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A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid

Science China Life Sciences 2024年第10期67卷 2213-2223页

作者： Jingge Lian Liu Yang Hanbo Tan Shaoyi Su Leonor Serrano Lopes Fangxiao Cheng Junhao Yan Yu Fu Wanyi Fu Zhaoheng Xie Jianfei Sun Jicong Zhang Zhiqian Tong Yajuan Gao Hongbin Han Department of Radiology Peking University Third Hospital Beijing Key Laboratory of Magnetic Resonance Imaging technology Institute of medical technology Peking University Health Science Center Department of Informatics Technical University of Munich Department of Anatomy and Histology School of Basic Medical SciencesPeking University Department of Neurology Peking University Third Hospital Department of Electronic Engineering Tsinghua University State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast University School of biological Science and medical Engineering Beihang University Key Laboratory of Alzheimer's Disease of Zhejiang Province Institute of AgingSchool of Mental HealthWenzhou Medical University NMPA Key Laboratory for Evaluation of medical Imaging Equipment and Technique

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation(EAI), for accelerating interstitial fluid(ISF)drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS). In this study, the method of EAI was modified(m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model. The results demonstrated the accumulation of IL-1β, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

关键词： ischemic stroke brain extracellular space interstitial fluid modified epidural arterial implantation

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Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

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Chinese Journal of Chemical Engineering 2024年第4期68卷 156-164页

作者： Kexin Zhang Wenmin Zhang Heng An Zhe Huang Yanzhen Wen Xiangyu Jiao Yongqiang Wen College of Chemical Engineering and technology Taiyuan University of Science and TechnologyTaiyuan 030024China Beijing Key Laboratory for Bioengineering and Sensing technology Daxing Research InstituteSchool of Chemistry&Biological EngineeringUniversity of Science&Technology BeijingBeijing 100083China

Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on *** stem cells(MSCs)promote diabetic wound *** when MSCs aggregate into multicellular spheroids,their therapeutic effect is ***,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid *** this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous *** thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable *** the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound *** importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound *** NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

关键词： Electrospinning Homogenization Biomedical engineering Nanomaterials Stem cell spheroids Diabetic wound healing

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Neutralization of SARS-CoV-2 infection by antibodies targeting diverse epitopes

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Genes & Diseases 2024年第4期11卷 134-137页

作者： Shusheng Wang Yunji Liao Kaiyong Yang Hang Ma Zhangyi Song Haiqiu Huang Li Zhang Ailing Wang Lei Han Jiawei Zhang Hui Chen Haiyang Yin Yantin Bian Hua Jiang Xiaodong Xiao Yueqing Xie Yunsheng Yuan Jianwei Zhu Engineering Research Center of Cell and therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Jecho laboratories Inc.FrederickMD 21704USA Jecho Institute Co. Ltd.Shanghai 200240China

The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic *** and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 *** a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike *** of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.

关键词： antibodies inhibited monoclonal

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Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies

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Cancer Communications 2024年第3期44卷 408-432页

作者： Lu Tang Huan Zhang Fen Zhou Qiuzhe Wei Mengyi Du Jianghua Wu Chenggong Li Wenjing Luo Jie Zhou Xindi Wang Zhaozhao Chen Yinqiang Zhang Zhongpei Huang Zhuolin Wu Yuxi Wen Huiwen Jiang Danying Liao Haiming Kou Wei Xiong Heng Mei Yu Hu Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Clinical medical Center of Cell Therapy For Neoplastic Disease WuhanHubeiP.R.China Key Laboratory of biological Targeted Therapy the Ministry of EducationWuhanHubeiP.R.China Department of Thoracic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Key Laboratory of biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China

Background:Chimeric antigen receptor T(CAR-T)therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignan-cies,but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully *** study aims to explore the molecular deter-minants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical ***:The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated *** in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T *** addition,the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular ***:The CRISPR/Cas9-based knockout screening showed that the enrich-ment of autophagy-related genes(ATG3,BECN1,and RB1CC1)provided protec-tion of cancer cells from CD19 CAR-T cell-mediated *** findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of ***,higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer respon-siveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T *** RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell *** inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and ***,our study revealed that cancer-intrinsic

关键词： CAR-T resistance Autophagy Immune evasion Apoptosis Chemotaxis

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Automated screening of primary cell-based aptamers for targeting and therapy of pancreatic cancer

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Chinese Chemical Letters 2024年第2期35卷 300-304页

作者： Zhukang Guo Baijiang Jin Yile Fang Lian Jin Song Li Yan Deng Zhu Chen Hui Chen Yuanying Zhang Rabia Usman Nongyue He State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Hunan Key Laboratory of Biomedical Nanomaterials and Devices Hunan University of TechnologyZhuzhou 412007China Department of Molecular Biology Jiangsu Cancer HospitalNanjing 210009China

Although it has been developed for many years, nucleic acid aptamer screening technology still fails to be widely used, a considerable part of it is due to the variability of tumor cell morphology, which leads to the use of immortalized cell lines in the laboratory to screen nucleic acid aptamers for recognition ability of tumor cells in the diseased *** address this, primary cells that can be stably passaged were isolated and extracted from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice in this ***, an automated screening instrument for nucleic acid aptamers developed autonomously by our group was used to perform efficient aptamer screening using a limited number of cells, and the obtained nucleic acid aptamers were affinity verified at the cellular ***, to answer the question of the cell growth environment difference on the recognition ability of nucleic acid aptamers, we verified its targeting ability to tumors in vivo on a nude mice xenograft tumor model, and further used a common antitumor drug doxorubicin combined with nucleic acid aptamers to verify the drug loading ability of this aptamer combined with the targeting therapeutic ability.

关键词： Aptamer Cell-SELEX Automatic instrument Combination therapy Pancreatic cancer

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Potential clinical application of microRNAs in bladder cancer

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The Journal of Biomedical Research 2024年第04期 289-306页

作者： Pei Wang Xiaowei Wei Xiaojun Qu Yefei Zhu Laboratory Medicine Center the Second Affiliated Hospital of Nanjing Medical University School of biological Science and medical Engineering Southeast University

Bladder cancer(BC) is the tenth most prevalent malignancy globally, presenting significant clinical and societal challenges because of its high incidence, rapid progression, and frequent recurrence. Presently, cystoscopy and urine cytology serve as the established diagnostic methods for BC. However, their efficacy is limited by their invasive nature and low sensitivity. Therefore, the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC, as well as for facilitating an optimal tumor treatment and an improved prognosis. microRNAs(miRNAs), short noncoding RNA molecules spanning around 20–25 nucleotides, are implicated in the regulation of diverse carcinogenic *** altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC. Investigations into aberrant miRNAs derived from blood, urine, or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease. Simultaneously, the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC. This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression, and systematically summarizes their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets for BC. Additionally, we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

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Potential clinical application of microRNAs in bladder cancer

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Journal of Biomedical Research 2024年第4期38卷 289-306页

作者： Pei Wang Xiaowei Wei Xiaojun Qu Yefei Zhu Laboratory Medicine Center the Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210011China School of biological Science and medical Engineering Southeast UniversityNanjingJiangsu 210096China

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent ***,cystoscopy and urine cytology serve as the established diagnostic methods for ***,their efficacy is limited by their invasive nature and low ***,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved ***(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic *** altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of *** into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the ***,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of *** review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for ***,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

关键词： bladder cancer microRNAs biomarker diagnosis detection method

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Cancer organoids:A platform in basic and translational research

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Genes & Diseases 2024年第2期11卷 614-632页

作者： Xin Ma Qin Wang Guozheng Li Hui Li Shouping Xu Da Pang Department of Breast Surgery Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Sino-Russian medical Research Center Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Heilongjiang Academy of medical Sciences HarbinHeilongjiang 150086China Department of Pharmacology (The State-Province Key laboratories of Biomedicine-Pharmaceutics of China) College of Pharmacy of Harbin Medical UniversityHarbinHeilongjiang 150086China

An accumulation of previous work has established organoids as good preclinical models of human tumors,facilitating translation from basic research to clinical *** are changing the paradigm of preclinical cancer research because they can recapitulate the heterogeneity and pathophysiology of human cancers and more closely approximate the complex tissue environment and structure found in clinical tumors than in vitro cell lines and animal ***,the potential applications of cancer organoids remain to be comprehensively *** the review,we firstly describe what is currently known about cancer organoid culture and then discuss in depth the basic mechanisms,including tumorigenesis and tumor metastasis,and describe recent advances in patient-derived tumor organoids(PDOs)for drug screening and immunological ***,the present challenges faced by organoid technology in clinical practice and its prospects are *** review highlights that organoids may offer a novel therapeutic strategy for cancer research.

关键词： Drug assays Immunotherapy Mechanism research Organoids Precision medicine

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Targeting lipid metabolism overcomes BTK inhibitor resistance in diffuse large B-cell lymphoma

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Medicine in Novel technology and Devices 2024年第2期22卷 9-14页

作者： Zhuojun Liu Chenyue Wu Zhaohua Yao Yuxuan Wang Zhe Yu Jian Yu School of biological Science and medical Engineering Beihang UniversityBeijing100191China Key Laboratory of Biomechanics and Mechanobiology Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing100191China Shandong Provincial Third Hospital Shandong250031China

Exploring novel therapeutic targets of Diffuse large B cell lymphoma(DLBCL)to overcome its resistance to Bruton's Tyrosine Kinase(BTK)inhibitors is a key *** metabolism,crucial in the resistance landscape of various cancers,may unlock new aspects of BTK inhibitor resistance in *** the known importance of lipid metabolism in oncological resistance patterns,its intricate role in DLBCL and its resistance to BTK inhibitor therapies remains largely *** review will explore the complex relationship between lipid metabolism and BTK inhibitor resistance,giving new insights for improving the effectiveness of BTK inhibitors and developing innovative combination treatment methods for *** review holds the potential for guiding future research directions,optimizing existing therapeutic processes,and inspiring the development of innovative combinatorial therapeutic strategies that improve outcomes in patients with DLBCL.

关键词： Diffuse large B-Cell lymphoma BTK inhibitor resistance Lipid metabolism Fatty acid Cholesterol

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From ancient wisdom to modern science:Gut microbiota sheds light on property theory of traditional Chinese medicine

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Journal of Integrative Medicine 2024年第4期22卷 413-444页

作者： Ya-nan Yang Jia-guo Zhan Ying Cao Chong-ming Wu School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China Tianjin Key Laboratory of therapeutic Substance of Traditional Chinese Medicine Tianjin 301617China

The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia(2020 edition) to compile a list of Chinese materia medica(CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria,while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin(Liver) and Taiyin(Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.

关键词： Traditional Chinese medicine Property theory Gut microbiota Four natures Five flavors Meridian tropism

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