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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State key laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen Chen Xiaolin Zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li Department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong province key laboratory of Orthopedics and Traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan Chen Hongxia Deng Nannan Zhang Department of Obstetrics and Gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina key laboratory of Birth Defects and Women and Children’s Diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina laboratory of Reproductive Endocrinology and Reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National Center for Birth Defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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Enhanced subacute ischemic stroke treatment via multistage drug delivery system design for combination therapy

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Science China Chemistry 2025年

作者： Xihan Xu Juan-Juan Li Jiamin Li Hui-Yan Zhang Yilin Qi Bing-Sen Shi Tianqi Li Shan-Shan Su Weitao Zhao Chang Chen Zhongying Gong Huiyu Liu Ke-Rang Wang Dong-Sheng Guo Xue Xue State key laboratory of Medicinal Chemical Biology College of Pharmacy Nankai University College of Chemistry State Key Laboratory of Elemento-Organic Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Frontiers Science Center for New Organic Matter Collaborative Innovation Center of Chemical Science and EngineeringNankai University College of Chemistry and Materials Science State Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education) Key Laboratory of Chemical Biology of Hebei Province Hebei Research Center of the Basic Discipline of Synthetic Chemistry Hebei University Department of Neurology Tianjin First Central Hospital School of Medicine Nankai University Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic-Inorganic Composites Beijing Laboratory of Biomedical Materials Bionanomaterials & Translational Engineering Laboratory Beijing Key Laboratory of BioprocessBeijing University of Chemical Technology

The management of acute ischemic stroke remains challenging due to its abrupt onset and the narrow treatment window,resulting in high rates of disability and *** therapy for neuroprotection and neurorepair strategies provided new hopes for subacute stroke *** we designed a multistage nanodelivery system that matches the unique microenvironment of the subacute phase of stroke,which utilizes calixarene as a building block to effectively load the neuroprotective drug *** calixarene is designed with glycosidic linkages targeting the glucose transporter 1 (GLUT1)on the blood-brain barrier (BBB) and azo bonds that are responsive to hypoxic ***,the decomposed calixarene molecules themselves possess intrinsic bio-activation to modulate inflammatory responses,achieving a multistage therapeutic approach that transitions from targeting to release and finally to *** approach combines anti-inflammation and neuroprotection,providing a multi-level treatment *** system was validated in a rat model of permanent middle cerebral artery occlusion (pMCAO),demonstrating that intravenous administration of the nanodelivery system repairs brain damage and improves motor function 24 h post-pMCAO *** work offers a precise and integrative strategy for stroke patients missing the acute therapy window to improve functional recovery and enhance the effect of comprehensive treatment.

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Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells

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Signal Transduction and Targeted therapy 2020年第1期5卷 1953-1966页

作者： Chao Ni Qing-Qing Fang Wu-Zhen Chen Jin-Xing Jiang Zhou Jiang Jun Ye Ting Zhang Liu Yang Fan-Bo Meng Wen-Jie Xia Miaochun Zhong Jian Huang Department of Breast Surgery Second Affiliated HospitalZhejiang UniversityHangzhouZhejiang 310009China key laboratory of tumour microenvironment and immune therapy of zhejiang province Second Affiliated HospitalZhejiang UniversityHangzhouZhejiang 310009China key laboratory of tumour Molecular Diagnosis and Individualized Medicine of zhejiang province Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhouZhejiang 310014China Department of Thyroid and Breast Surgery Affiliated Hospital of Shaoxing UniversityShaoxingZhejiang 312099China Department of Thyroid and Breast Surgery Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhouZhejiang 310014China

γδT cells have been reported to exert immunosuppressive functions in multiple solid malignant diseases,but their immunosuppressive functional subpopulation in breast cancer(BC)is still ***,we collected 40 paired BC and normal tissue samples from Chinese patients for ***,we showed thatγδT1 cells comprise the majority of CD3+T cells in BC;next,we found that CD73+γδT1 cells were the predominant regulatory T-cell(Treg)population in BC,and that their prevalence in peripheral blood was also related to tumour *** addition,CD73+γδT1 cells exert an immunosuppressive effect via adenosine *** also found that BC could modulate CD73 expression onγδT cells in a non-contact *** microarray analysis and functional experiments indicated that breast tumour cell-derived exosomes(TDEs)could transmit lncRNA SNHG16,which upregulates CD73 expression,to Vδ1 T *** the mechanism,SNHG16 served as a ceRNA by sponging miR-16–5p,which led to the derepression of its target gene SMAD5 and resulted in potentiation of the TGF-β1/SMAD5 pathway to upregulate CD73 expression in Vδ1 T *** results showed that the BC-derived exosomal SNHG16/miR-16–5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation,thus inducing CD73 expression in Vδ1 T *** results first identify the significance of CD73+Vδ1 Tregs in BC,and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.

关键词： CD73 cancer Treg

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Endothelial cells in colorectal cancer

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 946-956页

作者： Wu-Zhen Chen Jing-Xin Jiang Xiu-Yan Yu Wen-Jie Xia Peng-Xin Yu Ke Wang Zhi-Yong Zhao Zhi-Gang Chen Department of Surgical Oncology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina key laboratory of Tumor microenvironment and immune therapy of zhejiang province HangzhouChina Department of Breast Surgery Zhejiang Provincial People’s HospitalHangzhou 310000Zhejiang ProvinceChina Department of Administrative Office the First People’s Hospital of JiandeHangzhou 310000Zhejiang ProvinceChina

The dependence of tumor growth on neovascularization has become an important aspect of cancer *** angiogenesis is one of the key mechanisms of tumorigenesis,growth and *** key events involved in this process are endothelial cell proliferation,migration,and vascular *** studies have revealed the importance of tumor-associated endothelial cells(TECs)in the development and progression of colorectal cancer(CRC),including epithelial proliferation,stem cell maintenance,angiogenesis,and immune *** of research have identified that the molecular basis of tumor angiogenesis includes vascular endothelial growth factors(VEGFs)and their receptor family,which are the main targets of antiangiogenesis *** and their receptors play key roles in the pathology of angiogenesis,and their overexpression indicates poor prognosis in *** article reviews the characteristics of the tumor vasculature and the role of TECs in different stages of CRC and immune *** also discuss the biological effects of VEGFs and their receptor family as angiogenesis regulators and emphasize the clinical implications of TECs in clinical treatment.

关键词： Colorectal cancer Tumor-associated endothelial cells Heterogeneity Vascular endothelial growth factor immune remodeling

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Modifying metabolic and immune hallmarks of cancer by a copper complex

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Science China Chemistry 2025年

作者： Chengyan Chu Yunhua Zhang Chengyuan Qian Xiuzhi Yang Yicun Shang Zijian Guo Xiaoyong Wang State key laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University State key laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment （TIME）.Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex （DDCu） was designed to influence the energy metabolism of cancer cells and reshape the *** restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor ***,DDCu was reduced to Cu+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe–S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer ***,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4+and CD8+T cells,and reversed the *** a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi Department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of General Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

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Energy metabolism in cancer stem cells

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World Journal of Stem Cells 2020年第6期12卷 448-461页

作者： Xuan Zhu Hui-Hui Chen Chen-Yi Gao Xin-Xin Zhang Jing-Xin Jiang Yi Zhang Jun Fang Feng Zhao Zhi-Gang Chen Department of Radiation Oncology the First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310000Zhejiang ProvinceChina The key laboratory of Cancer Prevention and Intervention China National Ministry of EducationHangzhou 310000Zhejiang ProvinceChina Department of Breast Surgery the Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310000Zhejiang ProvinceChina key laboratory of Tumor microenvironment and immune therapy of zhejiang province Hangzhou 310000Zhejiang ProvinceChina Institute of Cancer and Basic Medicine Chinese Academy of SciencesCancer Hospital of the University of Chinese Academy of SciencesZhejiang Cancer HospitalHangzhou 310000Zhejiang ProvinceChina

Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of *** contrast,most cancer cells use less efficient glycolysis to produce ATP and essential *** cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth.A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells(CSCs).New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer *** can dynamically transform their metabolic state to favor glycolysis or oxidative *** mechanism of the metabolic plasticity of CSCs has not been fully elucidated,and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor *** CSC metabolism may provide new and effective methods for the treatment of *** this review,we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs,and discuss the clinical implications of targeting CSC metabolism.

关键词： Cancer stem cells Differentiated cancer cells Metabolic characteristics Oxidative phosphorylation Glycolysis Tumor microenvironment Metabolic interplay

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Tumor circulome in the liquid biopsies for digestive tract cancer diagnosis and prognosis

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World Journal of Clinical Cases 2020年第11期8卷 2066-2080页

作者： Long Chen Yu Chen Yuan-Ling Feng Yan Zhu Li-Quan Wang Shen Hu Pu Cheng Department of Radiotherapy Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina Department of Pediatric Surgery Guangdong Women and Children HospitalGuangzhou 511400Guangdong ProvinceChina Department of Obstetrics The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina Department of Respiratory Shulan HospitalHangzhou 310004Zhejiang ProvinceChina Department of Gynecology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina key laboratory of Tumor microenvironment and immune therapy of zhejiang province Hangzhou 310052Zhejiang ProvinceChina

Digestive tract cancer is one of the main diseases that endanger human *** present,the early diagnosis of digestive tract tumors mainly depends on serology,imaging,endoscopy,and so *** tissue specimens are the gold standard for cancer diagnosis,with the rapid development of precision medicine in cancer,the demand for dynamic monitoring of tumor molecular characteristics has *** biopsy involves the collection of body fluids via noninvasive approaches,and analyzes biological markers such as circulating tumor cells,circulating tumor DNA,circulating cell-free DNA,microRNAs,and *** recent years,liquid biopsy has become more and more important in the diagnosis and prognosis of cancer in clinical practice due to its convenience,non-invasiveness,high specificity and it overcomes temporal-spatial ***,this review summarizes the current evidence on liquid biopsies in digestive tract cancers in relation to diagnosis and prognosis.

关键词： Digestive tract cancer Liquid biopsy Tumor circulome Tumor progression Diagnosis Prognosis

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