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AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification

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Research 2024年第3期6卷 151-167页

作者： Hong Wang Jj Liu Xiaojun Zhu Bin Yang Zuping He Xudong Yao Department of Urology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Urologic Cancer institute School of MedicineTongji UniversityShanghaiChina. Department of Urology Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotChina. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province School of MedicineHunan Normal UniversityThe Engineering Research Center of Reproduction and Translational Medicine of Hunan ProvinceChangshaChina Shanghai Key Laboratory of Reproductive medicine Shanghai Jiao Tong University School of MedicineShanghaiChina.

Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality *** prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic ***,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be *** this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free *** of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their *** pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a ***1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination *** RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A ***,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in ***,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

关键词： Prostate TPM1 m6A

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Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

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Acta Pharmaceutica Sinica B 2024年第1期14卷 365-377页

作者： Dandan Ling Xueli Jia Ke Wang Qiucheng Yan Bochuan Yuan Lina Du Miao Li Yiguang Jin Anhui Medical university Hefei 230032China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer *** therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response ***,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung *** preparation processes were simple,only involving film formation,electroporation,and pore ***@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer *** the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its ***,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the ***@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

关键词： Apoptosis Bacterial ghost Cancer cell membrane Immune stimulation Liposome Lung targeting Metastatic lung cancer Paclitaxel

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Development of a competitive array for discriminative determination of amphenicols in egg based on ribosomal protein L16

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Food Quality and Safety 2024年第1期8卷 105-114页

作者：才艺马宁吴宁鹏王建平 College of Veterinary medicine Hebei Agricultural UniversityBaodingChina Henan institute of Veterinary Drug and Feed Control ZhengzhouChina

Objective:Amphenicols(chloramphenicol,thiamphenicol and forfenicol)can cause aplastic anaemia and other severe side effects to consumers;therefore,it is necessary to inspect their residues in foods of animal ***,there has been no report on the use of amphenicols receptor for the determination of their residues,and none of the previously reported immunoassays for amphenicols can differentiate the specifc *** and Methods:In this study,the ribosomal protein L16 of Escherichia coli was frst expressed,and its intermolecular interaction mechanisms with the three amphenicols was studied using the molecular docking *** protein was then combined with three enzymelabelled conjugates to develop a direct competitive array on microplate for determination of the three drugs in ***:Due to the use of principal component analysis to analyse the data,this method could discriminate the three drugs in the range 0.1–10 ng/mL,and the limits of detection for the three drugs were in the range of 0.0002–0.0009 ng/*** analysis results for the unknown egg samples were consistent with a liquid chromatography–tandem mass spectrometry method,and the method performances were superior to the previous immunoassays for ***:This is the frst paper reporting the use of ribosomal protein L16 to develop a competitive array for discriminative determination of amphenicols in food samples.

关键词： Amphenicols ribosomal protein L16 recognition mechanism competitive array discriminative determination egg.

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PD-L1-driven efficient enrichment and elimination of circulating cancer cells by magnetic MoSe_(2) nanosheet

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Nano Research 2024年第5期17卷 4350-4358页

作者： Hongjie Huang Binhua Zou Shanlin Zhu Xingchen Zhang Jiale Huang Jinlin Wang Xiaoling Li Tianfeng Chen The Sixth Affiliated Hospital Jinan UniversityDongguan 523566China Department of Chemistry Institute of Food Safety and NutritionJinan UniversityGuangzhou 510632China Department of Rehabilitation medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Pulmonary and Critical Care medicine Guangzhou Institute of Respiratory HealthNational Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineState Key Laboratory of Respiratory DiseasesThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer *** presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer ***,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing *** summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.

关键词： circulating tumor cells selenide photothermal therapy(PTT) natural killer(NK)cell immunotherapy

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Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

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World Journal of Gastroenterology 2024年第24期30卷 3086-3105页

作者： Miao-Miao Lin Shan-Shan Yang Qiu-Yue Huang Guang-Hui Cui Xiao-Fen Jia Yao Yang Zong-Ming Shi Hui Ye Xue-Zhi Zhang Department of Integrated Traditional Chinese and Western medicine Peking University First HospitalBeijing 100034China institute of Integrated Traditional Chinese and Western medicine Peking UniversityBeijing 100034China

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric *** infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to *** has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in *** In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected *** vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,*** most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm *** assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm *** violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP *** effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain ***-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD *** HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the *** had str

关键词： Qingre Huashi decoction Helicobacter pylori Drug resistance Biofilm Metabolomics

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Genomics,transcriptomics,and peptidomics of the greater wax moth Galleria mellonella neuropeptides and their expression in response to lead stress

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Insect Science 2024年第3期31卷 773-791页

作者： Li-Lin Luo Yang Lin Jun-Hong Linghu Wei Gong Yuan-Hong Luo Man Liu Dao-Chao Jin Guy Smagghe Tong-Xian Liu Shun-Hua Gui Tian-Ci Yi Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region Institute of EntomologyGuizhou UniversityGuiyangGuizhouChina Guizhou institute of Biology Guizhou Academy of SciencesGuiyangChina institute of Plant Health and medicine Guizhou UniversityGuiyangChina

Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of *** an integrated approach of multiomics,we identified neuropeptide precursors in the greater wax moth Galleria mellonella,which is a harmful pest of honeybee hives with a worldwide ***,a total of 63 and 67 neuropeptide precursors were predicted and annotated in the *** genome and transcriptome,in which 40 neuropeptide precursors were confirmed in the *** ***,we identified 12 neuropeptide precursor genes present in *** but absent in honeybees,which may be potential novel pesticide target *** hives were contaminated with heavy metals such as lead,enabling its bioaccumulation in *** bodies through the food chain,we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of *** neuropeptide *** treatment by Pb,the expression of neuropeptide F1 was found to be significantly downregulated,implying that this neuropeptide might be associated with responding to the heavy metal stress in *** study comprehensively identified neuropeptide precursors in ***,and discussed the effects of heavy metals on insect neuropeptides,with the example of *** results are valuable for future elucidation of how neuropeptides regulate physiological functions in *** and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.

关键词： Galleria mellonella genomics heavy metal stress neuropeptide peptidomics transcriptomics

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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou Clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for Clinical Molecular Laboratory medicine of Children’s Hospital of Chongqing Medical university Chongqing 400014China Clinical Research institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su institute of Translational medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for Translational medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

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Targeting the organelle for radiosensitization in cancer radiotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 52-71页

作者： Xiaoyan Sun Linjie Wu Lina Du Wenhong Xu Min Han institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Afliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou institute of Innovative medicine Zhejiang UniversityHangzhou 310058China Jinhua institute of Zhejiang university Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

关键词： Cancer radiotherapy Organelle-target Radiosensitization Boron neutron capture therapy Nanomedicines

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Multidimensional Analgesia of Acupuncture by Increasing Expression of MD2 in Central Nervous System

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Chinese Journal of Integrative medicine 2024年第11期30卷 1035-1044页

作者： LI Wan-rong REN Lu-lu ZHAO Tian-tian DAI Dan-qing GAO Xiao-fei LIANG Hua-zheng XIONG Li-ze Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Shanghai Fourth People's Hospital School of Medicine Tongji University Clinical Research Center for Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University Translational Research institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University Department of Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University School of Rehabilitation Southwest Jiaotong University Monash Suzhou Research institute

Objective:To investigate changes of myeloid differentiation factor 2（MD2） in inflammationinduced pain and acupuncture-mediated ***:Mice were randomly divided into three groups by a random number table method:saline group（n=16）,complete Freund's adjuvant（CFA） group（n=24） and CFA+electroacupuncture（EA） group（n=26）.Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli（ST 36） to alleviate *** mice in the CFA+EA group received EA treatment（30 min/d for 2 weeks） 24 h after *** in the saline and CFA groups received sham ***-Frey test and Hargreaves test were used to assess the pain *** and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 ***:CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling（P0.05）.Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray（PAG） and locus coeruleus（LC） after CFA injection on day 7（P<0.01 for PAG,P<0.05 for LC） and EA significantly reversed this decrease（P<0.01 for PAG,P<0.05 for LC）.Conclusion:The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certai

关键词： dorsal horn electroacupuncture inflammation-induced pain locus coeruleus myeloid differentiation factor 2 periaqueductal gray

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