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https://www.readbyqxmd.com/read/27931510/generation-of-equine-induced-pluripotent-stem-cells-and-analysis-of-their-therapeutic-potential-for-muscle-injuries
#1
Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Jin-Kyu Park, Se-Il Park, Ssang-Goo Cho, Hong Kyun Kim, Shin-Yoon Kim, Kyu-Shik Jeong
Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/mdx mice...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27931284/microrna-92a-promotes-colorectal-cancer-cell-growth-and-migration-by-inhibiting-klf4
#2
Huiqing Lv, Zhongmin Zhang, Yaoxia Wang, Chenglin Li, Weihong Gong, Xin Wang
Colorectal cancer (CRC) is the third most common malignancy with high mortality around the world. However, the biological mechanism of CRC carcinogenesis is not completely known. In the present study, we determined the role of miR-92a in the regulation of CRC cell motility. Expression of miR-92a is aberrantly upregulated in human CRC tissues and cultured cells, as shown by RT-PCR analysis. The effects of miR-92a on the proliferation and migration of human CRC SW620 and LoVo cells were measured by CCK-8 and Transwell assay, respectively...
May 2016: Oncology Research
https://www.readbyqxmd.com/read/27925189/hbx-drives-alpha-fetoprotein-expression-to-promote-initiation-of-liver-cancer-stem-cells-through-activating-pi3k-akt-signal-pathway
#3
Mingyue Zhu, Wei Li, Yan Lu, Xu Dong, Bo Lin, Yi Chen, Xueer Zhang, Junli Guo, Mengsen Li
Hepatitis B virus (HBV)-X protein (HBx) plays critical role in inducing the malignant transformation of liver cells. Alpha fetoprotein (AFP) expression is closely related to hepatocarcinogenesis. We report that Oct4, Klf4, Sox2 and c-myc expression positively associated with AFP(+)/HBV(+) hepatocellular carcinoma(HCC) tissues, and the expression of the stemness markers CD44, CD133 and EpCAM was significantly higher in AFP(+)/HBV(+) HCC tissues compared to normal liver tissues or AFP(-)/HBV(-) HCC tissues. AFP expression turned on prior to expression of Oct4, Klf4, Sox2 and c-myc, and the stemness markers CD44, CD133 and EpCAM in the normal human liver L-02 cell line or CHL cell lines upon transfection with MCV-HBx vectors...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27924515/effect-of-kruppel-like-factor-4-on-notch-pathway-in-hepatic-stellate-cells
#4
Yin-Kai Xue, Jun Tan, Dong-Wei Dou, Ding Chen, Lu-Jia Chen, Huan-Ping Ren, Li-Bo Chen, Xin-Gao Xiong, Hai Zheng
The relationship between Kruppel-like factor 4 (KLF4) and the Notch pathway was determined to investigate the effect of KLF4 on the activation of hepatic stellate cells and underlying mechanisms. Fifty SPF BALB/c mice were randomly divided into two groups. A liver fibrosis model was established in 25 mice as the experimental group, and the remaining 25 mice served as controls. On the day 0, 7, 14, and 35, liver tissues were removed for immunofluorescent detection. The Notch pathway inhibitor DAPT was added to the primary original hepatic stellate cells, and KLF4 and Notch-associated factor expression was detected by qRT-PCR...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27923814/mir-483-targeting-of-ctgf-suppresses-endothelial-to-mesenchymal-transition-therapeutic-implications-in-kawasaki-disease
#5
Ming He, Zhen Chen, Marcy Martin, Jin Zhang, Panjamaporn Sangwung, Brian Woo, Adriana Tremoulet, Chisato Shimizu, Mukesh K Jain, Jane C Burns, John Shyy
RATIONALE: Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. OBJECTIVE: We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis...
December 6, 2016: Circulation Research
https://www.readbyqxmd.com/read/27918060/effect-of-small-molecules-on-cell-reprogramming
#6
REVIEW
M Baranek, A Belter, M Z Naskręt-Barciszewska, M Stobiecki, W T Markiewicz, J Barciszewski
The essential idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are able to indefinitely self-renew and differentiate into all cell types of the body which makes them a potent substantial player in regenerative medicine. The easily accessible source of induced pluripotent stem cells may allow obtaining and cultivating tissues in vitro. Reprogramming refers to regression of mature cells to its initial pluripotent state. One of the approaches affecting pluripotency is the usage of low molecular mass compounds that can modulate enzymes and receptors leading to the formation of pluripotent stem cells (iPSCs)...
December 5, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27917474/germacrone-inhibits-adipogenesis-and-stimulates-lipolysis-via-the-amp-activated-protein-kinase-signalling-pathway-in-3t3-l1-preadipocytes
#7
Yuan-Ri Guo, Se-Young Choung
OBJECTIVES: In a previous study, we reported that Aster spathulifolius Maxim extract (ASE) inhibited lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Of the components in ASE, germacrone (GM) was identified as a potent bioactive constituent. GM is known for its anticancer and antiviral activity. However, the effects of GM and the molecular mechanism by which GM regulates adipogenesis and lipolysis were not reported. Therefore, we investigated the effect of GM on adipogenesis and lipolysis and to elucidate its underlying molecular mechanism...
December 5, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27909734/klf4-inhibits-tumor-growth-and-metastasis-by-targeting-microrna-31-in-human-hepatocellular-carcinoma
#8
Chuan Tian, Shanshan Yao, Li Liu, Youcheng Ding, Qingwang Ye, Xiao Dong, Yong Gao, Ning Yang, Qi Li
MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA‑31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA‑31 in hepatocellular carcinoma (HCC)...
November 24, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27907214/derivation-of-induced-trophoblast-cell-lines-in-cattle-by-doxycycline-inducible-piggybac-vectors
#9
Takamasa Kawaguchi, Dooseon Cho, Masafumi Hayashi, Tomoyuki Tsukiyama, Koji Kimura, Shuichi Matsuyama, Naojiro Minami, Masayasu Yamada, Hiroshi Imai
Trophectoderm lineage specification is one of the earliest differentiation events in mammalian development. The trophoblast lineage, which is derived from the trophectoderm, mediates implantation and placental formation. However, the processes involved in trophoblastic differentiation and placental formation in cattle remain unclear due to interspecies differences when compared with other model systems and the small repertoire of available trophoblast cell lines. Here, we describe the generation of trophoblast cell lines (biTBCs) from bovine amnion-derived cells (bADCs) using an induced pluripotent stem cell technique...
2016: PloS One
https://www.readbyqxmd.com/read/27907090/forkhead-box-c1-regulates-human-primary-keratinocyte-terminal-differentiation
#10
Lianghua Bin, Liehua Deng, Hengwen Yang, Leqing Zhu, Xiao Wang, Michael G Edwards, Brittany Richers, Donald Y M Leung
The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation...
2016: PloS One
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#11
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27900211/in-vivo-expression-of-reprogramming-factors-increases-hippocampal-neurogenesis-and-synaptic-plasticity-in-chronic-hypoxic-ischemic-brain-injury
#12
Soohyun Wi, Ji Hea Yu, MinGi Kim, Sung-Rae Cho
Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#13
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27894081/mbd3-inhibits-formation-of-liver-cancer-stem-cells
#14
Ruizhi Li, Qihua He, Shuo Han, Mingzhi Zhang, Jinwen Liu, Ming Su, Shiruo Wei, Xuan Wang, Li Shen
Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893734/an-ipsc-derived-vascular-model-of-marfan-syndrome-identifies-key-mediators-of-smooth-muscle-cell-death
#15
Alessandra Granata, Felipe Serrano, William George Bernard, Madeline McNamara, Lucinda Low, Priya Sastry, Sanjay Sinha
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS-hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in Marfan aortas, including defects in fibrillin-1 accumulation, extracellular matrix degradation, transforming growth factor-β (TGF-β) signaling, contraction and apoptosis; abnormalities were corrected by CRISPR-based editing of the FBN1 mutation...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27884981/tissue-damage-and-senescence-provide-critical-signals-for-cellular-reprogramming-in-vivo
#16
Lluc Mosteiro, Cristina Pantoja, Noelia Alcazar, Rosa M Marión, Dafni Chondronasiou, Miguel Rovira, Pablo J Fernandez-Marcos, Maribel Muñoz-Martin, Carmen Blanco-Aparicio, Joaquin Pastor, Gonzalo Gómez-López, Alba De Martino, Maria A Blasco, María Abad, Manuel Serrano
Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27881420/elongation-of-long-chain-fatty-acid-family-member-6-elovl6-driven-fatty-acid-metabolism-regulates-vascular-smooth-muscle-cell-phenotype-through-amp-activated-protein-kinase-kr%C3%A3-ppel-like-factor-4-ampk-klf4-signaling
#17
Hiroaki Sunaga, Hiroki Matsui, Saki Anjo, Mas Risky A A Syamsunarno, Norimichi Koitabashi, Tatsuya Iso, Takashi Matsuzaka, Hitoshi Shimano, Tomoyuki Yokoyama, Masahiko Kurabayashi
BACKGROUND: Fatty acids constitute the critical components of cell structure and function, and dysregulation of fatty acid composition may exert diverging vascular effects including proliferation, migration, and differentiation of vascular smooth muscle cells (VSMCs). However, direct evidence for this hypothesis has been lacking. We investigated the role of elongation of long-chain fatty acid member 6 (Elovl6), a rate-limiting enzyme catalyzing the elongation of saturated and monounsaturated long-chain fatty acid, in the regulation of phenotypic switching of VSMC...
November 23, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27879219/induced-pluripotent-stem-cells-ipscs-derived-from-cerebrotendinous-xanthomatosis-ctx-patient-s-fibroblasts-carrying-a-r395s-mutation
#18
Philip Höflinger, Stefan Hauser, Yvonne Theurer, Stefanie Weißenberger, Carlo Wilke, Ludger Schöls
Induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX) patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27879213/generation-of-hexa-deficient-hipscs-from-fibroblasts-of-a-tay-sachs-disease-patient
#19
Zhong Liu, Rui Zhao
Human iPSC line TSD-01-hiPSC was generated from fibroblasts of a patient with infantile Tay-Sachs disease (TSD). The patient is compound heterozygous at the HEXA gene by carrying a 1278insTATC allele and an IVS12+1G>C allele. STEMCCA lentivirus, which expresses OCT4, SOX2, KLF4, and c-MYC from a polycistronic transcript, were used for reprogramming. TSD-01-hiPSC express pluripotency markers such as OCT4, SOX2, NANOG, Tra-1-60, and alkaline phosphatase, and can differentiate into tissues from all the three embryonic germ layers...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27878761/genome-wide-association-analysis-of-the-sense-of-smell-in-u-s-older-adults-identification-of-novel-risk-loci-in-african-americans-and-european-americans
#20
Jing Dong, Annah Wyss, Jingyun Yang, T Ryan Price, Aude Nicolas, Michael Nalls, Greg Tranah, Nora Franceschini, Zongli Xu, Claudia Schulte, Alvaro Alonso, Steven R Cummings, Myriam Fornage, Dmitri Zaykin, Leping Li, Xuemei Huang, Stephen Kritchevsky, Yongmei Liu, Thomas Gasser, Robert S Wilson, Philip L De Jager, Andrew B Singleton, Jayant M Pinto, Tamara Harris, Thomas H Mosley, David A Bennett, Stephanie London, Lei Yu, Honglei Chen
The human sense of smell decreases with age, and a poor sense of smell are among the most important prodromal symptoms of several neurodegenerative diseases. Recent evidence further suggests a racial difference in the sense of smell among U.S. older adults. However, no genome-wide association study (GWAS) on the sense of smell has been conducted in African-Americans (AAs). We performed the first genome-wide meta-analysis of the sense of smell among 1979 AAs and 6582 European-Americans (EAs) from three U.S. aging cohorts...
November 23, 2016: Molecular Neurobiology
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