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Degradable nanocatalyst enables antitumor/antibacterial therapy and promotion of wound healing for diabetes via self-enhanced cascading reaction

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Chinese Chemical Letters 2023年第7期34卷 155-161页

作者： Xiang Wang Cheng Ding Ziwen Zhang Chunlin Li Dongmiao Cao Linjing Zhao Guoying Deng Yu Luo Chunping Yuan Jie Lu Xijian Liu School of Chemistry and Chemical Engineering Shanghai Engineering Technology Research Center for Pharmaceutical Intelligent EquipmentShanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNAInstitute for Frontier Medical TechnologyShanghai University of Engineering ScienceShanghai201620China Affiliated Sixth People's Hospital Shanghai JiaoTong UniversityShanghai 200233China Trauma Center Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 201620China

Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical *** is urgent to develop effective therapies to reach oncotherapy/antiinfection/promotion of wound healing combined ***,we propose CS/MnO_(2)-GO_x (CMGO_x)nanocatalysts for the specific catalytic generation of ~·OH to inhibit tumors and bacteria in a hyperglycemic *** good biocompatible chitosan (CS),as a carrier for the catalyst,exhibits excellent antibacterial effect as well as promotes wound *** oxidase (GO_x) is loaded on the surface of CS nanoparticles to generate H_(2)O_(2) and gluconic acid by consuming glucose (starvation therapy,ST) and O_(2).The MnO_(2) depletes glutathione (GSH) to produce Mn^(2+),amplifying oxidative stress and further promoting the activity of Mn^(2+)-mediated Fenton-like reaction to produce~·OH (chemodynamic therapy,CDT)in weak acidic ***,the produced gluconic acid lowers the p H of the environment,enhancing chemodynamic therapy (ECDT).The tumor cells and bacteria are efficiently eliminated by the synergistic effect of ST and *** MnO_(2) nanoparticles at neutral environment decomposes H_(2)O_(2) into O_(2),which cooperate with CS to promote *** self-enhanced cascade reaction of CMGO_x in situ exhibits excellent effects of antitumor/antibacterial therapy and promotion of wound healing,offering a promising integrated treatment for diabetic patients after tumor surgical resection.

关键词： Self-cascade reaction Starvation therapy Chemodynamic therapy Antitumor Antibacterial Wound healing

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Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong Jinyao Shi Jingpu Wang Ting Guo Xiaofang Xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li Jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric ***: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric ***: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing

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Identiffcation and Analysis of Sex-Biased Copy Number Alterations

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Health Data Science 2024年第1期4卷 355-363页

作者： Chenhao Zhang Yang Yang Qinghua Cui Dongyu Zhao Chunmei Cui Department of Biomedical Informatics Center for Noncoding RNA MedicineState Key Laboratory of Vascular Homeostasis and RemodelingSchool of Basic Medical SciencesPeking University38 Xueyuan RdBeijing 100191China Department of Biochemistry and Biophysics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China School of Sports Medicine Wuhan Institute of Physical EducationNo.461 Luoyu Rd.Wuchang DistrictWuhan 430079Hubei ProvinceChina

Background:Sex difference has long been recognized at cancer incidence,outcomes,and responses to *** the somatic mutation proffles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex ***,it is still a demand for indepth scrutinizing the sex-biased characteristics of genome instability to link the clinical differences for individual cancer ***:Here,we utilized a published framework devised to speciffcally compare the copy number proffles between 2 groups to identify the sex-biased copy number alterations(CNAs)across 16 cancer types from the The Cancer Genome Atlas Program database,and dissected the impact of those ***:Totally,81 male-biased CNA regions and 23 female-biased CNA regions in 16 cancer types were *** annotation analysis showed that several critical biological functions associated with sex-biased CNAs are shared in multiple cancer types,including immune-related pathways and regulation of cellular *** sex-biased CNAs have a substantial effect on transcriptional consequence,where the average of over 68%of genes have a linear relationship with CNAs across cancer types,and 14%of those genes are affected by the combination of the sex and copy ***,29 sex-biased CNA regions show latent capacity to be sex-speciffc prognostic biomarker such as CNA on 11q13.4 for head and neck cancer and lung ***:This analysis offers new insights into the role of sex in cancer etiology and prognosis through a detailed characterization of sex differences in genome instability of diverse cancers.

关键词： alterations utilized latent

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Microrna–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 1030-1042页

作者： Yicong Shen Yuanxu Gao Jiangcheng Shi Zhou Huang Rongbo Dai Yi Fu Yuan Zhou Wei Kong Qinghua Cui Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao Special Administrative Region 999078China Department of Biomedical Informatics Center for Noncoding RNA MedicineSchool of Basic Medical SciencesPeking UniversityBeijing 100191China

Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly *** main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug *** medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be ***,we proposed a novel algorithm to quantify disease relations based on a large accumulated microrna–disease association dataset and then built a disease network covering 15 disease classes and 304 *** revealed some patterns for these *** instance,diseases tended to be clustered and coherent in the ***,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in *** on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of ***,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.

关键词： Abdominal aortic aneurysm Network medicine Microrna-derived disease network Autoimmune disease Methotrexate

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YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

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Frigid Zone medicine 2024年第1期4卷 51-64页

作者： Fangfang Bi Miao Cao Yuquan Wang Qingming Pan Zehong Jing Danyang Bing Lifang Lyu Tong Yu Tianyu Li Xuelian Li Haihai Liang Hongli Shan Yuhong Zhou Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Shanghai Frontiers Science Research Center for Druggability of Cardiovascular noncoding RNA Institute for Frontier Medical TechnologyShanghai University of Engineering ScienceShanghai 201620China Department of Basic Medicine Xiamen Medical CollegeXiamen 361023China

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold ***1 is an rna-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein *** YBX1,as an individual rna-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely ***:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)*** protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride *** vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic *** to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac *** of endogenous YBX1 by shrna partially aggravated ischemia-induced cardiac *** hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by sirna had the opposite *** of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing *** hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT ***:YBX1 protected the heart

关键词： YBX1 PI3K/AKT apoptosis mitochondrial function myocardial infarction

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Visualized and cascade-enhanced gene silencing by smart DNAzyme-graphene nanocomplex

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Nano Research 2020年第8期13卷 2165-2174页

作者： Lingjie Ren Xiaoxia Chen Chang Feng Lei Ding Xiaomin Liu Tianshu Chen Fan Zhang Yanli Li Zhongliang Ma Bo Tian Xiaoli Zhu Center for Molecular Recognition and Biosensing School of Life SciencesShanghai UniversityShanghai200444China School of Medical Shanghai UniversityShanghai200444China Lab for Noncoding RNA and Cancer School of Life SciencesShanghai UniversityShanghai200444China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200032China

BCL-2 gene as well as its products is recognized as a promising target for the molecular targeted therapy of ***,due to certain defense measures of tumor cells,the therapeutic effect based on the gene silencing of BCL-2 is greatly *** we fabricate a smart response nucleic acid therapeutic that could silence the gene effectively through a dual-targeted and cascade-enhanced *** brief,nano-graphene oxide(GO),working as a nano-carrier,is loaded with a well-designed DNAzyme,which can target and silence the BCL-2 ***,upon binding with the BCL-2 mrna,the enzymatic activity of the DNAzyme can be initiated,cutting a substrate oligonucleotide to produce an anti-nucleolin aptamer ***,a nucleolar phosphoprotein,is known as a stabilizer of BCL-2 *** binding and inactivating the nucleolin,AS1411 can destabilize BCL-2 *** this means of simultaneously targeting mrna and its stabilizer in an integrated system,effective silencing of the BCL-2 gene of tumor cells is achieved at both the cellular and in vivo *** being dosed with this nucleic acid therapeutic and without any chemotherapeutics,apoptosis of tumor cells at the cellular level and apparent shrinkage of tumors in vivo are *** labeling a molecular beacon on the substrate of DNAzyme,visualization of the enzymatic activity as well as the tumor in vivo can be also *** work presents a pure bio-therapeutic strategy that has positive implications for enhancing tumor treatment and avoiding side effects of chemotherapeutics.

关键词： BCL-2 gene gene silencing DNAzyme graphene oxide AS1411

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Author Correction: Catestatin attenuates endoplasmic reticulum induced cell apoptosis by activation type 2 muscarinic acetylcholine receptor in cardiac ischemia/reperfusion

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Scientific reports 2020年第1期10卷 19543页

作者： Feng Liao Yang Zheng Junyan Cai Jinghui Fan Jing Wang Jichun Yang Qinghua Cui Guoheng Xu Chaoshu Tang Bin Geng Department of Physiology and Pathophysiology School of Basic Medical Science Peking University Beijing P.R. China. Center for Noncoding RNA Medicine Peking University Health Science Center Beijing 100191 China. Department of Physiology and Pathophysiology School of Basic Medical Science Peking University Beijing P.R. China. bingeng@***. Center for Noncoding RNA Medicine Peking University Health Science Center Beijing 100191 China. bingeng@***.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Modeling of Microrna-Derived Disease Network Repurposes Methotrexate for the Prevention and Therapy of Abdominal Aortic Aneurysm

SSRN

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SSRN 2020年

作者： Gao, Yuanxu Shen, Yicong Shi, Jiangcheng Huang, Zhou Fu, Yi Zhou, Yuan Kong, Wei Cui, Qinghua Department of Biomedical Informatics Department of Physiology and Pathophysiology Center for Noncoding RNA Medicine MOE Key Lab of Cardiovascular Sciences School of Basic Medical Sciences Peking University 38 Xueyuan Rd Beijing100191 China

Highlights ● We presented a computational model to built human disease network from mirna-disease association data;● Applying the presented model, we built a mirna-derived human disease network which covers 15 disease classes and includes 304 diseases;● We revealed a number of patterns for the disease network, for example diseases tend to be clustered and coherent in the network;● We repurposed methotrexate, a drug for autoimmune disease, to be a possible drug to prevent the formation and inhibit the development of AAA, a common serious disease without drugs in clinics. © 2020, The Authors. All rights reserved.

关键词： Disease control

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Identification and Analysis of Human Sex-biased Micrornas

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Genomics, Proteomics & Bioinformatics 2018年第3期16卷 200-211页

作者： Chunmei Cui Weili Yang Jiangcheng Shi Yong Zhou Jichun Yang Qinghua Cui Yuan Zhou Department of Biomedical Informatics Department of Physiology and Pathophysiology Center for Noncoding RNA Medicine MOE Key Laboratory of Cardiovascular Sciences School of Basic Medical Sciences Peking University Department of Physiology and Pathophysiology Center for Noncoding RNA Medicine School of Basic Medical SciencesPeking University Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University

Sex differences are widely observed under various circumstances ranging from physiolog- ical processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of micrornas （mirnas）, an important class of non-coding rnas, become increasingly accessible. However, comprehensive analysis of sex difference in mirna expression has not been performed. Here, we identified the differentially-expressed miR- NAs between males and females by examining the transcriptomic datasets available in public data- bases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased mirnas （FmiRs） and 163 male-biased mirnas （MmiRs） across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In *** enrichment analysis of mirnas show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased mirnas together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.

关键词： Sex bias Micrornas Conservation Disease association Personalized medicine

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Human colorectal cancer cells frequently express IgG and display unique Ig repertoire

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World Journal of Gastrointestinal Oncology 2019年第3期11卷 195-207页

作者： Zi-Han Geng Chun-Xiang Ye Yan Huang Hong-Peng Jiang Ying-Jiang Ye Shan Wang Yuan Zhou Zhan-Long Shen Xiao-Yan Qiu Department of Immunology School of Basic Medical SciencesPeking University NHC Key Laboratory of Medical Immunology (Peking University) Key Laboratory of Molecular Immunology Chinese Academy of Medical Sciences Department of Gastrointestinal Surgery Peking University People's Hospital Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research Institute of Computational Medicine School of Artificial Intelligence Hebei University of Technology Department of Biomedical Informatics School of Basic Medical Sciences Center for Noncoding RNA Medicine Peking University

BACKGROUND There is growing evidence proving that many human carcinomas, including colon cancer, can overexpress immunoglobulin(Ig); the non B cancer cell-derived Ig usually displayed unique V(D)J rearrangement pattern that are distinct from B cell-derived Ig. Especially, the cancer-derived Ig plays important roles in cancer initiation, progression, and metastasis. However, it still remains unclear if the colon cancer-derived Ig can display unique V(D)J pattern and sequencing, which can be used as novel target for colon cancer *** To investigate the Ig repertoire features expressed in human colon cancer *** Seven cancerous tissue samples of colon adenocarcinoma and corresponding noncancerous tissue samples were sorted by fluorescence-activated cell sorting using epithelial cell adhesion molecule as a marker for epithelial cells. Ig repertoire sequencing was used to analyze the expression profiles of all 5 classes of Ig heavy chains(IgH) and the Ig repertoire in colon cancer cells and corresponding normal epithelial *** We found that all 5 IgH classes can be expressed in both colon cancer cells and normal epithelial cells. Surprisingly, unlike the normal colonic epithelial cells that expressed 5 Ig classes, our results suggested that cancer cells most prominently express IgG. Next, we found that the usage of Ig in cancer cells caused the expression of some unique Ig repertoires compared to normal cells. Some VH segments, such as VH3-7, have been used in cancer cells, and VH3-74 was frequently present in normal epithelial cells. Moreover, compared to the normal cell-derived Ig, most cancer cell-derived Ig showed unique VHDJH ***, even if the same VHDJH pattern was seen in cancer cells and normal cells, cancer cell-derived IgH always displayed distinct hypermutation hot *** We found that colon cancer cells could frequently express IgG and unique IgH repertoires, which may be involved in carcinogenesis of colon

关键词： Immunoglobulin repertoire Sequencing Colorectal cancer VDJ pattern VJ pattern

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