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mtDNA-triggered pH response signal-amplified fluorescent probe for multiple cell discrimination

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Chinese Chemical Letters 2024年第3期35卷 363-368页

作者： Tianping Xia Yanxian Hou Zhuoran Xia Gengwen Chen Peichen Tang Jiangli Fan Xiaojun Peng State Key laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical EngineeringDalian University of TechnologyDalian 116024China hematology Reagent R&D Department Mindray Bio-medical Electronics Co.Ltd.Shenzhen 518132China Research Institute of Dalian University of Technology in Shenzhen Shenzhen 518057China

Developing fluorescence probes with multiple responses has vital significance but remains ***,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell *** probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic *** the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor *** study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.

关键词： Fluorescence probe Mitochondrial DNA pH response Peripheral blood cells Multiple cell detection

Complete blood and urine paraprotein tests as response assessments in multiple myeloma patients treated with bortezomib,cyclophosphamide,and dexamethasone

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Chronic Diseases and Translational Medicine 2024年第1期10卷 62-68页

作者： Xialu Lan Fujing Zhang Chen Yang Wei Su Jianhua Du Shuangjiao Liu Miao Chen Bing Han Daobin Zhou Junling Zhuang Department of hematology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina Department of laboratory Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina

Background: This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma(MM)during the induction phase of treatment with bortezomib,cyclophosphamide,and dexamethasone(BCD).Methods :We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1,2013 to December 31,***: There were 107 patients with International Staging System(ISS)III and 51 with paraprotein of light *** these,77 completed nine cycles of the BCD *** the number of treatment cycles increased,the proportions of serum and urine immunofixation electrophoresis(IFE)tests elevated from 40.39%to 62.22%and 16.75%to 37.78%,*** than 90%of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle,but that of urinary M protein was less than 60%.The detection rate of urinary M protein in light chain MM was more than 70%per *** with a very good partial response(VGPR)had longer progression-free survival(PFS)than those with uncertain VGPR(32 vs.26 months,p=0.0336).Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation,those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly(27 vs.22 months,p=0.059).Conclusion: Urinary M protein detection rate is significantly lower than that in serum,leading to an overestimation of efficacy,premature reduction of treatment intensity,and shortened *** response assessments are critical to treatment decisions and clinical diagnoses.

关键词： bortezomib light chain subtype multiple myeloma response assessment

Overcoming adaptive resistance in AML by synergistically targeting FOXO3A-GNG7-mTOR axis with FOXO3A inhibitor Gardenoside and rapamycin

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Genes & Diseases 2024年第1期11卷 397-412页

作者： Zhe Chen Qian Guo Shichen Huang Lei Li Feng Wu Zhilong Liu Zhigang Li Tao Chen Guanbin Song Shuangnian Xu Jieping Chen Yu Hou Department of hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Institute of Life Sciences Chongqing Medical UniversityChongqing 400016China Key laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Chongqing Foreign Language School Chongqing 400039China

Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive response signaling weakens the cytotoxic effect of FOxO3A depletion on AML ***,we show that FOxO3A deficiency induces a compensa-tory response involved in the reactive activation of mTOR that leads to signaling rebound and adaptive *** metabolism acts downstream of mTOR to provoke activa-tion of JNK/c-JUN via reactive oxygen species(ROS).At the molecular level,FOXO3A directly binds to the promoter of G protein gamma subunit 7(GNG7)and preserves its expression,while GNG7 interacts with mTOR and restricts phosphorylated activation of ***,combinatorial inhibition of FOXO3A and mTOR show a synergistic cytotoxic effect on AML cells and prolongs survival in a mouse model of *** a structure-based virtual screening,we report one potent small-molecule FOxO3A inhibitor(Gardenoside)that exhibits a strong effect of anti-FOXO3A DNA *** synergizes with rapamycin to substantially reduce tumor burden and extend survival in AML patient-derived xenograft *** results demonstrate that mTOR can mediate adaptive resistance to FOxO3A inhibition and validate a combinatorial approach for treating AML.

关键词： AML Combinatorial inhibition FOXO3A GNG7 mTOR

Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

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Journal of Environmental Sciences 2024年第5期139卷 460-472页

作者： Sujie Sun Li Zhang Xue Li Lu Zang Ling Huang Junquan Zeng Zigang Cao Xinjun Liao Zilin Zhong Huiqiang Lu Jianjun Chen Jiangxi Engineering laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of OrgansCenter for Clinical Research Center of the Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Translational Research Institute of Brain and Brain-like Intelligence Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationDepartment of PediatricsShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China State Environmental Protection Key laboratory of Environmental Health Impact Assessment of Emerging Contaminants School of Environmental Sciences and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Interventional and Vascular Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Department of Internal Medicine and hematology Affiliated Hospital of Jinggangshan UniversityJi’an 343009China

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water ***,little is known regarding its toxic effects on cardiovascular ***,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L *** showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart ***,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart *** sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic ***-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular ***-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism ***-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting ***,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

关键词： Hexafluoropropylene oxide trimer acid Heart development Vascular development Hemopoiesis Zebrafish embryos

Chidamide plus prednisone,cyclophosphamide,and thalidomide for relapsed or refractory peripheral T-cell lymphoma:A multicenter phase II trial

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Chinese Medical Journal 2024年第13期137卷 1576-1582页

作者： Jinhua Liang Li Wang Xiaodong Wang Guohui Cui Jianfeng Zhou Tongyao Xing Kaixin Du Jingyan Xu Luqun Wang Rong Liang Biyun Chen Jian Cheng Haorui Shen Jianyong Li Wei Xu Department of hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key laboratory of hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China Department of hematology Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of Medicine of University of Electronic Science and Technology of ChinaChengduSichuan 610000China Department of hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of hematology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210008China Department of hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China Department of hematology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China Department of hematology Fujian Provincial HospitalFuzhouFujian 350001China Department of hematology Zhongda HospitalMedical School of Southeast UniversityNanjingJiangsu 210009China

Background:Although the treatment of peripheral T-cell lymphoma(PTCL)has undergone advancements during the past several years,the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory(R/R)*** phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone,cyclophosphamide,and thalidomide(CPCT)for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of ***:We conducted a multicenter phase II clinical trial in which we combined chidamide(30 mg twice weekly)with prednisone(20 mg daily after breakfast),cyclophosphamide(50 mg daily after lunch),and thalidomide(100 mg daily at bedtime)(the CPCT regimen)for a total of fewer than 12 cycles as an induction-combined treatment period,and then applied chidamide as single-drug ***-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine *** primary objective was to assess the overall response rate(ORR)after the treatment with ***:Of the 45 enrolled patients,the optimal ORR and complete response(CR)/CR unconfirmed(CRu)were 71.1%(32/45)and 28.9%(13/45),respectively,and after a median follow-up period of 56 months,the median progression-free survival(PFS)and overall survival(OS)were 8.5 months and 17.2 months,*** five-year PFS and OS rates were 21.2%(95%confidence interval[CI],7.9-34.5%)and 43.8%(95%CI,28.3-59.3%),*** most common adverse event was neutropenia(20/45,44.4%),but we observed no treatment-related ***:The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various *** Registration:***,NCT02879526.

关键词： Peripheral T-cell lymphoma Chidamide Prednisone Cyclophosphamide Thalidomide All-oral regimen

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

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World Journal of Diabetes 2024年第5期15卷 914-922页

作者： Ying Zhang Teng Li Chao-Yan Yue Yun Liu Department of laboratory Medicine Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Interventional Radiology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina Department of hematology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and *** To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM *** The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed *** these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative *** diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic *** Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,*** AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,*** D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can

关键词： Gestational diabetes mellitus D-dimer Hemoglobin Fetal growth restriction Fasting blood glucose

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

The non-canonical poly(A)polymerase FAM46C promotes erythropoiesis

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Journal of Genetics and Genomics 2024年第6期51卷 594-607页

作者： Ke Yang Tiangi Zhu Jiaying Yin Qiaoli Zhangg Jing Li Hong Fan Gajing Han Weiyin Xu Nan Liu Xiang Lv Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Liangzhu laboratory Zhejang UniversityHangzhouZhejang 311121China Institute of hematology Zhejiang UniversityHangzhouZhejiang 311121China The State Key laboratory for Complex Severeand Rare DiseasesHaihe Laboratory of Cell EcosystemDepartment of PathophysiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Medical Epigenetics Research Center Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

The post-transcriptional regulation of mRNA is a crucial component of gene *** disruption of this process has detrimental effects on the normal development and gives rise to various *** for novel post-transcriptional regulators and exploring their roles are essential for understanding development and *** a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell ***46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroidspecific *** demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent ***,we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox *** conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.

关键词： FAM46C TENT5C Poly(A)polymerase Erythroblasts Post-transcriptional regulation Erythroid-specific enhancer

Single-cell RNA sequencing reveals abnormal transcriptome signature of erythroid progenitors in pure red cell aplasia

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Genes & Diseases 2024年第1期11卷 49-52页

作者： Yumei Liu Haiyue Niu Jie Ren Zhiqin Wang Li Yan Limin Xing Zonghong Shao Rong Fu Zhigang Cai Huaquan Wang Department of hematology Tianjin Medical University General HospitalTianjin 300052China School of Basic Medical Sciences Tianjin Medical UniversityTianjin 300070China

Pure red cell aplasia(PRCA)is a bone marrow failure syndrome characterized by severe anemia,reticulocytopenia,selective reduction,and even the absence of bone marrow erythroid precursors,while leukocyte and platelet counts are normal.1 Acquired PRCA can be divided into primary and *** are mediated by immune *** in the quantity and dysfunction of committed erythroid progenitors(EPs),including burst forming uniterythroid(BFU-E)and colony forming unit-erythroid(CFU-E),may be the source of reduced erythropoiesis and needs to be elucidated.

关键词： progenitor anemia leukocyte