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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway

Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia zhao yan-na YU Xiao-ling YIN Li-ming Department of Hematology Tongde Hospital of Zhejiang ProvinceHangzhou310012China Institute of Hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China

Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell *** AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow *** morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,*** protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western ***-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were *** of subcutaneous tumor tissue were observed after hematoxylin and eosin ***1 and GATA-1 expressions were detected by immunohistochemical *** The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor ti

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Effects of Bufalin on Up-regulating Methylation of Wilm's Tumor 1 Gene in Human Erythroid Leukemic Cells

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Chinese Journal of Integrative Medicine 2017年第4期23卷 288-294页

作者： WANG Li-pei zhao yan-na SUN Xin GAO Rui-lan College of Basic Medical Sciences Zhejiang Chinese Medical University Institution of Oncology Zhejiang Provincial People's Hospital

Objective To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm’ tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells. Methods The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRna and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, Dna methylation of WT1 and protein expression levels of Dna methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively. Results The bufalin was effective to inhibit proliferation of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%±2.1% to 87.2%±5.4% with an half maximal inhibit concentration (IC50) of 0.046 μmol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The proliferation index of cell cycle decreased from 76.4%±1.9% to 49.7%±1.3%. The expression levels of WT1 mRna and its protein reduced gradually with increasing doses of bufalin, meanwhile, the methylation status of WT1 gene changed from unmethylated into partially or totally methylated. While, the expression levels of DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-dependent manner. Conclusions Bufalin can not only significantly inhibit the proliferation of HEL cells and arrest cell cycle at G0/G1 phase, but also induce cellular apoptosis and down-regulate the expression level of WT1. Our results provide the evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1 methylation status which is related to the up-regulation of DNMT3a and DNMT3b proteins in erythroid leukemic HEL cells.

关键词： bufalin human erythroid leukemic cells Wilm’s tumor 1 gene methylation Dna methyltransferase 3a Dna methyltransferase 3b

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Chinese Medicine Treatment on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

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Chinese Journal of Integrative Medicine 2020年第5期26卷 324-329页

作者： WU Xiao-long ZHUANG Hai-feng zhao yan-na YU Xiao-ling DAI Tie-ying GAO Rui-lan Institute of Hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou(310006)China

Graft-versus-host disease(GVHD)is the most common complication after allogeneic hematopoietic stem cell transplantation,and also an important factor affecting the survival and quality of life in patients after ***,immunosuppressive therapy is commonly used for GVHD,but the curative effect is not *** to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of *** this paper,we summarize the latest progress in pathogenesis,prevention and treatment of GVHD with Chinese medicine(CM).We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.

关键词： Chinese medicine hematopoietic stem cell transplantation graft-versus-host disease

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Chinese Medicine Regulates Dna Methylation to Treat Haematological Malignancies:A New Paradigm of"State-Target Medicine"

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Chinese Journal of Integrative Medicine 2022年第6期28卷 560-566页

作者： SHEN Feng-lin zhao yan-na YU Xiao-ling WANG Bo-lin WU Xiao-long LAN Gao-chen GAO Rui-lan Institute of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310006China

Aberrant regulation of Dna methylation plays a crucial causative role in haematological malignancies(HMs).Targeted therapy,aiming for Dna methylation,is an effective mainstay of modem medicine;however,many issues remain to be *** progress of epigenetic studies and the proposed theory of"state-target medicine"have provided conditions to form a new treatment paradigm that combines the"body state adjustment"of CM with targeted *** discussed the correlation between Chinese medicine(CM)syndromes/states and Dna methylation in this ***,the latest research findings on the intervention and regulation of Dna methylation in HMs,including the core targets,therapy status,CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of"state-target synchronous conditioning"pattern of integrative medicine for HMs,simultaneously leading a new perspective in clinical diagnosis and therapy.

关键词： haematological malignancies Dna methylation Chinese medicine state-target medicine

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Using Longitudinal Fins to Improve the Melting Performance of Stearic Acid in Thermal Energy Storage Devices

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Journal of Thermal Science 2024年第5期33卷 1672-1687页

作者： yan Suying LIU Yiran AO Ci zhao Xiaoyan ZHANG na ZHANG Ruiying AHMADI Mohammad Hossein School of Energy and Power Engineering Inner Mongolia University of TechnologyHohhot 010051China Institute of Engineering Thermophysics Chinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100190China School of Materials Science and Engineering Inner Mongolia University of TechnologyHohhot 010051China Faculty of Mechanical Engineering Shahrood University of TechnologyShahroodIran

The heat transfer efficiency of a thermal energy storage unit(TESU)can be improved by the addition of novel longitudinal fins.A series of TESUs are analyzed using the finite volume method(FVM)to determine the effect of fin angle on the heat transfer *** the fin angle increases,the TES rate first increases,then decreases,reaching a maximum rate at 60°,where the melting time is less by 30.9%,28.58%,21.99%,9.02%,and 18.1%than at 0°,15°,30°,45°,and 80°,*** addition,it is found that the melting time of the phase change material is significantly greater at the bottom of the *** time percentage of this stage decreases as the fin angle increases through these percentages by 7%,14%,23%,33%,and 20%,***,the response surface methodology(RSM)is applied to optimize the longitudinal fin by minimizing the total melting *** analysis concludes that a fin angle of 58.68°reduces the complete melting time of the stearic acid by 44%below the time at 0°.These findings fill a gap in knowledge of the effect on melting performance of the design angle of longitudinal fins and provide a reference for the design of horizontally placed longitudinal finned thermal energy storage units.

关键词： thermal energy storage melting rate enhancement longitudinal fins fin angle phase change materials

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Ginseng-Derived Panaxadiol Saponins Promote Hematopoiesis Recovery in Cyclophosphamide-Induced Myelosuppressive Mice:Potential Novel Treatment of Chemotherapy-Induced Cytopenias

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Chinese Journal of Integrative Medicine 2018年第3期24卷 200-206页

作者： SUN Xin zhao yan-na QIAN Song GAO Rui-lan YIN Li-ming WANG Li-pei CHONG Beng-hock ZHANG Su-zhan Department of Oncology The Second Affiliated HospitalMedical College of Zhejiang University Department of Oncology Zhejiang Provincial People's Hospital Institution of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical University Department of Hematology St George Sutherland Hospital

Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide（CTX）.Methods：Mice with myelosuppression induced by CTX were treated with PDS-C at a low-（20 mg/kg）,moderate-（40 mg/kg）,or high-dose（80 mg/kg） for 7 consecutive *** level of peripheral white blood cell（WBC）,neutrophil（NEU） and platelet（PLT） were measured,the histopathology and colony formation were observed,the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western ***：In response to PDS-C therapy,the peripheral WBC,NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent ***,bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells（P〈0.01）.PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice,as evidenced by significantly increase in colony formation units-granulocytes/monocytes and-megakaryocytes（P〈0.01）.The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway,this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase（p-MEK） and extracellular signal-regulated kinases（p-ERK）,and receptor tyrosine kinase（C-kit） and globin transcription factor 1（GATA-1） in hematopoietic cells of CTX-treated mice（P〈0.05）.Conclusions：PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice,probably mediated by a mechanism involving MEK and ERK protein kinases,and C-kit and GATA-1 transcription ***-C may potentially be a novel treatment of mye

关键词： panaxadiol saponins component ginsenosides chemotherapy-induced myelosuppression mitogen-activated protein kinase extracellular signal-regulated kinase receptor tyrosine kinase globin transcription factor 1 Chinese medicine

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Properties of collective flow and pion production in intermediate-energy heavy-ion collisions with a relativistic quantum molecular dynamics model

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Nuclear Science and Techniques 2024年第1期35卷 155-169页

作者： Si-na Wei zhao-Qing Feng School of Physics and Optoelectronics South China University of TechnologyGuangzhou 510640China

The relativistic mean-field approach was implemented in the Lanzhou quantum molecular dynamics transport model(***). Using the ***, the properties of collective flow and pion production were investigated systematically for nuclear reactions with various isospin asymmetries. The directed and elliptic flows of the *** are able to describe the experimental data of STAR Collaboration. The directed flow difference between free neutrons and protons was associated with the stiffness of the symmetry energy, that is, a softer symmetry energy led to a larger flow difference. For various collision energies, the ratio between the π^(-) and π^(+) yields increased with a decrease in the slope parameter of the symmetry energy. When the collision energy was 270 MeV/nucleon, the single ratio of the pion transverse momentum spectra also increased with decreasing slope parameter of the symmetry energy in both nearly symmetric and neutron-rich ***, it is difficult to constrain the stiffness of the symmetry energy with the double ratio because of the lack of threshold energy correction on the pion production.

关键词： Heavy-ion collision Collective flow Pion production Symmetry energy Relativistic mean field

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Nickel-catalyzed carbonylative four-component 1,4-dicarbofunctionalization of 1,3-enynes

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Science China Chemistry 2024年第6期67卷 2029-2038页

作者： yan zhao Qi-Chao Shan Hong Xin Pin Gao Xu yang Xin-Hua Duan Li-na Guo Department of Chemistry School of ChemistryXi’an Key Laboratory of Sustainable Energy Material Chemistry and Engineering Research Center of Energy StorageMaterials and DevicesMinistry of EducationXi’an Jiaotong UniversityXi’an710049China School of Electrical Engineering Xi’an Jiaotong UniversityXi’an710049China

An efficient Ni-catalyzed four-component 1,4-carbocarbonylation of 1,3-enynes with activated alkyl halides and arylboronic acids under atmospheric pressure of CO is *** tuning the electronic and steric effects of alkyl radicals,both electronrich and electron-deficient 1,3-enynes were compatible with this *** protocol features mild conditions,broad substrate scope,excellent functional group compatibility and facile gram-scale synthesis,providing a practical approach to the quaternary carbon center-containing allenyl *** study revealed that the acyl-NiIIspecies plays an important role in both the coupling and the alkyl radical generation processes.

关键词： Ni catalysis four-component 1 4-carbocarbonylation 1 3-enynes

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Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice

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Chinese Journal of Integrative Medicine 2019年第12期25卷 902-910页

作者： ZHENG Zhi-yin YU Xiao-ling DAI Tie-ying YIN Li-ming zhao yan-na XU Min ZHUANG Hai-feng Chong Beng Hock GAO Rui-lan Institution of Hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou(310006)China Department of Hematology St George HospitalSt George Clinical SchoolUniversity of New South WalesKogarah(NSW 2217)Australia

Objective: To investigate the potential efficacy of panaxadiol saponins component(PDS-C) in the treatment of aplastic anemia(AA) model mice. Methods: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C(20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine(40 mg/kg), and andriol(25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and Fox P3 proteins were detected by flow cytometry and Western blot. Results: The peripheral blood of white blood cell(WBC), platelet, neutrophil counts and hemoglobin(Hb) concentration were significantly decreased in the model group compared with the normal group(all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group(all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers(all P<0.01). Furthermore,PDS-C therapy increased peripheral blood CD3^+ and CD3^+CD4^+ cells and reduced CD3^+CD8^+ cells(P<0.05 or P<0.01). Meanwhile, PDS-C treatme

关键词： Panaxadiol saponins component aplastic anemia hematopoiesis T lymphocyte

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Dynamic Response Impact of Vehicle Braking on Simply Supported Beam Bridges with Corrugated Steel Webs Based on Vehicle-Bridge Coupled Vibration Analysis

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 3467-3493页

作者： yan Wang Siwen Li na Wei School of Civil Engineering Zhengzhou UniversityZhengzhou450001China

A novel approach for analyzing coupled vibrations between vehicles and bridges is presented,taking into account spatiotemporal effects and mechanical phenomena resulting fromvehicle *** modeling and solution of bridge vibrations induced by vehicle deceleration are realized using this *** method’s validity and reliability are substantiated through numerical examples.A simply supported beam bridge with a corrugated steel web is taken as an example and the effects of parameters such as the initial vehicle speed,braking acceleration,braking location,and road surface roughness on the mid-span displacement and impact factor of the bridge are *** results show that vehicle braking significantly amplifies mid-span displacement and impact factor responses in comparison to uniform vehicular motion across the ***,the influence of wheelto-bridge friction forces is of particular significance and cannot be *** the vehicle initiates braking near the middle of the span,both the mid-span displacement and impact factor of the bridge exhibit substantial increases,further escalating with higher braking *** favorable road surface conditions,the midspan displacement and the impact factor during vehicle braking may exceed the design values stipulated by *** is important to note that road surface roughness exerts a more pronounced effect on the impact factor of the bridge in comparison to the effects of vehicle braking.

关键词： Corrugated steel web girder bridges simply supported beam bridges vehicle-bridge coupled vibration braking impact factor

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