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Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio Charles A.Dinarello Ruben Lopez-Vales department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

γδT cells:Major advances in basic and clinical research in tumor immunotherapy

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Chinese Medical Journal 2024年第1期137卷 21-33页

作者： Yueqi Zhao Peng Dong Wei He Jianmin Zhang Hui Chen department of Immunology CAMS Key Laboratory for T Cell and ImmunotherapyState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

γδT cells are a kind of innate immune T *** have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain ***,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)*** increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT ***,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is *** review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

关键词： Gamma-delta T-cells T cell receptor CD1a Tumor immunotherapy Receptors,chimeric antigen Vδ1 cells αβT cells

TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

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Oncology Research 2024年第1期32卷 151-161页

作者： HEE JU SONG TAEHEE KIM HAN NA CHOI SOO JIN KIM SANG DO LEE department of physiology School of MedicineChungnam National UniversityDaejeon35015Korea

Lung cancer has the highest mortality rate among all cancers,in part because it readily *** tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and *** secrete several cytokines,including interleukin(IL)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several ***responsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and ***,the mechanisms by which it increases lung cancer migration remain ***,in this study,we aimed to elucidate the mechanisms by which IL-1βand TonEBP affect lung cancer cell migration and *** found that A549 cocultured-MΦ-secreted IL-1βinduced A549 cell migration and invasion via the PAK1 *** deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1β–induced migration and ***1 phosphorylation,which was promoted by IL-1β,was reduced when TonEBP was *** results suggest that TonEBP plays an important role in IL-1βinduction and invasiveness of A549 cells via the PAK1 *** findings could be valuable in identifying potential targets for lung cancer treatment.

关键词： Lung cancer TonEBP Tumor microenvironment Tumor-associated macrophage IL-1β

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National Translational Science Center for molecular Medicine and department of cell Biology Fourth Military Medical UniversityXi'an 710000China department of Neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis

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Chinese Medical Journal 2024年第13期137卷 1592-1602页

作者： Jingyi Han Xue Zhang Menghua Cai Feng Tian Yi Xu Hui Chen Wei He Jianmin Zhang Hui Tian department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China CAMS Key Laboratory of T cell and Immunotherapy Department of ImmunologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Medical Molecular BiologyBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of cell Ecosystem Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill *** inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still *** cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in ***,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet ***,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ***:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of *** macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome *** of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of *** between two groups were performed with a two-sided unpaired ***:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced *** deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-*** in TSPO-KO macrophages tended to depolarize in response to cellular *** increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membr

关键词： Acute respiratory distress syndrome Acute lung injury 18-kDa translocator protein Macrophage NLRP3 inflammasome Inflammation

WNT/β-catenin signaling in hepatocellular carcinoma:The aberrant activation,pathogenic roles,and therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 727-746页

作者： Anna Gajos-Michniewicz Malgorzata Czyz department of molecular Biology of Cancer Medical University of LodzLodz 92-215Poland

Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular *** arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative *** role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively ***,we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to *** outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in *** discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.

关键词： Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity

Alternative splicing and related RNA binding proteins in human health and disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone Tumor Institution 200000 ShanghaiChina department of Biochemistry and molecular cell Biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

Endomembrane-biased dimerization of ABCG16 and ABCG25 transporters determines their substrate selectivity in ABA-regulated plant growth and stress responses

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molecular Plant 2024年第3期17卷 478-495页

作者： Yeling Zhou Yuzhu Wang Dong Zhang Jiansheng Liang institute of Plant and Food Science Department of BiologySchool of Life SciencesSouthern University of Science and Technology(SUSTech)Shenzhen 518055China Key Laboratory of molecular Design for Plant cell Factory of Guangdong Higher Education Institutes Southern University of Science and Technology(SUSTech)Shenzhen 518055China jiangsu Key Laboratory of Crop Genetics and physiology/Co-lnnovation Center for Modern Production Technology of Grain Crops Key Laboratory of Plant Functional Genomics of the Ministry of EducationYangzhou UniversityYangzhou 225009China

ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various *** Arabidopsis,the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress *** this study,we revealed that two Arabidopsis ABCG transporters,ABCG16 and ABCG25,engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester(ABA-GE),*** first revealed that ABCG16 contributes to osmotic stress tolerance via ABA *** specifically,ABCG16 induces cellular ABA efflux in both yeast and plant *** FRET analysis,we showed that ABCG16 forms oblig-atory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA,undergoing notable conformational ***,we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum(ER)membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco *** specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhib-itory role of these twoABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER *** endomembrane-specific analysis of the FRET signals derived from the homo-or heterodimerized ABcG complexes allowed us to link endomembrane-biased dimerization to the transloca-tion of distinct substrates by ABcG transporters,providing a prototypic framework for understanding the omnipotence of ABcG transporters in plant development and stress responses.

关键词： abscisic acid ABCG transporter dimerization endomembrane substrate selectivity

Emerging role of cellular senescence in normal lung development and perinatal lung injury

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 10-16页

作者： Phyllis A.Dennery Hongwei Yao department of molecular Biology Cell Biology&BiochemistryDivision of Biology and MedicineBrown UniversityProvidenceRI 02912USA department of Pediatrics Warren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external *** cells are typically enlarged and flattened,and characterized by numerous molecular *** latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory *** features vary depending on the stressor leading to senescence and the type of *** senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related ***,senescence can also both promote and inhibit wound healing *** recently report that senescence as a programmed pro-cess contributes to normal lung *** senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this ***,this senescence results in neonatal lung *** this review,we briefly discuss the molecular features of *** then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving ***,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关键词： Senescence Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics