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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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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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Development of innovative tripartite partnership for China’s engagement in global health: recommendations from China-Tanzania Cooperation Project on Malaria Control

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贫困所致传染病(英文) 2024年第2期13卷 63-65页

作者： Ma Xuejiao Lu Shenning Ding Wei Deng Shanying Wang Duoquan Xiao Ning Mlacha Yeromin Husain Lewis Zhou Xiaonong 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 Biology WHO Collaborating Center for Tropical Diseases National Center for International Research On Tropical Diseases Shanghai China University of Hong Kong Hong Kong China School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai China Ifakara Health Institute Dar-es-Salaam Tanzania Institute of Development Studies Brighton UK

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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li Department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

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Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

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infectious Microbes & diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen 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 MedicineHangzhouChina

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses *** following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation *** were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV *** analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS *** IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating ***,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two *** data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy

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Chromosome-level genome assembly of Oncomelania hupensis: the intermediate snail host of Schistosoma japonicum

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infectious diseases of Poverty 2024年第1期13卷 16-26页

作者： Qin Liu Lei Duan Yun-Hai Guo Li-Min Yang Yi Zhang Shi-Zhu Li Shan Lv Wei Hu Nan-Sheng Chen Xiao-Nong Zhou National Institute of Parasitic diseases at Chinese center for Disease Control and Prevention(Chinese centerfor tropical diseases research) NHC Key Laboratory of Parasite and Vector BiologyWHO Collaborating Centre for Tropical DiseasesNational Center for International Research on Tropical DiseasesNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesShanghai 200025People's Republic of China School of Global Health Chinese Center for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghai 200025People's Republic of China School of Life Science Fudan UniversityShanghai 200438People's Republic of China CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdaoShandong 266071People'sRepublicofChina

Background Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and *** hupensis (Gastropoda: Pomatiopsidae) is the unique intermediate host ofS. japonicum. A complete genome sequence ofO. hupensis will enable the fundamental understanding of snail biology as well as its co-evolution with theS. japonicum parasite. Assembling a high-quality reference genome ofO. hupehensis will provide data for further research on the snail biology and controlling the spread ofS. *** The draft genome was de novo assembly using the long-read sequencing technology (PacBio Sequel II) and corrected with Illumina sequencing data. Then, using Hi-C sequencing data, the genome was assembled at the chromosomal level. CAFE was used to do analysis of contraction and expansion of the gene family and CodeML module in PAML was used for positive selection analysis in protein coding *** A total length of 1.46 Gb high-qualityO. hupensis genome with 17 unique full-length chromosomes (2n = 34) of the individual including a contig N50 of 1.35 Mb and a scaffold N50 of 75.08 Mb. Additionally, 95.03% of these contig sequences were anchored in 17 chromosomes. After scanning the assembled genome, a total of 30,604 protein-coding genes were predicted. Among them, 86.67% were functionally annotated. Further phylogenetic analysis revealed thatO. hupensis was separated from a common ancestor ofPomacea canaliculata andBellamya purificata approximately 170 million years ago. Comparing the genome ofO. hupensis with its most recent common ancestor, it showed 266 significantly expanded and 58 significantly contracted gene families (P < 0.05). Functional enrichment of the expanded gene families indicated that they were mainly involved with intracellular, DNA-mediated transposition, DNA integration and transposase *** Integrated use of multiple sequencing technol

关键词： Schistosomiasis Schistosoma japonicum Oncomelania hupensis Chromosome-level genome

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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang 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 Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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Global outreach and networking promotion to accelerate tropical diseases elimination

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贫困所致传染病(英文) 2024年第03期13卷 1-5页

作者： Lv Shan Zhou Xiao-Nong National Institute of Parasitic diseases at Chinese center for Disease Control and Prevention (Chinese center for tropical diseases research) NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases Shanghai People’s Republic of China School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Institute of One Health Shanghai Jiao Tong University Shanghai People’s Republic of China Hainan center for tropical diseases research (Hainan Subcenter of Chinese center for tropical diseases research) Haikou People’s Republic of China

Cooperation and networking are powerful tools in the combating against tropical diseases. Cooperation on a global scale is essential due to the transboundary nature of tropical diseases. Networking plays a pivotal role in facilitating such cooperation. Both cooperation and networking can foster innovation in disease control programmes. Collaborative research can lead to the development of new drugs and vaccines, while shared surveillance data can enable the early detection and control of disease epidemics. Therefore, consensus of cooperation and networking has been reached during the 7th Symposium on Surveillance-Response Systems Leading to tropical diseases Elimination, which reflected in the two documents, i.e.,Consensus for Transboundary tropical diseases Control, andAction Consensus of the Network of WHO Collaborating Centres Related to NTDs. These documents will improve the efforts in the fighting against tropical diseases through collective actions to achieve the United Nations’ Sustainable Development Goals (SDGs).

关键词： tropical diseases Cooperation Networking Elimination Sustainable development goals

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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen Zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China 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 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term *** competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC *** on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is ***:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in *** function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory *** the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC ***-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment ***:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was *** inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC *** analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC ***:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Eliciting CD4-mimicking broadly neutralizing antibodies:new avenues towards the rational design of an HIV vaccine

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Signal Transduction and Targeted Therapy 2024年第3期9卷 836-838页

作者： Frauke Muecksch Oliver T.Fackler Department of infectious diseases Heidelberg UniversityMedical Faculty HeidelbergVirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany Chica and Heinz Schaller(CHS)research Group Department of Infectious DiseasesVirologyUniversity Hospital HeidelbergHeidelbergGermany Department of infectious diseases Heidelberg UniversityMedical Faculty HeidelbergIntegrative VirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany German Centre for Infection research(DZIF) Partner Site HeidelbergHeidelbergGermany

In a study recently published in Cell,Saunders et *** that a new anti-HIV vaccine triggers antibody responses resembling CD4-binding site broadly neutralizing antibody precursors in rhesus macaques.1 This study provid... 详细信息

关键词： al. vaccine rational

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