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Chinese medical Journal 2024年第8期137卷 883-886页

作者： Xiaoshuang Wang Jing Wang Tao Cheng institute of basic medical sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

The institute of basic medical sciences(IBMS)is a global leader in biomedical research and advanced medical *** year(2023)marks the 65^(th)anniversary of its foundation at the Chinese Academy of medical sciences(CAMS)and School of basic Medicine(SBM)of the Peking Union medical College(PUMC).In the beginning,the IBMS and SBM incorporated the premedical departments of the PUMC,which was established by the Rockefeller Foundation in *** then,these departments have been committed to undertakingrstrate medical science research in China.

关键词： basic IBMS foundation

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

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

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Neural Regeneration research 2024年第6期19卷 1241-1248页

作者： Tingting Han Yuxiang Xu Lin Sun Makoto Hashimoto Jianshe Wei institute for Brain sciences research School of Life Sciences Henan University College of Chemistry and Molecular sciences Henan University Department of basic Technology Tokyo Metropolitan Institute of Medical Science

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging; they have a great impact on the aging process and are the main risk factors for neurodegeneration. Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases. This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s chorea, and Parkinson’s disease. This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states. Therefore, inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

关键词： aging Alzheimer's disease cytokines Huntington's disease microglia neurodegenerative diseases neuroinflammation neuroprotection neurotoxicity Parkinson's disease

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

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

Caloric restriction,Sirtuins,and cardiovascular diseases

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Chinese medical Journal 2024年第8期137卷 921-935页

作者： Ziyu Wei Bo Yang Huiyu Wang Shuangjie Lv Houzao Chen Depei Liu State Key Laboratory of Common Mechanism research for Major Diseases Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

Caloric restriction(CR)is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases,including cardiovascular ***,a family of nicotinamide adenine dinucleotide(NAD^(+))-dependent histone deacetylases,have emerged as key regulators of cellular metabolism,stress responses,and the aging process,serving as energy status sensors in response to ***,the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains *** review not only provided an overview of recent research investigating the interplay between Sirtuins and CR,specifically focusing on their potential implications for cardiovascular health,but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via *** has also been shown to have considerable impact on specific metabolic organs,leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular *** direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular *** the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

关键词： Caloric restriction Sirtuins Cardiovascular diseases Healthy lifestyle Dietary

Circulating levels of advanced glycation end products in females with polycystic ovary syndrome:a meta-analysis

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Reproductive and Developmental Medicine 2024年第2期8卷 93-100页

作者： Seyed Sobhan Bahreiny Akram Ahangarpour Mojtaba Aghaei Student research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran medical basic sciences research institute Physiology Research CenterDepartment of PhysiologySchool of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Polycystic ovary syndrome(PCOS)is a common endocrine disorder characterized by a hormonal imbalance that affects females of reproductive *** association between advanced glycation end products(AGEs)and PCOS has attracted considerable attention in recent years,highlighting the potential of AGEs as biomarkers for this *** the present systematic review and meta-analysis,we aimed to examine the association between AGEs and PCOS,evaluate their potential as biomarkers,and improve our understanding of the pathophysiology of PCOS and its associated metabolic complications.A literature search was performed using various databases from January 2000 to March 2023 to identify relevant studies investigating the association between AGEs and *** effect estimates were calculated using standardized mean differences(SMD)with 95%confidence intervals(CIs).Sub-group and meta-regression analyses were performed to examine potential sources of *** meta-analysis included six studies with a total of 623 *** results revealed a significant increase in circulating AGE levels in females with PCOS compared to healthy females(SMD=2.35;95%CI:1.10-3.60;P<0.001).Significant heterogeneity was observed between the studies(I2=96.37%;P<0.001),indicating the presence of several factors influencing the ***-group analyses based on body mass index,age,and homeostatic model assessment for insulin resistance indicated differential effects of AGEs on specific *** systematic review and meta-analysis support the association between elevated AGE levels and PCOS,thereby suggesting the potential role of AGEs as biomarkers in PCOS.

关键词： Polycystic ovary syndrome PCOS Advanced glycation end products AGEs Biomarker Meta-analysis

Signaling pathways governing the behaviors of leukemia stem cells

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Genes & Diseases 2024年第2期11卷 830-846页

作者： Shirin Azizidoost Ava Nasrolahi Mohadeseh Sheykhi-Sabzehpoush Amir Anbiyaiee Seyed Esmaeil Khoshnam Maryam Farzaneh Shahab Uddin Atherosclerosis research Center Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Infectious Ophthalmologic research Center Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Department of Laboratory Imam Khomeini Hospital ComplexTehran University of Medical SciencesTehran ***Iran Department of Surgery School of MedicineAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Persian Gulf Physiology research Center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Fertility Infertility and Perinatology Research CenterAhvaz Jundishapur University of Medical SciencesAhvaz ***Iran Translational research institute and Dermatology institute Academic Health SystemHamad Medical CorporationDoha 3050Qatar

Leukemia is a malignancy in the blood that develops from the lymphatic system and bone *** various treatment options have been used for different types of leukemia,understanding the molecular pathways involved in the development and progression of leukemia is *** studies showed that leukemia stem cells(LSCs)play essential roles in the pathogenesis of leukemia by targeting several signaling pathways,including Notch,Wnt,Hedgehog,and *** are highly proliferative cells that stimulate tumor initiation,migration,EMT,and drug *** review summarizes cellular pathways that stimulate and prevent LSCs'self-renewal,metastasis,and tumorigenesis.

关键词： Leukemia Leukemia stem cells Pathogenesis Signaling pathways Stem cells

The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience research Center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience research Center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope