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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

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Genome Analysis of Plasmodium falciparum:A Preliminary Observation-Sierra Leone,2022-2023

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China CDC weekly 2024年第17期6卷 368-373页

作者： Tianyu Wang Haimo Shen Bin Xu Wanxuan Yang Shenbo Chen Junhu Chen National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector BiologyWHO Collaborating Centre for Tropical DiseasesNational Centre for International Research on Tropical DiseasesShanghaiChina School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical CollegeHangzhou CityZhejiang ProvinceChina School of Global Health Chinese Centre for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina Hainan Tropical diseases research center(Hainan Sub-center Chinese Center for Tropical Diseases Research)Haikou CityHainan ProvinceChina.

What is already known about this topic?Sierra Leone,with a gross domestic product(GDP)per capita below$300 and significant poverty,ranks among the world’s least developed countries(LDCs).Despite its modest population of 8.6 million,the nation reports approximately 2.6 million malaria cases ***,there has been no reporting on the malaria genome data from this *** is added by this report?In this study,we present the first reported wholegenome sequence analysis of 19 high parasite-density Plasmodium falciparum isolates from Sierra Leone,providing insights into the genomic epidemiology of this high-prevalence *** found a high degree of relatedness among infections and substantial genetic diversity,consistent with the gradual reduction in overall case ***,our whole-genome analysis revealed that,beyond drug-resistance genes,gene families related to blood cell invasion,immune evasion,and others are undergoing directional *** suggests that the population in Sierra Leone has developed a relatively strong acquired *** are the implications for public health practice?The genomic data not only facilitate the creation of single nucleotide polymorphism barcodes for case tracking but also enable the analysis of evolving transmission dynamics and selection ***,the samples from Sierra Leone exhibited higher selective pressures on resistance genes compared to those from Asia,a trend not commonly observed in other African *** suggests that less stringent healthcare systems and inconsistent treatment strategies can subject parasites to increased drug pressure,thereby accelerating the development of resistant strains.

关键词： epidemiology invasion Observation

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Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

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International Journal of Oral Science 2024年第2期16卷 306-321页

作者： Jiayi Wu Feifei Li Peng Yu Changhao Yu Chuyi Han Yitian Wang Fanyuan Yu Ling Ye State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal *** extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances *** knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic *** to date,the absence of promising therapeutic biomaterials/scaffolds *** reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of *** address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial *** data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony ***,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were *** study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

关键词： injuries healing suture

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Advances in the Treatment of Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 878-885页

作者： Zelu Meng Yida Yang State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Autoimmune hepatitis(AIH)is a chronic,progressive inflammatory liver disease caused by autoimmune reactions,with an unknown *** left untreated,it can progress to cirrhosis,liver failure,or even *** most patients respond well to first-line treatments,a significant number experience poor responses or intolerance,requiring the use of second-or third-line *** research into the pathogenesis of AIH is leading to the development of novel therapeutic *** review summarized recent advancements in the treatment of AIH both domestically and internationally.

关键词： Hepatitis,Autoimmune Immunosuppression Treatment Management Update Remission Induction Long-term Prognosis

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Magnesium promotes vascularization and osseointegration in diabetic states

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International Journal of Oral Science 2024年第1期16卷 122-133页

作者： Linfeng Liu Feiyu Wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian Wang Hanwen Li Quan Yuan Shiwen Zhang State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral *** has been proved to promote bone healing under normal ***,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic *** generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased *** then developed Mg-coating implants with hydrothermal *** implants successfully improved the vascularization and osseointegration in diabetic ***,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under ***,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

关键词： healing diabetic impaired

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Emerging roles of exosomes in oral diseases progression

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International Journal of Oral Science 2024年第1期16卷 36-51页

作者： Jiayi Wang Junjun Jing Chenchen Zhou Yi Fan State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.

关键词： diseases diagnosis salivary

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Omics for deciphering oral microecology

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International Journal of Oral Science 2024年第2期16卷 197-207页

作者： Yongwang Lin Xiaoyue Liang Zhengyi Li Tao Gong Biao Ren Yuqing Li Xian Peng State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases West China Hospital of StomatologySichuan UniversityChengduChina

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic *** technological innovations are propelling the characterization and manipulation of oral ***-throughput sequencing enables comprehensive taxonomic and functional profiling of oral *** long-read platforms improve genome assembly from complex ***-cell genomics provides insights into uncultured *** imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing *** techniques link phylogenetic identity with *** spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for *** facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput *** integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and ***,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic *** convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

关键词： insight holds oral

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Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of Oral diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering research center of Oral Biomaterials Chengdu 610041China Department of Head and Neck Oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment Side effect

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Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

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Journal of Pharmaceutical Analysis 2024年第4期14卷 619-621页

作者： Xuefeng Zhang Hao Xu Tong Zhou Xiaodong Feng Qianming Chen State Key Laboratory of Oral diseases National Center of StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China

Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.

关键词： SOX2 therapeutic squamous

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Accelerating the Control and Elimination of Major Parasitic diseases in China—On World NTD Day 2024

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China CDC weekly 2024年第6期6卷 95-99页

作者： Yuwan Hao Tian Tian Zelin Zhu Yijun Chen Jing Xu Shuai Han Menbao Qian Yi Zhang Shizhu Li Qiang Wang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute of Parasitic DiseasesChinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research)Key Laboratory on Parasite and Vector BiologyMinistry of HealthWHO Centre for Tropical Diseases National center for International research on Tropical diseases Ministry of Science and TechnologyShanghaiChinaSchool of Global HealthChinese Center for Tropical Diseases Research-Shanghai Jiao Tong University School of MedicineShanghaiChina

Neglected tropical diseases(NTDs)are a group of diseases associated with poverty that affect over 1 billion people worldwide(1).On May 31,2021,the World Health Assembly(WHA)officially recognized January 30 as World Neglected Tropical diseases Day through decision WHA74(18).This designation aims to raise awareness about the severe impact of NTDs on disadvantaged populations and to mobilize support for control,elimination,and eradication efforts.

关键词： diseases diseases disadvantage

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