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Targeting stem cell signaling pathways for drug discovery:advances in the Notch and Wnt pathways

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Science China(Life Sciences) 2014年第6期57卷 575-580页

作者： AN Songzhu Michael DING Qiang ZHANG Jie XIE JingYi LI LingSong Curegenix Inc. Center for Stem Cell and NanoMedicine Shanghai Advanced Research InstituteChinese Academy of Sciences

signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular *** stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and *** embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and *** adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative *** complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and *** the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling ***,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical *** progress has been made and several promising drug candidates have entered into clinical *** review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

关键词： stem cell drug discovery signaling pathways Notch Wnt cancer

The global integrative network:integration of signaling and metabolic pathways

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aBIOTECH 2022年第4期3卷 281-291页

作者： Yuying Lin Shen Yan Xiao Chang Xiaoquan Qi Xu Chi Department of Dermatology Xuan Wu HospitalBeijing100053China Agricultural Information Institute Chinese Academy of Agricultural ScienceBeijing100081China Key Laboratory of Plant Molecular Physiology Institute of BotanyChinese Academy of SciencesBeijing100093China The Innovative Academy of Seed Design Chinese Academy of SciencesBeijing100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing100101China

The crosstalk between signaling and metabolic pathways has been known to play key roles in human diseases and plant biological *** integration of signaling and metabolic pathways can provide an essential reference framework for crosstalk ***,current databases use distinct structures to present signaling and metabolic pathways,which leads to the chaos in the integrated ***,for the metabolic pathways,the metabolic enzymes and the reactions are disconnected by the current widely accepted layout of edges and nodes,which hinders the topological analysis of the integrated ***,we propose a novel“meta-pathway”structure,which uses the uniformed structure to display the signaling and metabolic pathways,and resolves the difficulty in linking the metabolic enzymes to the reactions *** compiled a comprehensive collection of global integrative networks(GINs)by merging the meta-pathways of 7077 *** demonstrated the assembly of the signaling and metabolic pathways using the GINs of four species—human,mouse,Arabidopsis,and *** all of the nodes were assembled into one major network for each of the four species,which provided opportunities for robust crosstalk and topological analysis,and knowledge graph construction.

关键词： signaling pathways Metabolic pathways Integration Crosstalk of pathways

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

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Engineering 2024年第6期37卷 138-151页

作者： Peng Wang Liping Qian Huixin Liang Jianhao Huang Jing Jin Chunmei Xie Bin Xue Jiancheng Lai Yibo Zhang Lifeng Jiang Lan Li Qing Jiang State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing 210008China Jiangsu Engineering Research Center for 3D Bioprinting Nanjing 210008China Institute of Medical 3D Printing Nanjing UniversityNanjing 210093China Centre for Experimental Animals Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing 210008China College of Aeroplane Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210016China National Laboratory of Solid State Microstructures Department of PhysicsNanjing UniversityNanjing 210093China Department of Chemical Engineering Stanford UniversityStanfordCA 94305USA Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of MedicineOrthopedic Research Institute of Zhejiang UniversityKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang ProvinceHangzhou 310009China

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of ***,the mechanical properties of hydrogel scaffolds and natural skin are substantially ***,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed *** Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine ***,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional *** results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the *** modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic *** an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound ***,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the ***,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress *** together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

关键词： Polyvinyl alcohol/acrylamide hydrogel Mechanical property enhancement Paracrine effect Skin regeneration signaling pathways

Computational and bioinformatics tools for understanding disease mechanisms

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BIOCELL 2024年第6期48卷 935-944页

作者： MOHD ATHAR ANU MANHAS NISARG RANA AHMAD IRFAN Physics Department University of CagliariCittadella UniversitariaMonserrato(CA)09042Italy Department of Chemistry School of Energy TechnologyPandit Deendayal Energy UniversityGandhinagar382426India Department of Chemistry College of ScienceKing Khalid UniversityAbha61413Saudi Arabia

Computational methods have signiﬁcantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein *** article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease *** utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identiﬁcation of potential drug *** bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.

关键词： Interaction database Disease mechanisms Protein function Network analysis Bioinformatics Genetic variations Protein-protein interactions signaling pathways

B7 homolog 3 in pancreatic cancer

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World Journal of Gastroenterology 2024年第31期30卷 3654-3667页

作者： Dijana Perovic Marija Dusanovic Pjevic Vladimir Perovic Milka Grk Milica Rasic Maja Milickovic Tanja Mijovic Petar Rasic Institute of Human Genetics Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Institute of Microbiology and Immunology Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia“Dr.Vukan Cupic”Belgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia

Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival *** B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy *** modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of ***,the impact of B7-H3 on the survival of patients with PC remains a subject of ***,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in ***,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to *** preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor ***,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical *** review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.

关键词： B7 homolog 3 Pancreatic cancer Prognosis signaling pathways Immunotherapy

Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai Li Zhouping Tang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

Nanomaterials for neurodegenerative diseases:Molecular mechanisms guided design and applications

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Nano Research 2022年第4期15卷 3299-3322页

作者： Tianzhong Li Xueyan Hou Yu Qi Xiaohan Duan Pengcheng Yan Haoru Zhu Zhongjian Xie Han Zhang Shenzhen International Institute for Biomedical Research Shenzhen 518110China International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen 518060China School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhou 325035China Institute of Pediatrics Shenzhen Children’s HospitalShenzhen 518038China

Successful treatment of neurodegenerative diseases(NDDs),including Alzheimer’s disease(AD),Parkinson’s disease(PD),and Huntington’s disease(HD),remains a significant challenge for neurologists due to the undesirable curative *** from surgeries,most drugs are only used to relieve the patients’symptoms without a permanent cure of the *** development of novel biomaterials targeting NDDs is greatly hindered by the limited understanding of underlying molecular *** the difficulties in NDD drug development and clinical trials,a comprehensive and up-to-date review of disease pathogenesis and related novel therapies are *** the current article,the basic concepts and pathogenic characteristics of NDDs are firstly *** the detailed description of molecular mechanisms underlying three common NDDs,recent advances of drug development based on targeting different pathogenic mechanisms are ***,this review will be beneficial to address the gap between materials and targeted mechanisms while simultaneously provide suggestions for the future design of precise NDD medicine.

关键词： neurodegenerative diseases molecular mechanisms nanomaterials signaling pathways protein aggregation

Novel strategies for the treatment of osteoarthritis based on biomaterials and critical molecular signaling

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Journal of Materials Science & Technology 2023年第18期149卷 42-55页

作者： Xingyun Huang Zhiyong Wang Huaiyu Wang Di Chen Liping Tong Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Osteoarthritis(OA)is a degenerative disease involving entire *** is often initiated from the low-grade inflammation in synovial tissue and then affects articular cartilage and subchondral *** risk factors,such as aging,mechanical overloading,trauma,overuse,*** involved in OA *** approaches have been utilized to repair cartilage *** them,biomaterials-based mes-enchymal stromal cell(MSCs)therapy is considered as the most promising *** burgeoning material science and manufacturing technologies,such as 3D printing,allow us to mimic native articu-lar cartilage and regulate the artificial cartilage development,regeneration and functional *** this review article,we will summarize the recent progress of biomaterials combined with MSCs or chon-drocytes in repairing cartilage damage induced by *** typical natural and synthetic biomaterials,such as collagen,alginate,hyaluronic acid and poly(ethylene glycol),polylactide acid,polyurethane,*** cartilage repairing will be ***,critical signaling pathways associated with the pro-gression of OA,as well as the targeted pharmacologic,genetic therapies and tissue engineering scaffolds for OA and cartilage repairing are *** will also provide our prospects for future directions in this active research area.

关键词： Osteoarthritis Cartilage Repairing Biomaterials 3D printing signaling pathways

Articulating beneficial rhizobacteria-mediated plant defenses through induced systemic resistance:A review

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Pedosphere 2023年第4期33卷 556-566页

作者： Aniruddh RABARI Janki RUPARELIA Chaitanya Kumar JHA Riyaz Z.SAYYED Debasis MITRA Ankita PRIYADARSHINI Ansuman SENAPATI Periyasamy PANNEERSELVAM Pradeep K.DAS MOHAPATRA Department of Microbiology and Biotechnology Gujarat UniversityAhmedabadGujarat 380006(India) Microbiology Department Gujarat Arts and Science CollegeEllisbridgeAhmedabadGujarat 380006(India) Department of Microbiology PSGVP Mandal's ArtsScience and Commerce CollegeMaharashtraShahada 425409(India) Department of Microbiology Raiganj UniversityRaiganjUttar DinajpurWest Bengal 733134(India) Crop Production Division Indian Council of Agriculture Research(ICAR)-National Rice Research InstituteCuttackOdisha 753006(India) Professor A.K.B.Environment Conservation Centre Raiganj UniversityRaiganjWest Bengal 733134(India)

Induced systemic resistance(ISR)is a mechanism by which certain plant beneficial rhizobacteria and fungi produce immunity,which can stimulate crop growth and resilience against various phytopathogens,insects,and *** beneficial rhizobacteria and fungi improve plant performance by regulating hormone signaling,including salicylic acid(SA),jasmonic acid(JA),prosystemin,pathogenesis-related gene 1,and ethylene(ET)pathways,which activate the gene expression of ISR,the synthesis of secondary metabolites,various enzymes,and volatile compounds that ultimately induce defense mechanisms in *** protect themselves from disease,plants have various advanced defense mechanisms in which local acquired resistance,systemic gene silencing,systemic wound response,systemic acquired resistance(SAR),and ISR are *** rhizobacteria activate the SA-dependent SAR pathway by producing SA at the root’s *** contrast,other rhizobacteria can activate different signaling pathways independent of SA(SA-independent ISR pathways)such as those dependent on JA and ET *** main objective of this review is to provide insight into the types of induced resistance utilized for plant *** to this,the genetic approaches used to suppress disease-causing genes,i.e.,RNA interference and antisense RNA,which are still underutilized in sustainable agriculture,along with the current vision for virus-induced gene silencing are also discussed.

关键词： biocontrol gene silencing local acquired resistance phytohormone secondary induced resistances signaling pathways systemic acquired resistance