultures of hBMSCs or hADSCs were grown in chondrogenic medium (CTR), in the presence of TNFα and/or IL1β, or synovial fluid from OA patients...
October 14, 2016: Journal of Cellular Physiology
Andrew Tai, Martin Cheung, Yong-Heng Huang, Ralf Jauch, Marianne E Bronner, Kathryn S E Cheah
During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification...
October 13, 2016: Scientific Reports
Takanori Eguchi, Satoshi Kubota, Masaharu Takigawa
Promoter analysis is the most basics in the analysis of gene regulation. Luciferase gene is the most commonly used reporter gene in promoter analysis. Luciferase is an enzyme that is used when firefly and Renilla reniformis (sea pansy) emit light. The first experimental step in this reporter gene assay is to connect a particular DNA segment to a luciferase gene. The second step is to transfect the reporter construct into the cells. Thereafter, stable luciferase will be produced with the help of transcriptional machinery, mRNA transporters, and translational machinery in the cells...
2017: Methods in Molecular Biology
Honghai Xia, Jun Cao, Qing Li, Yang Lv, Weidong Jia, Weihua Ren, Qingyu Cheng, Xiaoyuan Song, Geliang Xu
The recent identification of "Side Population" (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 10(2) cells/mouse). The mRNA microarray analysis of the SP vs...
October 11, 2016: Scientific Reports
Monica Cipollini, Stefano Landi, Federica Gemignani
BACKGROUND: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro-RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal antibodies. METHODS: The present review is focused on candidate genes having convincing biological evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression...
October 6, 2016: Current Pharmaceutical Design
Zhiguo Yuan, Shuyun Liu, Chunxiang Hao, Weimin Guo, Shuang Gao, Mingjie Wang, Mingxue Chen, Zhen Sun, Yichi Xu, Yu Wang, Jiang Peng, Mei Yuan, Quan-Yi Guo
Tissue-engineered meniscus regeneration is a very promising treatment strategy for meniscus lesions. However, generating the scaffold presents a huge challenge for meniscus engineering as this has to meet particular biomechanical and biocompatibility requirements. In this study, we utilized acellular meniscus extracellular matrix (AMECM) and demineralized cancellous bone (DCB) to construct three different types of three-dimensional porous meniscus scaffold: AMECM, DCB, and AMECM/DCB, respectively. We tested the scaffolds' physicochemical characteristics and observed their interactions with meniscus fibrochondrocytes to evaluate their cytocompatibility...
December 2016: Biomaterials
V Chauhan, V P Jyotsna, V Jain, R Khadgawat, R Dada
46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis...
October 6, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Prabhuanand Selvaraj, Lan Xiao, Cheol Lee, Saravana R K Murthy, Niamh X Cawley, Malcolm Lane, Istvan Merchenthaler, Sohyun Ahn, Y Peng Loh
Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF-α1, which inhibits proliferation and promotes differentiation of neural stem cell/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing β-catenin. NF-α1 induced differentiation of neural stem cells to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2-Sox9 signaling pathway...
October 6, 2016: Stem Cells
Martin Franke, Daniel M Ibrahim, Guillaume Andrey, Wibke Schwarzer, Verena Heinrich, Robert Schöpflin, Katerina Kraft, Rieke Kempfer, Ivana Jerković, Wing-Lee Chan, Malte Spielmann, Bernd Timmermann, Lars Wittler, Ingo Kurth, Paola Cambiaso, Orsetta Zuffardi, Gunnar Houge, Lindsay Lambie, Francesco Brancati, Ana Pombo, Martin Vingron, Francois Spitz, Stefan Mundlos
Chromosome conformation capture methods have identified subchromosomal structures of higher-order chromatin interactions called topologically associated domains (TADs) that are separated from each other by boundary regions. By subdividing the genome into discrete regulatory units, TADs restrict the contacts that enhancers establish with their target genes. However, the mechanisms that underlie partitioning of the genome into TADs remain poorly understood. Here we show by chromosome conformation capture (capture Hi-C and 4C-seq methods) that genomic duplications in patient cells and genetically modified mice can result in the formation of new chromatin domains (neo-TADs) and that this process determines their molecular pathology...
October 5, 2016: Nature
Fei Chen, Hao Yao, Minjun Wang, Bing Yu, Qinggui Liu, Jianxiu Li, Zhiying He, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their abilities for self-renewal and bi-potential differentiation. However, the molecular mechanism regulating proliferation and differentiation of iHepSCs is poorly understood. In this study, we provide evidence that the homeodomain transcription factor, Pitx2, is essential to maintain iHepSCs stem cell characteristics. Suppressing Pitx2 expression in iHepSCs by lentivirus mediated specific shRNA markedly reduced the expression of the hepatic stem cell-associated genes (Lgr5, EpCAM, and Sox9) with concomitant inhibition of proliferation by blocking the G1/S phase transition, and these phenotypic changes were reversed upon re-expression of Pitx2...
September 30, 2016: International Journal of Biochemistry & Cell Biology
Mar Orriols, Saray Varona, Silvia Aguiló, María Galán, José Martínez González, Cristina Rodríguez
INTRODUCTION: Fibulin-5 (FBLN5) is an elastogenic protein critically involved in extracellular matrix (ECM) remodelling, a key process in abdominal aortic aneurysm (AAA). However, the possible contribution of FBLN5 to AAA development has not been addressed. METHODS: Expression levels were determined by real-time PCR and Western blot in human abdominal aorta from patients with AAA or healthy donors, as well as in human aortic vascular smooth muscle cells (VSMC). Lentiviral transduction, transient transfections, and chromatin immunoprecipitation (ChIP) assays were also performed...
September 27, 2016: Clínica e Investigación en Arteriosclerosis
Naimisha Beeravolu, Jared Brougham, Irfan Khan, Christina McKee, Mick Perez-Cruet, Rasul G Chaudhry
Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease (DDD), stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into nucleus pulposus (NP) in situ...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Christopher B Horner, Koji Hirota, Junze Liu, Maricela Maldonado, B Hyle Park, Jin Nam
Biomechanical forces have been shown to significantly affect tissue development, morphogenesis, pathogenesis and healing, especially in orthopaedic tissues. Such biological processes are critically related to the differentiation of human mesenchymal stem cells (hMSCs). However, the mechanistic details regarding how mechanical forces direct MSC differentiation and subsequent tissue formation are still elusive. Electrospun three-dimensional scaffolds were utilized to culture and subject hMSCs to various magnitudes of dynamic compressive strains at 5, 10, 15, or 20% (ε = 0...
September 29, 2016: Journal of Tissue Engineering and Regenerative Medicine
Zhaoting Yang, Yan Cui, Weidong Ni, Seokhyung Kim, Yanhua Xuan
PURPOSE: The hedgehog (Hh) pathway is involved in cancer stem cell (CSC) maintenance in various tumors. Glioma-associated oncogene homolog 1 (Gli1) is a key mediator of the Hh pathway; however, its expression and clinical significance in esophageal squamous cell carcinoma (ESCC) have not been reported. In this study, we aimed to reveal clinical significance of Gli1 expression in ESCC and further investigate the potential of Gli1 as a CSC regulator of ESCC by comparing its expression with expressions of other stemness genes in ESCC...
September 28, 2016: Journal of Cancer Research and Clinical Oncology
Taek Hwan Lee, SeonJu Park, Guijae Yoo, Cheongyun Jang, Mi-Hyun Kim, Seung Hyun Kim, Sun Yeou Kim
Agastache rugosa (Fisch. & C. A. Mey.) Kuntze has been well-known for its antioxidative properties. This study investigated the anti-melanogenesis effect of demethyleugenol β-d-glucopyranoside (1) from A. rugosa by studying molecular regulation of melanogenesis in melan-a mouse melanocytes and normal human epidermal melanocytes (NHEMs) and in in vivo models. The SRY (sex-determining region on the Y chromosome)-related high-mobility group (HMG) box 9 (SOX9), one of the critical factors that affect skin pigmentation, is up-regulated...
October 5, 2016: Journal of Agricultural and Food Chemistry
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