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1m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment显示文摘AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways.Suomi MG Fouraschen Petra E de Ruiter Jaap Kwekkeboom Ron WF de Bruin Geert Kazemier Herold J Metselaar Hugo W Tilanus Luc JW van der Laan Jeroen de Jonge 2013World Journal of Transplantation2013,3,3:6
2High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6.Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders 2016Horticulture Research2016,3,1:6
3Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van 1997Cell1997,,2:6
4Artificial intelligence in gastroenterology: A state-of-the-art review显示文摘The development of artificial intelligence(AI)has increased dramatically in the last 20 years,with clinical applications progressively being explored for most of the medical specialties.The field of gastroenterology and hepatology,substantially reliant on vast amounts of imaging studies,is not an exception.The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions(e.g.,identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus,pancreatic malignancies),detection of lesions(e.g.,polyp identification and classification,small-bowel bleeding lesion on capsule endoscopy,pancreatic cystic lesions),development of objective scoring systems for risk stratification,predicting disease prognosis or treatment response[e.g.,determining survival in patients post-resection of hepatocellular carcinoma),determining which patients with inflammatory bowel disease(IBD)will benefit from biologic therapy],or evaluation of metrics such as bowel preparation score or quality of endoscopic examination.The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract,including the upper,middle and lower tracts;IBD;the hepatobiliary system;and the pancreas,discussing the findings and clinical applications,as well as outlining the current limitations and future directions in this field.Paul T Kröner Megan ML Engels Benjamin S Glicksberg Kipp W Johnson Obaie Mzaik Jeanin E van Hooft Michael B Wallace Hashem B El-Serag Chayakrit Krittanawong 2021World Journal of Gastroenterology2021,27,40:6
5Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial显示文摘Jeanin E van Hooft Willem A Bemelman Bas Oldenburg Andreas W Marinelli Martijn F Lutke Holzik Marina J Grubben Mirjam A Sprangers Marcel G Dijkgraaf Paul Fockens 2011Lancet Oncology2011,,4:3
6miR147b:白细胞介素-1β介导的人类星形胶质细胞炎症中的新型关键调节因子显示文摘星形胶质细胞是大脑炎症过程的重要介质,可能在包括癫痫在内的几种神经系统疾病中起重要作用。星形胶质细胞中可生产几种miRNA,是炎症通路的关键调节因子,还可能用作治疗靶标。本研究将探索在体外IL-1β介导的炎症条件下,星形胶质细胞内生成的miRNA及其功能,并在人癫痫脑组织中验证。我们通过测序评估IL-1β刺激的人胎儿星形胶质细胞培养物中的miRNA和mRNA表达。使用miRNA模拟物在细胞培养物中过表达miRNA。使用原位杂交技术检测患有结节性硬化症复合体或颞叶癫痫伴海马硬化患者的切除脑组织中miRNA的表达。我们发现了2种差异表达的miRNA:miR146a和miR147b,它们与免疫/炎症反应相关基因的表达增加有关。既往有研究报道,在星形胶质细胞和结节性硬化复合细胞培养物中使用IL-1β刺激后,miR147b的过表达降低了促炎介质IL-6和COX-2的表达。miR146a和miR147b过表达降低了星形胶质细胞的增殖并促进人神经干细胞的神经元分化。miR147b在致癫痫脑中的星形胶质细胞中表达增加。由于其抗炎和恢复异常星形细胞增殖和促进神经元分化的能力,miR146a和miR147b作为与炎症相关的神经疾病(例如癫痫)的潜在治疗靶标值得进一步研究。van Scheppingen J Mills JD Zimmer TS Broekaart DWM Iori V Bongaarts A Anink JJ Iyer AM Korotkov A Jansen FE van Hecke W Spliet WG van Rijen PC Baayen JC Vezzani A van Vliet EA Aronica E 聂昊 2018神经损伤与功能重建2018,13,12:3
7A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species显示文摘Quantitative trait loci(QTL)mapping approaches rely on the correct ordering of molecular markers along the chromosomes,which can be obtained from genetic linkage maps or a reference genome sequence.For apple(Malus domestica Borkh),the genome sequence v1 and v2 could not meet this need;therefore,a novel approach was devised to develop a dense genetic linkage map,providing the most reliable marker-loci order for the highest possible number of markers.The approach was based on four strategies:(i)the use of multiple full-sib families,(ii)the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism(SNP)markers,(iii)the construction of a single backcross-type data set including all families,and(iv)a two-step map generation procedure based on the sequential inclusion of markers.The map comprises 15417 SNP markers,clustered in 3 K HaploBlock markers spanning 1267 cM,with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM.Moreover,chromosome 5 was oriented according to its homoeologous chromosome 10.This map was useful to improve the apple genome sequence,design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies.Its collinearity with the genome sequences v1 and v3 are reported.To our knowledge,this is the shortest published SNP map in apple,while including the largest number of markers,families and individuals.This result validates our methodology,proving its value for the construction of integrated linkage maps for any outbreeding species.Erica A Di Pierro Luca Gianfranceschi Mario Di Guardo Herma JJ Koehorst-van Putten Johannes W Kruisselbrink Sara Longhi Michela Troggio Luca Bianco Hélène Muranty Giulia Pagliarani Stefano Tartarini Thomas Letschka Lidia Lozano Luis Larisa Garkava-Gustavsson Diego Micheletti Marco CAM Bink Roeland E Voorrips Ebrahimi Aziz Riccardo Velasco François Laurens W Eric van de Weg 2016Horticulture Research2016,3,1:3
8Biomimetic extraction as a tool to identify chemicals with high bioconcentration potential: an illustration by two fragrances in sewage treatment plant effluents and surface waters显示文摘Verbruggen E M J van Loon W M G M and Tonkes M Environ Sci Te0,,:2
9Stem cells for cardiac repair: an introduction显示文摘Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms,though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation.There are still severalmajor hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.Bastiaan C du Pr(e) Pieter A Doevendans Linda W van Laake 2013Journal of Geriatric Cardiology2013,10,2:2
10Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial显示文摘Friedrich W Mohr Marie-Claude Morice A Pieter Kappetein Ted E Feldman Elisabeth St?hle Antonio Colombo Michael J Mack David R Holmes Marie-angèle Morel Nic Van Dyck Vicki M Houle Keith D Dawkins Patrick W Serruys 2013The Lancet . 2013 (9867)2013,,9867:2
11Interstitial radiation therapy for early-slagenasal vestibule cancer: A continuing quest for optimal tumor control and cosmesis显示文摘Levendag P C Nijdam W M van Moolenburgh S E 2006Int Radiat Oncol Biol Phys2006,66,1:1
12Sorption of benzene,toluene,ethylbenzene,and xylene (BTEX) compounds by hectorite clays exchanged with aromatic organic cations显示文摘JAYNES W E VANS G F 1999Clays Clay Miner1999,47,3:1
13A new technique of reversibly adsorbed phosphate显示文摘 Fokkink L G J Van Reimsdijk W H 1987Soil Sci Soc Am J1987,51,:1
14Overexpression of a novel Arabidopsis gene related to putative zinc-transporter genes from animals can lead to enhanced zinc resistance and accumulation显示文摘VAN DER ZAAL B J NEUTEBOOM L W PINAS J E 1999Plant Physiology1999,119,:1
15Simultaneous nitrification and denitrification in aerobic chemostat culture of Thiosphaera patotropha显示文摘ROBERTSON L A VAN NIEL E W J TORREMANS R A M 1988Applied Environmental Microbiology1988,54,11:1
16Hierarchical crosstraining in work-in-process-constrained systems 显示文摘Gel E S Hopp W J Van Oyen M P 2007lie Transactions2007,39,2:1
17The Influence of Crosslinkage on the Distribution Cofficients and Anion Exchange Behavior of Some Elements in Hydrochloric Acid显示文摘Van der Walt T N Strelow F W E Verheij R 1985Solvent Extr Ion Exc1985,3,:1
18Effects of organic forms of zinc on growth performance,tissue zinc distribution,and immune response of weanling pigs显示文摘Van Heugten E T Spears J W Kegley E B 2003J Anim Sci2003,81,:1
19Ecological footprints of Benin, Bhutan, Costa Rica and the Netherlands 显示文摘van Vuuren D P Smeets E M W 2000Ecological Economics2000,34,:1
20A Wavelet-Based Watermarking Algorithm for Ownership Verification of Digital Images 显示文摘WWNG Y W DOHERTY J F VAN DYCK R E 2002IEEE Transactions on Image Processing2002,11,2:1
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