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OUGENE： a disease associated over-expressed and under-expressed gene database

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Science Bulletin 2016年第10期61卷 752-754页

作者： Xiaoyong Pan Hong-Bin Shen Section for Animal Genetics Bioinformatics and Breeding Center for Non-Coding RNA in Technology and Health University of Copenhagen 1870 Frederiksberg Denmark Department of Disease Systems Biology Novo NordiskFoundation Center for Protein Research University ofCopenhagen 1870 Frederiksberg Denmark Institute of Image Processing and Pattern Recognition Shanghai Jiao Tong University and Key Laboratory of System Control and Information Processing Ministry of Education of China Shanghai 200240 China

Gene over-expression or under-expression is closely associated with human diseases, which contributes to phenotypic variations and diversity. To our best knowledge, there is no single open specific resource available to provide the association information between gene over- or under-expression and various diseases. In this study, we presented a comprehensive disease-associated over- and under-expressed gene database （OUGene） based on our proposed text mining pipeline and several open curated databases. It contains total 41,269 unique associa- tions between 7,238 over- or under-expressed genes and 1,480 diseases, which are supported by 81,974 evidence sentences from 56,442 articles. The OUGene is compre- hensive and covers most important therapeutic areas. Meanwhile a new scoring system is designed to rank the associations based on benchmarking against hand-curated data. OUGene provides an easy-of-use web interface for researchers to analyze these data and visualize the associ- ated networks, which can give insights to the complex relationships between over- and under-expressed genes and diseases at a system level. It is available at ***. ***/bioinf/OUGene/.

关键词： Text mining Gene over- and under-expression Disease Database

Ticagrelor Protects against Sepsis-Induced Acute Kidney Injury through an Adenosine Receptor-Dependent Pathway

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Current Medical Science 2022年第3期42卷 505-512页

作者： Yu-han CAO Qian-cheng XU Yu-wei WANG Yang LING Cong FU Department of Nephrology Yi Ji Shan Hospital affiliated to Wan Nan Medical CollegeWuhu 241000China Key laboratory of non-coding rna Transformation Research of Anhui Higher Education Institution Wan Nan Medical CollegeWuhu 241000China Department of Critical Care Medicine Yi Ji Shan Hospital affiliated to Wan Nan Medical CollegeWuhu 241000China Department of Cardiology Yi Ji Shan Hospital Affiliated to Wan Nan Medical CollegeWuhu 241000China

Objective Ticagrelor is a widely used anti-platelet ***,the mechanisms by which ticagrelor protects against sepsis-induced acute kidney injury(AKI)have not been clearly *** designed this study to explore the protective effect of ticagrelor on sepsis-induced AKI and to explore the underlying *** C57BL6J mice received oral ticagrelor(20 mg/kg and 50 mg/kg)for 7 days,and then caecal ligation and puncture(CLP)were *** adenosine receptor antagonist,CGS15943,was administered(10 mg/kg,intraperitoneal injection)to block the adenosine pathway 2 h before *** 24 h,serum creatinine levels were *** acid-Schiff(PAS)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining were employed to analyze pathological changes and cell *** concentrations of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and mrna expression of tissue TNF-αand IL-1βwere *** blotting analysis was used to determine AKT and mammalian target of rapamycin(mTOR)protein expression in the *** PAS staining showed less swelling of renal tubules,and TUNEL staining revealed less cell apoptosis in the ticagrelor group than in the CLP *** creatinine levels were significantly lower in the ticagrelor group than in the CLP ***,significantly lower serum and kidney levels of TNF-αand IL-1βwere observed in the ticagrelor ***15943 blocked the effects of *** blotting analysis showed increased phosphorylation of AKT and mTOR in the kidneys of the 50 mg/kg ticagrelor *** adenosine receptor antagonist inhibited the activation of AKT and *** This study demonstrates that the protective effect of ticagrelor on sepsis-induced AKI depends on adenosine receptor activation and the subsequent increase of AKT and mTOR phosphorylation.

关键词： sepsis acute kidney injury adenosine phosphatidyl-inositol 3-kinase mammalian target of rapamycin

Whole genome sequencing and its applications in medical genetics

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Frontiers of Electrical and Electronic Engineering in China 2016年第2期4卷 115-128页

作者： Jiaxin Wu Mengmeng Wu Ting Chen Rui Jiang MOE Key laboratory of bioinformatics Bioinformatics Division and Center for Synthetic&Systems BiologyTNLIST Department of Automation Tsinghua UniversityBeijing 100084China

Fundamental improvement was made for genome sequencing since the next-generation sequencing （NGS） came out in the 2000s. The newer technologies make use of the power of massively-parallel short-read DNA sequencing, genome alignment and assembly methods to digitally and rapidly search the genomes on a revolutionary scale, which enable large-scale whole genome sequencing （WGS） accessible and practical for researchers. Nowadays, whole genome sequencing is more and more prevalent in detecting the genetics of diseases, studying causative relations with cancers, making genome-level comparative analysis, reconstruction of human population history, and giving clinical implications and instructions. In this review, we first give a typical pipeline of whole genome sequencing, including the lab template preparation, sequencing, genome assembling and quality control, variants calling and annotations. We compare the difference between whole genome and whole exome sequencing （WES）, and explore a wide range of applications of whole genome sequencing for both mendelian diseases and complex diseases in medical genetics. We highlight the impact of whole genome sequencing in cancer studies, regulatory variant analysis, predictive medicine and precision medicine, as well as discuss the challenges of the whole genome sequencing.

关键词： whole genome sequencing whole exome sequencing next-generation sequencing non-coding regulatoryvariant

The DrugPattern tool for drug set enrichment analysis and its prediction for beneficial effects of oxLDL on type 2 diabetes

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Journal of Genetics and Genomics 2018年第7期45卷 389-397页

作者： Chuanbo Huang Weili Yang Junpei wang Yuan Zhou Bin Geng Georgios Kararigas Jichun Yang Qinghua Cui Department of Biomedical Informatics Department of Physiology and Pathophysiology MOE Key Lab of Cardiovascular Sciences School of Basic Medical Sciences Center for Non-Coding RNA Medicine Peking UniversityBeijing 100191China School of Mathematics Sciences Huaqiao University Quanzhou 362021 China Hypertension Center Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease National Center for Cardiovascular Diseases Beijing 100037 China Charit-Universitatsmedizin Berlin. Corporate Member of Freie Universitat Berlin Humboldt-Universitat zu Berlin Berlin Institute of Health Institute of Gender in Medicine and Center for Cardiovascular Research. DZHK (German Centre for Cardiovascular Research) 10115 Berlin Germany Center of bioinformatics Key Laboratory for Neuro-lnformation of Ministry of Education School of Life Science and Technology University of Electronic Science and Technology of China Chengdu 610054 China

Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bio- informatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules of a list of drugs are limited. In this study, we developed a web-based tool, DrugPattern, for drug set enrichment analysis. We first collected and curated 7019 drug sets, including indications, adverse reactions, targets, pathways, etc. from public databases. For a list of interested drugs, DrugPat- tern then evaluates the significance of the enrichment of these drugs in each of the 7019 drug sets. To validate DrugPattern, we employed it for the prediction of the effects of oxidized low-density lipoprotein （oxLDL）, a factor expected to be deleterious. We predicted that oxLDL has beneficial effects on some diseases, most of which were supported by evidence in the literature. Because DrugPattern predicted the potential beneficial effects of oxLDL in type 2 diabetes （T2D）, animal experiments were then performed to further verify this prediction. As a result, the experimental evidences validated the DrugPattern prediction that oxLDL indeed has beneficial effects on T2D in the case of energy restriction. These data confirmed the prediction accuracy of our approach and revealed unexpected protective roles for oxLDL in various diseases. This study provides a tool to infer patterns and rules in biomedical datasets based on drug set enrichment analysis.

关键词： Enrichment analysis Drug Data mining oxLDL Type 2 diabetes

Biliary tract cancer stem cells-translational options and challenges

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World Journal of Gastroenterology 2017年第14期23卷 2470-2482页

作者： Christian Mayr Matthias Ocker Markus Ritter Martin Pichler Daniel Neureiter Tobias Kiesslich Department of Internal Medicine I Paracelsus Medical University laboratory for Tumour Biology and Experimental Therapies Institute of Physiology and PathophysiologyParacelsus Medical University Tanslational Medicine Oncology Department of Gastroenterology CBF CharitéUniversity Medicine Berlin laboratory for Tumour Biology and Experimental Therapies(TREAT) Laboratory for Functional and Molecular Membrane PhysiologyParacelsus Medical University Department for Radon Therapy Research Ludwig Boltzmann Cluster for Arthritis and RehabilitationInstitute of Physiology and PathophysiologyParacelsus Medical University Research Unit for non-coding rna and genome editing in cancer Division of OncologyDepartment of Internal MedicineMedical University of Graz Institute of Pathology Paracelsus Medical University Cancer Cluster Salzburg

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-rnas and the tumor microenvironment with cancer stem cells.

关键词： Biliary tract cancer cancer stem cells Cancer stem cell markers Tumor microenvironment Micro-rnas

Polyphenols from Securidaca inappendiculata alleviated acute lung injury in rats by inhibiting oxidative stress sensitive pathways

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Chinese Herbal Medicines 2021年第3期13卷 381-388页

作者： Cong-lan Ji Sheng Dai Hong Liu Ji-yang Dong Chun-sheng Liu Jian Zuo Department of Pharmacy Anhui College of Traditional Chinese MedicineWuhu 241000China Department of Electronic Science Xiamen UniversityXiamen 361005China Yijishan Hospital Wannan Medical CollegeWuhu 241000China Key laboratory of non-coding rna Transformation Research of Anhui Higher Education Institution(Wannan Medical College) Wuhu 241000China Provincial Engineering laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui(Wannan Medical College) Wuhu 241000China

Objective:Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south *** this study,we aimed to explore its bioactive constituent which contributes to the anti-inflammatory ***:Polyphenol-enriched and polyphenol-deprived fractions(PRF and PDF,respectively)were separated from the ethanolic extract by HPD300 macroporous resin-based method,and their antiinflammatory activities were investigated on a lipopolysaccharide(LPS)-induced acute lung injury(ALI)model in *** possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 ***:Both Folin-Ciocalteu and^(1)H nuclear magnetic resonance(NMR)analyses showed that polyphenolic content in PRF was approximately 10 times higher than that of PDF,and this observation reflected in their antioxidative *** but not PDF significantly decreased the level of malondialdehyde,suppressed the expression of nicotinamide phosphoribosyltransferase(NAMPT)protein,and improved the severity of ALI in *** at 10μg/mL effectively downregulated the expression of proteins NAMPT,HMGB1,TLR4,and p-p65,and scavenged the intracellular reactive oxygen species(ROS)in LPS-primed RAW264.7 cells.N-acetyl-L-cysteine exhibited similar inhibitory effects on ROS production and NAMPT-mediated TLR4/NF-κB activation in vitro,whereas nicotinamide mononucleotide antagonized all the changes induced by PRF during ***:As an antioxidant,PRF exhibited potent anti-inflammatory activity under both in vivo and in vitro conditions by downregulating NAMPT and TLR4/NF-κ***,polyphenols were identified as important bioactive constituents in *** targeting oxidative stress-sensitive proinflammatory pathways.

关键词： antioxidant polyphenols reactive oxygen species(ROS) Securidaca inappendiculata Hassk TLR4/NF-κB

Emerging roles of non-coding rnas in epigenetic regulation

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Science China(Life Sciences) 2016年第3期59卷 227-235页

作者： Juan Chen Yuanchao Xue Key Lab of rna biology Institute of Biophysics Chinese academy of Sciences

Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of rna transcripts that do not code for proteins. These non-coding rnas(nc rnas) highlight the central role of rna in gene regulation. nc rnas are arbitrarily divided into two main groups: The first includes small rnas, such as mi rnas, pi rnas, and endogenous si rnas, that usually range from 20 to 30 nt, while the second group includes long non-coding rnas(lnc rnas), which are typically more than 200 nt in length. These nc rnas were initially thought to merely regulate gene expression at the post-transcriptional level, but recent studies have indicated that nc rnas, especially lnc rnas, are extensively associated with diverse chromatin remodeling complexes and target them to specific genomic loci to alter DNA methylation or histone status. These findings suggest an emerging theme of nc rnas in epigenetic regulation. In this review, we discuss the wide spectrum of nc rnas in the regulation of DNA methylation and chromatin state, as well as the key questions that needs to be investigated and acknowledging the elegant design of these intriguing macromolecules.

关键词： non-coding rnas lncrnas DNA methylation chromatin remodeling

Small rna in rice genome

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Science China(Life Sciences) 2002年第5期45卷 497-503页

作者：王凯朱小蓬钟兰陈润生 Beijing Genomics Institute/Center of Genomics and bioinformatics Chinese Academy of Sciences Beijing 101300 China Beijing Genomics Institute/Center of Genomics and Bioinformatics Chinese Academy of Sciences Beijing 101300 China College of Life Sciences Peking University Beijing 100871 China Beijing Genomics Institute/Center of Genomics and Bioinformatics Chinese Academy of Sciences Beijing 101300 China laboratory of bioinformatics Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Rice has many characteristics of a model plant. The recent completion of the draft of the rice genome represents an important advance in our knowledge of plant biology and also has an important contribution to the understanding of general genomic evolution. Besides the rice genome finishing map, the next urgent step for rice researchers is to annotate the genes and noncoding functional sequences. The recent work shows that noncoding rnas (ncrnas) play significant roles in biological systems. We have explored all the known small rnas (a kind of ncrna) within rice genome and other six species sequences, including Arabidopsis, maize, yeast, worm, mouse and pig. As a result we find 160 out of 552 small rnas (srnas) in database have homologs in 108 rice scaffolds, and almost all of them (99.41%) locate in intron regions of rice by gene predication. 19 srnas only appear in rice. More importantly, we find two special U14 srnas: one is located in a set of srna ZMU14SNR9(s) which only appears in three plants, 86% sequences of them can be compared as the same sequence in rice, Arabidopsis and maize; the other conserved srna XLHS7CU14 has a segment which appears in almost all these species from plants to animals. All these results indicate that srna do not have evident borderline between plants and animals.

关键词： ncrna, srna, conserved sequences, plant-specific srna gene.

A Novel Structural Measure Separating non-coding rnas from Genomic Backgrounds

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Tsinghua Science and Technology 2015年第5期20卷 474-483页

作者： Yingfeng Wang Russell L.Malmberg Liming Cai the School of Information Technology Middle Georgia State University Department of Plant Biology and Institute of bioinformatics University of Georgia Department of Computer Science and Institute of bioinformatics University of Georgia

rna secondary structure has become the most exploitable feature for ab initio detection of non-coding rna（nc rna） genes from genome sequences. Previous work has used Minimum Free Energy（MFE） based methods developed to identify nc rnas by measuring sequence fold stability and certainty. However, these methods yielded variable performances across different nc rna species. Designing novel reliable structural measures will help to develop effective nc rna gene finding tools. This paper introduces a new rna structural measure based on a novel rna secondary structure ensemble constrained by characteristics of native rna tertiary structures. The new method makes it possible to achieve a performance leap from the previous structure-based methods. Test results on standard nc rna datasets（benchmarks） demonstrate that this method can effectively separate most nc rnas families from genome backgrounds.

关键词： rna secondary structure rna tertiary structure Inside algorithm