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Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

Current Medical Science 2024年第3期44卷 611-622页

作者： Ying CHEN Bi-xia LI Ting-ting NIU Shu-jun YANG Li-chao WU Le-huai SHI Duo-bing ZOU Ning-ning WU Li-xia SHENG Xiao YAN Gui-fang OUYANG Qi-tian MU Laboratory of stem cell Transplantation The First Affiliated Hospital of Ningbo UniversityNingbo315300China Ningbo Clinical Research center For Hematologic Malignancies Ningbo315300China department of Hematology The First Affiliated Hospital of Ningbo UniversityNingbo315300China School of Medicine Hangzhou City UniversityZhejiang UniversityHangzhou310000China Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province Ningbo315300China

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast *** studies have demonstrated that circular RNAs play a role in AML *** this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this *** Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also *** growth was assessed using the cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow ***,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA *** Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell *** pull-down and sequencing identified miR-652-3p as a target microRNA of circ_*** growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p *** suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML *** Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

关键词： acute myeloid leukemia circ_0012152 miR-652-3p SOX4 cell growth

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stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 18-34页

作者： Yuankai Sun Xinchi Jiang Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin center for stem cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China department of Pharmacy The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Ischemic stroke(IS)causes severe disability and high mortality *** cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current ***’s cell homing,differentiation and paracrine abilities give hope for *** studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and *** improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic ***,many problems must be resolved before SC therapy can be clinically *** issues include production quality and quantity,stability during transportation and storage,as well as usage ***,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy *** aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

关键词： Ischemic stroke stem cell therapy stem cell modification cell therapy challenge

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Engineering of ovarian tissue for ovarian dysfunctions:A review

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Asian pacific Journal of Reproduction 2024年第1期13卷 3-11页

作者： Aliya Zhylkybekova Gulbakit KKoshmaganbetova Myltykbay SRysmakhanov Nurgul Abdullayevna Abenova Nadiar Maratovich Mussin Asset Askerovich Kaliyev Mahdi Mahdipour Amin Tamadon department of Evidence-Based Medicine and Scientific Management West Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan department of Surgery and Urology No.2 West Kazakhstan Medical UniversityAktobeKazakhstan department of Surgery and Transplantation Aktobe Medical CenterAktobeKazakhstan department of Internal Diseases West Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan stem cell Research center Tabriz University of Medical SciencesTabrizIran department of Reproductive biology Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran department for Scientific Work West-Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan

This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or *** loss of ovarian function can lead to infertility,osteoporosis,and cardiovascular *** replacement therapy is a common treatment,but it has limitations and *** review focuses on two main approaches in tissue engineering:scaffold-based(3D printing,electrospinning,decellularization)and scaffold-free(stem cell transplantation,organoid cultivation).Both approaches show promise in preclinical studies for creating functional ovarian *** include vascularization,innervation,long-term function,and *** these challenges,tissue engineering offers a potential avenue for restoring fertility and hormone balance in women with ovarian dysfunction.

关键词： Female gonads Tissue engineering Estrogen Reproductive system

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Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires

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Cancer Innovation 2024年第3期3卷 1-21页

作者： Yulin Xu Wei Shan Qian Luo Meng Zhang Dawei Huo Yijin Chen Honghu Li Yishan Ye Xiaohong Yu Yi Luo He Huang Bone Marrow Transplantation center The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu Laboratory Zhejiang UniversityHangzhouChina Institute of Hematology Zhejiang UniversityHangzhouChina Zhejiang Province Engineering Research center for stem cell and Immunity Therapy HangzhouChina School of Medicine Zhejiang UniversityHangzhouChina

Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast ***,approaches to obtain cancer-reactive TCR-T cells have been ***:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune *** steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized *** human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and *** fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 ***,human T cells were processed for TCRβ-chain(TRB)sequencing *** the repertoires had been constructed,features such as the fraction,diversity,and immune signature were ***:The results demonstrated an increase in diversity and clonality of T cells after *** preferential usage and features of TRBV,TRBJ,and the V–J combination were also *** stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 *** burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized ***:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T *** platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.

关键词： cancer-targeted T-cell receptor T(TCR-T)cells circulating hematopoietic stem and progenitor cells(HSPCs) humanized mouse model steady-state peripheral blood T-cell receptorβ-chain(TRB) three-dimensional culture

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XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for cell Therapy of Soochow University ChangzhouJiangsu 213003PR China department of stem cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

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NF-κB in biology and targeted therapy:new insights and translational implications

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing Guo Yizi Jin Xinyu Chen Xiaomin Ye Xin Shen Mingxi Lin Cheng Zeng Teng Zhou Jian Zhang department of Medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 ***,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory ***,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment *** this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB *** investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR *** physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also ***,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and ***,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and ***,we provide an outlook for research in the field of NF-κB *** hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of biology Medicine and HealthThe University of ManchesterManchesterUK department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina department of stem cell biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina department of Physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

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Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen department of Systems biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family center for Leukemia Research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA department of Biochemistry and Molecular biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

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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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A pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2679-2693页

作者： Junzhi Yi Hui Zhang Fangyuan Bao Zhichu Chen Yuliang Zhong Tianning Ye Xuri Chen Jingyi Qian Mengya Tian Min Zhu Zhi Peng Zongyou Pan Jianyou Li Zihao Hu Weiliang Shen Jiaqi Xu Xianzhu Zhang Youzhi Cai Mengjie Wu Hua Liu Jing Zhou Hongwei Ouyang department of Sports Medicine of the Second Affiliated Hospital and Liangzhu LaboratoryZhejiang University School of MedicineHangzhouChina Dr.Li Dak Sum&Yip Yio Chin center for stem cells and Regenerative Medicine Zhejiang University School of MedicineHangzhouChina Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesHangzhouChina The MOE Key Laboratory of Biosystems Homeostasis&Protection The Key Laboratory of Cancer Molecular Cell Biology of Zhejiang ProvinceLife Sciences InstituteZhejiang UniversityHangzhouChina department of Orthopedics Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhouChina China Orthopedic Regenerative Medicine Group(CORMed) HangzhouChina department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

The knee joint has long been considered a closed *** pathological effects of joint diseases on distant organs have not been ***,our clinical data showed that post-traumatic joint damage,combined with joint bleeding(hemarthrosis),exhibits a worse liver function compared with healthy *** mouse model,hemarthrosis induces both cartilage degeneration and remote liver ***,we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4^(+)T cells in peripheral blood and *** of CD4^(+)T cells reverses hemarthrosis-induced liver *** of cartilage matrix induced by hemarthrosis upregulates serological type Ⅱ collagen(COL Ⅱ),which activates CD4^(+)T *** application of a COL Ⅱ antibody blocks the ***,bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood ***-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig *** together,our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells,which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease.

关键词： degeneration damage inhibited

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