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Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer

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National Science Review 2024年第1期11卷 94-106页

作者： Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei Liu Hexiang Deng Shuang Peng Xiang Zhou College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers-Ministry of Education Wuhan University department of Digestive Surgical Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and Technology department of Clinical Laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University College of Chemistry and Materials Science Hubei Engineering University department of Pharmacology School of Pharmacy China Medical University Taikang Center for Life and Medical Sciences Wuhan University department of hematology Zhongnan Hospital of Wuhan University

Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf ***, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

关键词： MOF circulating cell-free RNA biomarker liver cancer diagnosis

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Therapeutic strategies of targeting nonapoptotic regulated cell death (RCD) with smallmolecule compounds in cancer

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2815-2853页

作者： Xin Jin Wenke Jin Linlin Tong Jia Zhao Lan Zhang Na Lin department of Ultrasound Department of Medical Oncology and Department of Hematologythe First Hospital of China Medical UniversityChina Medical UniversityShenyang 110001China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological *** subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis,facilitating development,and modulating *** evidence has recently revealed that RCD evasion is frequently the primary cause of tumor *** non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse,comparable to ***,they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic *** an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines,a growing number of small-molecule compounds targeting single or multiple pathways have been discovered,providing novel strategies for current cancer *** this review,we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines,mainly including autophagy-dependent cell death,ferroptosis,cuproptosis,disulfidptosis,necroptosis,pyroptosis,alkaliptosis,oxeiptosis,parthanatos,mitochondrial permeability transition(MPT)-driven necrosis,entotic cell death,NETotic cell death,lysosome-dependent cell death,and immunogenic cell death(ICD).Furthermore,we focused on discussing the pharmacological regulatory mechanisms of related small-molecule *** brief,these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines,ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.

关键词： Regulated cell death(RCD) Non-apoptotic RCD subroutine Autophagy Ferroptosis Necroptosis Regulatory mechanism Small-molecule compound Cancer therapy

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Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

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World Journal of Stem Cells 2024年第2期16卷 163-175页

作者： Yan Ren Yan-Ni Cui Hong-Wei Wang The Second Clinical Medical College Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of hematology The Second Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina department of hematology Key Laboratory of Molecular Diagnosis and Treatment of Blood Diseases in Shanxi ProvinceTaiyuan 030001Shanxi ProvinceChina

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital ***(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet *** a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and ***,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or *** propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of *** To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and *** CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental *** cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured ***-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant ***-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead *** Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly

关键词： Hematopoietic stem cells Nicotinamide Concentration Proliferation Differentiation Sirtuin 1

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Mechanism and application of feedback loops formed by mechanotransduction and histone modifications

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Genes & Diseases 2024年第5期11卷 198-218页

作者： Han Sun Yafang Gao Xinyu Ma Yizhou Deng Lintao Bi Lisha Li department of hematology and Oncology China-Japan Union HospitalJilin UniversityChangchunJilin 130021China The Key Laboratory of Pathobiology Ministry of EducationCollege of Basic Medical SciencesJilin UniversityChangchunJilin 130021China

Mechanical stimulation is the key physical factor in cell *** acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specific signature alterations during the pathological *** research continues,the role of epigenetic science in mechanotransduction is attracting ***,the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been *** focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease ***,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling *** and epigenetic changes could be potential markers and therapeutic targets in clinical practice.

关键词： FAK Histone modifications MAPK Mechanotransduction RhoA WNT/b-catenin YAP/TAZ

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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao Shanghai Institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina department of Nuclear Medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU department of hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells via nuclear factor-κB signaling

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World Journal of Stem Cells 2024年第2期16卷 151-162页

作者： Jing-Yi Li Ting-Ting Wang Li Ma Yu Zhang Di Zhu department of Medical Cosmetology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China department of General Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Plastic Surgery China-Japan Friendship HospitalBeijing 100029China Senior department of hematology The Fifth Medical CentreGeneral Hospital of Chinese People’s Liberation ArmyBeijing 100071China department of Orthopaedic Surgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic *** osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone *** domain-containing 1C(JMJD1C)has been demonstrated to suppress *** To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying *** BMSCs were isolated from mouse bone marrow *** Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of *** marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase *** related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western ***-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 *** The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was ***1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly *** of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in ***,JMJD1C expression decreased during BMM osteoclast *** The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

关键词： Osteoporosis Mesenchymal stem cells Osteogenesis Jumonji domain-containing 1C Nuclear factor-κB

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RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 307-318页

作者： Lu Xu Zhi-Hao Xie Jun Li Shi Tao Fang-Li Ren Yin-Yin Wang Zhi-Jie Chang Xin-Bao Hao department of hematology The First Affiliated Hospital of Hainan Medical UniversityHaikou570102China State Key Laboratory of Membrane Biology School of MedicineTsinghua UniversityBeijing 100084China Heya Beijing Med-Biotech Inc. Beijing 100084China department of hematology Roswell Park Comprehensive Cancer CenterNY 14263USA

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic ***:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival *** vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and ***:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor *** vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling ***:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular *** RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

关键词： RPRD1B RNAPⅡ Diffuse large B-cell lymphoma NF-κB Apoptosis

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Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan Dai Haixiang Sun Jianwu Dai Yali Hu department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive *** we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so *** verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical *** 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January *** per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control *** ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)*** group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic *** incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were *** conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

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Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications

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Chinese Medical Journal 2024年第10期137卷 1151-1159页

作者： Chunlan Zhang Yun Qin Yu Wu Heng Xu Yang Shu department of hematology West China HospitalSichuan UniversityChengduSichuan 610041China department of Radiology West China HospitalSichuan UniversityChengduSichuan 610041China department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine West China HospitalSichuan UniversityChengduSichuan 610041China department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China Institute of General Surgery West China HospitalSichuan UniversityChengduSichuan 610041China department of General Surgery Gastric Cancer Center and Laboratory of Gastric CancerWest China HospitalSichuan UniversityChengduSichuan 610041China

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is a well-established oncogenic long non-coding RNA,the higher expression of which is strongly correlated with cancer events such as tumorigenesis,progression,metastasis,drug resistance,and treatment outcome in solid ***,a series of studies has highlighted its potential role in hematological malignancies in terms of these *** to solid cancers,MALAT1 can regulate various target genes via sponging and epigenetic mechanisms,but the miRNAs sponged by MALAT1 differ from those identified in solid *** this review,we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies,including regulation of cell proliferation,metastasis,stress response,and ***,MALAT1 expression is related to poor treatment outcome and drug resistance,therefore exhibiting potential prognostic value in multiple myeloma,lymphoma,and ***,we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

关键词： Long non-coding RNA Hematological malignancies Tumorigenesis Metastasis Drug resistance Prognostic biomarker

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