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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

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

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第11期30卷 1497-1523页

作者： Qi-Ying Wei Feng Jin Zhong-Yu Wang Bing-Jie Li Wen-Bo Cao Zhi-Yan Sun Sai-Jun Mo department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of Perioperative Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Division of Special Service Department of Basic OncologySchool of Basic MedicineZhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of basic Science of Oncology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths *** increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality ***,there is currently no specific and effective marker to predict and treat metastasis in ***(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in *** are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of ***,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic *** review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

关键词： MicroRNAs Esophageal squamous cell carcinoma Metastasis Signaling pathway Epigenetics mechanism

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

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

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Research 2024年第2期6卷 401-415页

作者： Jiadi Lv Xiaohan Liu Yabo Zhou Feiran Cheng Haoran Chen Shunshun Li Dianheng Wang Li Zhou Zhenfeng Wang Nannan Zhou Jie Chen Bo Huang department of Immunology&State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical College(PUMC)Beijing100005China department of Histology and Embryology Basic Medical CllegeChina Medical UniversityShenyangLiaoning 11122China department of Immunology Basic Medical Cllege China Medical UniversityShenyangLiaoning 110122China department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Solid tumor cells live in a highly dynamic mechanical *** the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an ***,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like ***,integrin?was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and *** also restoredβ8 expression,thereby forming a closed mechanical ***,MAFG expression is correlated with worse *** findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

关键词： activation thereby MAF

Progress in gut microbiota-host interaction

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Science China(Life Sciences) 2024年第5期67卷 851-853页

作者： Changtao Jiang department of Immunology School of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking UniversityBeijing 100191China

Recently,the gut microbiota has been recognized as a novel endocrine organ in the human *** produces various bioactive metabolites and participates in metabolic *** addition,the gut microbiota is involved in the metab... 详细信息

关键词： metabolism drugs processes