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DLX3(Q178R)mutation delays osteogenic differentiation via H19/miR-29c-3p/KDM5B axis in TDO-iPSCs-derived MSCs

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Genes & Diseases 2024年第4期11卷 49-52页

作者： liying Dong Na Zhao Dongmei Wang Meng Wang Yixin Zhang Liangjie Sun Chong Ding Yixiang Wang Zeyun ma Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China Department of Oral and maxillofacial Surgery Peking University School and Hospital of StomatologyBeijing 100081China National Engineering Laboratory for Digital and material Technology of Stomatology Peking University School and Hospital of StomatologyBeijing 100081China Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of StomatologyBeijing 100081China The Second Clinical Division Peking University School and Hospital of StomatologyBeijing 100081China Department of VIP Service Peking University School and Hospital of StomatologyBeijing 100081China Department of Restorative Dentistry and Biomaterials Sciences Harvard School of Dental MedicineBostonMA 02115USA Department of Prosthodontics Fudan UniversityShanghai 200001China Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological HospitalFudan UniversityShanghai 200001China

Tricho-dento-osseous(TDO)syndrome is a rare autosomal dominant disease resulting from distal-less homeobox 3(DLX3)mutation.1,2 Accumulative bone density in alveolar bone is a clinically favorable phenotype for TDO patients.However,the limited number of bone marrow mesenchymal stem cells(BMSCs)in TDO patients restricts their application.

关键词： patients clinically alveolar

Phlorizin alleviates deltamethrin-induced oxidative stress in brine shrimp Artemia

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Journal of Oceanology and Limnology 2024年第1期42卷 163-173页

作者： Dandan ma Qingli ZHOU liying SUI Qingbin GUO Huanhuan LIU Honghe LIANG Zhenjing LI Zhongna SANG School of Food Science and Engineering Tianjin University of Science and TechnologyTianjin 300457China Asian Regional Artemia Reference Center Key Laboratory of Marine Resource Chemistry and Food Technology(TUST)Ministry of EducationTianjin University of Science and TechnologyTianjin 300457China Subtropical Crops Research Institute of Guangxi Zhuang Autonomous Region Nanning 530001China Department of Nutrition and Food Hygiene School of Public HealthTianjin Medical UniversityTianjin 300070China

Deltamethrin(DEL),a commonly used pyrethroid pesticide,results in higher reactive oxygen species(ROS)levels in aquatic animals,which consequently unbalance the redox state.Phlorizin(PHL)is a flavonoid and a natural product promising to prevent or reduce pesticide-induced oxidative stress.Artemia is a micro-crustacean widely used in marine hatcheries and an experimental aquatic organism for environmental toxicology research.This research aimed to evaluate the toxicity of DEL on Artemia and the antioxidative effect of PHL against the toxicity.Results show that 0.08-mg/mL PHL exerted its antioxidative effects on hatching percentage of the cysts in 24-h incubation and on body length and survival rate of Artemia in 12-d culture.After 12-d culture,12-,24-,and 36-h DEL exposure showed significant drops in SOD,CAT,and GSH-Px enzyme activities,and significant increases in ROS and malondialdehyde(MDA)levels in Artemia(Pmage by possibly regulating the Nrf2signaling pathway.This study provided a theoretical basis for PHL to reduce pesticide-induced toxicity in aquatic animals.

关键词： Artemia deltamethrin phlorizin oxidative stress

MiR-3653 blocks autophagy to inhibit epithelial-mesenchymal transition in breast cancer cells by targeting the autophagy-regulatory genes ATG12 and AMBRA1

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Chinese Medical Journal 2023年第17期136卷 2086-2100页

作者： Huachen Song Zitong Zhao liying ma Bailin Zhang Yongmei Song State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Breast Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:Metastasis is the main cause of tumor-associated death and mainly responsible for treatment failure of breast cancer.Autophagy accelerates tumor metastasis.In our work,we aimed to investigate the possibility of microRNAs(miRNAs)which participate in the regulation of autophagy to inhibit tumor metastasis.Methods:MiRNA array and comprehensive analysis were performed to identify miRNAs which participated in the regulation of autophagy to inhibit tumor metastasis.The expression levels of miR-3653 in breast cancer tissues and cells were detected by quantitative real-time polymerase chain reaction.In vivo and in vitro assays were conducted to determine the function of miR-3653.The target genes of miR-3653 were detected by a dual luciferase reporter activity assay and Western blot.The relationship between miR-3653 and epithelial-mesenchymal transition(EMT)was assessed by Western blot.Student’s t-test was used to analyze the difference between any two groups,and the difference among multiple groups was analyzed with one-way analysis of variance and a Bonferroni post hoc test.Results:miR-3653 was downregulated in breast cancer cells with high metastatic ability,and high expression of miR-3653 blocked autophagic flux in breast cancer cells.Clinically,low expression of miR-3653 in breast cancer tissues(0.054±0.013 vs.0.131±0.028,t=2.475,P=0.014)was positively correlated with lymph node metastasis(0.015±0.004 vs.0.078±0.020,t=2.319,P=0.023)and poor prognosis(Pmalignant phenotypes of breast cancer cells,including proliferation,migration(MDA-MB-231:0.353±0.013 vs.1.000±0.038,t=16.290,Pmation(MDA-MB-231:0.472±0.022 vs.1.000±0.022,t=16.620,P<0.001;MDA-MB-468:0.650±0.040 vs.1.000±0.098,t=3.297,P=0.030).The autophagy-associated genes autophagy-related gene 12(ATG12)and activating molecule in bec

关键词： Breast cancer miR-3653 Autophagy Autophagy-related gene 12 Activating molecule in beclin 1-regulated autophagy protein 1 Epithelial-mesenchymal transition

Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection

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Virologica Sinica 2022年第3期37卷 370-379页

作者： Xiaolong Tian Binbin Hong Xiaoyi Zhu Desheng Kong Yumei Wen Yanling Wu liying ma Tianlei Ying MOE/NHC Key Laboratory of Medical Molecular Virology School of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai200032China Central Laboratory The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou362000China State Key Laboratory of Infectious Disease Prevention and Control National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Shanghai Engineering Research Center for Synthetic Immunology Shanghai200032China Shanghai Key Laboratory of Lung Inflammation and Injury Shanghai200032China

Advancements in high-throughput sequencing(HTS)of antibody repertoires(Ig-Seq)have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale.However,currently,only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions,possibly limited by inadequate sequencing depth and throughput.To better understand how HIV-1 infection would impact humoral immune system,in this study,we systematically analyzed the differences between the IgM(HIV-IgM)and IgG(HIV-IgG)heavy chain repertoires of HIV-1 infected patients,as well as between antibody repertoires of HIV-1 patients and healthy donors(HH).Notably,the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries,and the diversity of unique clones in HIV-IgG remarkably reduced.In aspect of somatic mutation rates of CDR1 and CDR2,the HIV-IgG repertoire was higher than HIV-IgM.Besides,the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire,presumably caused by the great number of novel VDJ rearrangement patterns,especially a massive use of IGHJ6.Moreover,some of the B cell clonotypes had numerous clones,and somatic variants were detected within the clonotype lineage in HIV-IgG,indicating HIV-1 neutralizing activities.The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.

关键词： Ig-seq HIV-1 Antibody repertoire VDJ rearrangement Junctional diversity

Discovery of novel 4-phenylquinazoline-based BRD4 inhibitors for cardiac fibrosis

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Acta Pharmaceutica Sinica B 2022年第1期12卷 291-307页

作者： Zhangxu He Haomiao Jiao Qi An Xin Zhang Dan Zengyangzong Jiale Xu Hongmin Liu liying ma Wen Zhao State Key Laboratory of Esophageal Cancer Prevention and Treatment Key Laboratory of Advanced Pharmaceutical TechnologyMinistry of Education of ChinaSchool of Pharmaceutical SciencesZhengzhou UniversityZhenzhou 450001China China Meheco Topfond Pharmaceutical Co. Zhumadian 463000China

Bromodomain containing protein 4(BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases,including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library(enamine). Then, structure-activity relationship(SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation in vitro and cardiac fibrosis in vivo, which was correlated with the decreased expression of BRD4 downstream target c-MYC as well as the depressed TGF-β1/Smad2/3 signaling pathway.Taken together, our findings indicate that novel BRD4 inhibitor C-34 tethering a 4-phenylquinazoline scaffold can serve as a lead compound for further development to treat fibrotic cardiovascular disease.

关键词： BRD4 Inhibitor 4-Phenylquinazoline Cardiac fibrosis

Lithiophilic seeds and rigid arrays synergistic induced dendrite-free and stable Li anode towards long-life lithium-oxygen batteries

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Journal of Energy Chemistry 2022年第10期31卷 268-276,I0006页

作者： Yue Li Haichang Zhang Rui Zhang Junwei Sha liying ma Dongdong Zhao Chunsheng Shi Naiqin Zhao School of materials Science and Engineering and Tianjin Key Laboratory of Composite and Functional materials Tianjin UniversityTianjin 300350China Key Laboratory of Advanced Ceramics and machining Technology of Ministry of Education Tianjin 300072China Collaborative Innovation Center of Chemical Science and Engineering Tianjin 300072China China Science and Technology on Power Sources Laboratory Tianjin Institute of Power SourcesTianjin 300384China

High energy density lithium-oxygen battery(LOB) is currently regraded as a promising candidate for next-generation power system.However,the dendrite and instability issues of Li metal anode lead to its poor cyclic stability and low energy density.In this work,lithiophilic Al_(2) O_(3) seeds induced rigid carbon nanotube arrays(CNTA)/three-dimensional graphene(3 DG) is developed as a host material for Li anode,namely Al_(2) O_(3)-CNTA/3 DG.It is demonstrated that the lithiophilic feature of Al_(2) O_(3) seeds and the enhanced rigidity of arrays can synergistically induce the uniform Li flux,inhibit the collapse of arrays,and stabilize electrolyte/electrode interfaces.As a result,the Al_(2) O_(3)-CNTA/3 DG-Li anode delivers a high Coulombic efficiency above 97% after 140 cycles(8 mah cm^(-2) at 4 ma cm^(-2)).With this anode and the breathable CNTA/3 DG cathode,the full LOB exhibits a significantly increased life-span up to 160 cycles(500 mah g^(-1) at 100 ma g^(-1)),which is almost 3 times longer than that with pure Li foil as the anodes.This work demonstrates a new approach to highly reversibly long-cycling performance of LOBs towards practical application.

关键词： Caron nanotube array Al_(2)O_(3) Li-O_(2)battery Li metal Anode

Tumor-derived miR-20b-5p promotes lymphatic metastasis of esophageal squamous cell carcinoma by remodeling the tumor microenvironment

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Signal Transduction and Targeted Therapy 2023年第2期8卷 369-372页

作者： Zitong Zhao Liyan Xue Leilei Zheng liying ma Zhuo Li Ning Lu Qimin Zhan Yongmei Song State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Laboratory of Molecular Oncology Peking University Cancer HospitalBeijingChina

DEAREDITOR,Esophageal squamous cell carcinoma(ESCC)is one of the most common fatal malignancies worldwide and is especially common in East Asian regions,including China.Screening lymph node metastasis(LNM)-related biomarkers and elucidating the mechanism could provide promising therapeutic targets and help ESCC patients to select reasonable individual therapies.

关键词： metastasis squamous esophageal

Identification and Validation of Vascular-Associated Biomarkers for the Prognosis and Potential Pathogenesis of Hypertension Using Comprehensive Bioinformatics Methods

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World Journal of Cardiovascular Diseases 2024年第3期14卷 115-128页

作者： Xiangguang Chang Lei Guo liying Zou Yazhao ma Jilin Feng Department of Laboratory Yangbi Yi Autonomous County People’s Hospital Dali China Department of Obstetrics and Gynecology Yangbi Yi Autonomous County People’s Hospital Dali China Department of Infectious Diseases Yangbi Yi Autonomous County People’s Hospital Dali China Medical Community Office Yangbi Yi Autonomous County People’s Hospital Dali China

Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.

关键词： Hypertension Biomarkers Differentially Expressed Genes Vascular Development and Angiogenesis Bioinformatics Analysis

Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods

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Health 2024年第3期16卷 173-186页

Background: Hypertension is a universal risk factor for cardiovascular diseases and is thus the leading cause of death worldwide. The identification of novel prognostic and pathogenesis biomarkers plays a key role in disease management. Methods: The GSE145854 and GSE164494 datasets were downloaded from the Gene Expression Omnibus (GEO) database and used for screening and validating hypertension signature genes, respectively. Gene Ontology (GO) enrichment analysis was performed on the differentially expressed genes (DEGs) related to calcium ion metabolism in patients with hypertension. The core genes related to immune infiltration were analyzed and screened, and the activity of the signature genes and related pathways was quantified using gene set enrichment analysis (GSEA). The infiltration of immune cells in the blood samples was analyzed, and the DEGs that were abnormally expressed in the clinical blood samples of patients with hypertension were verified via RT-qPCR. Results: A total of 176 DEGs were screened. GO showed that DEGs was involved in the regulation of calcium ion metabolism in biological processes (BP), actin mediated cell contraction, negative regulation of cell movement, and calcium ion transmembrane transport, and in the regulation of protease activity in molecular functions (MF). KEGG analysis revealed that the DEGs were involved mainly in the cGMP-PKG signaling pathway, ubiquitin-protein transferase, tight junction-associated proteins, and the regulation of myocardial cells. MF analysis revealed the immune infiltration function of the cells. RT-qPCR revealed that the expression of Cacna1d, Serpine1, Slc8a3, and Trpc4 was up regulated in hypertension, the expression of Myoz2 and Slc25a23 was down regulated. Conclusion: Cacna1d, Serpine1, Slc8a3, Trpc4, Myoz2 and Slc25a23 may be involved in the regulation of calcium metabolism pathways and play key roles in hypertension. These differentially expressed calcium metabolism-related genes may serve as prognostic markers of hypertension.

关键词： Hypertension Biomarkers Differentially Expressed Genes Ca2+ Metabo-lism Bioinformatics Analysis