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A novel FGFR1 inhibitor CYY292 suppresses tumor progression,invasion,and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis

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Genes & Diseases 2024年第1期11卷 479-494页

作者： Yanran Bi Ruiling Zheng Jiahao Hu Ruiqing Shi Junfeng Shi Yutao Wang Peng Wang Wenyi Jiang Gyudong Kim Zhiguo Liu Xiaokun Li Li Lin School of Pharmaceutical Science Wenzhou Medical UniversityWenzhouZhejiang 325035China College of pharmacy and Research Institute of Drug Development Chonnam National UniversityGwangju 61186Republic of Korea Department of Dermatology Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhouZhejiang 325000China Zhejiang Lab for Regenerative Medicine Oujiang LaboratoryWenzhouZhejiang 325035China

Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to *** growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and ***1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall *** rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in ***292 also exerted an effect on the conserved Ser777 residue of ***292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene *** vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than ***292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM *** study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.

关键词： Blood-brain barrier EMT FGFR1 FGFR1 inhibitor Glioblastoma

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Quorum Sensing:An Emerging Role for Vibrio Infection and Host Defense

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Infectious Microbes & Diseases 2024年第2期6卷 47-55页

作者： Hao-Nan Lin Xian-Hui Huang Xin-Jun Miao Wei-Lin Hu Yong-Liang Lou Dan-Li Xie The School of Laboratory Medicine&Life Sciences Wenzhou Medical UniversityWenzhouChina Key Laboratory of Laboratory Medicine Ministry of Education of ChinaWenzhouChina wenzhou Key Laboratory of Sanitary Microbiology WenzhouChina Department of Emergency Wenzhou Central HospitalWenzhouZhejiangChina Department of Microbiology School of MedicineZhejiang UniversityHangzhouChina Zhuji Institute of Biomedical Research School of PharmacyWenzhou Medical UniversityZhujiChina

Quorum sensing(QS)is a mechanism that allows bacteria to regulate various physiological and biochemical functions by secreting,sensing and responding to signaling molecules called autoinducers(AIs).In Vibrio species,QS plays a crucial role in modulating different biological *** can influence the formation of biofilms,which are communities of bacteria encased in a protective *** also controls flagella formation and motility,ensuring that Vibrio *** move efficiently in response to environmental ***ally,QS in Vibrio *** the production of different virulence factors based on cell *** enables the bacteria to adjust their virulence strategies accordingly,enhancing *** also influences the interaction between Vibrio *** their ***ing infection by Vibrio spp.,QS can affect the host immune response and colonization *** the role of QS in these interactions is crucial for unraveling the complex dynamics between Vibrio *** the *** summary,research on QS in Vibrio *** revealed its significance in regulating various biological phenotypes,controlling virulence factor production and affecting host de*** provides valuable insights into the intricate mechanisms underlying microbial behavior,host adaptation and Vibrio ***.

关键词： quorum sensing Vibrio species biological phenotype bacterial virulence host defense

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Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3295-3311页

作者： Ao Wang Yi Zhang Xinting Lv Guang Liang Department of pharmacy and Institute of Inflammation Zhejiang Provincial Affiliated People’s HospitalHangzhou Medical CollegeHangzhou 310014China Key Laboratory of Natural Medicines of the Changbai Mountain Ministry of EducationYanbian UniversityYanji 133002China Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China

Protein tyrosine phosphorylation is a post-translational modification that regulates protein structure to modulate demic organisms’homeostasis and *** physiological process is regulated by two enzyme families,protein tyrosine kinases(PTKs)and protein tyrosine phosphatases(PTPs).As an important regulator of protein function,PTPs are indispensable for maintaining cell intrinsic physiology in different systems,as well as liver physiological and pathological *** of PTPs has been implicated in multiple liver-related diseases,including chronic liver diseases(CLDs),hepatocellular carcinoma(HCC),and liver injury,and several PTPs are being studied as drug therapeutic ***,given the regulatory role of PTPs in diverse liver diseases,a collated review of their function and mechanism is ***,based on the current research status of targeted therapy,we emphasize the inclusion of several PTP members that are clinically significant in the development and progression of liver *** an emerging breakthrough direction in the treatment of liver diseases,this review summarizes the research status of PTP-targeting compounds in liver diseases to illustrate their potential in clinical ***,this review aims to support the development of novel PTP-based treatment pathways for liver diseases.

关键词： Tyrosine phosphorylation PTPs Signal transduction CLDs HCC Allosteric inhibitor PROTACs Drug development

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang Laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical Science Wenzhou Medical University Institute of Life Sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

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Corrigendum to"A novel FGFR1 inhibitor CYY292 suppresses tumor progression,invasion,and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis"[Genes&Diseases 11(2024)479-494]

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Genes & Diseases 2024年第3期11卷 485-490页

作者： Yanran Bi Ruiling Zheng Jiahao Hu Ruiqing Shi Junfeng Shi Yutao Wang Peng Wang Wenyi Jiang Gyudong Kim Zhiguo Liu Xiaokun Li Li Lin School of Pharmaceutical Science Wenzhou Medical UniversityWenzhou 325035China College of pharmacy and Research Institute of Drug Development Chonnam National UniversityGwangju 61186Republic of Korea Department of Dermatology Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhou 325000China Zhejiang Lab for Regenerative Medicine Oujiang LaboratoryWenzhou 325035China

The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image ***,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image *** have attached the original data to show that this was also an unintentional *** assure you that these two corrections do not alter the scientificconclusionof thearticle.

关键词： GSK3β invasion metastasis

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pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 781-794页

作者： Shuai Guo Chunhui Li Changrong Wang Xiaowen Cao Xinyue Liu Xing-Jie Liang Yuanyu Huang Yuhua Weng School of medical Technology Advanced Research Institute of Multidisciplinary ScienceSchool of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of pharmacy Shandong New Drug Loading&Release Technology and Preparation Engineering LaboratoryBinzhou Medical UniversityYantai 264003China School of Ophthalmology and Optometry School of Biomedical EngineeringThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Chinese Academy of Sciences(CAS) Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and ***,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant *** this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple *** evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the *** are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal *** study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

关键词： SiRNA Oculardeliverysystem Block polymer Endosomalescape Retinal neovascularization Blood-retinal barrier VEGFA Safety

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Interleukin-6 induces cognitive impairment via toll-like receptor 4(TLR4)-mediated neuroinflammation and neurodegeneration in mice with chronic kidney disease

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Neuroprotection 2024年第3期2卷 203-215页

作者： Yangping Shentu Shuqing Ma Simin Ye Yaozhe Ying Luhui Wang Yun Zhu YunTing Wang Nan Jiang Zongyuan Zhao Chenfei Zheng Chaosheng Chen Yongheng Bai Ying Zhou Department of Pathology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina wenzhou medical university WenzhouZhejiangChina Department of Nephrology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTexasUSA Institute of Chronic Nephropathy Wenzhou Medical UniversityWenzhouZhejiangChina Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina

Backgrounds:Past epidemiological and experimental studies in rodents have demonstrated that chronic kidney disease(CKD)leads to cognitive ***,the underlying mechanism requires further ***,a mouse model of CKD was established using conventional 5/6 *** aimed to examine the relationship between CKD and cognitive impairment and elucidate the underlying ***:Cognitive behavior was assessed using the Morris water maze,novel object recognition test,and fear conditioning *** experiments were also conducted to investigate the underlying molecular ***:Our clinical data revealed a decrease in cognitive function among patients with CKD,accompanied by elevated plasma levels of pro-inflammatory cytokines.A positive correlation between cytokine concentrations and serum creatinine levels,as well as a significant positive correlation with cognitive dysfunction,were *** analyzes demonstrated that hippocampal cytokine levels were positively correlated with serum creatinine levels and cognitive dysfunction in CKD model ***,20 mg/mL interleukin-6(IL-6)significantly decreased HT22 cell activity in ***,HT22 cells treated with IL-6 showed increased expression levels of toll-like receptor 4(TLR4)and myeloid differentiation primary response gene 88(MyD88),thereby inducing the nuclear factor kappa-B p65 inflammatory pathway and mitochondria-dependent *** CKD mouse model showed increased expression of TLR4 and cytokines in the ***4 knockdown antagonized the IL-6-mediated pro-inflammatory and pro-apoptotic effects in HT22 ***4 knockdown in the CKD model mice decreased hippocampal inflammation and increased the number of neuron dendrites,thus ameliorated cognitive ***:These results suggest that IL-6 triggers TLR4 activation to induce neuroinflammation and neurodegeneration in CKD,ultimately culminate in cognitive impairment.

关键词： 5/6 nephrectomy chronic kidney disease cognitive impairment IL-6 TLR4

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Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023 edition)

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Chinese Herbal Medicines 2024年第1期16卷 3-12页

作者： Qing Zhao Tong Wang Hongbin Wang Peng Cao Chengyu Jiang Hongzhi Qiao Lihua Peng Xingdong Lin Yunyao Jiang Honglei Jin Huantian Zhang Shengpeng Wang Yang Wang Ying Wang Xi Chen Junbing Fan Bo Li Geng Li Bifeng Liu Zhiyang Li Suhua Qi Mingzhen Zhang Jianjian Zheng Jiuyao Zhou Lei Zheng Kewei Zhao Guangdong Engineering Research Center of Chinese Herbal Vesicles The Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis The Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Institute of Life and Health Engineering the First Affiliated HospitalJinan UniversityGuangzhou 510630China School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 510006China College of pharmacy Nanjing University of Chinese MedicineNanjing 210046China Institute of Basic Medicine Chinese Academy of Medical SciencesBeijing 100005China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310030China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Department of Bone and Joint Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510630China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoAomen 999078China Shanghai Jiao Tong university Affiliated Sixth People’s Hospital Shanghai 200233China School of Basic medical Sciences Southern Medical UniversityGuangzhou 510515China School of Life Sciences Nanjing UniversityNanjing 210008China Nanfang Hospital Southern Medical UniversityGuangzhou 510515China Laboratory Animal Center Guangzhou University of Chinese MedicineGuangzhou 510405China College of Life Science and Technology Huazhong University of Science and TechnologyWuhan 430074China Nanjing university medical School Affiliated Nanjing Drum Tower Hospital Nanjing 210008China School of medical and Technology Xuzhou Medical UniversityXuzhou 221004China School of Basic medical Sciences Xi’an Jiaotong UniversityXi’an 710065China The First Affiliated Hospital of wenzhou medical university WenZhou 325035China

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization,led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles,research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles,Professional Committee on Extracellular Vesicle Research and Application,Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal *** on the collation of relevant literature,we have adopted the Delphi method,the consensus meeting method combined with the nominal group method to form a discussion draft of“Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023)”.The first draft was discussed in online and offline meetings on October 12,14,November 2,2022 and April and May 2023 on the current status of research,nomenclature,isolation methods,quality standards and research applications of extracellular vesicles of Chinese herbal medicines,and 13 consensus opinions were finally *** the Third Academic Conference on Research and Application of Chinese Herbal Vesicles,held on May 26,2023,Kewei Zhao,convenor of the consensus,presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal *** consensus highlights the characteristics and advantages of Chinese medicine,inherits the essence,and keeps the righteousness and innovation,aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad,decode the mystery behind Chinese herbal vesicles together,establish a safe,effective and controllable accurate Chinese herbal vesicle prevention and treatment system,and build a bridge for Chinese medicine to the world.

关键词： Chinese herbal medicine extracellular vesicles research application consensus

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Tumor microenvironment of cancer stem cells:Perspectives on cancer stem cell targeting

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Genes & Diseases 2024年第3期11卷 275-302页

作者： Qianqian Guo Yi Zhou Tianyuan Xie Yin Yuan Huilong Li Wanjin Shi Lufeng Zheng Xiaoman Li wenzhou Zhang Department of pharmacy The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450003China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingJiangsu 210023China School of Life Science and Technology Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNanjingJiangsu 211198China

There are few tumor cell subpopulations with stem cell characteristics in tumor tis-sue,defined as cancer stem cells(CSCs)or cancer stem-like cells(CSLCs),which can recon-struct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited *** microenvironment that CsCs depend on consists of various cellular components and corresponding medium *** these factors existing at a variety of levels and forms,cytokine networks and numerous signal pathways play an important role in signaling *** factors promote or maintain cancer cell stem-ness,and participate in cancer recurrence,metastasis,and *** review aims to summarize the recent molecular data concerning the multilayered relationship between CsCs and CsC-favorable *** also discuss the therapeutic implications of target-ing this synergistic interplay,hoping to give an insight into targeting cancer cell stemness for tumortherapyandprognosis.

关键词： Cancer stem cells Cancerstem-like cells Cellular factors Non-cellularfactors Tumor microenvironment

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