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Comparative study of anti-inflammatory effects of different processed products through the COX-2/PGE2 signaling pathway: based on network pharmacology and molecular docking

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Pharmacology Discovery 2024年第2期4卷 32-45页

作者： Ping Chen Yun-Yun Quan An-Qi Zeng Ying Dai Jin Zeng translational Chinese Medicine Key Laboratory of Sichuan Province Sichuan Academy of Chinese Medicine SciencesChengdu 610041China translational Chinese Medicine Key Laboratory of Sichuan Province Sichuan Institute for Translational Chinese MedicineChengdu 610041China

Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory *** aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for *** production of NO and inflammatory cytokines were measured by ELISA *** Real-time PCR(qRT-PCR)was utilized to measure the mRNA ***-2/PGE2 signaling pathway-associated proteins were determined by western ***:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating *** in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 *** 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and ***:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.

关键词： Radix Aconiti Lateralis Preparata(Fu-zi) rheumatoid arthritis anti-inflammatory network pharmacology COX-2/PGE2 signaling pathway

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The role of proteasomes in tumorigenesis

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Genes & Diseases 2024年第4期11卷 155-169页

作者： Xiangyi Zhou Ruqing Xu Yue Wu Li Zhou Tingxiu Xiang Department of Oncology The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key Laboratory of translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China

Protein homeostasis is the basis of normal life activities,and the proteasomefamily plays an extremely important function in this *** proteasome 2os is a concentric circle structure with twoαrings and twoβrings *** proteasome 2os can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits(such as 19S,11S,and 200 PA),which is performed by its active subunitβ1,β2,andβ*** proteasome can degrade misfolded,excess proteins tomaintain *** the same time,it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their *** can affect the development of tumors from several aspects including tumor signaling pathways such as NF-kB and p53,cell cycle,immune regulation,and drug ***-encoding genes have been found to be overexpressed in a variety of tumors,providing a potential novel target for cancer *** addition,proteasome inhibitors such as bortezomib,carfilzomib,and ixazomib have been put into clinical application as the first-line treatment of multiple *** and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma,non-small cell lung cancer,glioblastoma,and ***,proteasome inhibitors are not much effective due to their tolerance and singleness in other ***,further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.

关键词： Bortezomib Cancer therapy Immunoproteasome Multiplemyeloma Proteasome 20S Proteasome inhibitor Thymoproteasom

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Unlocking epigenetics for precision treatment of Ewing’s sarcoma

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Chinese Journal of Cancer Research 2024年第3期36卷 322-340页

作者： Zhehao Fan Shuangshuang Dong Ning Wang Muhammad Babar Khawar Jingcheng Wang Haibo Sun Institute of translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental&translational Non-Coding RNA Research Yangzhou 225001China Department of Pathology Northern Jiangsu People’s Hospital Affiliated to Yangzhou University/Clinical Medical CollegeYangzhou UniversityYangzhou 225001China Department of Orthopedics Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhou 225001China

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young *** the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains ***,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS *** regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating *** studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug *** review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

关键词： Ewing’s sarcoma epigenetic targets drug resistance drug development

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MAL2 DNA methylation serves as a biomarker for the diagnosis and prognosis of glioma

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Genes & Diseases 2024年第5期11卷 36-39页

作者： Hao Luo Xing Xiao Weiliang Hou Jing Cai Ming Chen Qisheng Tang Yusheng Tong Zengxin Qi Kaicheng Li Liang Chen Department of Neurosurgery Huashan HospitalShanghai Medical CollegeState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain Science and Institutes of Brain ScienceFudan UniversityShanghai 200040China National Center for Neurological Disorders Shanghai 200040China Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration Shanghai 200040China Tianqiao and Chrissy Chen Institute Clinical translational Research Center Shanghai 200040China Shanghai QuietD Biotechnology Co. Ltd.Shanghai 201210China

Glioma is a common and malignant brain tumor,and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for *** candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for *** analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of *** findings also showed that MAL2 was more highly methylated in glioma than in other *** constructed diagnostic model can distinguish glioma from other cancers with high sensitivity(93.3%)and specificity(86.5%).Additionally,a risk score model was built based on MAL2 methylation to assess the prognosis of glioma。

关键词： glioma diagnosis MAL

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Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 49-68页

作者： Xumei Ouyang Yu Liu Ke Zheng Zhiqing Pang Shaojun Peng Zhuhai Institute of translational Medicine Zhuhai Precision Medical CenterZhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 519000China Key Laboratory of Smart Drug Delivery Ministry of EducationDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China School of Materials science and Engineering Dongguan University of TechnologyDongguan 523808China

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side *** several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease *** glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological ***,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical *** polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and *** nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated *** impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical *** realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical ***,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their ***,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

关键词： Zwitterionic polymer Nano drug delivery system Biological barrier Targeting delivery Disease treatment

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Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

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Regeneration of copper catalysts mediated by molybdenum-based oxides

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Journal of Energy Chemistry 2024年第8期95卷 618-625,I0013页

作者： Changyu Ding Xiaoli Pan Isla E.Gow Xia Wu Hongchen Cao Zhounan Yu Xiaoyan Liu Xiaofeng Yang Qinggang Liu Yanqiang Huang CAS Key Laboratory of science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina University of Chinese Academy of sciences Beijing 100049China Cardiff Catalysis Institute School of ChemistryTranslational Research HubCardiff UniversityCardiff CF244HQUnited Kingdom College of Chemistry Chemical Engineering and Resource UtilizationNortheast Forestry UniversityHarbin 150040HeilongjiangChina

Cu catalysts,known for their unparalleled catalytic capabilities due to their unique electronic structure,have faced inherent challenges in maintaining long-term effectiveness under harsh hydrogenation ***,we demonstrate a molybdenum-mediated redispersion behavior of Cu under hightemperature oxidation *** oxidized Cu nanoparticles with rich metal-support interfaces tend to dissolve into the MoO_(3)support upon heating to 600℃,which facilitates the subsequent regeneration in a reducing atmosphere.A similar redispersion phenomenon is observed for Cu nanoparticles supported on Zn O-modified MoO_(3).The modification of ZnO significantly improves the performance of the Cu catalyst for CO_(2)hydrogenation to methanol,with the high activity being well maintained after four repeated oxidation-reduction *** situ spectroscopic and theoretical analyses suggest that the interaction involved in the formation of the copper molybdate-like compound is the driving force for the redispersion of *** method is applicable to various Mo-based oxide supports,offering a practical strategy for the regeneration of sintered Cu particles in hydrogenation applications.

关键词： Cu-based catalysts Aggregation Regeneration Oxidation CO_(2)hydrogenation

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Progress on early diagnosing Alzheimer’s disease

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Frontiers of Medicine 2024年第3期18卷 446-464页

作者： Yixin Chen Murad Al-Nusaif Song Li Xiang Tan Huijia Yang Huaibin Cai Weidong Le Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical UniversityDalian116021China Transgenic Section Laboratory of NeurogeneticsNational Institute on AgingNational Institutes of HealthBethesdaMD20892USA Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChinese Academy of Sciences Sichuan Translational Medicine Research HospitalChengdu610072China

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition *** disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to *** detection of AD is crucial for better diagnosis and more effective ***,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease ***,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of *** non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive *** research advances have identified several biofluid biomarkers as early indicators of *** review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the ***,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

关键词： Alzheimer’s disease early diagnosis non-cognitive symptoms biomarkers

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Metal nanoparticles for cancer therapy:Precision targeting of DNA damage

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1132-1149页

作者： Qian Chen Chunyan Fang Fan Xia Qiyue Wang Fangyuan Li Daishun Ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Frontiers science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China World Laureates Association(WLA)Laboratories Shanghai 201203China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Cancer,a complex and heterogeneous disease,arises from genomic ***,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical ***,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical *** nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer *** customizable physicochemical properties enable the development of targeted and personalized treatment *** this review,we delve into the design principles and optimization strategies of metal *** shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal *** encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune ***,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle ***,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.

关键词： DNA damage Metal nanoparticles Nucleus-targeting DNA repair inhibition Immune response Size optimization Stimuli-responsiveness Surface modification

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Iridoids modulate inflammation in diabetic kidney disease: A review

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Journal of Integrative Medicine 2024年第3期22卷 210-222页

作者： Tong-yi Zhou Na Tian Liu Li Rong Yu The First Clinical College of Chinese Medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Hunan Provincial Key Laboratory of translational Research in Traditional Chinese Medicine Prescriptions and Zheng Changsha 410208Hunan ProvinceChina

In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical *** has become a pervasive complication of type 2 *** the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic ***,primarily derived from the potent components of traditional herbs,have been the subject of long-standing *** data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of *** article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this ***,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic *** review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.

关键词： Diabetic kidney disease Iridoids Gut-kidney axis Traditional Chinese medicine monomer Inflammation

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