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The roles and mechanisms of SREBP1 in cancer development and drug response

Genes & Diseases 2024年第4期11卷 258-269页

作者： Ying He Shasha Qi Lu Chen Jinyu Zhu Linda Liang Xudong Chen Hao Zhang Lvjia Zhuo Shujuan Zhao Shuiping Liu Tian Xie School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang 311121China Key laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer Centre SingaporeSingapore 169610Singapore

Cancer occurrence and development are closely related to increased lipid produc-tion and glucose *** are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and *** regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid *** addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly ***,no review of sREBP1 in cancer biology has yet been ***,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ***-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

关键词： Cancer drug Lipid metabolism reprogramming Resistance SREBP1

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Mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1317-1328页

作者： Jiawen Yang Aixuan Zhou Minyi Li Qiaoxian He Jingwei Zhou Jacques Crommen Wentao Wang Zhengjin Jiang Qiqin Wang Institute of Pharmaceutical Analysis College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China laboratory for the Analysis of Medicines Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium SCIEX Shanghai 200050China

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge *** this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first *** from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported *** the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum *** also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient ***,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful ***,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

关键词： Therapeutic monoclonal antibody Mimotope peptide Precise recognition peptide-based biomaterials Biotransformation Patient serum

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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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Click chemistry and natural products

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Chinese Journal of Natural Medicines 2024年第2期22卷 97-99页

作者： ZHANG Chen WU Jianbing ZHANG Yihua HUANG Zhangjian State Key laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China State Key laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Key Laboratory of Natural Medicines Active Components and Drug Release TechnologySchool of PharmacyXinjiang Medical UniversityUrumqi 830054China

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,*** Sharpless,and Danish scientist Morten *** for their contributions to the development of click chemistry and bioorthogonal chemi... 详细信息

关键词： Click chemistry Natural product Target identification drug discovery

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Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-Hsi Wu Program in Clinical drug development from Herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China Program in drug Discovery and development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of Pharmacy Taipei Medical UniversityTaipei 11031China Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary *** traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut *** aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured *** indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of *** was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in ***,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured *** conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

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Rational design of hydroxytricyanopyrrole-based probes with high affinity and rapid visualization for amyloid-β aggregates in vitro and in vivo

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Chinese Chemical Letters 2024年第5期35卷 290-295页

作者： Jiajia Lv Jie Gao Hongyu Li Zeli Yuan Nan Dong School of Chemistry and Chemical engineering Guizhou UniversityGuiyang 550025China School of Pharmacy Zunyi Medical UniversityZunyi 563003China Guizhou International Scientific and Technological Cooperation Base for Medical Photo-Theranostics Technology and Innovative drug development Zunyi 563003China

As key biomarkers,amyloid-β(Aβ)plaques are frequently used to diagnose Alzheimer’s disease(AD).Although fluorescence imaging has proven to be effective in detecting these plaques,the gold standard probe thioflavin T(ThT),used for Aβaggregates,cannot be applied in vivo owing to its invasive ***,the development of novel fluorescent probes capable of identifying Aβplaques in situ is *** on the ThT structure,twoπ-conjugated heterocyclic D-π-A probes were designed bearing the hydroxytricyanopyrrole acceptor and N,N-dimethylaminophenyl *** probes exhibited red to near-infrared fluorescence emission(λ_(max)=732 nm),large Stokes shifts(>100 nm),exceptional signal-to-noise ratio,rapid response(development of the Aβ*** study expands the family of N,N-dimethylaminophenyl-based Aβ-sensitive fluorophores,with NTHTCP emerging as a highly promising imaging agent.

关键词： Amyloid-β Fluorescent probe Hydroxytricyanopyrrole Fluorescence imaging Alzheimer’s disease

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Infection with SARS-CoV-2 can cause pancreatic impairment

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China national laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping national laboratory(CPNL) Beijing 102206China State Key laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

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Advanced nano-based strategies for mRNA tumor vaccine

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Acta Pharmaceutica Sinica B 2024年第1期14卷 170-189页

作者： Yangqi Qu Jingjing Xu Tong Zhang Qinjun Chen Tao Sun Chen Jiang Key laboratory of Smart drug Delivery(Ministry of Education) Minhang HospitalState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune *** with the technological breakthroughs in genetic engineering and delivery systems,messenger ribonucleic acid(mRNA)technology has achieved unprecedented development and application over the last few years,especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic,which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in ***,unlike infectious disease vaccines,which mainly induce humoral immunity,tumor vaccines also need to activate potent cellular immunity to control tumor growth,which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells(APCs).Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges,as well as future considerations of mRNA tumor vaccines and their delivery systems.

关键词： mRNA vaccine Nanoparticle Tumor vaccine Delivery system Stability Targeting Transfection Immunogenicity

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Allogenic microglia replacement:A novel therapeutic strategy for neurological disorders

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Fundamental Research 2024年第2期4卷 237-245页

作者： Yanxia Rao Bo Peng Department of laboratory animal Science MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Department of Neurosurgery Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceMOE Innovative Center for New Drug Development of Immune Inflammatory DiseasesFudan UniversityShanghai 200000China Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226001China

Microglia are resident immune cells in the central nervous system(CNS)that play vital roles in CNS development,homeostasis and disease *** defects in microglia lead to microglial dysfunction,which in turn leads to neurological *** correction of the specific genetic defects in microglia in these disorders can lead to therapeutic *** genetic defect correction approaches are dependent on viral vectorbased genetic defect ***,the viruses used in these approaches,including adeno-associated viruses,lentiviruses and retroviruses,do not primarily target microglia;therefore,viral vector-based genetic defect corrections are ineffective in *** replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy *** this paper,we systematically review the history,rationale and therapeutic perspectives of microglia replacement,which would be a novel strategy for treating CNS disorders.

关键词： Microglia Replacement Microglia replacement Microglia depletion Microglia-free niche CSF1R

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina Key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina Key laboratory of animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina national Institute on drug Dependence and Beijing Key laboratory of drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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