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autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer

Journal of Integrative Medicine 2024年第3期22卷 295-302页

作者： Zhengting Deng Shufang Liang Guokai Huang Yuqian Wang Xiaoyu Tu Yani Zhang Shu Li Tao Liu Binbin Cheng Taizhou Hospital of Traditional Chinese Medicine Nanjing University of Chinese MedicineTaizhou 225300Jiangsu ProvinceChina Oncology Department of Traditional Chinese Medicine The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China School of Traditional Chinese Medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Gastroenterology Baoshan Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 201900China

Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer ***: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron ***: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax ***, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell *** starvation increased autophagy and amplified the effect of As2O3on cell ***: As2O3induces apoptosis and autophagy in liver cancer cells. autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights

关键词： Apoptosis Arsenic trioxide autophagy Primary liver cancer

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Genes & Diseases 2024年第1期11卷 367-381页

作者： Yunchao Zhang Jiayu Tang Cheng Wang Qinxiu Zhang Anqi Zeng Linjiang Song School of Medical and Life Sciences Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China Institute of Translational Pharmacology and Clinical Application Sichuan Academy of Chinese Medical ScienceChengduSichuan 610041China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China

The incidence and mortality rates of cancer are increasing every year worldwide but the survival rate of cancer patients is still ***,it is necessary to further elucidate the molecular mechanisms involved in tumor development and drug resis-tance to improve cancer cure or survival *** recent years,autophagy has become a hot topic in the field of oncology research,which plays a double-edged role in tumorigenesis,pro-gression,and drug ***,long non-coding RNA(lncRNA)has also been shown to regulate autophagy,and the two-sided nature of autophagy determines the dual regulatory role of autophagy-related IncRNAs(ARlncRNAs).Therefore,ARlncRNAs can be effective ther-apeutic targets for various ***,the high abundance and stability of ARlncR-NAs in tumor tissues make them promising *** this review,we summarized the roles and mechanisms of ARlncRNAs in tumor cell proliferation,apoptosis,migration,invasion,drug resistance,angiogenesis,radiation resistance,and immune *** addition,we described the clinical significance of these ARlncRNAs,including as biomarkers/therapeutic targets and their association with clinical drugs.

关键词： Apoptosis autophagy Biomarker Cancer Drug resistance LncRNA

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autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis

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Frontiers of Medicine 2024年第3期18卷 538-557页

作者： Yue Yuan Jiaxuan Li Xun Lu Min Chen Huifang Liang Xiao-ping Chen Xin Long Bixiang Zhang Song Gong Xiaowei Huang Jianping Zhao Qian Chen Division of Gastroenterology Department of Internal Medicine at Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of Hepato–Pancreato–Biliary Diseases Wuhan430030China Department of Trauma Surgery Tongji Trauma CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Schistosoma infection is one of the major causes of liver *** roles of hepatic progenitor cells(HPCs)in the pathogenesis of liver fibrosis have been ***,the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains *** study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal *** activation of HPCs was verified by immunohistochemistry(IHC)and immunofluorescence(IF)staining in fibrotic liver from patients and mice with Schistosoma japonicum *** coculturing HPCs with hepatic stellate cells(HSCs)and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays,we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal *** autophagy by the autophagy inhibitor chloroquine(CQ)significantly diminished liver fibrosis and granuloma formation in ***-infected ***-secreted extracellular vehicles(EVs)were further isolated and studied by miRNA ***-1306-3p,miR-493-3p,and miR-34a-5p were identified,and their distribution into EVs was inhibited due to impaired autophagy in HPCs,which contributed to suppressing HSC *** conclusion,we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in *** the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

关键词： schistosomiasis hepatic progenitor cell autophagy extracellular vesicle fibrosis miRNA

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autophagy in neural stem cells and glia for brain health and diseases

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Neural Regeneration Research 2024年第4期19卷 729-736页

作者： Aarti Nagayach Chenran Wang Department of Cancer Biology University of Cincinnati College of Medicine

autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and *** facilities the utilization of energy and the microenvironment for developing neural stem *** arbitrates structural and functional remodeling during the cell differentiation *** also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of *** recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the *** cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured ***,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative *** review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

关键词： astrocyte autophagy glia microglia neural stem cells neurodegenerative diseases neurodevelopmental disorders oligodendrocyte

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autophagy and circadian rhythms:interactions and clinical implications

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BIOCELL 2024年第1期48卷 33-45页

作者： TIANKAI DI ZHIFEI ZHOU FEN LIU YUJIANG CHEN LULU WANG State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China Department of Stomatology The 969th HospitalJoint Logistics Support Force of the Chinese People’s Liberation ArmyHohhot010000China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Clinical Research Center of Shaanxi Province for Dental and Maxillofacial DiseasesDepartment of Pediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’an710000China Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’an710032China

autophagy is a widespread biological process that controls cellular growth,survival,development,and *** rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and *** of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian *** has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal *** can modulate circadian rhythms by breaking down proteins that regulate the circadian *** potential regulatory connection between the two has been a popular subject of clinical and fundamental *** the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the *** present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.

关键词： autophagy Circadian rhythms Mechanism Application

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Bionic immunoactivator copresenting autophagy promoting and costimulatory molecules for synergistic cancer immunotherapy

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Nano Research 2024年第3期17卷 1710-1724页

作者： Yiwei Peng Yiliang Yang Zhenzhen Yang Datong Gao Jiajia Li Qi Sun Yitian Du Meng Lin Xianrong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Immunotherapy has great promise in improving malignant tumor ***,the efficacy of existing strategies is often limited by the immunosuppressive ***,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune ***-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor ***-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive ***-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold *** group)in mouse tumor model after intravenous or subcutaneous ***,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and *** findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor *** these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.

关键词： in situ bionic immunoactivator autophagy glucocorticoid-induced tumor necrosis factor receptor(GITR)agonist platelets and platelet microparticles cancer immunotherapy

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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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Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine?autophagy regulation also works

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Chinese Chemical Letters 2024年第6期35卷 474-479页

作者： Yuanyi Zhou Ke Ma Jinfeng Liu Zirun Zheng Bo Hu Yu Meng Zhizhong Li Mingshan Zhu Postdoctoral Innovation Practice Base The First and Fifth Affiliated Hospital of Jinan UniversityGuangzhou 510632China Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People’s Hospital)Heyuan 517465China School of Environment Jinan UniversityGuangzhou 511443China Department of Nephrology The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China

Exploring the therapeutic effect of single atom catalysts beyond reactive oxygen species(ROS)modulation would boost the prosperity of nanomedicine in cancer *** as a vital therapy target offers new options for the control of renal cell carcinoma(RCC)***,Fe single atom-decorated graphene oxide(Fe_(1)-GO)nanosheet is developed to be a feasible autophagy inducer in RCC *** the well-dispersed O-Fe_(1)-O active sites,Fe_(1)-GO kills ACHN cells effectively but maintains acceptable cytotoxicity to the normal podocyte and HK2 ***-depth analyses ascribe the inhibition of ACHN cells to the upregulated autophagy instead of the commonly known catalytic ROS *** in vivo therapeutic effect of Fe_(1)-GO nanomedicine is also validated by the RCC-bearing BALB/c mice model,realizing an 89% reduction of tumor weight and good *** work provides new insights into the design of autophagy regulators as well as potential therapeutic strategies for RCC treatment.

关键词： Fe single atom autophagy Renal cell carcinoma Graphene oxide Cancer therapy

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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CD200Rhigghh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells

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Cellular & Molecular Immunology 2024年第4期21卷 349-361页

作者： Ye Seon Kim Yu Sun Jeong Geon Ho Bae Ji Hyeon Kang Mingyu Lee Brian A.Zabel Yoe-Sik Bae Department of Biological Sciences Sungkyunkwan UniversitySuwon16419Republic of Korea Department of Health Science and Technology SAIHSTSungkyunkwan UniversitySeoul06351Republic of Korea Palo Alto Veterans Institute for Research Veterans Affairs HospitalPalo AltoCA94304USA

Distinct neutrophil populations arise during certain pathological *** generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain *** this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))*** to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-α*** soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) *** administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased *** analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection *** together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.

关键词： Sepsis Neutrophils CD200R autophagy IGF-1 Regulatory T cells

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