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Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

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World Journal of Gastroenterology 2024年第18期30卷 2391-2396页

作者： Michele Barone section of Gastroenterology Department of Precision and Regenerative Medicine-Jonian Area-University of BariBari 70124Italy

This editorial contains comments on the article by Zhao et al in print in the World Journal of *** mechanisms responsible for hepatic fibrosis are also involved in ***,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human ***-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of ***,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)*** this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this ***,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

关键词： Renin-angiotensin system Liver fibrosis Hepatic stellate cells Autophagy Hepatocellular carcinoma

Glial progenitor heterogeneity and plasticity in the adult spinal cord

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Neural Regeneration Research 2024年第12期19卷 2567-2568页

作者： Haichao Wei Jia Qian Wu Department of Neurosurgery McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTXUSA Center for Stem cell and Regenerative Medicine UT Brown Foundation Institute of Molecular MedicineHoustonTXUSA MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous *** progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific ***,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous *** development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.

关键词： functions plasticity thoroughly

A High-Contrast Autolysosome Probe for Detecting Interaction between Autophagosomes and Autolysosomes in Mitophagy

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Chinese Journal of Chemistry 2024年第8期42卷 858-866页

作者： Weihua Wang Chu Han Shengjie Xie Zisong Cong Zixuan Yang Yuxin Feng Limin Xiang Heng Song College of Chemistry and molecular Sciences Wuhan UniversityWuhanHubei430072 China

Comprehensive Summary,Autophagy is a multi-step cell metabolism process in which cells remove damaged and unwanted *** autophagy,autophagosomes fuse with lysosomes to form *** membrane components are recycled from autolysosomes through the autophagosomal components recycling(ACR),while lysosomal components circulate on the autolysosomal surface through the autophagic lysosome reformation(ALR)*** contain components from autophagosomes and ***,whether there is a fusion between autolysosome and autophagosome or lysosome at the organelle level remains *** this study,a pH and viscosity dual-controlled mitochondria-targeting fluorescent probe Mito-Q was designed based on an asymmetric norcyanine to achieve the high-contrast imaging of mitochondria-containing ***-Q not only effectively detected mitochondrial viscosity changes and mitophagy with high sensitivity,but more importantly,the fusion of mitochondria-containing autolysosomes and autophagosomes(FMAA)was observed during autophagy by the real-time confocal imaging of HeLa cells.

关键词： Mitophagy Autolysosomes Bioimaging Biosensors Fluorescence imaging

The transcriptional control of LcIDL1–LcHSL2 complex by LcARF5 integrates auxin and ethylene signaling for litchi fruitlet abscission

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Journal of Integrative Plant biology 2024年第6期66卷 1206-1226页

作者： Xingshuai Ma Zidi He Ye Yuan Zhijian Liang Hang Zhang Vilde Olsson Lalun Zhuoyi Liu Yanqing Zhang Zhiqiang Huang Yulian Huang Jianguo Li Minglei Zhao State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern AgricultureKey Laboratory of Biology and Genetic Improvement of Horticultural Crops(South China)Ministry of Agriculture and Rural AffairsGuangdong Litchi Engineering Research CenterCollege of HorticultureSouth China Agricultural UniversityGuangzhou 510642China Dongguan Botanical Garden Dongguan 523128China section for Genetics and Evolutionary biology Department of BiosciencesUniversity of OsloBlindernveien 31Oslo 0316Norway College of Agriculture Guangxi UniversityNanning 530004China

At the physiological level,the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in ***,the underlying molecular mechanisms remain ***,we identified transcription factors involved in indoleacetic acid(IAA)and ethylene(ET)signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION(IDA)and its receptor HAESA(HAE),which are key components initiating ***,litchi IDAlike 1(LcIDL1)interacts with the receptor HAESA-like2(LcHSL2).Through in vitro and in vivo experiments,we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and ***,we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates *** expression of IDA and HSL2 homologs was enhanced in Lc ARF5and Lc EIL3 transgenic Arabidopsis plants,but reduced in ein3 eil1 ***,the expressions of LcIDL1 and LcHSL2 were significantly decreased in Lc ARF5-and LcEIL3-silenced fruitlet abscission zones(FAZ),which correlated with a lower rate of fruitlet *** of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid(the precursor of ethylene)levels in the litchi FAZ,followed by abscission *** this process,LcRF5 and LcEIL3 were induced in the ***,our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5(LcARF5)-LcIDL1/LcHSL2 and LcEIL3–LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.

关键词： auxin ethylene fruit abscission IDA–HAE/HSL2 litchi

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

Generation and characterization of nanobodies targeting GPCR

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Biophysics Reports 2024年第1期10卷 22-30页

作者： Shenglan Zhang Zhiran Fan Jianfeng Liu Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) cellular Signaling laboratory International Research Center for Sensory Biology and Technology of MOST Key Laboratory of Molecular Biophysics of MOE College of Life Science and Technology Huazhong University of Science and Technology

G protein-coupled receptors(GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH(variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in Escherichia coli(E. coli) and purified to characterize their binding potency.

关键词： Nanobody Single domain antibody Heavy chain-only antibody GPCR G protein-coupled receptor

Modeling tuberous sclerosis complex with human induced pluripotent stem cells

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World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing Wen Department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in molecular and Systems Pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA Department of cell biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA Department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and ***,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum *** in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling *** models have been widely used to study the effect of TSCl/2 genes on the development and function of the *** considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human *** sources Literature reviews and research articles were published in PubMed-indexed *** Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human *** In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

利用探针跳跃式扫描离子电导显微镜技术揭示结直肠癌单细胞层面对H_(2)O_(2)良性应激的动态响应

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Science Bulletin 2024年第12期69卷 1909-1919页

作者：王东 Emily Woodcock 杨羲 Hiromi Nishikawa Elena V.Sviderskaya Masanobu Oshima Christopher Edwards 张彦军 Yuri Korchev WPI Nano Life Science Institute(WPI-Nano LSI) Kanazawa UniversityKanazawa 920-1192Japan Department of Medicine Imperial College LondonLondon W120NNUnited Kingdom cell biology Research Centre Molecular and Clinical Sciences Research InstituteSt George’sUniversity of LondonLondon SW170REUnited Kingdom

Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))*** clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its paradoxical role as a promoter of cancer *** the dynamics of cancer cell H_(2)O_(2)eustress at the single–cell level is *** this study,non–contact hopping probe mode scanning ion conductance microscopy(HPICM)with high-sensitive Pt–functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H_(2)O_(2)gradients in individual colorectal cancer Caco–*** explored the relationship between cellular mechanical properties and H_(2)O_(2)*** to 0.1 or 1 mmol/L H_(2)O_(2)eustress increased the extracellular to intracellular H_(2)O_(2)gradient from 0.3 to 1.91 or 3.04,***,cellular F–actin–dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H_(2)O_(2)*** H_(2)O_(2)–induced stiffness modulated AKT activation positively and glutathione peroxidase 2(GPX2)expression *** findings unveil the failure of some H_(2)O_(2)-targeted therapies due to their ineffectiveness in generating H_(2)O_(2),which instead acts eustress to promote cancer cell *** research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells'antioxidant defense,illuminating the exploitation of H_(2)O_(2)eustress for survival at the single–cell *** GPX and/or catalase(CAT)enhances the cytotoxic activity of H_(2)O_(2)eustress against CRC cells,which holds significant promise for developing innovative therapies targeting cancer and other H_(2)O_(2)-related inflammatory diseases.

关键词： SPM Nanoprobe Nanobiology SECM ROS Stiffness

HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui Liu Ying He Zidong Zhao Tongfeng Liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan Liu Tianyou Cheng Yong Liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China Medical School of Guizhou University Guiyang 550025China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing University Medical School Nanjing 210046China Hubei Key Laboratory of cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of Medical molecular biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake