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Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

World Journal of Gastroenterology 2020年第33期26卷 4889-4899页

作者： Ronald neil Kostoff Michael Brandon Briggs Darla Roye Shores School of Public Policy Georgia Institute of TechnologyGainesvilleVA 20155United States Independent Consultant RoscommonMI 48653United States The Hopkins Resource for Intestinal Vitality and Enhancement the Johns Hopkins University School of MedicineBaltimoreMD 21287United States

Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed *** often includes lifelong immunosuppressive therapy and *** is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential *** of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug *** study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of *** searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from *** most recent 350 records were further analyzed for *** 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD *** of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and *** further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three ***-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.

关键词： Treatment repurposing Treatment repositioning Inflammatory bowel disease Literature-based discovery Text mining Crohn’s disease Ulcerative colitis Novel treatments

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Pierre Koenig, 1925-2004

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作者： neil Jackson.

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High-Level Accumulation of Exogenous Small RNAs Not Affecting Endogenous Small RNA Biogenesis and Function in Plants

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Journal of Integrative Agriculture 2014年第5期13卷 1017-1023页

作者： SHEN Wan-xia neil A Smith ZHOU Chang-yong WANG Ming-bo College of Plant Protection Southwest University CSIRO Plant Industry National Citrus Engineering Research Center Citrus Research Institute Chinese Academy of Agricultural Sciences

RNA silencing is a fundamental plant defence and gene control mechanism in plants that are directed by 20-24 nucleotide （nt） small interfering RNA （siRNA） and microRNA （miRNA）. Infection of plants with viral pathogens or transformation of plants with RNA interference （RNAi） constructs is usually associated with high levels of exogenous siRNAs, but it is unclear if these siRNAs interfere with endogenous small RNA pathways and hence affect plant development. Here we provide evidence that viral satellite RNA （satRNA） infection does not affect siRNA and miRNA biogenesis or plant growth despite the extremely high level of satRNA-derived siRNAs. We generated transgenic Nicotiana benthamiana plants that no longer develop the specific yellowing symptoms generally associated with infection by Cucumber mosaic virus （CMV） Y-satellite RNA （Y-Sat）. We then used these plants to show that CMV Y-Sat infection did not cause any visible phenotypic changes in comparison to uninfected plants, despite the presence of high-level Y-Sat siRNAs. Furthermore, we showed that the accumulation of hairpin RNA （hpRNA）-derived siRNAs or miRNAs, and the level of siRNA-directed transgene silencing, are not significantly affected by CMV Y-Sat infection. Taken together, our results suggest that the high levels of exogenous siRNAs associated with viral infection or RNAi-inducing transgenes do not saturate the endogenous RNA silencing machineries and have no significant impact on normal plant development.

关键词： Nicotiana benthamiana transformation satellite RNA RNA silencing small RNA

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Gene expression profiling of MYC-driven tumor signatures in porcine liver stem cells by transcriptome sequencing

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World Journal of Gastroenterology 2015年第7期21卷 2011-2029页

作者： Rajagopal N Aravalli neil C Talbot Clifford J Steer Department of Radiology University of Minnesota Medical School Minneapolis Beltsville Agricultural Research Center US Department of Agriculture Departments of Medicine and Genetics Cell Biology and Development University of Minnesota

AIM:To identify the genes induced and regulated by the MYC protein in generating tumors from liver stem ***:In this study,we have used an immortal porcine liver stem cell line,PICM-19,to study the role of c-MYC in ***-19 cells were converted into cancer cells(PICM-19-CSCs)by overexpressing human *** identify MYC-driven differential gene expression,transcriptome sequencing was carried out by RNA sequencing,and genes identified by this method were validated using real-time *** vivo tumorigenicity studies were then conducted by injecting PICM-19-CSCs into the flanks of immunodeficient ***:Our results showed that MYC-overexpressing PICM-19 stem cells formed tumors in immunodeficient mice demonstrating that a single oncogene was sufficient to convert them into cancer cells(PICM-19-CSCs).By using comparative bioinformatics analyses,we have determined that>1000 genes were differentially expressed between PICM-19 and *** ontology analysis further showed that the MYCinduced,altered gene expression was primarily associated with various cellular processes,such as metabolism,cell adhesion,growth and proliferation,cell cycle,inflammation and ***,six genes expressed by PICM-19 cells(CDO1,C22orf39,DKK2,ENPEP,GPX6,SRPX2)were completely silenced after MYC-induction in PICM-19-CSCs,suggesting that the absence of these genes may be critical for ***:MYC-driven genes may serve as promising candidates for the development of hepatocellular carcinoma therapeutics that would not have deleterious effects on other cell types in the liver.

关键词： Hepatocellular carcinoma MYC Stem cells Gene expre

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Norse mythology

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作者： neil Gaiman.

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Acoustofluidic scanning fluorescence nanoscopy with a large field of view

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Microsystems & Nanoengineering 2024年第3期10卷 159-167页

作者： Geonsoo Jin neil Upreti Joseph Rich Jianping Xia Chenglong Zhao Tony Jun Huang Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA The MITRE Corporation McLeanVA 22102USA

Large-field nanoscale fluorescence imaging is invaluable for many applications,such as imaging subcellular structures,visualizing protein interactions,and high-resolution tissue ***,conventional fluorescence microscopy requires a trade-off between resolution and field of view due to the nature of the optics used to form the *** overcome this barrier,we developed an acoustofluidic scanning fluorescence nanoscope that simultaneously achieves superior resolution,a large field of view,and strong fluorescent *** acoustofluidic scanning fluorescence nanoscope utilizes the superresolution capabilities of microspheres that are controlled by a programmable acoustofluidic device for rapid fluorescence enhancement and *** acoustofluidic scanning fluorescence nanoscope resolves structures that cannot be resolved with conventional fluorescence microscopes with the same objective lens and enhances the fluorescent signal by a factor of~5 without altering the field of view of the *** improved resolution realized with enhanced fluorescent signals and the large field of view achieved via acoustofluidic scanning fluorescence nanoscopy provides a powerful tool for versatile nanoscale fluorescence imaging for researchers in the fields of medicine,biology,biophysics,and biomedical engineering.

关键词： field resolution utilize

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Biology neil A. Campbell...[et al.]. 5th ed.

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1999年

作者： neil A. Campbell...[et al.].

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Validity of long-term and short-term recall of occupational sitting time in Finnish and Chinese office workers

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Journal of Sport and Health Science 2020年第4期9卷 345-351页

作者： Ying Gao neil J.Cronin Nina Nevala Taija Finni Neuromuscular Research Center Faculty of Sport and Health SciencesUniversity of Jyv€askyl€aJyv€askyl€a FI-40014Finland Finnish Institute of Occupational Health Helsinki FI-00250Finland

Background:As sedentary behavior is a global health issue,there is a need for methods of self-reported sitting *** accuracy and reliability of these methods should also be tested in various populations and different cultural *** study examined the validity of longterm and short-term recall of occupational sitting time in Finnish and Chinese ***:Two cohort groups of office-based workers(58.6%female,age range 2267 years)participated:a Finnish group(FIN,n=34)and a Chinese group(CHI,n=36).Long-term(past 3-month sitting)and short-term(daily sitting assessed on 5 consecutive days)single-item measures were used to assess self-reported occupational sitting *** from each participant were compared to objectively measured occupational sitting time assessed via thigh-mounted accelerometers,with Spearman’s rho(r)used to assess validity and the Bland-Altman method used to evaluate *** of variation depicted day-to-day variability of time spent on sitting at ***:In the total study sample,the results showed that both long-term and short-term recall correlated with accelerometer-derived sitting time(r=0.532,95%confidence intervals(CI):0.3360.684,p<0.001;r=0.533,95%CI:0.4490.607,p<0.001,respectively).Compared to objectively measured sitting time,self-reported occupational sitting time was 2.4%(95%CI:0.5%to 5.3%,p=0.091)and 2.2%(95%CI:0.7%3.6%,p=0.005)greater for long-term and short-term recall,*** agreement level was within the range21.2%to 25.9%for long-term recall,and24.2%to 28.5%for short-term *** a 5-day work week,day-to-day variation of sitting time was 9.4%§11.4%according to short-term recall and 10.4%§8.4%according to accelerometry-derived occupational sitting ***:Overall,both long-term and short-term self-reported instruments provide acceptable measures of occupational sitting time in an office-based workplace,but their utility at the individual level is limited due

关键词： Accelerometry Daily recall Office workers Questionnaire Self-report Sitting time Validity

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The role of lactose in weanling pig nutrition:a literature and meta-analysis review

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Journal of Animal Science and Biotechnology 2021年第2期12卷 462-478页

作者： Jinbiao Zhao Zeyu Zhang Shuai Zhang Greg Page neil W.Jaworski State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityNo.2 Yuanmingyuan West RoadBeijing 100193China Trouw Nutrition Innovation Stationsstraat 773800AG AmersfoortNetherlands

Lactose plays a crucial role in the growth performance of pigs at weaning because it is a palatable and easily digestible energy source that eases the transition from milk to solid ***,the digestibility of lactose declines after weaning due to a reduction in endogenous lactase activity in *** a result,some lactose may be fermented in the gastrointestinal tract of *** of lactose by intestinal microbiota yields lactic acid and volatile fatty acids,which may positively regulate the intestinal environment and microbiome,resulting in improved gastrointestinal health of weanling *** hypothesize that the prebiotic effect of lactose may play a larger role in weanling pig nutrition as the global feed industry strives to reduce antibiotic usage and pharmacological levels of zinc oxide and supra-nutritional levels of *** presented in this review indicates that high dietary lactose improves growth performance of piglets,as well as the growth of beneficial bacteria,particularly Lactobacillus,with the positive effects being more pronounced in the first 2 weeks after ***,the risk of post-weaning diarrhea may increase as pigs get older due to reduced lactase activity,high dietary lactose concentrations,and larger feed intakes,all of which may lead to excessive lactose fermentation in the intestine of the ***,dietary lactose levels exert different effects on growth performance and gastrointestinal physiological functions in different feeding phases of weanling ***,no formal recommendation of lactose for weanling pigs has been reported.A meta-analysis approach was used to determine that diets fed to swine should include 20%,15%,and 0 lactose from d 0-7,d 7-14,and d 14-35 post-weaning,***,sustainable swine production demands that economics must also be taken into account as lactose and lactose containing ingredients are ***,alternatives to lactose,so called“lactose equivalents

关键词： Growth performance Gut health Gut microbiota Lactose Lactose equivalents Weanling pig

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Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury

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World Journal of Gastroenterology 2004年第12期10卷 1699-1708页

作者： neil Kaplowitz Gastroenterology/Liver Division Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA

Deficiencies in vitamins or other factors(B6,B12,folic acid, betaine)and genetic disorders for the metabolism of the non-protein amino acid-homocysteine(Hcy)lead to hyperhomocysteinemia(HHcy).HHcy is an integral component of several disorders including cardiovascular disease,neurodegeneration,diabetes and alcoholic liver *** unleashes mediators of inflammation such as NFκB,IL-1β,IL-6,and IL-8,increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide(NO),and induces endoplasrnic reticulum(ER)stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation,and *** models have played an important role in determining the biological effects of *** stress may also be involved in other liver diseases such as α_1-antitrypsin(α_1-AT)deficiency and hepatitis C and/or B virus *** research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury,study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans,and examine polymorphisrn of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.

关键词： Animals Endoplasmic Reticulum Humans Hyperhomocysteinemia Liver Diseases, Alcoholic Oxidative Stress

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