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Chromatin conformation of human oral epithelium can identify orofacial cleft missing functional variants

International Journal of Oral Science 2022年第4期14卷 497-508页

作者： Yao Xiao Shengbo Jiao Miao He Da Lin Huanyan Zuo Jiahao Han Yonghua Sun Gang Cao Zhi Chen Huan Liu The State Key Laboratory Breeding Base of Basic Science of Stomatology&Key Laboratory for Oral Biomedicine of Ministry of Education School and Hospital of StomatologyWuhan University237 Luoyu RoadWuhanChina Department of Stomatology Nanfang HospitalSouthern Medical UniversityGuangzhouChina State Key Laboratory of Freshwater Ecology and Biotechnology Hubei Hongshan LaboratoryInstitute of HydrobiologyInnovation Academy for Seed DesignChinese Academy of SciencesWuhanChina College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijingChina State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhanChina Taikang Center for Life and Medical Sciences Wuhan UniversityWuhanChina

Genome-wide association studies(GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts(OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability,suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line(HIOEC) using RNA-seq, ATAC-seq,H3K27ac Ch IP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only(NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification *** total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epitheliumexpressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.

关键词： epithelium functional variants

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Protein profiles of enzymatically isolated rumen epithelium in sheep fed a fibrous diet

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Journal of Animal Science and Biotechnology 2019年第2期10卷 449-462页

作者： J.J.Bond A.J.Donaldson J.V.F.Coumans K.Austin D.Ebert D.Wheeler V.H.Oddy NSW Department of Primary Industries Extensive Livestock Industry CentreUniversity of New EnglandTrevenna RdArmidaleNSW 2351Australia School of Rural Medicine University of New EnglandArmidaleNSW 2351Australia NSW Department of Primary Industries Orange Agricultural InstituteOrangeNSW 2800Australia.

Background: The rumen wall plays a major role in efficient transfer of digested nutrients in the rumen to peripheral tissues through the portal venous system. Some of these substrates are metabolised in the epithelium during this process. To identify the specific proteins involved in these processes, we used proteomic technologies. Protein extracts were prepared from ventral rumen tissue of six sheep fed a fibrous diet at 1.5× maintenance energy *** a newly developed method, we were able to enzymatically isolate the epithelial cells from underlying tissue layers, thus allowing cytosol and membrane fractions to be independently analysed using liquid chromatography tandem mass spectrometry(LC MS/MS).Results: Using our procedure we identified 570 epithelial proteins in the Ovis aries sequence database. Subcellular locations were largely cytosolic(n = 221) and extracellular(n = 85). However, a quarter of the proteins identified were assigned to the plasma membrane or organelle membranes, some of which transport nutrients and metabolites. Of these 91 were transmembrane proteins(TMHMM), 27 had an N-terminal signal peptide(signalP) and TMHMM motif,13 had a glycosylphosphatidylinositol(GPI) anchor and signalP sequence, 67 had beta(β) strands or 17 β strands and a transit peptide sequence, indicating the identified proteins were integral or peripheral membrane proteins. Subunits of the 5 protein complexes involved in mitochondrial cellular energy production were well represented. Structural proteins(15%), proteins involved in the metabolism of lipids and proteins(26%) and those with steroid or cytokine action were a feature of the ***: Our research has developed a procedure to isolate rumen epithelium proteins from the underlying tissue layers so that they may be profiled using proteomic technologies. The approach improves the number of proteins that can be profiled that are specific to the epithelium of the rumen wall. It provides new insights

关键词： epithelium Metabolism Nutrition Proteome Rumen Sheep

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Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3455-3465页

作者： Yang Peng Shi-ying Chen Zhao-ni Wang Zi-qing Zhou Jing Sun Gui-an Zhang Jia Li Lei Wang Jin-cun Zhao Xiao Xiao Tang De-Yun Wang Nan-shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouGuangdongChina Department of Otolaryngology Infectious Diseases Translational Research ProgramYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Guangzhou Laboratory GuangzhouChina

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells(AECs)is a quick way to find novel treatments for *** screening has found dicoumarol(DCM),a natural anticoagulant,to be a potential SARS-CoV-2 inhibitor,but its inhibitory effects and possible working mechanisms remain *** air-liquid interface culture of primary human AECs.

关键词： Omi infection epithelium

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Mechanism of exogenous nucleic acids and their precursors improving the repair of intestinal epithelium after 7-irradiation in mice

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World Journal of Gastroenterology 2000年第5期6卷 709-717页

作者： Da Xiang Cui~1 Guei Ying Zeng~2 Feng Wang~1 Jun Rong Xu~1 Dong Qing Ren~2 Yan Hai Guo~1 Fu Rong Tian~2 Xiao Jun Yan~1 Yu Hou~1 Cheng Zhi Su~1 1 Institute of Genetic Diagnosis of the Fourth Military Medical University,Xi’an 710032,China 2 Department of Irradiation Medicine of the Fourth Military Medical University,Xi’an 710032,China Da Xiang Cui Feng Wang Jun Rong Xu Yan Hai Guo Xiao Jun Yan Yu Hou Cheng Zhi Su Institute of Genetic Diagnosis of the Fourth Military Medical University Xi’an 710032 China Guei Ying Zeng Dong Qing Ren Fu Rong Tian Department of Irradiation Medicine of the Fourth Military Medical University Xi’an 710032 China

AIM To clone expressed genes associated withrepair of irradiation-damaged mice intestinalgland cells treated by small intestinal RNA,andto explore the molecular mechanism ofexogenous nucleic acids improving repair ofintestinal *** The animal mode of test group andcontrol group was established,forty-five micebeing irradiated by γ ray were treated with smallintestinal RNA as test group,forty mice beingirradiated by γ ray were treated withphysiological saline as control group,five micewithout irradiation were used as normal control,their jejunal specimens were collectedrespectively at 6h,12h,24h,4d and 8d *** by using LD-PCR based onsubtractive hybridization,these gene fragmentsdifferentially expressed between test group andcontrol group were obtained,and then werecloned into T vectors as well as *** sequences were ***,if being new sequences,they were submitted to *** Ninety clones were associated withrepair of irradiation-damaged intestinal glandcells treated by intestinal *** clonesfrom test group of 6h,12h,24h,4d and 8dwere respectively 18,22,25,13,*** screening against GeneBank,18 of which werenew sequences,the others were dramaticallysimilar to the known sequences,mainly similarto hsp,Nmi,Dutt1,alkaline phosphatase,homeobox,anti-CEA ScFv antibody,arginine/serine kinase and BMP-4,*** genefragments were new sequences,their acceptnumbers in GeneBank were *** Ninety clones were obtained tobe associated with repair of irradiation-damagedmice intestinal gland cells treated by smallintestinal RNA,which may be related toabnormal expression of genes and matchedproteins of hsp,Nmi,Duttl,Na,K-ATPase,alkalineph-osphatase,glkA,single strandedreplicative centromeric gene as well as 18 newsequences.

关键词： radiation ionizing intestine small/injuries RNA gene expression nucleic acids/therapeutic use polymerase chain reaction repair intestinal epithelium mice

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Grainy head signaling regulates epithelium development and ecdysis in Blattella germanica

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Insect Science 2021年第2期28卷 485-494页

作者： Zheng Zhao Liang Li Min Cheng An-Di Jing Su-Ning Liu Shi-Ming Zhu Er-Xia Du Sheng Li Yun-Xia Luan Chong-Hua Ren Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Institute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhouChina Guangmeiyuan R&D Center Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied TechnologySouth China Normal UniversityMeizhouGuangdong ProvinceChina

The transcription factor grainy head(Grh)functions in the protection of the epithelium against the external environment by generating strongly adhesive layers,and this function is conserved in vertebrates and *** Drosophila,the top model for holometabolous insects,Grh is necessary during embryonic development,epidermal differentiation,central nervous system specification and epithelial ***,the function of this gene in hemimetabolous insect epithelia remains *** examine the function of Grh signaling in regulating epithelium development in Hemimetabola,we focused on the Blattella germanica epidermal layer using a gene knockdown *** spatiotemporal expression pattern of BgGrh was detected,and knockdown of Bg-Grh and BgCad96ca,which provide positive feedback to BgGrh,caused severe defects in new epithelium development and impeded the molting process required to discard the old *** of the expression of BgGrh and BgCad96ca caused increased expression of chitin synthase gene{BgCHSl)and chitinase gene{BgCht5),the upregulations of which should be mediated by the higher level of hormone receptor 3{BgHr3)*** conclusion,epithelium development is regulated by Grh signaling,which might represent a potential target for the control of urban pest cockroaches.

关键词： BgCad96ca cockroach ecdysis epithelium Grh signaling

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Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2586-2599页

作者： Yuan Hou Yadi Zhou Michaela U.Gack Justin D.Lathia Asha Kallianpur Reena Mehra Timothy A.Chan Jae U.Jung Lara Jehi Charis Eng Feixiong Cheng Genomic Medicine Institute Lerner Research InstituteCleveland ClinicClevelandOHUSA Florida Research and Innovation Center Cleveland ClinicPort Saint LucieFLUSA Department of Cardiovascular and Metabolic Science Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Population and Quantitative Health Sciences Case Western Reserve UniversityClevelandOHUSA Neurological Institute Cleveland ClinicClevelandOHUSA Center for Immunotherapy and Precision Immuno-Oncology Cleveland ClinicClevelandOHUSA Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineClevelandOHUSA Case Comprehensive Cancer Center Case Western Reserve University School of MedicineClevelandOHUSA

Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial,and the underlying mechanisms of COVID-19 in a sex-specific manner remain *** we inspected sex differences in SARS-CoV-2 infection,hospitalization,admission to the intensive care unit(ICU),sera inflammatory biomarker profiling,and single-cell RNA-sequencing(scRNA-seq)profiles across nasal,bronchoalveolar lavage fluid(BALF),and peripheral blood mononuclear cells(PBMCs)from COVID-19 patients with varying degrees of disease *** propensity score-matching observations revealed that male individuals have a 29%elevated likelihood of SARS-CoV-2 positivity,with a hazard ratio(HR)1.32(95%confidence interval[Cl]1.18-1.48)for hospitalization and HR 1.51(95%Cl 1.24-1.84)for admission to *** from male patients at hospital admission had elevated neutrophil-lymphocyte ratio and elevated expression of inflammatory markers(C-reactive protein and procalcitonin).We found that SARS-CoV-2 entry factors,including ACE2,TMPRSS2,FURIN,and NRP1,have elevated expression in nasal squamous cells from male individuals with moderate and severe *** observed male-biased transcriptional activation in SARS-CoV-2-infected macrophages from BALF and sputum samples,which offers potential molecular mechanism for sex-biased susceptibility to viral ***-cell interaction network analysis reveals potential epithelium-immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in ***,monocyte-elevated expression of Toll-like receptor 7{TLR7)and Bruton tyrosine kinase{BTK)is associated with severe outcomes in males with *** summary,these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.

关键词： elevated epithelium analysis

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SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl^(−) accumulation in respiratory epithelium

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Signal Transduction and Targeted Therapy 2022年第8期7卷 3080-3092页

作者： Lei Chen Wei-Jie Guan Zhuo-Er Qiu Jian-Bang Xu Xu Bai Xiao-Chun Hou Jing Sun Su Qu Ze-Xin Huang Tian-Lun Lei Zi-Yang Huang Jincun Zhao Yun-Xin Zhu Ke-Nan Ye Zhao-Rong Lun Wen-Liang Zhou Nan-Shan Zhong Yi-Lin Zhang School of Life Sciences Sun Yat-sen UniversityGuangzhouChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouChina Guangzhou Laboratory GuangzhouChina

SARS-CoV-2,the culprit pathogen of COVID-19,elicits prominent immune responses and cytokine *** Cl^(−)is a crucial regulator of host defense,whereas the role of Cl^(−)signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains *** using human respiratory epithelial cell lines,primary cultured human airway epithelial cells,and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge,we demonstrated that SARS-CoV-2 nucleocapsid(N)protein could interact with Smad3,which downregulated cystic fibrosis transmembrane conductance regulator(CFTR)expression via *** intracellular Cl^(−)concentration([Cl^(−)]i)was raised,resulting in phosphorylation of serum glucocorticoid regulated kinase 1(SGK1)and robust inflammatory *** or knockout of SGK1 abrogated the N protein-elicited airway ***,N protein promoted a sustained elevation of[Cl^(−)]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4(PDE4).Rolipram,a selective PDE4 inhibitor,countered airway inflammation by reducing[Cl^(−)]*** findings suggested that Cl^(−)acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 *** the Cl^(−)signaling pathway might be a novel therapeutic strategy for COVID-19.

关键词： inflammation respiratory epithelium

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Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3767-3782页

作者： Jiang He Liyu Liu Feiyu Tang You Zhou Huan Liu Can Lu Deyun Feng Hong Zhu Yitao Mao Zhi Li Lu Zhang Yuemei Duan Zhi Xiao Musheng Zeng Liang Weng Lun-Quan Sun Department of Oncology Xiangya Cancer CenterXiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China Department of Pathology Tongji Medical College Union HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Pathology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Radiology Xiangya HospitalCentral South UniversityChangsha 410078China Institute of Gerontological Cancer Research National Clinical Research Center for GerontologyChangsha 410008China Department of Breast Surgery Xiangya HospitalCentral South UniversityChangsha 410078China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhou 510060China Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer Changsha 410008China Center for Molecular Imaging of Central South University Xiangya HospitalChangsha 410008China

Epstein-Barr virus(EBV)and human papillomavirus(HPV)infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma,***,clinical analyses demonstrate that EBV or HPV is associated with improved response of patients,although underlying mechanism remains ***,we reported that the oncoproteins of DNA viruses,such as LMP1 of EBV and E7 of HPV,inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved *** of PERK led to increased level of reactive oxygen species(ROS)that promoted tumor and enhanced the efficacy of chemotherapy in ***,disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse *** findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.

关键词： chemotherapy epithelium cervical

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Intravitreal fluorogold tracing as a method to label retinal neurons and the retinal pigment epithelium

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Neural Regeneration Research 2021年第10期16卷 2000-2001页

作者： Francisco Javier Valiente-Soriano Fernando Lucas-Ruiz Juan A.Miralles de Imperial-Ollero Manuel Vidal-Sanz Marta Agudo-Barriuso Departamento de Oftalmología Facultad de MedicinaUniversidad de Murcia and Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca(IMIB-Arrixaca)MurciaSpain

Techniques to label the neuroretina and the retinal pigment epithelium(RPE)have been the topic of many studies for *** reliability and reproducibility of these techniques are essential to investigate retinal alterations of ocular pathologies and possible *** particular,the study of the integrity of the RPE is of great importance in pathologies such as retinitis pigmentosa or age-related macular degeneration(Gu et al.,2012;Fisher and Ferrington,2018;Zhang et al.,2019).The most common approaches use antibodies to identify different cell ***,we have described a novel technique to study the integrity of the neuroretina and the RPE,as well as the functionality of the RPE in rats(Valiente-Soriano et al.,2020).

关键词： epithelium al. alterations

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Pterygial body epithelium domination of pterygial proliferation with TCF4 as a potential key factor

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International Journal of Ophthalmology(English edition) 2018年第9期11卷 1467-1474页

作者： Cong Nie Xin-Chun Zhang Si-Ying Xu Ya-Dan Quan Zhi-Xin Tang Rong Lu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen University Department of Prosthodontics Hospital of StomatologyGuangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen University

AIM： To characterize the proliferative capacity of pterygial epithelium in different regions（head, neck and body） of pterygium and explore the function of transcription factor 4（TCF4） in pterygium ***： Thirty pterygium tissues and 10 normal conjunctival tissues were obtained from Zhongshan Ophthalmic Center（ZOC） and Guangdong Eye Bank, respectively. Proliferative capacity of head, neck and body in pterygial epithelium was measured using clonal analysis, fold growth analysis and expression profile of proliferative markers revealed by immunofluorescent staining and real-time PCR. The expression of TCF4 was highlighted by double immunofluorescent staining with other proliferation related markers such as proliferating cell nuclear antigen（PCNA） and ATP-binding cassette subfamily G member 2（ABCG2）.RESULTS： The proliferative potential of pterygial epithelium was higher than that of normal conjunctival epithelium. High expression levels of proliferative markers（P63α, PCNA and ABCG2） in pterygial body epithelium were observed in immunofluorescent staining and real-time PCR（P〈0.05）. Also, epithelial cells isolated from pterygial body demonstrated higher proliferative capacity in clonal analysis and fold growth analysis, than those isolated from the head and neck regions. The TCF4 expression in pterygial epithelium was similar to other proliferative markers（P63α, PCNA and ABCG2）, as higher in pterygial body than head and neck. Moreover, TCF4 showed coexpression with other proliferation-related markers（PCNA and ABCG2） in the double immunofluorescent staining ***： The proliferative capacity in pterygial body epithelium is prominent than the head and neck regions, and upregulated TCF4 may be associated with enhanced proliferation in the pterygium.

关键词： pterygium epithelium proliferation transcription factor 4

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