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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases

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BIOCELL 2024年第4期48卷 559-569页

作者： YARA ALZGHOUL HALA J.BANI ISSA AHMAD K.SANAJLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT EJLAL ABU-EL-RUB FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH department of basic medical sciences Faculty of MedicineYarmouk UniversityIrbidJordan

Mesenchymalstemcells(MSCs)*** the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart *** can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental *** from various sources differ in their regenerative and therapeutic abilities for cardiovascular *** this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.

关键词： Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells Cardiomyocytes Regeneration Myocardial infarction Mesenchymal stem cells Differentiation Immunomodulation

The next decade of SET:from an oncoprotein to beyond

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Journal of Molecular Cell Biology 2024年第1期16卷 1-14页

作者： Han Yao Meng Zhang Donglai Wang State Key Laboratory of Common Mechanism Research for Major Diseases&department of medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

This year marks the fourth decade of research into the protein SET,which was discovered in *** was initially identified as an oncoprotein but later shown to be a multifaceted protein involved in regulating numerous biological processes under both physiological and pathophysiological *** dysfunction is closely associated with diseases,such as cancer and Alzheimer's *** the increasing understanding of how SET works and how it is regulated in cells,targeting aberrant SET has emerged as a potential strategy for disease *** this review,we present a comprehensive overview of the advancements in SET studies,encompassing its biological functions,regulatory networks,clinical implications,and pharmacological ***,we provide insights into the future prospects of SET research,with a particular emphasis on its promising potential in the realm of immune modulation.

关键词： SET biological process regulatory mechanism disease therapy

Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Tsung-Hsien Chuang Rong Xiang Yunping Luo department of Immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China Immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC department of Immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung *** stem cells(CSCs)have been identified as a crucial player in immunotherapy-related ***,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with *** adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain ***,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung ***,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A *** CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in ***,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing *** results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages

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World Journal of Stem Cells 2024年第4期16卷 434-443页

作者： Fatimah Almahasneh Ejlal Abu-El-Rub Ramada R Khasawneh Rawan Almazari department of basic medical sciences Faculty of MedicineYarmouk UniversityIrbid 21163Jordan

BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory *** passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized *** To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of *** In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and ***,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,*** Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress *** P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at *** cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was *** the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at *** These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.

关键词： Mesenchymal stem cells High glucose Hypoxia Stressful microenvironment Serial passage Senescence Apoptosis

Effect of Eu3+,Bi3+,and Li+ doping on luminescent property of GdNbO4

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Journal of Rare Earths 2024年第1期42卷 66-75页

作者： S.W.Wi Y.S.Lee department of Physics and Integrative Institute of basic sciences Soongsil University

We investigated the emission properties of Eu3+-doped GdNbO4-based oxide phosphors,aiming at improving the Eu3+emission by codoping of Bi3+and Li+.Eu3+singly doped,Eu3+and Bi3+doubly doped,and Eu3+,Bi3+,and Li+triply doped GdNbO4were prepared using a high-temperature solid-state reaction *** red-orange emissions from Eu3+in the singly doped samples are significantly improved by the codoping of Bi3+,mainly due to the energy transfer from Bi3+to Eu3+.The additional codoping of Li+is found to increase the Eu3+emission *** improvement might be attributed to the increase in the photoluminescent quantum yield originating from larger grain sizes and better crystallinity.A detailed analysis of the X-ray diffraction pattern and the asymmetric ratio estimated from the photoluminescence spectra show that the local lattice environment around Eu3+in GdNbO4does not change significantly with the codoping of Bi3+and Li+.Our results indicate that Li+doping is a promising way to improve the emission properties of rare-earth ion-doped GdNbO4phosphors.

关键词： Eu 3+ GdNbO 4 Codoping of Li + Photoluminescence Sensitizer Rare earths

DDAH1 promotes neurogenesis and neural repair in cerebral ischemia

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2097-2118页

作者： Qiming Gao Pinfei Ni Yilin Wang Peiyun Huo Xiaojie Zhang Sihan Wang Fuyao Xiao Yixuan Li Wei Feng Juntao Yuan Teng Zhang Qiang Li Boyu Fan Yuhao Kan Zhirui Li Yimiao Qi Junfei Xing Zhenghong Yang Haixiao Cheng Xinran Gao Xiaoyan Feng Ming Xue Yang Liu Yumin Luo Zhongbing Lu Yuming Zhao department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Cerebrovascular Diseases Research Institute and department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China State Key Laboratory for Structural Chemistry of Unstable and Stable Species Institute of ChemistryChinese Academy of SciencesBeijing 100190China College of Life Science University of Chinese Academy of SciencesBeijing 100049China department of Laboratory Animal School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly *** RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke *** dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed *** expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS *** comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic *** a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

关键词： DDAH1 Neurogenesis Neural repair ChAT HIF-1α ACh Stroke ADMA

Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-β1-mediated ROS/IL-8/SMAD3 axis

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Journal of Environmental sciences 2024年第7期141卷 139-150页

作者： Shahrzad Molavinia Dian Dayer Mohammad Javad Khodayar Gholamreza Goudarzi Maryam Salehcheh Cellular and Molecular Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran department of Toxicology School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran Student Research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Toxicology Research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Air Pollution and Respiratory Diseases Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Iranian Scientific Association of Clean Air TehranIran

Epidemiological evidence presents that dust storms are related to respiratory diseases,such as pulmonary fibrosis(PF).However,the precise underlying mechanisms of SPM-elicited adverse effects still need to be ***-mesenchymal transition(EMT)process is a characteristic of *** discussed whether suspended particulate matter(SPM)is involved in EMT induction via transforming growth factor-β1(TGF-β1).In this study,a detailed elemental analysis(55 elements),particle size,and morphology were *** investigate the toxicity of SPM,an MTT test was performed to detect cell ***,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated *** DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species(ROS).The ELISA assay demonstrated increased levels of interleukin-8(IL-8)and TGF-β1 in the *** blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent *** of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were *** findings indicated that SPM triggered EMT by induction of oxidative stress,inflammation,and the TGF-β1/SMAD3 pathway activation.

关键词： Particulate matter TGF-β1 Oxidative stress Epithelial-mesenchymal transition Pulmonary fibrosis Cells

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