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

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

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Protein tyrosine phosphatases:emerging role in cancer therapy resistance

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Cancer Communications 2024年第6期44卷 637-653页

作者： Min Zhao Wen Shuai Zehao Su Ping Xu Aoxue Wang Qiu Sun Guan Wang Innovation center of Nursing research Nursing Key Laboratory of Sichuan ProvinceDepartment of BiotherapyCancer Center and State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalWest China School of NursingSichuan UniversityChengduSichuanP.R.China West China biomedical Big Data center Med-X Center for InformaticsSichuan UniversityChengduSichuanP.R.China Emergency Department Zigong Fourth People’s HospitalChengduSichuanP.R.China

Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular *** of signal transduction proteins caused by protein tyrosine phosphatases(PTPs)contributed their role as a convergent node to mediate cross-talk between signaling *** the context of cancer,PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical *** is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor *** evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors,reversing drug resistance that was responsible for clinical failures during cancer *** covered:This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint *** opinion:This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor *** clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.

关键词： cancer treatment combination therapy drug resistance protein tyrosine phosphatase

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The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 619-631页

作者： Sijia Wu Zhiwei Fan Pora Kim Liyu Huang Xiaobo Zhou School of Life Science and Technology Xidian UniversityXi’an 710071China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610040China center for Computational Systems Medicine School of Biomedical InformaticsThe University of Texas Health Science Center at HoustonHoustonTX 77030USA

Adenosine-to-inosine(A-to-I)RNA editing,constituting nearly 90%of all RNA editing events in humans,has been reported to contribute to the tumorigenesis in diverse ***,the comprehensive map for functional A-to-I RNA editing events in cancers is still *** fill this gap,we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome *** individual candidate among1,500,000 quantified RNA editing events,we performed diverse types of downstream functional ***,we identified 24,236 potentially functional A-to-I RNA editing events,including the cases in APOL1,IGFBP3,GRIA2,BLCAP,and *** events might play crucial roles in the scenarios of tumorigenesis,due to their tumor-related editing frequencies or probable effects on altered expression profiles,protein functions,splicing patterns,and microRNA regulations of tumor *** functional A-to-I RNA editing events(https://***/CAeditome/)will help better understand the cancer pathology from the A-to-I RNA editing aspect.

关键词： A-to-I RNA editing Cancer Protein recoding Alternative splicing MicroRNA regulation

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A meta-analysis of oxidative stress markers in schizophrenia

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Science China(Life Sciences) 2010年第1期53卷 112-124页

作者： ZHANG Ming1,2,ZHAO ZhongMing3,HE Lin1,2,4 & WAN ChunLing1,2 1 Bio-X center,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200030,China 2 Institutes for Nutritional Sciences,Shanghai Institute of Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 3 Departments of biomedical informatics,Psychiatry,and Cancer Biology,Vanderbilt University Medical center,Nashville,TN 37232,USA 4 Institutes of biomedical Sciences,Fudan University,Shanghai 200032,China Bio-X center Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) Shanghai Jiao Tong University Shanghai China Institutes for Nutritional Sciences Shanghai Institute of Biological Sciences Chinese Academy of Sciences Shanghai China Departments of biomedical informatics Psychiatry and Cancer Biology Vanderbilt University Medical Center Nashville USA Institutes of biomedical Sciences Fudan University Shanghai China

Oxidative stress has been identified as a possible element in the neuropathological processes of schizophrenia(SCZ).Alteration of oxidative stress markers has been reported in SCZ studies,but with inconsistent *** evaluate the risk of oxidative stress to schizophrenia,a meta-analysis was conducted,including five markers of oxidative stress [thiobarbituric reactive substances(TBARS),nitric oxide(NO),catalase(CAT),glutathione peroxidase(GP) and superoxide dismutase(SOD)] in SCZ patients versus healthy *** study showed that TBARS and NO significantly increased in SCZ,while SOD activity significantly decreased in the disorganized type of SCZ *** significant effect size was found for the activities of GP and CAT in SCZ patients(P>0.05).Egger’s regression test observed no significant publication bias across the oxidative stress markers,but found high heterogeneities in all the 5 *** subgroup analysis suggested that the ethnicity,sample size of patients and sample sources may contribute to the heterogeneity of the results for TBARS,NO and *** result further demonstrated the involvement of oxidative stress in the pathophysiology of schizophrenia.

关键词： schizophrenia oxidative stress meta-analysis lipid peroxidation nitric oxide antioxidant enzymes

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Modeling the causal regulatory network by integrating chromatin accessibility and transcriptome data

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National Science Review 2016年第2期3卷 240-251页

作者： Yong Wang Rui Jiang Wing Hung Wong Department of Statistics Department of Biomedical Data ScienceBio-X ProgramStanford University Academy of Mathematics and Systems Science National Center for Mathematics and Interdisciplinary SciencesChinese Academy of Sciences MOE Key Laboratory of Bioinformatics Bioinformatics Division and Center for Synthetic and Systems BiologyTNLISTDepartment of AutomationTsinghua University

Cell packs a lot of genetic and regulatory information through a structure known as chromatin,*** is wrapped around histone proteins and is tightly packed in a remarkable *** express a gene in a specific coding region,the chromatin would open up and DNA loop may be formed by interacting enhancers and ***,the mediator and cohesion complexes,sequence-specific transcription factors,and RNA polymerase Ⅱ are recruited and work together to elaborately regulate the expression *** is in pressing need to understand how the information,about when,where,and to what degree genes should be expressed,is embedded into chromatin structure and gene regulatory *** to large consortia such as Encyclopedia of DNA Elements(ENCODE) and Roadmap Epigenomic projects,extensive data on chromatin accessibility and transcript abundance are available across many tissues and cell *** rich data offer an exciting opportunity to model the causal regulatory ***,we will review the current experimental approaches,foundational data,computational problems,interpretive frameworks,and integrative models that will enable the accurate interpretation of regulatory ***,we will discuss the efforts to organize,analyze,model,and integrate the DNA accessibility data,transcriptional data,and functional genomic regions *** believe that these efforts will eventually help us understand the information flow within the cell and will influence research directions across many fields.

关键词： gene regulatory network open chromatin DNA accessibility transcription factor colocalization statistical model data integration

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Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors

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Protein & Cell 2014年第1期5卷 48-58页

作者： Kejing Zhang Guang-Hui Liu Fei Yi Nuria Montserrat Tomoaki Hishida Concepcion Rodriguez Esteban Juan Carlos Izpisua Belmonte] Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Department of Molecular and Cellular Physiology Stanford University School of Medicine 265 Campus Drive StanfordCA 94305 USA center for Regenerative Medicine in Barcelona Dr. Aiguader 88 08003 Barcelona Spain biomedical research Networking center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) BarcelonaSpain

The generation of functional retinal pigment epithelium （RPE） is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration （AMD）. Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Bestl：：GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Bestl：：GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmen- tation upon activation of Retinoic acid （RA） and Sonic Hedgehog （SHH） signaling pathways. Our study not only established an ideal platform to investigate the tran- scriptional network regulating the RPE cell fate deter- mination, but also provided an alternative strategy to generate functional RPE cells that complement the useof pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration.

关键词： retinal pigment epithelium fibroblasts,direct conversion

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A CT-based radiomics nomogram for prediction of human epidermal growth factor receptor 2 status in patients with gastric cancer

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Chinese Journal of Cancer research 2020年第1期32卷 62-71页

作者： Yexing Li Zixuan Cheng Olivier Gevaert Lan He Yanqi Huang Xin Chen Xiaomei Huang Xiaomei Wu Wen Zhang Mengyi Dong Jia Huang Yucun Huang Ting Xia Changhong Liang Zaiyi Liu Department of Radiology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Graduate College Shantou University Medical CollegeShantou 515041China School of Medicine South China University of TechnologyGuangzhou 510006China stanford center for biomedical informatics research Department of Medicineand Department of Biomedical Data ScienceStanford UniversityCalifornia 94305USA Graduate College Southern Medical UniversityGuangzhou 510515China Department of Radiology Guangzhou First People’s HospitalGuangzhou 510180China Department of Radiology Zhuhai Hospital of Traditional Chinese and Western MedicineZhuhai 519000China Department of Radiology The Fifth People’s Hospital of ZhuhaiZhuhai 519055China

Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric ***: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation ***: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was ***: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.

关键词： Gastric cancer human epidermal growth factor receptor 2 radiomics X ray computed tomography

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CircAST:Full-length Assembly and Quantification of Alternatively Spliced Isoforms in Circular RNAs

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Genomics, Proteomics & Bioinformatics 2019年第5期17卷 522-534页

作者： Jing Wu Yan Li Cheng Wang Yiqiang Cui Tianyi Xu Chang Wang Xiao Wang Jiahao Sha Bin Jiang Kai Wang Zhibin Hu Xuejiang Guo Xiaofeng Song Department of biomedical Engineering Nanjing University of Aeronautics and AstronauticsNanjing 211106China School of biomedical Engineering and informatics Nanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Nanjing Medical UniversityNanjing 211166China center of Pathology and Clinical Laboratory Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China center for Cellular and Molecular Therapeutic Children’s Hospital of PhiladelphiaPhiladelphiaPA 19104USA

Circular RNAs(circ RNAs),covalently closed continuous RNA loops,are generated from cognate linear RNAs through back splicing events,and alternative splicing events may generate different circ RNA isoforms at the same ***,the challenges of reconstruction and quantification of alternatively spliced full-length circ RNAs remain *** the basis of the internal structural characteristics of circ RNAs,we developed Circ AST,a tool to assemble alternatively spliced circ RNA transcripts and estimate their expression by using multiple splice *** studies showed that Circ AST correctly assembled the full sequences of circ RNAs with a sensitivity of 85.63%–94.32%and a precision of 81.96%–87.55%.By assigning reads to specific isoforms,Circ AST quantified the expression of circ RNA isoforms with correlation coefficients of 0.85–0.99 between theoretical and estimated *** evaluated Circ AST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circ RNAs and identified 380 circ RNAs with full-length sequences different from those of their corresponding cognate linear ***-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms,thus further indicating the good performance of Circ AST,especially for isoforms with low *** also applied Circ AST to published experimental data and observed substantial diversity in circular transcripts across samples,thus suggesting that circ RNA expression is highly *** AST can be accessed freely at https://***/xiaofengsong/CircAST.

关键词： Circular RNA Full-length reconstruction Isoform quantification Multiple splice graph model Transcriptome

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Use of a rat model to characterize 35 arterial pulse wave parameters in a comparative study of isoflurane and Zoletil/ xylazine anesthesia and the effect of Acanthopanax senticosus extract

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Animal Models and Experimental Medicine 2023年第5期6卷 474-488页

作者： Anton Misak Marian Grman Lenka Tomasova Ondrej Makara Zuzana Rostakova Iveta Waczulikova Karol Ondrias Institute of Clinical and Translational research Department of Molecular PhysiologyBiomedical Research CenterSlovak Academy of SciencesBratislavaSlovak Republic Forest Arboretum Liptovsky Hradok Liptovsky HradokSlovak Republic Institute of Measurement Science Department of Theoretical MethodsSlovak Academy of SciencesBratislavaSlovak Republic Faculty of Mathematics Physics and InformaticsComenius UniversityBratislavaSlovak Republic

Background : Information obtained from arterial pulse waveforms (APW) can be usefulfor characterizing the cardiovascular system. To achieve this, it is necessary to know thedetailed characteristics of APWs in different states of an organism, which would allowAPW parameters (APW- Ps) to be assigned to particular (patho)physiological ***, our work aimed to characterize 35 APW- Ps in rats under the influence ofisoflurane (ISO) and Zoletil/xylazine (ZO/XY) anesthesia and to study the effect of rootextract from Acanthopanax senticosus (ASRE) in these anesthetic *** : The right jugular vein of anesthetized rats was cannulated for the administrationof ASRE and the left carotid artery for the detection of APWs from which 35APW- Ps were *** : We obtained data on 35 APW- Ps, which significantly depended on the anesthesia,and thus, they characterized the cardiovascular system under these two *** transiently modulated all 35 APW- Ps, including a transient decrease insystolic and diastolic blood pressure (BP) and heart rate or increases in pulse BP, d P /d t max , and systolic and diastolic areas. Whereas the transient effects of ASRE weresimilar, the extract had prolonged disturbing effects on the cardiovascular system inrats under ZO/XY but not under ISO anesthesia. This negative effect can result fromthe disturbance caused by ZO/XY anesthesia on the cardiovascular *** : We characterized 35 APW- Ps of rats under ISO and ZO/XY anesthesiaand found that ASRE contains compounds that can modulate the properties of thecardiovascular system, which significantly depended on the status of the cardiovascularsystem. This should be considered when using ASRE as a nutritional supplementby individuals with cardiovascular problems.

关键词： Acanthopanax senticosus arterial pulse waveform blood pressure hemodynamic parameters isoflurane Zoletil/xylazine

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High-throughput experimental methods for investigating biomolecular condensates

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Quantitative Biology 2021年第3期9卷 255-266页

作者： Taoyu Chen Qi Lei Minglei Shi Tingting Li Department of biomedical informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China MOE Key Laboratory of Bioinformatics Bioinformatics Division and Center for Synthetic&Systems BiologyTNLISTSchool of MedicineTsinghua UniversityBeijing 100084China

Background:The concept of biomolecular condensate was put forward recently to emphasize the ability of certain cellular compartments to concentrate molecules and comprise proteins and nucleic acids with specific biological functions,from ribosome genesis to RNA *** to their unique role in biological processes,it is crucial to investigate their compositions,which is a primary determinant of condensate ***:Since a wide range of macromolecules comprise biomolecular condensates,it is necessary for researchers to investigate them using high-throughput methodologies while low-throughput experiments are not efficient *** high-throughput methods usually purify interacting protein libraries from condensates before being scanned in mass *** is possible to extract organelles as a whole for specific condensates for further analysis,however,most condensates do not have a distinguishable marker or are sensitive to shear force to be extracted as a *** tagging allows a comprehensive view of interacting proteins of target molecule yet only proteins with strong bonds may be pulled *** labeling serves as a complementary method to label more dynamic proteins with weaker interactions,increasing sensitivity while decreasing ***-based fluorescent screening takes another path by scanning images automatically to illustrate the condensing state of biomolecules within membraneless organelles,which is a unique feature unlike the previous mass spectrometry-based ***:This review presents a rough glimpse into high-throughput methodologies for biomolecular condensate investigation to encourage usage of bioinformatic tools by researchers in relevant fields.

关键词： biomolecular condensates high-throughput phase separation interaction

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