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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of cellular&molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of Stem cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen Khawaja Husnain Haider Department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and molecular biology Department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal ***,structural and functional recovery is a senile process involving multifaceted cellular and molecular *** contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large *** advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic *** recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome Mesenchymal stem cells Nerve injury Stem cells Secretome Regeneration

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz Computational biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of cell biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury

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Genes & Diseases 2024年第1期11卷 449-463页

作者： Yixin Ma Lili Huang Zheng Zhang Pengfei Yang Qingsong Chen Xujia Zeng Fangyan Tan Chunxia Wang Xiongzhong Ruan Xiaohui Liao Department of Nephrology The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China Department of cell biology and Genetics Chongqing Medical UniversityChongqing 400016China Centre for Nephrology Royal Free and University College Medical SchoolUniversity College LondonRoyal Free CampusRowland Hill StreetLondon NW32PFUnited Kingdom Centre for Lipid Research Key Laboratory of Molecular Biology on Infectious DiseasesMinistry of EducationChongqing Medical UniversityChongqing 400016China Kuanren Laboratory of Translational Lipidology Centre for Lipid ResearchSecond Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Reactive oxidative species(ROos)production-driven ferroptosis plays a role in acute kidney injury(Akl).However,its exact molecular mechanism is poorly *** receptor CD36 has important roles in oxidizing lipids,lipid accumulation,metabolic syndrome,and insulin resistance in chronic kidney disease,but its roles remain unexplored in *** present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and *** expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function,which might serve as an independent biomarker for AKl ***,in adult mice subjected to AKl,deletion of CD36(CD36-/-)induced tubular cell Ros accumulation,ferroptosis activation,and renal ***,combining LC-MS/MS,co-IP,and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1(FSP1)and regulate its ubiquitination at sites K16 and K24,leading to FSP1 degradation and progression of ferroptosis in *** present results emphasize a novel mechanism of CD36 in cisplatin-induced *** discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for ***,CD36 may play a key role in the progression of ***,targeting CD36 may provide a promising treatment option for AKI.

关键词： Acute kidney injury CD36 Ferroptosis FSP1 Ubiquitin-dependent degradation

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5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncology Research 2024年第6期32卷 1047-1061页

作者： KIMBERLY FENECH ISAAC MICALLEF BYRON BARON Centre for molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor Genetics and biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed *** many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation ***:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of *** 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

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High-resolution spatiotemporal mapping:a comprehensive view of eukaryotic cell cycle proteome dynamics

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2354-2356页

作者： Jing Zou Ziran Qin Long Zhang Life Sciences Institute Second Affiliated Hospital of the Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell BiologyZhejiang UniversityHangzhouZhejiangChina The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors The First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangChina Cancer Center Zhejiang UniversityHangzhouZhejiangChina

In a recent study published in cell,Litsios et *** a highresolution spatiotemporal map of the eukaryotic cell cycle proteome.1 They identified proteome-level changes in both abundance and spatial distribution throughout the cell cycle and provided a valuable resource for future exploration into the global proteome dynamics that drive cell cycle progression(https://***/cellcycle).

关键词： al. cycle dynamics

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COVID-19 vaccines and beyond

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cellular & molecular Immunology 2024年第3期21卷 207-209页

作者： Yiyuan Liu Danying Li Jiahuai Han State Key Laboratory of cellular Stress biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamenFujianChina Laboratory Animal Center Xiamen UniversityXiamenFujianChina Research Unit of cellular Stress of CAMS Cancer Research Center of Xiamen UniversityXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenFujianChina

Hundreds of vaccines have been developed worldwide for Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the cause of Coronavirus disease 2019(COVID-19),since the beginning of the *** vaccines have saved innumerable lives and contributed to partial control of the COVID-19 *** of the vaccines approved for clinical use exhibit satisfactory initial protection rates against corresponding ***,vaccine protection declines over time,with almost all vaccines falling below 50%protection after 6 months[1].In the case of natural infections,protection lasts longer,but the incidence of reinfection is also quite high.

关键词： vaccines acute beyond

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Chimeric Monkey Born Alive with a High Contribution of Donor cells

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Neuroscience Bulletin 2024年第6期40卷 849-851页

作者： Jia Huang Jun Wu Department of molecular biology University of Texas Southwestern Medical CenterDallasTX75390USA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTX75390USA Cecil H.and Ida Green Center for Reproductive biology Sciences University of Texas Southwestern Medical CenterDallasTX75390USA

Chimeras,which consist of cells from different individuals or different species,represent an important tool in biological *** in the early twentieth century,studies on chimeras have been focusing on understanding fundamental genetic and cellular developmental *** the advances in genetic engineering and embryonic stem cell(ESC)technology,chimeras have become an important tool for the generation of transgenic animals.

关键词： mechanisms. advances developmental

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Metabolic plasticity of T cell fate decision

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Chinese Medical Journal 2024年第7期137卷 762-775页

作者： Xiaoli Pan Jiajia Wang Lianjun Zhang Guideng Li Bo Huang National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Key Laboratory of Synthetic biology Regulatory Element Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Department of Immunology&National Key Laboratory of Medical molecular biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China Department of Biochemistry&molecular biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei 430030China

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T *** antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory ***,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted *** studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell *** this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory ***,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted *** the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

关键词： T cell immunotherapy T cell differentiation T cell exhaustion Metabolic reprogramming Tumor microenvironment

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Root-derived long-distance signals trigger ABA synthesis and enhance drought resistance in Arabidopsis

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Journal of Genetics and Genomics 2024年第7期51卷 749-761页

作者： Qian-Qian Liu Jin-Qiu Xia Jie Wu Yi Han Gui-Quan Zhang Ping-Xia Zhao Cheng-Bin Xiang Division of Life Sciences and Medicine Division of Molecular&Cell BiophysicsHefei National Science Center for Interdisciplinary Sciences at the MicroscaleUniversity of Science and Technology of ChinaThe Innovation Academy of Seed DesignChinese Academy of SciencesHefeiAnhui 230027China College of Life Sciences Anhui Agricultural UniversityHefeiAnhui 230036China College of Agronomy South China Agricultural UniversityGuangzhouGuangdong 510642China School of biology and Basic Medical Sciences Soochow UniversitySuzhouJiangsu 215123China

Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress,with reactive oxygen species(ROS)emerging as pivotal systemic signals in plant stress ***,the exact role of ROS as root-to-shoot signals in the drought response has not been *** this study,we reveal that compared with wild-type plants,ferric reductase defective 3(frd3)mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3(NCED3)transcript levels and abscisic acid(ABA)contents in leaves as well as increased hydrogen peroxide(H_(2)O_(2))levels in roots and *** experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype,indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in ***,the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion,suggesting that H_(2)O_(2)may be involved in long-distance ***,the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 *** together,our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance,providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.

关键词： frd3 Drought resistance Root-to-shoot long-distance signals Reactive oxygen species(ROS) H_(2)O_(2) Iron ABA

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