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https://www.readbyqxmd.com/read/28935668/chemical-reprogramming-of-mouse-embryonic-and-adult-fibroblast-into-endoderm-lineage
#1
Shangtao Cao, Shengyong Yu, Yan Chen, Xiaoshang Wang, Chunhua Zhou, Yuting Liu, Junqi Kuang, He Liu, Dongwei Li, Jing Ye, Yue Qing, Shilong Chu, Linlin Wu, Lin Guo, Yinxiong Li, Xiaodong Shu, Jiekai Chen, Jing Liu, Duanqing Pei
We report here an approach to redirect somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts (MEFs) to epithelial-like cells (ciELC) with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting ELCs that can be further reprogrammed to endodermal progenitor cells (ciEPC). Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocytes that can rescue mice from acute live injury...
September 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928864/high-immunoreactivity-of-duox2-is-associated-with-poor-response-to-preoperative-chemoradiation-therapy-and-worse-prognosis-in-rectal-cancers
#2
Shih-Chun Lin, I-Wei Chang, Pei-Ling Hsieh, Ching-Yih Lin, Ding-Ping Sun, Ming-Jen Sheu, Ching-Chieh Yang, Li-Ching Lin, Hong-Lin He, Yu-Feng Tian
Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28926866/expression-of-imprinted-genes-kcnq1-and-cdkn1c-during-the-course-of-differentiation-from-mouse-embryonic-stem-cells-into-islet-like-cells-in-vitro
#3
Feng Liu, Peng Yu-Huan, Li Qiang, Liu Chanchan
To study the effects of inducement on the expression of mouse embryonic stem cells SF1-G imprinted genes, Kcnq1 and Cdkn1c during the course of differentiation into islet-like cells in vitro. Mouse embryonic fibroblasts (MEFs) were isolated from pregnant mice embryos and fibroblast feeder cells were prepared by treating 3-5th generations MEFs with Mitomycin C. Moreover, mouse embryonic stem cells were induced to differentiate into islet-like cells directly. RT-PCR and Immunofluorescence staining were used to test the expression of islet cell-specific markers...
September 19, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28926719/exosomes-derived-from-embryonic-stem-cells-inhibit-doxorubicin-and-inflammation-induced-pyroptosis-in-muscle-cells
#4
Zahra Tavakoli Dargani, Reetu Singla, Taylor Johnson, Rakesh C Kukreja, Dinender Kumar Singla
Doxorubicin (Dox) is an effective anticancer drug. Unfortunately, it causes cardio and muscle toxicity due to increased oxidative stress and inflammation; however, it remains unknown whether Dox induces "pyroptosis"- an inflammation mediated cell death. We investigated whether Dox induces pyroptosis in mouse soleus muscle (Sol 8) cells in vitro and to show the protective effect of embryonic stem cells-exosomes (ES-exos) on pyroptosis. Doxorubicin and inflammation induced in vitro model was generated. Pyroptosis was confirmed using immunohistochemistry and western blotting of putative markers caspase-1, IL1β and pro-inflammatory cytokine IL-18...
September 19, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28924038/passive-dna-demethylation-preferentially-up-regulates-pluripotency-related-genes-and-facilitates-the-generation-of-induced-pluripotent-stem-cells
#5
Songwei He, Hao Sun, Lilong Lin, Yixin Zhang, Jinlong Chen, Lining Liang, Yuan Li, Mengdan Zhang, Xiao Yang, Xiaoshan Wang, Fuhui Wang, Feiyan Zhu, Jiekai Chen, Duanqing Pei, Hui Zheng
A high proliferation rate has been observed to facilitate somatic cell reprogramming, but the pathways that connect proliferation and reprogramming have not been reported. DNA methyltransferase 1 (DNMT1) methylates hemimethylated CpG sites produced during S phase and maintains stable inheritance of DNA methylation. Impairing this process results in passive DNA demethylation. In this study, we show that the cell proliferation rate positively correlated with the expression of Dnmt1 in G1 phase. In addition, as determined by whole genome bisulfate sequencing and high-performance liquid chromatography, global DNA methylation of mouse embryonic fibroblasts (MEFs) was significantly higher in G1 phase than in G2/M phase...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915637/btk-suppresses-myeloma-cellular-senescence-through-activating-akt-p27-rb-signaling
#6
Chunyan Gu, Hailin Peng, Yue Lu, Hongbao Yang, Zhidan Tian, Gang Yin, Wen Zhang, Sicheng Lu, Yi Zhang, Ye Yang
We previously explored the role of BTK in maintaining multiple myeloma stem cells (MMSCs) self-renewal and drug-resistance. Here we investigated the elevation of BTK suppressing MM cellular senescence, a state of irreversible cellular growth arrest. We firstly discovered that an increased expression of BTK in MM samples compared to normal controls by immunohistochemistry (IHC), and significant chromosomal gain in primary samples. In addition, BTK high-expressing MM patients are associated with poor outcome in both Total Therapy 2 (TT2) and TT3 cohorts...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904206/a-disease-associated-frameshift-mutation-in-caveolin-1-disrupts-caveolae-formation-and-function-through-introduction-of-a-de-novo-er-retention-signal
#7
Courtney A Copeland, Bing Han, Ajit Tiwari, Eric D Austin, James E Loyd, James D West, Anne K Kenworthy
Caveolin-1 (CAV1) is an essential component of caveolae and is implicated in numerous physiological processes. Recent studies have identified heterozygous mutations in the CAV1 gene in patients with pulmonary arterial hypertension (PAH), but the mechanisms by which these mutations impact caveolae assembly and contribute to disease remain unclear. To address this question, we examined the consequences of a familial PAH-associated frameshift mutation in CAV1, P158PfsX22, on caveolae assembly and function. We show that C-terminus of the CAV1 P158 protein contains a functional ER-retention signal that inhibits ER exit and caveolae formation and accelerates CAV1 turnover in Cav1(-/-) MEFs...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28903506/a-population-based-assessment-of-the-impact-of-7-and-13-valent-pneumococcal-conjugate-vaccines-on-macrolide-resistant-invasive-pneumococcal-disease-emergence-and-decline-of-streptococcus-pneumoniae-serotype-19a-cc320-with-dual-macrolide-resistance-mechanisms
#8
Max R Schroeder, Scott T Chancey, Stephanie Thomas, Wan-Hsuan Kuo, Sarah W Satola, Monica M Farley, David S Stephens
Background: Macrolide efflux encoded by mef(E)/mel and ribosomal methylation encoded by erm(B) confer most macrolide resistance in Streptococcus pneumoniae. Introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) in 2000 reduced macrolide-resistant invasive pneumococcal disease (MR-IPD) due to PCV7 serotypes (6B, 9V, 14, 19F, and 23F). Methods: In this study, the impact of PCV7 and PCV13 on MR-IPD was prospectively assessed. A 20-year study of IPD performed in metropolitan Atlanta, Georgia, using active, population-based surveillance formed the basis for this study...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28903387/hyperactivated-mtorc1-downregulation-of-foxo3a-pdgfr%C3%AE-akt-cascade-restrains-tuberous-sclerosis-complex-associated-tumor-development
#9
Li Wang, Zhaofei Ni, Yujie Liu, Shuang Ji, Fuquan Jin, Keguo Jiang, Junfang Ma, Cuiping Ren, Hongbing Zhang, Zhongdong Hu, Xiaojun Zha
Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor α (PDGFRα) expression was mediated by mTORC1...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899780/hydrogen-peroxide-production-is-affected-by-oxygen-levels-in-mammalian-cell-culture
#10
Lucas A Maddalena, Shehab M Selim, Joao Fonseca, Holt Messner, Shannon McGowan, Jeffrey A Stuart
Although oxygen levels in the extracellular space of most mammalian tissues are just a few percent, under standard cell culture conditions they are not regulated and are often substantially higher. Some cellular sources of reactive oxygen species, like NADPH oxidase 4, are sensitive to oxygen levels in the range between 'normal' physiological (typically 1-5%) and standard cell culture (up to 18%). Hydrogen peroxide in particular participates in signal transduction pathways via protein redox modifications, so the potential increase in its production under standard cell culture conditions is important to understand...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28893373/peroxiredoxin-i-participates-in-the-protection-of-reactive-oxygen-species-mediated-cellular-senescence
#11
Young-Ho Park, Hyun-Sun Kim, Jong-Hee Lee, Seon-A Choi, Jin-Man Kim, Goo Taeg Oh, Sang Won Kang, Sun-Uk Kim, Dae-Yeul Yu
Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity in a variety of tissues...
September 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28886341/cdk10-mutations-in-humans-and-mice-cause-severe-growth-retardation-spine-malformations-and-developmental-delays
#12
Christian Windpassinger, Juliette Piard, Carine Bonnard, Majid Alfadhel, Shuhui Lim, Xavier Bisteau, Stéphane Blouin, Nur'Ain B Ali, Alvin Yu Jin Ng, Hao Lu, Sumanty Tohari, S Zakiah A Talib, Noémi van Hul, Matias J Caldez, Lionel Van Maldergem, Gökhan Yigit, Hülya Kayserili, Sameh A Youssef, Vincenzo Coppola, Alain de Bruin, Lino Tessarollo, Hyungwon Choi, Verena Rupp, Katharina Roetzer, Paul Roschger, Klaus Klaushofer, Janine Altmüller, Sudipto Roy, Byrappa Venkatesh, Rudolf Ganger, Franz Grill, Farid Ben Chehida, Bernd Wollnik, Umut Altunoglu, Ali Al Kaissi, Bruno Reversade, Philipp Kaldis
In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice...
September 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28886186/the-cardiac-calsequestrin-gene-transcription-is-modulated-at-the-promoter-by-nfat-and-mef-2-transcription-factors
#13
Rafael Estrada-Avilés, Gabriela Rodríguez, Angel Zarain-Herzberg
Calsequestrin-2 (CASQ2) is the main Ca2+-binding protein inside the sarcoplasmic reticulum of cardiomyocytes. Previously, we demonstrated that MEF-2 and SRF binding sites within the human CASQ2 gene (hCASQ2) promoter region are functional in neonatal cardiomyocytes. In this work, we investigated if the calcineurin/NFAT pathway regulates hCASQ2 expression in neonatal cardiomyocytes. The inhibition of NFAT dephosphorylation with CsA or INCA-6, reduced both the luciferase activity of hCASQ2 promoter constructs (-3102/+176 bp and -288/+176 bp) and the CASQ2 mRNA levels in neonatal rat cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28881432/protein-4-1r-is-involved-in-the-transport-of-5-aminolevulinic-acid-by-interaction-with-gats-in-mef-cells
#14
Shuwei Ning, Qiaozhen Kang, Dandan Fan, Jingjing Liu, Chaoyue Xue, Xiaolin Zhang, Cong Ding, Jianying Zhang, Qian Peng, Zhenyu Ji
5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) has been successfully used in the treatment of cancers. However, the mechanism of 5-ALA transportation into cancer cells is still not fully elucidated. Previous studies have confirmed that the efficiency of 5-ALA-PDT could be affected by the membrane skeleton protein 4.1R. In this study we investigated the role of 4.1R in the transport of 5-ALA into cells. Wild-type (4.1R(+/+) ) and 4.1R gene knockout (4.1R(-/-) ) mouse embryonic fibroblast (MEF) cells were incubated with 1 mM 5-ALA and different concentrations of specific inhibitors of GABA transporters GAT(1-3)...
September 7, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28878875/the-effects-of-17-alpha-estradiol-to-inhibit-inflammation-in-vitro
#15
Roberta S Santos, Luciana A de Fatima, Aaron P Frank, Everardo M Carneiro, Deborah J Clegg
BACKGROUND: 17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown. METHODS: To begin to address this, we analyzed the ability of 17 α-E2 and 17 β-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ERα (ERKO) male and female mice...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28877982/non-canonical-regulation-of-insulin-mediated-erk-activation-by-phosphoinositide-3-kinase-%C3%AE
#16
Maradumane L Mohan, Arunachal Chatterjee, Swetha Ganapathy, Sromona Mukherjee, Sowmya Srikanthan, George P Jolly, Rohit S Anand, Sathyamangla V Naga Prasad
Classically Class IB Phosphoinositide 3-kinase (PI3Kγ) plays a role in ERK activation following G-protein coupled receptor (GPCR) activation. Knock-down of PI3Kγ unsuspectingly resulted in loss of ERK activation to receptor tyrosine kinase-agonists like epidermal growth factor or insulin. Mouse embryonic fibroblasts (MEFs) or primary adult cardiac fibroblasts isolated from PI3Kγ knock-out mice (PI3KγKO) showed loss in insulin-stimulated ERK activation. However, expression of kinase-dead PI3Kγ resulted in rescue of insulin-stimulated ERK activation...
September 6, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28877759/the-effects-of-17-alpha-estradiol-to-inhibit-inflammation-in-vitro
#17
Roberta S Santos, Luciana A de Fatima, Aaron P Frank, Everardo M Carneiro, Deborah J Clegg
BACKGROUND: 17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown. METHODS: To begin to address this, we analyzed the ability of 17 α-E2 and 17 β-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ERα (ERKO) male and female mice...
September 6, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28876505/n-3-oxo-acyl-homoserine-lactone-induces-apoptosis-primarily-through-a-mitochondrial-pathway-in-fibroblasts
#18
Aaron M Neely, Guoping Zhao, Christian Schwarzer, Nicole S Stivers, Aaron G Whitt, Shuhan Meng, Joseph A Burlison, Terry E Machen, Chi Li
N-(3-oxododecanoyl)-homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum-sensing molecule for bacteria-bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signaling pathway(s) leading to C12-triggered cell death is (are) still not completely known. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in "initiator" caspases or "effector" caspases...
September 6, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28874882/glucosyltransferase-activity-of-clostridium-difficile-toxin-b-triggers-autophagy-mediated-cell-growth-arrest
#19
Ruina He, Jingyu Peng, Pengfei Yuan, Junjiao Yang, Xiaoji Wu, Yinan Wang, Wensheng Wei
Autophagy is a bulk cell-degradation process that occurs through the lysosomal machinery, and many reports have shown that it participates in microbial pathogenicity. However, the role of autophagy in Clostridium difficile infection (CDI), the leading cause of antibiotics-associated diarrhea, pseudomembranous colitis and even death in severe cases, is not clear. Here we report that the major virulent factor toxin B (TcdB) of Clostridium difficile elicits a strong autophagy response in host cells through its glucosyltransferase activity...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871046/loss-of-ocrl-increases-ciliary-pi-4-5-p2-in-oculocerebrorenal-syndrome-of-lowe
#20
Philipp P Prosseda, Na Luo, Biao Wang, Jorge A Alvarado, Yang Hu, Yang Sun
Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL1, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane poorly understood. Here we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P...
September 4, 2017: Journal of Cell Science
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