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The landscape and clinical relevance of intronic polyadenylation in human cancers

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Journal of Genetics and Genomics 2024年第10期51卷 1030-1039页

作者： Xiaomeng Cheng Guanghui Jiang Xiaolan Zhou Jing Wang Zhaozhao Zhao Jiayu Zhang Ting Ni State Key Laboratory of Genetic Engineering National Clinical Research Center for Aging and MedicineHuashan HospitalCollaborative Innovation Center of Genetics and DevelopmentHuman Phenome InstituteCenter for Evolutionary BiologyShanghai Engineering Research Center of Industrial MicroorganismsSchool of Life SciencesFudan UniversityShanghai 200438China MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock Insttutes of Biomedical SciencesSchool of Life SciencesInner Mongolia UniversityHohhotInner Mongolia 010070China

Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer ***,the comprehensive landscape of IPA events across various cancer types is ***,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)*** identify a total of 21,835 IPA events,almost half of which are ubiquitously *** identify 2761 unique dynamically changed IPA events across cancer ***,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic *** analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug ***,we develop a user-friendly data portal,IPACancer Atlas(http://***/Pancan_IPA),to search and explore IPAs in cancer.

关键词： Intronic polyadenylation Cancer Single nucleotide variant Drug sensitivity Database

Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events

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Stroke & Vascular Neurology 2024年第2期9卷 108-125,I0001-I0005页

作者： Miao Lin Liubing Hu Si Shen Jiyue Liu Yanyan Liu Yixian Xu Honglin Chen Kazuo Sugimoto Jianshuang Li Ikuo Kamitsukasa Takaki Hiwasa Hao Wang Anding Xu Stroke Center The First Affiliated HospitalJinan UniversityGuangzhouChina Department of Anesthesiology The First Affiliated HospitalJinan UniversityGuangzhouChina The biomedical Translational Research Institute Faculty of Medical ScienceJinan UniversityGuangzhouChina Department of Radiology Medical Imaging CenterThe First Affiliated HospitalJinan UniversityGuangzhouChina Department of Biochemistry and Genetics Graduate School of MedicineChiba UniversityChibaJapan Department of Neurology Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Department of Neurology Chiba Rosai HospitalChibaJapan Department of Neurology Chibaken Saiseikai Narashino HospitalChibaJapan Department of Neurological Surgery Graduate School of MedicineChiba UniversityChibaJapan

Background Atherosclerosis(AS)and tumours are the leading causes of death worldwide and share common risk factors,detection methods and molecular ***,searching for serum markers shared by AS and tumours is beneficial to the early diagnosis of *** The sera of 23 patients with AS-related transient ischaemic attack were screened by serological identification of antigens through recombinant cDNA expression cloning(SEREX),and cDNA clones were *** function enrichment analysis was performed on cDNA clones to identify their biological pathways and determine whether they were related to AS or ***,gene–gene and protein–protein interactions were performed and AS-associated markers would be *** expression of AS biomarkers in human normal organs and pan-cancer tumour tissues were ***,immune infiltration level and tumour mutation burden of various immune cells were *** curves analysis could show the expression of AS markers in *** AS-related sera were screened by SEREX,and 83 cDNA clones with high homology were *** functional enrichment analysis,it was found that their functions were closely related to AS and tumour *** multiple biological information interaction screening and the external cohort validating,poly(A)binding protein cytoplasmic 1(PABPC1)was found to be a potential AS *** assess whether PABPC1 was related to pan-cancer,its expression in different tumour pathological stages and ages was *** AS-associated proteins were closely related to cancer immune infiltration,we investigated and found that PABPC1 had the same role in ***,analysis of Kaplan-Meier survival curves revealed that high PABPC1 expression in pan-cancer was associated with high risk of *** Through the findings of SEREX and bioinformatics pan-cancer analysis,we concluded that PABPC1 might serve as a potential biomarker for the

关键词： diagnosis cancer organs

Wireless,battery-free,and fully implantable electrical neurostimulation in freely moving rodents

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Microsystems & Nanoengineering 2021年第4期7卷 127-138页

作者： Alex Burton Sang Min Won Arian Kolahi Sohrabi Tucker Stuart Amir Amirhossein Jong Uk Kim Yoonseok Park Andrew Gabros John A.Rogers Flavia Vitale Andrew G.Richardson Philipp Gutruf Department of biomedical Engineering University of ArizonaTucsonAZ 85721USA Department of Electrical and Computer Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Department of Neurosurgery Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Querrey Simpson Institute for Bioelectronics Northwestern UniversityEvanstonIL 60208USA Center for Bio-Integrated Electronics Northwestern UniversityEvanstonIL 60208USA Department of Mechanical Engineering Northwestern UniversityEvanstonIL 60208USA Department of biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Materials science and Engineering Northwestern UniversityEvanstonIL 60208USA Department of Neurological Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA Department of Neurology BioengineeringPhysical Medicine&RehabilitationCenter for Neuroengineering and TherapeuticsUniversity of PennsylvaniaPhiladelphiaPA 19104USA Bio5 Institute and Neuroscience GIPP University of ArizonaTucsonAZ 85721USA Department of Electrical and Computer Engineering University of ArizonaTucsonAZ 85721USA

Implantable deep brain stimulation(DBS)systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic ***,long-term efficacy of DBS is limited,and chronic neuroplastic changes and associated therapeutic mechanisms are not well *** and mechanistic investigation,typically accomplished in small animal models,is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise *** overcome these challenges,we demonstrate a fully implantable,wireless,battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real *** devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance,surface-engineered platinum *** devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid *** of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.

关键词： stimulation battery moving

Anti-cancer liposomal chemophototherapy using bilayer-localized photosensitizer and cabazitaxel

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Nano Research 2022年第5期15卷 4302-4309页

作者： Boyang Sun Sanjana Ghosh Xuedan He Wei-Chiao Huang Breandan Quinn Meiling Tian Dushyant Jahagirdar Moustafa T.Mabrouk Joaquin Ortega Yumiao Zhang Shuai Shao Jonathan F.Lovell Translational Medicine Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of biomedical Engineering University at BuffaloState University of New YorkBuffaloNY 14260USA Department of Anatomy and Cell Biology McGill UniversityMontrealQuebec H3A0C7Canada school of Chemical Engineering and Technology Tianjin UniversityTianjin 300000China

Photodynamic therapy(PDT)is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent ***,we demonstrated that liposomes containing a bilayer-anchored photosensitizer(porphyrin-phospholipid;PoP)can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with *** the present work,we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of ***(CTX)is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar%PoP,generating CTX-loaded PoP liposomes(CTX-PoP-Lip).CTX-PoP-Lip showed unilamellar vesicle morphology,and exhibited integrity in storage and serum,while maintaining drug stability under laser *** vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip,compared to control *** vivo pharmacokinetic analysis revealed that following intravenous administration to mice,CTX and PoP exhibited somewhat altered circulation profiles,suggesting that the CTX may have exchanged with serum factors in ***,when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors,tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were *** results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.

关键词： photodynamic therapy cabazitaxel liposome chemotherapy porphyrin-phospholipid

biomolecular basis of the role of diabetes mellitus in osteoporosis and bone fractures

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World Journal of Diabetes 2013年第4期4卷 101-113页

作者： Bipradas Roy Biotechnology and Genetic Engineering Life Science School Khulna University

Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old *** is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by *** aim of this review is to summarize the possible mechanisms through which diabetes may induce *** mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive *** negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone *** factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle *** decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.

关键词： Diabetes Osteoporosis Diabetic neuropathy Muscle atrophy Insulin Receptor activator for nuclear factor-B ligand Interleukin 6 AngiotensinⅡ Tumor necrosis factor Advanced glycation end product

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

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International Journal of Oral science 2022年第3期14卷 321-333页

作者： Mengqi Zhu Sainan Min Xiangdi Mao Yuan Zhou Yan Zhang Wei Li Li Li Liling Wu Xin Cong Guangyan Yu Department of Oral and Maxillofacial Surgery Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Department of Physiology and Pathophysiology Peking University School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular SciencesMinistry of Educationand Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijingChina Department of biomedical Informatics Peking University School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijingChina

Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully *** aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of *** found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS ***-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 ***,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito ***,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on *** together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.

关键词： Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis IgG

CD98 is a promising prognostic biomarker in biliary tract cancer

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Hepatobiliary & Pancreatic Diseases International 2014年第6期13卷 654-657页

作者： Kyoichi Kaira Yutaka Sunose Noboru Oriuchi Yoshikatsu Kanai Izumi Takeyoshi Department of Medicine and Molecular science Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Department of Thoracic and Visceral Surgery Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Department of Diagnostic Radiology and Nuclear Medicine Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Division of Biosystem Pharmacology Department of Pharmacology Graduate School of Medicine Osaka University Osaka Japan

ABSTRACT： CD98 has been described to play a crucial role in tumor progression and survival. However, the role of CD98 in biliary tract cancer remains unclear. We found that 36.7% of all patients with biliary tract cancer had a high CD98 expression. Statistical analysis using Spearman＇s rank correlation showed that CD98 was significantly correlated with L-type amino acid transporter 1 （LAT1, r=0.562, P〈0.001）, Ki-67 （r=0.230, P=0.006） and CD34 （r=0.290, P=0.005）. Multivariate analysis confirmed that a high CD98 expression was an independent prognostic factor for predicting poor outcome. CD98 is closely associated with tumor growth, biological aggressiveness, and survival of patients. With these data we proposed that CD98 expression is necessary for the development and pathogenesis of biliary tract cancer.

关键词： CD98 biliary tract cancer amino acid transporter prognostic factor

Influences of Reaction Parameters and Ce Contents on Structure and Properties of Nano-scale Ce-HA Powders

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Journal of Materials science & Technology 2014年第8期30卷 776-781页

作者： L.J.Sun D.G.Guo W.A.Zhao L.Y.Wang K.W.Xu State Key Laboratory for Mechanical Behavior of Materials School of Materials Science and EngineeringXi'an Jiaotong University Chao Family Comprehensive Cancer Center Department of Pharmaceutical SciencesUniversity of California Irvine Sue and Bill Gross Stem Cell Research Center University of California Irvine The Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life SciencesNankai University Xi'an University of Arts and science

Ce-incorporated apatite（Ce-HA） nano-scale particles with different Ce percentage contents（atomic ratio of Ce to Ce ＋ Ca is 5%,10%and 20%,respectively） were synthesized via a simple wet chemical method in this *** crystal structure,chemical groups,thermal stability,crystal morphologies and crystal sizes of the Ce-HA nano-particles were characterized by X-ray diffraction（XRD）,Fourier transform infrared spectroscopy（FTIR）,and transmission electron microscopy（TEM）.The influences of reaction temperature,reaction time,pH value,and the atomic ratio of Ce to Ce ＋ Ca on the structure and performance of Ce-HA particles were *** results show that the lattice constants,particle sizes,crystallinity and thermal stability of Ce-HA vary with the doped Ce *** the increase of Ce content,the lattice constants of the Ce-HA nano-particles remarkably increase but the particle size,crystallinity and thermal stability gradually *** reaction temperature as well as the reaction time has no significant effect on the properties of the final products,while the pH value has a direct relationship with their final chemical *** obtained Ce-HA nanosize particles possess potential application in preparing artificial bone implants,bone tissue engineering scaffold and other bioactive coatings.

关键词： Cerium Apatite Nano-scale powder Wet chemical approach biomedical materials

Pathway-based Analysis Tools for Complex Diseases: A Review

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Genomics, Proteomics & Bioinformatics 2014年第5期12卷 210-220页

作者： Lv Jin Xiao-Yu Zuo Wei-Yang Su Xiao-Lei Zhao Man-Qiong Yuan Li-Zhen Han Xiang Zhao Ye-Da Chen Shao-Qi Rao Institute for Medical Systems Biology and Department of Medical Statistics and Epidemiology School of Public HealthGuangdong Medical College Department of Medical Statistics and Epidemiology School of Public Health Sun Yat-Sen University Community Health Service Management Center of Panyu District Department of Statistical sciences School of Mathematics and Computational Science Sun Yat-Sen University

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehen- sive understanding of the molecular mechanisms underlying complex diseases. Extensive studies uti- lizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available path- way-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are dis- cussed. This review will provide a useful guide to dissect complex diseases.

关键词： Complex disease Pathway-based analysisAlgorithms Software and databases