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High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

Science China(Life Sciences) 2024年第5期67卷 879-891页

作者： Nianyi Zeng Fan Wu Junqi Lu Xiang Li Shaomei Lin Lang Zhou Zhongwei Wang Guangyan Wu Qingfa Huang Daowen Zheng Jie Gao Shan Wu Xiaojiao Chen Muxuan Chen Fanguo Meng Haitao Shang Yan He Peng Chen Hong Wei Zhuang Li Hongwei Zhou Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China department of Environmental Health Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhou 510515China Redox Medical Center for Public Health Soochow UniversitySuzhou 215301China Precision Medicine Institute The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic ***,the underlying mechanism remains *** the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut *** sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence *** microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight ***,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus *** administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the *** conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

关键词： fatty liver disease gut microbiota gut barrier high-fat diet oxidative stress reactive oxygen species

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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China department of pathology Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant *** specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to ***,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug *** investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were *** Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent *** through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma *** TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to ***,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ***,in turn,elevated ITPKB stability and impaired ROS ***,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse *** findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

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Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA department of Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA department of pathology and Laboratory Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

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International Journal of Oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He department of Oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina department of Oral pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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From text to image:challenges in integrating vision into ChatGPT for medical image interpretation

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Neural Regeneration research 2025年第2期20卷 487-488页

作者： Shunsuke Koga Wei Du department of pathology and Laboratory Medicine Hospital of the University of PennsylvaniaPhiladelphiaPAUSA

Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text *** potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical *** ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).

关键词： image diagnosis text

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The roles of macrophage migration inhibitory factor in retinal diseases

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Neural Regeneration research 2024年第2期19卷 309-315页

作者： Hongbing Zhang Xianjiao Zhang Hongsong Li Bing Wang Pei Chen Jiamin Meng Shaanxi Institute of Ophthalmology Xi’anShaanxi ProvinceChina department of Ophthalmology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina department of pathology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive *** are some evidences that MIF is involved in many vitreoretinal *** example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis *** also alleviates trauma-induced and glaucoma-induced optic nerve ***,MIF is critical for retinal/choroidal neovascularization,especially complex *** exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal *** protects uveal melanoma from attacks by natural killer *** mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt *** also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling *** review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

关键词： diabetic retinopathy glaucoma macrophage migration inhibitory factor migration inhibitory factor receptor optic neuropathy retinal degeneration retinal neovascular uveal melanoma uveitis

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Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang Li Mingchen Yu Huimin Hu Changqing Pan Di Wang Zhongfang Shi Xu Yan Xuesong Li Tao Jiang Wei Zhang department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China department of Urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China department of pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China National Clinical research Center for Neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid *** instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance ***,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less ***,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term *** this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented *** mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen *** type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell ***,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol *** mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR ***,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

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Myokines:metabolic regulation in obesity and type 2 diabetes

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Life Metabolism 2024年第3期3卷 21-45页

作者： Zhi-Tian Chen Zhi-Xuan Weng Jiandie D.Lin Zhuo-Xian Meng department of pathology and pathophysiology and department of Cardiology of the Second Affiliated Hospital School of MedicineZhejiang UniversityHangzhouZhejiang 310058China Key Laboratory of Disease Proteomics of Zhejiang Province School of MedicineZhejiang UniversityHangzhouZhejiang 310058China Zhejiang University-University of Edinburgh Institute(ZJE) School of MedicineZhejiang UniversityHainingZhejiang 314400China Life Sciences Institute and department of Cell and Developmental Biology University of MichiganAnn ArborMI 48109United States department of Geriatrics Affiliated Hangzhou First People’s HospitalHangzhouZhejiang 310006China

Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as *** myokine levels are associated with metabolic diseases,such as type 2 diabetes(T2D).The significance of interorgan crosstalk,particularly through myokines,has emerged as a fundamental aspect of nutrient and energy ***,a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major chal*** this review,we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades,namely interleukin 6(IL-6),irisin,myostatin(MSTN),growth differentiation factor 11(GDF11),fibroblast growth factor 21(FGF21),apelin,brain-derived neurotrophic factor(BDNF),meteorin-like(Metrnl),secreted protein acidic and rich in cysteine(SPARC),β-aminoisobutyric acid(BAIBA),Musclin,and Dickkopf 3(Dkk3).Related to these,we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and *** significant advancements in myokine research,many myokines remain challenging to measure accurately and investigate ***,new research techniques and detection methods should be developed and rigorously ***,developing a comprehensive perspective on myokine biology is crucial,as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.

关键词： myokines skeletal muscle obesity type 2 diabetes metabolism

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo D’Alessandro Steven L.Spitalnik Vassilis L.Tzounakas department of Biochemistry School of MedicineUniversity of Patras26504 PatrasGreece department of pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA Laboratory of Reliability and Quality Control in Laboratory Hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA Present address:Institute for Fundamental Biomedical research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood *** cells are defined as cells containing distinct nuclei and other membranous ***,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： membranous maintain

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Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou Huang Wen-Qing Ai Na Wei Ling-Shuang Zhu Zhi-Qiang Liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-Zhuo Hu Zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang Fang-Fang Liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan Guo Youming Lu Kai Shu Ling-Qiang Zhu Dan Liu department of pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China department of pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated Hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China Beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid Medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family *** genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of ***,the underlying mechanisms of social isolation in AD progression remain *** the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD *** also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related ***,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious ***,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its ***,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD *** together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology

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