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LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

Current Medical Science 2024年第1期44卷 81-92页

作者： Feng ZHANG Mohammed Awal Issah Hai-ying FU Hua-rong ZHOU Ting-bo LIU Jian-zhen SHEN Fujian Provincial Key Laboratory on hematology Fujian Medical Center of HematologyFujian Institute of HematologyClinical Research Center for Hematological Malignancies of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Tamale Technical University Faculty of Allied Health and Pharmaceutical SciencesDepartment of Medical Laboratory TechnologyTamale NS-011-2000Ghana department of hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese MedicineThe Third People's Hospital of Fujian ProvinceFuzhou 350122China

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation *** specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently ***,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient *** The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis *** expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 *** Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation ***1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 *** of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 *** and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 ***,YAP1 was distributed in the *** LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

关键词： acute lymphoblastic leukemia large tumor suppressor kinase 1 phosphorylation RNA-Seq Yesl-associated protein

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Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2885-2900页

作者： Porkizhi Arjunan Durga Kathirvelu Gokulnath Mahalingam Ashish Kumar Goel Uday George Zacharaiah Alok Srivastava Srujan Marepally Center for Stem cell Research(A Unit of inStem Bengaluru)Christian Medical College CampusBagayamVellore 632002Tamil NaduIndia Manipal academy for higher education Mangalore 576104KarnatakaIndia department of hematology Christian Medical College&HospitalVellore 632004Tamil NaduIndia department of Hepatology Christian Medical College&HospitalVellore 632004Tamil NaduIndia

Inherited genetic disorders of the liver pose a significant public health *** transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive *** overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable *** viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their *** a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and ***,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

关键词： Lipid nanoparticle Liver disorders Gene therapy Gene editing Nucleic acid delivery pDNA mRNA siRNA ASO Clinical trials

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UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

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BIOcell 2024年第6期48卷 959-970页

作者： JIAWEI YIN YONGSHENG WANG GUANGWEI WEI MINGXIN WEN department of Traumatology The Second Hospital of Shandong UniversityJinan250033China department of Pathology Weifang People’s HospitalWeifang261000China department of Human Anatomy Shandong University School of MedicineJinan250012China department of cell biology and Key Laboratory of Experimental Teratology Shandong University School of MedicineJinan250012China

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft ***:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent ***,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and *** UBE2T exhibited the opposite ***2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of *** target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in ***:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

关键词： UBE2T Breast cancer Breast cancer stem cell mTOR

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for Stem cell biology and Regenerative Medicine Stanford University School of MedicineStanford CA 94305USA department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong Hao Li Peng Liao Long Chen Yao Pan Yongqiang Zheng Changqing Zhang Delin Liu Minghao Zheng Junjie Gao Centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of cell biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s Hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace

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Skull and vertebral bone marrow in central nervous system inflammation

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Fundamental Research 2024年第2期4卷 246-250页

作者： Honglei Ren Qiang Liu department of Neurology Tianjin Neurological InstituteTianjin Institute of ImmunologyState Key Laboratory of Experimental HematologyInternational Joint Laboratory of Ocular DiseasesMinistry of EducationHaihe Laboratory of Cell EcosystemTianjin Medical University General HospitalTianjin 300052China

Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system(CNS).CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory ***,we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS ***,we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.

关键词： Central nervous system Bone marrow Hematopoiesis Immune cells Neuroinflammation Stroke Multiple sclerosis

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Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology

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Cancer Pathogenesis and Therapy 2024年第3期2卷 205-211页

作者： Yutong Wang Mengzhen Wang Bin Chu Minqiu Lu Lei Shi Shan Gao Yuan Chen Qin Yan Na Ji Li Bao department of hematology Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

Background:Multiple myeloma(MM)is a heterogeneous plasma-derived hematopoietic malignancy with complex genetic mutation contributing to the *** gene sequencing has been applied in MM,genetic features from Chinese MM patients are reported *** investigated the genetic mutation of newly diagnosed multiple myeloma(NDMM)patients and explore its correlation with cytogenetic abnormalities detected by fluorescence in situ hybridization(FISH).Methods:A total of 206 patients with NDMM were *** enriching plasma cells with CD138 magnetic beads,92 MM-related target gene mutations were detected by the Illumina sequencing platform,and six common genetic abnormalities were detected by ***:162 cases(78.6%)had at least one gene mutation detected by *** top 5 mutated genes were KRAS,NRAS,TRAF3,BRAF,and *** abnormalities detected by FISH have a certain correlation with gene mutations,t(11;14)translocations are often accompanied by CCND1 and TP53 mutations,KLHL6 in t(4;14),SP140,CDKN1B and PRKD2 in t(14;16)and t(14;20)*** mutation ratio was higher for EGR1,while lower of CCND1 in patients with gain *** TP53 mutation was more likely in patients with 17p *** gene mutation affects the pathway of the RNA process is more frequently occurring in males and age less than 70 years *** International Staging System(ISS)Stage Ⅲ correlated with gene mutations in the NK-κB pathway while Revised ISS(R-ISS)Stage Ⅲ correlated with the DNA damage repair ***:There are various gene mutations in NDMM patients,mainly RAS/MAPK and NF-κB pathway gene pathways.

关键词： Multiple myeloma Next-generation sequencing Genetics mutation

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Alternative splicing and related RNA binding proteins in human health and disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone Tumor Institution 200000 ShanghaiChina department of Biochemistry and Molecular cell biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

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Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen Chenhua Yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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