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A tunable, rapid, and precise drug control of protein expression by combining transcriptional and post-translational regulation systems

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Journal of Genetics and Genomics 2020年第11期47卷 705-712页

作者： Li Li Hongyi Meng Jianmin Zhang Yang Liu Qingjian Zou Yi Gao Huaqiang Yang Liangxue Lai Department of Hepatobiliary Surgery II Guangdong Provincial Research Center for Artificial Organ and Tissue EngineeringInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou510282China CAS Key Laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou510530China School of Biotechnology and Health Sciences Wuyi UniversityJiangmen529020China College of Animal Science South China Agricultural UniversityGuangzhou510642China

Rapid,precise,and tunable regulation of protein abundance would be significantly useful in a variety of biotechnologies and biomedical ***,we describe a system that allows tunable and rapid drug control of gene expression for either gene activation or inactivation in mammalian *** construct the system by coupling Tet-on 3 G and small molecule-assisted shutoff systems,which can respectively induce transcriptional activation and protein degradation in the presence of corresponding small *** dual-input drug inducer regulation system facilitates a bidirectional control of gene *** gene of interest can be precisely controlled by dual small molecules in a broad dynamic range of expression from overexpression to complete silence,allowing gene function study in a comprehensive expression *** results reveal that the bidirectional control system enables sensitive dosage-and time-dependent regulation for either turn-on or shutoff of gene *** also apply this system for inducible genome editing and gene activation mediated by clustered regularly interspaced short palindromic *** system provides an integrated platform for studying multiple biological processes by manipulating gene expression in a more flexible way.

关键词： Protein abundance Tet-on 3G SMASh Gene expression CRISPR Small molecule

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The role of YAP in the control of the metastatic potential of oral cancer

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Oncology research 2021年第6期29卷 377-391页

作者： USAMA SHARIF AHMAD KARTHIK SARAVANAN HONG WAN Centre for Oral Immunobiology and regenerative medicine Institute of DentistryBarts and the LondonSchool of Medicine and DentistryLondonE12ATUK

The Yes-associated protein(YAP)is a downstream effector of the Hippo pathway and acts as a key transcription co-factor to regulate cell migration,proliferation,and *** Hippo pathway is evolutionarily conserved and controls tissue growth and organ *** and heterogeneity of this pathway are found in cancers,including oral squamous cell carcinoma(OSCC),leading to overexpression of YAP and its regulated proliferation *** activity of YAP is associated with its nuclear expression and is negatively regulated by the Hippo kinase-mediated phosphorylation resulting in an induction of its cytoplasmic *** review focuses on the role of YAP in OSCC in the context of cancer metastatic potential and highlights the latestﬁndings about the heterogeneity of YAP expression and its nuclear transcription activity in oral cancer cell *** review also discusses the potential target of YAP in oral cancer therapy and the recentﬁnding of the unprecedented role of the desmosomal cadherin desmoglein-3(DSG3)in regulating Hippo-YAP signaling.

关键词： Review YAP Phospho-YAP Desmoglein-3 TAZ Hippo pathway desmosomes OSCC Oral cancer cell migration

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Epigenome-Metabolome-Epigenome signaling cascade in cell biological processes

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Journal of Genetics and Genomics 2022年第4期49卷 279-286页

作者： Linpeng Li Keshi Chen Yi Wu Ge Xiang Xingguo Liu CAS Key Laboratory of regenerative Biology Joint School of Life SciencesGuangzhou Medical UniversityGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Bioland Laboratory(Guangzhou regenerative medicine and Health Guangdong Laboratory) Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesGuangzhouGuangdong 510530China c Centre for regenerative medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many ***,the mechanisms of multilevel regulation of cell fate determination remain ***,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell *** this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic *** E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.

关键词： Cell biological processes Chromatin Epigenome Metabolome Signaling cascade

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Advances in ethnopharmacology,phytochemistry and pharmacology of Erigerontis Herba and its Chinese medicine prescriptions

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Traditional medicine research 2025年第1期10卷 44-61页

作者： Yang Zhou Yuan-Yan Huang Ding-Yue Shang Ying Chen Meng Tian Cheng-Yu Jin Xin Lu Bing-Chun Yan Han-Qing Pang institute of Translational medicine School of MedicineYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Integrated Traditional Chinese and Western medicine for Prevention and Treatment of Senile Diseases Yangzhou UniversityYangzhou 225009China School of medicine Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources Guangxi Normal UniversityGuiling 541004China.

Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away *** has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and *** review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of *** information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic *** is a member of Compositae family and is mainly grown in southern *** Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving *** now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other *** extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative ***,the major active compound of EH,has been used as a quality *** no obvious toxicity of EH has been *** to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine *** several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain *** fully exploi

关键词： Erigeron breviscapus traditional applications ethnopharmacology phytochemistry pharmacology

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Decoupling the role of chemistry and microstructure in hMSCs response to an osteoinductive calcium phosphate ceramic

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Bioactive Materials 2023年第1期19卷 127-138页

作者： V.P.Galván-Chacon D.de Melo Pereira S.Vermeulen H.Yuan J.Li P.Habibovic MERLN institute for Technology Inspired regenerative medicine Maastricht Universitythe Netherlands Kuros Biosciences BV 3723 MBBilthoventhe Netherlands

Calcium phosphates(CaP)are widely used synthetic bone graft substitutes,having bioactivity that is regulated by a set of intertwined physico-chemical and structural *** some CaPs have shown to be as effective in regenerating large bone defects as autologous bone,there is still the need to understand the role of individual material properties in CaP ***,we aimed to decouple the effects of chemical composition and surface-microstructure of a beta-tricalcium phosphate(TCP)ceramic,with proven osteoinductive potential,on human mesenchymal stromal cells(hMSCs)*** this end,we replicated the surface structure of the TCP ceramic into polylactic acid without inorganic additives,or containing the chemical constituents of the ceramic,i.e.,a calcium salt,a phosphate salt,or TCP *** microstructure of the different materials was characterized by confocal laser *** were cultured on the materials,and the expression of a set of osteogenic genes was *** cell culture medium was collected and the levels of calcium and phosphate ions were quantified by inductively-coupled plasma mass *** results revealed that none of the tested combinations of properties in polymer/composite replicas was as potent in supporting the osteogenic differentiation of hMSCs as the original ***,we observed some effects of the surface structure in the absence of inorganics,as well as combined effects of surface structure and the added salts,in particular calcium,on osteogenic *** approach presented here can be used to study the role of independent properties in other CaP-based biomaterials.

关键词： Calcium phosphate Microstructure Chemical composition Mesenchymal stromal cells Osteogenic differentiation

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Retinal regeneration requires dynamic Notch signaling

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Neural Regeneration research 2022年第6期17卷 1199-1209页

作者： Leah J.Campbell Jaclyn L.Levendusky Shannon A.Steines David R.Hyde Department of Biological Sciences Center for Zebrafish ResearchCenter for Stem Cells and Regenerative MedicineUniversity of Notre DameNotre DameINUSA

Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal *** signaling,which is a fundamental mechanism known to drive cell-cell communication,is required to maintain Müller glia in a quiescent state in the undamaged retina,and repression of Notch signaling is necessary for Müller glia to reenter the cell *** dynamic regulation of Notch signaling following retinal damage also directs proliferation and neurogenesis of the Müller glia-derived progenitor cells in a robust regeneration *** contrast,mammalian Müller glia respond to retinal damage by entering a prolonged gliotic state that leads to additional neuronal death and permanent vision *** the dynamic regulation of Notch signaling in the zebrafish retina may aid efforts to stimulate Müller glia reprogramming for regeneration of the diseased human *** findings identified DeltaB and Notch3 as the ligand-receptor pair that serves as the principal regulators of zebrafish Müller glia *** addition,multi-omics datasets and functional studies indicate that additional Notch receptors,ligands,and target genes regulate cell proliferation and neurogenesis during the regeneration time ***,our understanding of Notch signaling during retinal regeneration is *** fully appreciate the complex regulation of Notch signaling that is required for successful retinal regeneration,investigation of additional aspects of the pathway,such as post-translational modification of the receptors,ligand endocytosis,and interactions with other fundamental pathways is *** we review various modes of Notch signaling regulation in the context of the vertebrate retina to put recent research in perspective and to identify open areas of inquiry.

关键词： differentiation gliosis Müller glia neuronal progenitor cell Notch signaling proliferation quiescence retinal development retinal regeneration zebrafish

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Metabolism of pluripotent stem cells

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Frontiers in Biology 2016年第5期11卷 355-365页

作者： Liang Hu Edward Trope Qi-Long Ying Eli and Edythe Broad Center for regenerative medicine and Stem Cell research at USC Department of Stem Cell Biology and Regenerative Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA

BACKGROUND： Recently, growing attention has been directed toward stem cell metabolism, with the key observation that metabolism not only fuels the proper functioning of stem cells but also regulates the fate of these cells. There seems to be a clear link between the self-renewal ofpluripotent stem cells （PSCs）, in which cells proliferate indefinitely without differentiation, and the activity of specific metabolic pathways. The unique metabolism in PSCs plays an important role in maintaining pluripotency by regulating signaling pathways and resetting the epigenome. OBJECTIVE： To review the most recent publications concerning the metabolism of pluripotent stem cells and the role of metabolism in PSC self-renewal and differentiation. METHODS： A systematic literature search related to the metabolism of PSCs was conducted in databases including Medline, Embase, and Web of Science. The search was performed without language restrictions on all papers published before May 2016. The following keywords were used：＂metabolism＂ combined with either ＂embryonic stem cell＂ or ＂epiblast stem cell.＂ RESULTS： Hundreds of papers focusing specifically on the metabolism of pluripotent stem cells were uncovered and summarized. CONCLUSION： Identifying the specific metabolic pathways involved in pluripotency maintenance is crucial for progress in the field of developmental biology and regenerative medicine. Additionally, better understanding of the metabolism in PSCs will facilitate the derivation and maintenance of authentic PSCs from species other than mouse, rat, and human.

关键词： metabolism pluripotent stem cells pluripotency epigenetics

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Optogenetic neuroregeneration

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Neural Regeneration research 2022年第7期17卷 1468-1470页

作者： Harald Janovjak Sonja Kleinlogel EMBL Australia Australian Regenerative Medicine InstituteFaculty of MedicineNursing and Health SciencesMonash UniversityClayton/MelbourneAustralia institute of Physiology University of BernBernSwitzerland

Optogenetics is a powerful technology that employs light and genetics to manipulate physiology and behavior with unprecedented *** high acuity of light stimulation permits fine control both in space(e.g.,to target just one tissue in an animal)and in time(e.g.,to interfere with a specific disease stage),whilst genetic targeting restricts manipulation to a functionally-relevant cell population(Figure 1A).

关键词： stimulation manipulation Figure

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Identification of AOSC-binding proteins in neurons

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Chinese Journal of Oceanology and Limnology 2008年第4期26卷 394-399页

作者：刘明聂琴辛现良耿美玉 Department of Molecular pharmacology School of Medicine and Pharmacy Ocean University of China Division of Anti-tumor pharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences

Acidic oligosaccharide sugar chain （AOSC）, a D-mannuronic acid oligosaccharide, derived from brownalgaepolysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer＇s Disease （AD） drug candidate. The identification of AOSC-binding protein（s） in neurons is very important for understanding its action mechanism. To determine the binding protein（s） of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry （LC-MS/MS） analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 （AP-2） and amyloid precursor protein （APP）. These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.

关键词： AOSC Alzheimer's disease marine oligosaccharide binding protein(s)

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Supramolecular G-quadruplex hydrogels:Bridging fabrication to biomedical application

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Journal of Materials Science & Technology 2023年第24期155卷 238-252页

作者： Yuanfeng Li Junjie Chi Pingwei Xu Xing Dong Anh-Tuan Le Keqing Shi Yong Liu Jian Xiao Translational medicine Laboratory The Center of Wound Healing and Regenerative Medicine the First Affiliated Hospital of Wenzhou Medical University Zhejiang 325035 China School of Pharmaceutical Sciences Key Laboratory of Biotechnology and Pharmaceutical Engineering The Center of Wound Healing and Regenerative Medicine the First Affiliated Hospital Wenzhou Medical University Zhejiang 325035 China Wenzhou institute University of Chinese Academy of Sciences Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health) Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province Zhejiang 325001 China Phenikaa University Nano institute (PHENA) Phenikaa University Hanoi 12116 Viet Nam

G-quadruplex hydrogel is a class of self-assembled supramolecular hydrogel formed by guanine *** a biomimetic hydrogel,G-quadruplex hydrogels demonstrate wide biomedical applications,such as drug delivery,tissue engineering,and *** advantages of using G-quadruplex hydrogels include adequate biocompatibility and biodegradability,tunable multifunctionality,and cost-effective and large-scalable fabrication *** this review,we focus on recent progress in the fabrication and characterization of G-quadruplex hydrogels to help readers understand the principles of G-quadruplex hydrogel ***,the applications of G-quadruplex hydrogels in the biomedical area are discussed,aiming to pave the way for downward clinical or industry *** development of G-quadruplex hydrogel is still in its *** hope this review will boost the development of this area and that more applications of G-quadruplex hydrogel will be developed.

关键词： Guanosine DNA hydrogel Self-assembly Drug delivery Tissue engineering

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