检索结果-南通市图书馆

Sox9^(+) cells are required for salivary gland regeneration after radiation damage via the Wnt/β-catenin pathway

在线全文

学校读者我要写书评

暂无评论

Journal of Genetics and Genomics 2022年第3期49卷 230-239页

作者： Xiuyun Xu Gan Xiong Ming Zhang Jiaxiang Xie Shuang chen Kang Li Jingting Li Yong Bao cheng Wang demeng chen Department of Oral and Maxillofacial Surgery Hospital of StomatologyGuanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong 510030China Center for Translational Medicine Institute of Precision MedicineThe First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China

Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, and oral infection. Because of the lack of long-term treatment for the symptoms of xerostomia, current research has focused on finding endogenous stem cells that can differentiate into various cell lineages to replace lost tissues and restore functions. Here, we report that Sox9^(+)cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9^(+) cells, the salivary glands of irradiated mice showed more severe phenotypes and the reduced proliferative capacity. Analysis of online single-cell RNAsequencing data reveals the enrichment of the Wnt/β-catenin pathway in the Sox9^(+) cell population.Furthermore, treatment with a Wnt/β-catenin inhibitor in irradiated mice inhibits the regenerative capability of Sox9^(+) cells. Finally, we show that Sox9^(+) cells are capable of forming organoids in vitro and that transplanting these organoids into salivary glands after radiation partially restored salivary gland functions.These results suggest that regenerative therapy targeting Sox9^(+) cells is a promising approach to treat radiation-induced salivary gland injury.

关键词： Radiation-induced salivary gland injury Sox9 Wnt/β-catenin pathway Regeneration Organoids

Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression

在线全文

学校读者我要写书评

暂无评论

Cancer Communications 2022年第3期42卷 223-244页

作者： Jie chen Kang Li Jianwen chen Xiaochen Wang Rongsong Ling Maosheng cheng Zhi chen Fangfang chen Qianting He Shuai Li Caihua Zhang Yizhou Jiang Qianming chen Anxun Wang demeng chen Department of Oral and Maxillofacial Surgery Center for Translational Medicinethe First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Institute for Advanced Study Shenzhen UniversityShenzhenGuangdong 518000P.R.China School of Stomatology Cancer Centerand Key Laboratory of Oral Biomedical Research of Zhejiang ProvinceClinical Research Center of Oral Diseases of Zhejiang ProvinceStomatology HospitalZhejiang University School of MedicineHangzhouZhejiang 310006P.R.China

Background:Cancer cells selectively promote the translation of oncogenic tran-scripts to stimulate cancer progression.Although growing evidence has revealed that tRNA modifications and related genes participate in this process,their roles in head and neck squamous cell carcinoma(HNSCC)remain largely unchar-acterized.Here,we sought to investigate the function and mechanisms of the transfer RNA(tRNA)N7-methylguanosine(m'G)modification in regulating the occurrence and development of HNSCC.Methods:Cell lost of-function and gain-of function assays,xenograft models,conditional knockout and knockin mouse models were used to study the physi-ological functions of tRNA m'G modification in HNSCC tumorigenesis.tRNA modification and expression profiling,mRNA translation profiling and res-cue assays were performed to uncover the underlying molecular mechanisms.Single-cell RNA sequencing(scRNA seq)was conducted to explore the tumor microenvironment changes.Results:The tRNA.m7G methyltransferase complex components Methyltransferase-like 1(METTL1)/WD repeat domain 4(WDR4)were upregulated in HNSCC and associated with a poor prognosis.Functionally,METTL1/WDR4 promoted HNSCC progression and metastasis in cell-based and transgenic mouse models.Mechanistically,ablation of METTL1 reduced the m'G levels of 16 tRNAS,inhibiting the translation of a subset of oncogenic transcripts,including genes related to the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway.In addition,chemical modulators of the PI3K/Akt/mTOR signaling pathway reversed the effects of Mettll in mouse HNSCC.Furthermore,scRNA-seq results revealed that Mettll knockout in mouse tumor cells altered the immune landscape and cell-cell interaction between the tumor and stromal compartment.Conclusions:The tRNA m?G methyltransferase METTLI was found to promote the development and malignancy of HNSCC through regulating global mRNA translation,including the PI3K/AKT/mTOR signaling pathway,and found to alter immune landscape.

关键词： head and neck squamous cell carcinoma m7G modification metastasis METTL1 microenvi-ronment PI3K/AKT/mTOR signaling.scRNA-seq tRNA WDR4

Targeting cancer stem cells in squamous cell carcinoma

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Precision Clinical Medicine 2019年第3期2卷 152-165页

作者： demeng chen Cun-Yu Wang Laboratory of Molecular Signaling Division of Oral Biology and MedicineSchool of DentistryUCLALos AngelesCA 90095USA Department of Bioengineering Henry Samueli School of Engineering and Applied ScienceUCLALos AngelesCA 90095USA Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center UCLALos AngelesCA 90095USA

Head and neck squamous cell carcinoma(HNSCC)is a highly aggressive tumor and the sixth most common cancer worldwide.Current treatment strategies for HNSCC are surgery,radiotherapy,chemotherapy,immunotherapy or combinatorial therapies.However,the overall 5-year survival rate of HNSCC patients remains at about 50%.Cancer stem cells(CSCs),a small population among tumor cells,are able to self-renew and differentiate into different tumor cell types in a hierarchical manner,similar to normal tissue.In HNSCC,CSCs are proposed to be responsible for tumor initiation,progression,metastasis,drug resistance,and recurrence.In this review,we discuss the molecular and cellular characteristics of CSCs in HNSCC.We summarize current approaches used in the literature for identification of HNSCC CSCs,and mechanisms required for CSC regulation.We also highlight the role of CSCs in treatment failure and therapeutic targeting options for eliminating CSCs in HNSCC.

关键词： cancer stem cells head and neck squamous cell carcinoma lymph node metastasis resistance

Mettl5 mediated 18S rRNA N6-methyladenosine(m^(6)A)modification controls stem cell fate determination and neural function

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genes & Diseases 2022年第1期9卷 268-274页

作者： Lu Wang Yu Liang Rongzhi Lin Qiuchan Xiong Peng Yu Jieyi Ma Maosheng cheng Hui Han Xiaochen Wang Ganping Wang Fengyin Liang Zhong Pei demeng chen Quan Yuan Yi-Zhou Jiang Shuibin Lin Center for Translational Medicine Precision Medicine InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080PR China Institute for Advanced Study Shenzhen UniversityShenzhenGuangdong 518060PR China Department of Otorhinolaryngology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000PR China State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China Department of Neurology The First Affiliated HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological DiseasesNational Key Clinical Department and Key Discipline of NeurologyGuangzhouGuangdong 510080PR China

Ribosome RNA(rRNA)accounts for more than 80%of the cell's total RNA,while the physiological functions of rRNA modifications are poorly understood.Mutations of 18S rRNA m6A methyltransferase METTL5 cause intellectual disability,microcephaly,and facial dysmorphisms in patients,however,little is known about the underlying mechanisms.In this study,we identified METTL5 protein complex and revealed that METTL5 mainly interacts with RNA binding proteins and ribosome proteins.Functionally,we found that Mettl5 knockout in mESCs leads to the abnormal craniofacial and nervous development.Moreover,using Mettl5 knockout mouse model,we further demonstrated that Mettl5 knockout mice exhibit intellectual disability,recapitulating the human phenotype.Mechanistically,we found that Mettl5 maintains brain function and intelligence by regulating the myelination process.Our study uncovered the causal correlation between mis-regulated 18S rRNA m6A modification and neural function defects,supporting the important physiological functions of rRNA modifications in human diseases.

关键词： 18S rRNA Intellectual disability METTL5 N6-methyladenosine(m^(6)A) Neural development

Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

International Journal of Oral Science 2021年第3期13卷 271-281页

作者： Xiaochen Wang Kang Li Yuehan Wan Fangfang chen Maosheng cheng Gan Xiong Ganping Wang Shuang chen Zhi chen Jianwen chen Xiuyun Xu cheng Wang Liang Peng demeng chen Center for Translational Medicine Institute of Precision MedicineThe First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Oral and Maxillofacial Surgery Hospital of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhouChina Oncology Department Chinese PLA General HospitalBeijingChina

Methyltransferase like 13(METTL13),a kind of methyltransferase,is implicated in protein binding and synthesis.The upregulation of METTL13 has been reported in a variety of tumors.However,little was known about its potential function in head and neck squamous cell carcinoma(HNSCC)so far.In this study,we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level.Increased METTL13 was negatively associated with clinical prognosis.And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro.Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail,the key transcription factor in EMT,hence regulating the progression of EMT.Furthermore,Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes.Altogether,our study had revealed the oncogenic role of METTL13 in HNSCC,and provided a potential therapeutic strategy.

关键词： Snail EMT head

Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma

在线全文

学校读者我要写书评

暂无评论

International Journal of Oral Science 2023年第3期15卷 476-488页

作者： Xiuyun Xu Jiaxiang Xie Rongsong Ling Shengqi Ouyang Gan Xiong Yanwen Lu Bokai Yun Ming Zhang Wenjin Wang Xiqiang Liu demeng chen cheng Wang Hospital of Stomatology Sun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Stomatology Sun Yat-sen UniversityGuangzhouChina Guanghua School of Stomatology Sun Yat-sen UniversityGuangzhouChina Institute for Advanced Study Shenzhen UniversityShenzhenChina Department of Oral and Maxillofacial Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouChina Center for Translational Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.

关键词： CD36 metabolism adenoma

Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma

在线全文

学校读者我要写书评

暂无评论

Bone Research 2018年第2期6卷 197-203页

作者： demeng chen Zhiqiang Zhao Zixin Huang Du-Chu chen Xin-Xing Zhu Yi-Ze Wang Ya-Wei Yan Shaojun Tang Subha Madhavan Weiyi Ni Zhan-peng Huang Wen Li Weidong Ji Huangxuan Shen Shuibin Lin Yi-Zhou Jiang The Department of Dermatology Yale University Department of Musculoskeletal Oncology The First Affiliated Hospital Sun Yat-sen University State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University Institute for Advanced Study Shenzhen University Innovation Center for Biomedical Informatics Georgetown University Medical Center Department of Oncology Georgetown University Medical Center Department of Pharmaceutical and Health Economics School of Pharmacy University of Southern California Center for Translational Medicine The First Affiliated Hospital Sun Yat-sen University Department of Surgery The First Affiliated Hospital Sun Yat-sen University Biobank of Eye State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University

Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.

关键词： Super enhancer inhibitors suppress MYC driven transcriptional amplification tumor progression osteosarcoma

浅议世界自然遗产视野下自然景观保护管理的挑战

在线全文

学校读者我要写书评

暂无评论

自然与文化遗产研究 2024年第3期9卷 85-94页

作者：卢俊媛陈雪琦赵德猛王琦北京大学城市与环境学院北京100871 九寨沟风景名胜区管理局四川阿坝藏族羌族自治州623402

我国具有数量众多和独特的自然景观,这些自然景观构成我国自然遗产的重要部分,保护这些自然遗产是建设生态文明和贡献于构建人类命运共同体的重要任务。文章从“景观”与“自然景观”的概念入手,回顾了现代自然景观保护理念的发展,从世... 详细信息

我国具有数量众多和独特的自然景观,这些自然景观构成我国自然遗产的重要部分,保护这些自然遗产是建设生态文明和贡献于构建人类命运共同体的重要任务。文章从“景观”与“自然景观”的概念入手,回顾了现代自然景观保护理念的发展,从世界自然遗产视野出发,将自然景观定义为具有自然遗产价值的景观。使用世界遗产中心官网的数据梳理《世界遗产名录》中自然景观的分布、价值内涵和保存情况,总结国际上对世界自然遗产保护管理的认知以及自然景观保护管理面临的主要问题和原因,并通过对新疆天山和九寨沟风景名胜区2处案例地的分析,探讨中国世界自然遗产所面临的具体问题。总体上,自然景观的“景观”属性给保护管理带来了挑战,同时也影响了世界遗产组织的自然保护价值观的文化转向,此外地区一般性问题也给地区带来了关键挑战。

关键词：自然景观世界自然遗产保护管理价值内涵保存情况

Development of Gesture-Changeable under-actuated Humanoid Robotic Finger

同方期刊数据库博看期刊评论

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Mechanical Engineering 2010年第2期23卷 142-148页

作者： ZHANG Wenzeng CHE demeng chen Qiang DU Dong Key Laboratory for Advanced Materials Processing Technology of Ministry of Education Beijing 100084 China Department of Mechanical Engineering Tsinghua University Beijing 100084 China

Robotic fingers, which are the key parts of robot hand, are divided into two main kinds： dexterous fingers and under-actuated fingers. Although dexterous fingers are agile, they are too expensive. Under-actuated fingers can grasp objects self-adaptively, which makes them easy to control and low cost, on the contrary, under-actuated function makes fingers feel hard to grasp things agilely enough and make many gestures. For the purpose of designing a new finger which can grasp things dexterously, perform many gestures and feel easy to control and maintain, a concept called ＂gesture-changeable under-actuated＂（GCUA） function is put forward. The GCUA function combines the advantages of dexterous fingers and under-actuated fingers： a pre-bending function is embedded into the under-actuated finger. The GCUA finger can not only perform self-adaptive grasping function, but also actively bend the middle joint of the finger. On the basis of the concept, a GCUA finger with 2 joints is designed, which is realized by the coordination of screw-nut transmission mechanism, flexible drawstring constraint and pulley-belt under-actuated mechanism. Principle analyses of its grasping and the design optimization of the GCUA finger are given. An important problem of how to stably grasp an object which is easy to glide is discussed. The force analysis on gliding object in grasping process is introduced in detail. A GCUA finger with 3 joints is developed. Many experiments of grasping different objects by of the finger were carried out. The experimental results show that the GCUA finger can effectively realize functions of pre-bending and self-adaptive grasping, the grasping processes are stable. The GCUA finger excels under-actuated fingers in dexterity and gesture actions and it is easier to control and cheaper than dexterous hands, becomes the third kinds of finger.

关键词： robot technology robotic hand gesture-changeable under-actuation pre-bending self-adaptation