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| 1 | Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation显示文摘AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation. | Ashley M Lakner Cathy C Moore Alyssa A Gulledge Laura W Schrum | 2010 | World Journal of Gastroenterology2010，16，40： | 23 |
| 2 | Diffusion-weighted magnetic resonance imaging to predict response of hepatocellular carcinoma to chemoembolization显示文摘AIM: To investigate whether intra-procedural diffusion- weighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during trans- catheter arterial chemoembolization (TACE). METHODS: Sixteen patients (15 male), aged 59 ±11 years (range: 42-81 years) underwent a total of 21 separate treatments for unresectable HCC in a hybrid magnetic resonance/interventional radiology suite. Ana- tomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. Tumor enhancement and apparent diffusion coefficient (ADC, mm2/s) values were assessed immediately before and at 1 and 3 mo after TACE. We calculated the percent change (PC) in ADC values at all time points. We compared follow-up ADC values to baseline values using a paired t test (α = 0.05). RESULTS: The intra-procedural sensitivity, specificity, and positive and negative predictive values (%) for detecting a complete or partial 1-mo tumor response using ADC PC thresholds of ±5%, ±10%, and ±15% were 77, 67, 91, and 40; 54, 67, 88, and 25; and 46, 100, 100, and 30, respectively. There was no clear predictive value for the 3-mo follow-up. Compared to baseline, the immediate post-procedure and 1-mo mean ADC values both increased; the latter obtaining statistical significance (1.48 ± 0.29 mm2/s vs 1.65 ± 0.35 × 10-3 mm2/s, P < 0.014). CONCLUSION: Intra-procedural ADC changes of > 15% predicted 1-mo anatomical HCC response with the greatest accuracy, and can provide valuable feedback at the time of TACE. | Johnathan C Chung Neel K Naik Robert J Lewandowski Mary F Mulcahy Laura M Kulik Kent T Sato Robert K Ryu Riad Salem Andrew C Larson Reed A Omary | 2010 | World Journal of Gastroenterology2010，16，25： | 13 |
| 3 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 4 | Comparative transcriptomics of Central Asian Vitis vinifera accessions reveals distinct defense strategies against powdery mildew显示文摘Grape powdery mildew(PM),caused by the biotrophic ascomycete Erysiphe necator,is a devastating fungal disease that affects most Vitis vinifera cultivars.We have previously identified a panel of V.vinifera accessions from Central Asia with partial resistance to PM that possess a Ren1-like local haplotype.In this study,we show that in addition to the typical Ren1-associated late post-penetration resistance,these accessions display a range of different levels of disease development suggesting that alternative alleles or additional genes contribute to determining the outcome of the interaction with the pathogen.To identify potential Ren1-dependent transcriptional responses and functions associated with the different levels of resistance,we sequenced and analyzed the transcriptomes of these Central Asian accessions at two time points of PM infection.Transcriptomes were compared to identify constitutive differences and PM-inducible responses that may underlie their disease resistant phenotype.Responses to E.necator in all resistant accessions were characterized by an early up-regulation of 13 genes,most encoding putative defense functions,and a late down-regulation of 32 genes,enriched in transcriptional regulators and protein kinases.Potential Ren1-dependent responses included a hotspot of co-regulated genes on chromosome 18.We also identified 81 genes whose expression levels and dynamics correlated with the phenotypic differences between the most resistant accessions‘Karadzhandahal’,DVIT3351.27,and O34-16 and the other genotypes.This study provides a first exploration of the functions associated with varying levels of partial resistance to PM in V.vinifera accessions that can be exploited as sources of genetic resistance in grape breeding programs. | Katherine C H Amrine Barbara Blanco-Ulate Summaira Riaz Dániel Pap Laura Jones Rosa Figueroa-Balderas M Andrew Walker Dario Cantu | 2015 | Horticulture Research2015，2，1： | 3 |
| 5 | Heavy metal immobilization by chemical amendments in a polluted soil and influence on white lupin growth显示文摘 | Paola C Laura S Pietro M | 2005 | Chemosphere2005，60，： | 1 |
| 6 | Protective effects of N-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat显示文摘 | Salvatore C Emanuela M laura D | 2001 | FASEB J2001，15，： | 1 |
| 7 | Predictive models of the effect of temperature, pH and acetic and lactic acids on the growth of Listeria moocytogene显示文摘 | George S M Richardson Laura C C Peck M W | 1996 | International Journal of Food Microbiology1996，32，： | 1 |
| 8 | Micromechanical adhesion force measurements between hydrate particles in hydrocarbon oils and their modifications显示文摘 | Dieker Laura E Aman Zachary M George Nathan C | 2009 | Energy Fuelsy2009，23，： | 1 |
| 9 | Proyecyive effects of N-acetylcysteine on lung injury and red blood cell modification insuced by carrageenan in the rat显示文摘 | Salvatore C Emanuela M Laura D | 2001 | FASEB J2001，15，： | 1 |
| 10 | Micromechanical adhesion force measurements between hydrate particles in hydrocarbon oils and their modifications显示文摘 | Laura E D Zachary M A Nathan C G | 2009 | Energy Fuels2009，23，： | 1 |
| 11 | Evaluation of the interaction mechanisms between red muds and heavy metals显示文摘 | LAURA S PAOLA C PIETRO M | 2006 | Hazard Mater2006，136，3： | 1 |
| 12 | Mode of action of ferric and ferrous iron salts in activa- ted sludge 显示文摘 | Ioannis Oikonomidis Laura J Burrous Carliell-Marquet C M | 2010 | Journal of Chemical Technology and Bio- technology2010，85，8： | 1 |
| 13 | Micromechanical adhesion force measurements between hydrate particles in hydrocarbon oils and their modifications显示文摘 | Dieker Laura E Aman Zachary M George Nathan C Sum Amadeu K Sloan E D Koh C A | | 0，，： | 1 |
| 14 | Recombineering mycobacteria and their phages显示文摘 | Julia C V K Laura J M Graham F H | 2008 | Nat Rev Microbiol2008，6，11： | 1 |
| 15 | A geographic analysis of wind turbine placement in northern California显示文摘 | LAURA C R ROSS K M | 2006 | Energy Policy2006，34，15： | 1 |
| 16 | Protective effects of N- acetycysteine on lung injury and red blood cell modification induced by carrageenan in the rat 显示文摘 | Salvatore C Emanuela M Laura D | 2001 | Paseb J2001，15，7： | 1 |
| 17 | Spatially-resolved EELS analysis of antibody distribution on biofunctionalized magnetic nanoparticles显示文摘 | Raul A Laura D M Laura C Alvaro M Marcel T Valeria G Jesus M D L F Clara M Ricardo 1 | 2013 | ACS Nano2013，7，5： | 1 |
| 18 | Maize HapMap2 identifies extant variation from a genome in flux 显示文摘 | Jer-Ming Chia Chi Song Peter J Bradbury Denise Cos- tich Natalia de Leon John Doebley Robert J Elshire Brandon Gaut Laura Geller Jeffrey C Glaubitz Michael Gore Kate E Guill Jim Holland Matthew B Hufford Jinsheng Lai Meng Li Xin Liu Yanli Lu Richard Mc- Combie Rebecca Nelson Jesse Poland Boddupalli M Prasanna Tanja Pyhajarvi Tingzhao Rong Rajandeep S Sekhon Qi Sun Maud I Tenaillon Feng Tian Jun Wang Xun Xu Zhiwu Zhang Shawn M Kaeppler Jef- frey Ross-lbarra Michael D McMullen Edward S Buck- ler Gengyun Zhang Yunbi Xu Doreen Ware | 2012 | Nat Genet2012，，44： | 1 |
| 19 | Genetic diversity of twelve switchgrass populations using molecular and morphological mark- ers显示文摘 | Laura M C Joshua H Chris M | 2010 | Bioenerg Res2010，3，3： | 1 |
| 20 | Study of the Organic-lnorganic Phase Interactions in Polyester-Titania Hybrids显示文摘 | LAURA M C MARIASTELLA S ANTONINO P | 2008 | Polymer2008，49，5： | 1 |
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