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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

Military medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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Nutritional and therapeutic benefits of coconut milk and its potential as a plant-based functional yogurt alternative: a review

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Food Science and Human Wellness 2024年

作者： Gengghatarani Gengan Nurul Solehah Mohd Zaini Nazamid Saari Anis Shobirin Meor Hussin Ahmad Haniff Jaafar Hanan Hasan Elicia Jitming Lim Wan Abd Al Qadr Imad Wan-Mohtar Muhamad Hafiz Abd Rahim Functional Omics and Bioprocess Development Laboratory， Institute of biological Sciences， Faculty of Science， Universiti Malaya Faculty of Food Science and technology， Universiti Putra Malaysia School of Life and Environmental Sciences， The University of Sydney

Plant-based milks are on the rise due to an increased awareness of their sustainability and health benefits. Currently， dairy milk is the most nutritionally complete beverage， but it suffers from the presence of indigestible lactose and allergenic proteins. Coconut milk has been around for a long time， but its application is limited due to a perceived lack of specific nutrients， high saturated fat levels， and low acceptability. Recent evidence indicates， however， that the saturated fat and other plant-based components found in coconut milk are good for metabolic outcomes and brain health. The conversion of coconut milk to yoghurt will further improve its functionality by boosting its existing nutritional qualities. In this article， the nutritional value of coconut milk， as well as its potential downsides， its application as yoghurt， and suggestions for enhancing its nutritional functionality will be examined.

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun Xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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Recent progress of vaccines administration via microneedles for cancer immunotherapy

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Chinese Chemical Letters 2024年第3期35卷 96-103页

作者： Yuanzheng Chen Jiaojiao Zhu Jinsong Ding Wenhu Zhou Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Key Laboratory of biological Nanotechnology of National Health Commission Changsha 410008China

therapeutic cancer vaccines have undergone a resurgence in the past *** of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is considered to be an ideal treatment *** convenient administration,the recent development of microneedles(MNs)provides a safe,painless,and low-cost transdermal delivery strategy,which could bypass the first-pass metabolism of vaccines for enhanced stability and ***,the therapeutic effect of MNs-based cancer vaccines is not optimal,which is limited by the complex set of host,tumor,and environmental factors,as well as the limited vaccine loading ***,further improvements are still required to push their clinical *** this critical review,we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy,summarize the recent advances in MNs-based cancer vaccination,and provide an overview of various design strategies and mechanisms for active or passive targeting delivery,aiming to develop safer,more effective,and more stable MNs-based cancer ***,we briefly describe the potential of vaccine platforms in combination with other therapies,suggest the need to design vaccines according to specific circumstances,and discuss the biosafety of repeated administration for enhancing clinical efficacy.

关键词： Transdermal delivery Microneedles Cancer vaccine Immunotherapy Nanoparticle Lymph node

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Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

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Oncology Research 2024年第2期32卷 393-407页

作者： HONGYUAN LIANG YANQIU LI YONGGANG QU LINGYUN ZHANG Department of Radiology Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology The First Affiliated Hospital of China Medical UniversityShenyangChina Department of Clinical Medicine China Medical UniversityShenyangChina Department of medical Oncology The First Hospital of China Medical UniversityShenyangChina

Advanced LUAD shows limited response to treatment including immune *** the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response *** GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R *** constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression *** calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier *** also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model *** addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment *** also used the TIDE algorithm to predict immunotherapy responses in the CDI ***,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture *** study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with *** KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological *** study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk *** comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS *** addition,the study used unsupervised cluster analysis to d

关键词： Lung adenocarcinoma Programmed cell death Iron-death Drug sensitivity Cancer therapy

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限域空间反应合成氧化铁纳米颗粒

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Science China Materials 2024年第8期67卷 2447-2461页

作者：赵一帆吴临远李艳毛宇顾宁 Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical EngineeringSoutheast UniversityNanjing 210096China Nanjing Key Laboratory for Cardiovascular Information and Health Engineering Medicine Institute of Clinical MedicineNanjing Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210093China

氧化铁纳米颗粒(IONPs)在生物医学领域具有广阔的应用前景.以共沉淀法、热分解法、溶胶-凝胶法与水热法为代表的传统方法,在控制IONPs合成反应过程的物质交换存在一定局限性,或影响产物纯度及功能性.在限域空间内进行的合成反应,有望为I... 详细信息

氧化铁纳米颗粒(IONPs)在生物医学领域具有广阔的应用前景.以共沉淀法、热分解法、溶胶-凝胶法与水热法为代表的传统方法,在控制IONPs合成反应过程的物质交换存在一定局限性,或影响产物纯度及功能性.在限域空间内进行的合成反应,有望为IONPs合成过程精准控制以及产物性能提升提供有效的解决方案.限域空间合成方法与细胞利用纳米反应器精确控制系列化学反应的生物合成过程类似.本文聚焦于IONPs的限域空间合成,综述了目前实验室构建限域空间反应器制备IONPs的策略,旨在加深对纳米反应器在合成IONPs过程中所发挥作用的理解并推进其应用,进而推动开发具有更优异生物相容性和诊疗效应的IONPs.

关键词：纳米反应器物质交换氧化铁纳米颗粒热分解法生物合成过程产物纯度产物性能空间合成

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The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China(Life Sciences) 2024年第9期67卷 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang State Key Laboratory of New Pharmaceutical Preparations and Excipients/Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei ProvinceHebei UniversityBaoding 071002China CAS Key Laboratory for biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of ***,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been ***,the underlying mechanisms regulating the therapeutic escape remain *** this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the ***,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and ***,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关键词： therapeutic escape breast cancer stem cells motility p38/MAPK signaling pathway molecular mechanism

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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

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World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha Center for medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely *** presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for *** To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental *** A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy *** in plasma were set as exposures with ASD as the main *** causal relationships were estimated using the inverse variant weight(IVW)*** also performed leave-one-out sensitivity tests to validate the robustness of the *** on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and *** Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and *** Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and *** findings offer perspectives for the discovery of diagnos

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

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Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

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Oncology Research 2024年第5期32卷 983-998页

作者： ANDI ZHAO YUE WANG ZIJIN WANG QING SHAO QI GONG HUI ZHU SHIYA SHEN HU LIU XUEJUAN CHEN Department of Ophthalmology The First Affiliated Hospital with Nanjing Medical UniversityNanjing210029China The First Clinical medical College Nanjing Medical UniversityNanjing211166China Department of Ophthalmology Nanjing First HospitalNanjing Medical UniversityNanjing210006China

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple ***,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain *** this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative ***_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo ***,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target *** sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional *** assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling ***,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

关键词： Uveal melanoma Hsa_circ_0053943 IGF2BP3 EGFR MAPK/ERK signaling pathway

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