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Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 601-614页

作者： Bei Li Yong Zhang Xinyuan Liu Ziyang Zhang Shuqing Zhuang Xiaoli Zhong Wenbo Chen Yilin Hong Pingli Mo Shuhai Lin Shicong Wang Chundong Yu State Key Laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen361102China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development ZhangzhouFujian363000China Xiang'an hospital of xiamen university School of MedicineXiamen UniversityXiamen361005China Department of Cardiology Xiamen Key Laboratory of Cardiac ElectrophysiologyXiamen Institute of Cardiovascular DiseasesThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361003China

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is ***,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)***,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK *** of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating ***,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory ***,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

关键词： Pien Tze Huang Bile acids Sepsis Inflammation TGR5 STAT3-A20 signalling

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Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)genetransfected hepatic stellate cells

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 499-512页

作者： Hongyi LIU Yuanyuan ZHOU Peng GUO Xiongwei ZHENG Weibin CHEN Shichao ZHANG Yu FU Xu ZHOU Zheng WAN Bin ZHAO Yilin ZHAO Department of Oncology and Vascular Interventional Radiology Zhongshan Hospital Affiliated to Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361004China School of Medicine Xiamen UniversityXiamen 361102China xiamen Health and Medical Big Data Center Xiamen 361008China Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma(Zhongshan hospital Affiliated to xiamen university) Xiamen 361004China xiamen Key Laboratory of Cellular Intervention and Interventional Medical Materials Xiamen 361004China

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal ***,it has poor elasticity and compliance,leading to stenosis and *** ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial *** have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM ***,mechanical stimulation can encourage ECM secretion and remodeling of a fiber *** on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV ***,these HBX-HSCs were implanted into a polycaprolactonepolyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the *** obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after ***,the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula *** exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s *** study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.

关键词： Composite bilayer bionic blood vessel Extracellular matrix(ECM) Hepatic stellate cells(HSCs) Hepatitis B viral X(HBX)gene Mechanical force

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Tributyltin causes generational neurodevelopmental toxicity and the protective effect of folic acid in zebrafish

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Journal of Environmental Sciences 2024年第3期137卷 615-625页

作者： Haoxing Cai Naying Zheng Chen Tang Yuxuan Zhang Zhenghong Zuo Chengyong He State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiang’an Hospital of Xiamen UniversityXiamen UniversityXiamen 361005China

Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life *** aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual *** exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L *** neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the ***,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA *** summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.

关键词： Tributyltin Neurodevelopment Intergeneration DNA methylation Folic acid Zebrafish

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GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling

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Oncology Research 2024年第2期32卷 361-371页

作者： TINGTING LI WEI ZHONG LIU YANG ZHIYU ZHAO LI WANG CONG LIU WANYUN LI HAIYAN LV SHENGYU WANG JIANGHUA YAN TING WU GANG SONG FANGHONG LUO Cancer Research Center School of MedicineXiamen UniversityXiamen361000China Department of Pharmacy Xiamen Mental Health CenterXiamen Xianyue HospitalXiamen361000China

The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for *** study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in ***1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node ***1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC ***,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and ***,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 ***,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting *** together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

关键词： GIPC1 PDGFR Gastric cancer Proliferation Migration

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Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

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Frontiers of Medicine 2024年第2期18卷 375-393页

作者： Fu’an Xie Yujia Niu Lanlan Lian Yue Wang Aobo Zhuang Guangting Yan Yantao Ren Xiaobing Chen Mengmeng Xiao Xi Li Zhe Xi Gen Zhang Dongmei Qin Kunrong Yang Zhigang Zheng Quan Zhang Xiaogang Xia Peng Li Lingwei Gu Ting Wu Chenghua Luo Shu-Hai Lin Wengang Li Cancer Research Center Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen361102China xiamen university Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association Xiamen UniversityXiamen361102China Department of Laboratory Medicine Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China Department of Retroperitoneal Tumor Surgery Peking University International HospitalBeijing102206China School of Public Health Harvard UniversityBostonMA02115USA Laboratory of Biochemistry and Molecular Biology Research Department of Clinical LaboratoryFujian Medical University Cancer HospitalFuzhou350014China Surgery Department Affiliated Fuzhou First Hospital of Fujian Medical UniversityFuzhou350009China National Institute for Data Science in Health and Medicine Xiamen UniversityXiamen361102China Department of Hepatobiliary Surgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China

Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for *** proteomic and metabolic profiles of RLPS have remained *** aim of our study was to reveal the metabolic profile of ***,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during *** analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were *** particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor *** study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.

关键词： RLPS proteomics metabolomics lipidomics metabolism

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COVID-19 vaccines and beyond

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Cellular & Molecular Immunology 2024年第3期21卷 207-209页

作者： Yiyuan Liu Danying Li Jiahuai Han State Key Laboratory of Cellular Stress Biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamenFujianChina Laboratory Animal Center Xiamen UniversityXiamenFujianChina Research Unit of Cellular Stress of CAMS Cancer Research Center of Xiamen UniversityXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenFujianChina

Hundreds of vaccines have been developed worldwide for Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the cause of Coronavirus disease 2019(COVID-19),since the beginning of the *** vaccines have saved innumerable lives and contributed to partial control of the COVID-19 *** of the vaccines approved for clinical use exhibit satisfactory initial protection rates against corresponding ***,vaccine protection declines over time,with almost all vaccines falling below 50%protection after 6 months[1].In the case of natural infections,protection lasts longer,but the incidence of reinfection is also quite high.

关键词： vaccines acute beyond

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Anthrax lethal toxin and tumor necrosis factor-a synergize on intestinal epithelia to induce mouse death

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Protein & Cell 2024年第2期15卷 135-148页

作者： Xinhe Gao Teng Teng Yifei Liu Tingting Ai Rui Zhao Yilong Fu Peipei Zhang Jiahuai Han Yingying Zhang State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Research Unit of Cellular Stress of CAMS Xiang'an Hospital of Xiamen UniversityCancer Research Center of Xiamen UniversitySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Laboratory Animal Center Faculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China

Bacillus anthracis lethal toxin(LT)is a determinant of lethal *** function in myeloid cells is required for bacterial dissemination,and LT itself can directly trigger dysfunction of the cardiovascular *** interplay between LT and the host responses is important in the pathogenesis,but our knowledge on this interplay remains *** necrosis factor-a(TNF-a)is a pleiotropic pro-inflammatory cytokine induced by bacterial *** LT accumulates and cytokines,predominantly TNF,amass during *** infection,co-treatment of TNF+LT in mice was used to mimic in vivo conditions for LT to function in inflamed *** marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells(IECs)rather than that of hematopoietic cells led to LT+TNF-induced *** of p38a mitogen-activated protein kinase(MAPK)signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs,leading to intestinal damage and mouse ***,p38a inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 *** intestinal damage is one of the leading causes of lethality in anthrax patients,the IEC damage caused by LT+TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.

关键词： lethal toxin TNF p38a intestinal epithelial cell cell death

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Recent progress in co-detection of single-cell transcripts and proteins

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Nano Research 2024年第1期17卷 132-150页

作者： Shanqing Huang Qian Fan Yidi Wang Zhi Huang Weixiong Shi Yanli Gong Ting Yang Jie Wang Lingling Wu Chaoyong Yang Discipline of Intelligent Instrument and Equipment College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Institute of Molecular Medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of General Surgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361101China Research Center for Analytical Sciences Department of ChemistryCollege of SciencesNortheastern UniversityShenyang 110819China

Cellular heterogeneity is a universal property of living systems,and the interrogation of single cells facilitates in-depth understanding of distinct cellular states and functions in various biological ***-analysis of transcripts and proteins from the same single cells opens the way to decipher complex RNA regulatory frameworks and phenotypes,facilitating the understanding of cellular fate and function regulations,discovery of novel cell types,and construction of a high-resolution cell ***,we review the state-of-art advances in the development of methodologies for co-analysis of single-cell transcripts and ***,imaging-based methods are summarized with particular emphasis on optical and mass spectrometry ***,sequencing-based approaches for high-throughput and sensitive co-analysis of single-cell transcripts and proteins are described,including droplet-,microwell-,and split-pool-based ***,combined methods with more flexibility and universality are *** methods commonly employ different strategies or reactions to convert transcripts and proteins of single cells into distinct signals simultaneously,which can be detected by different instruments or ***,some perspectives on the future challenges and development trends in this field are presented.

关键词： single cell optical imaging mass spectrometry imaging single-cell RNA sequencing(scRNA-seq) co-detection

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Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 933-944页

作者： Zhi-Wen Xu Jing-Tao Zhu Hao-Yu Bai Xue-Jun Yu Qing-Qi Hong Jun You Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND Transanal endoscopic intersphincteric resection(ISR)surgery currently lacks sufficient clinical research and *** To investigate the clinical effectiveness of transanal endoscopic ISR,in order to promote the clinical application and development of this *** This study utilized a retrospective case series *** and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated hospital of xiamen university between May 2018 and May 2023 were *** patients underwent transanal endoscopic ISR as the surgical *** conducted this study to determine the perioperative recovery status,postoperative complications,and pathological specimen charac-teristics of this group of *** This study included 45 eligible patients,with no perioperative *** overall incidence of early complications was 22.22%,with a rate of 4.44%for Clavien-Dindo grade≥III *** patients(4.4%)developed anastomotic leakage after surgery,including one case of grade A and one case of grade *** pathological examination confirmed negative circumferential resection margins and distal resection margins in all *** mean distance between the tumor lower margin and distal resection margin was found to be 2.30±0.62 *** transanal endoscopic ISR procedure consistently yielded high quality pathological *** Transanal endoscopic ISR is safe,feasible,and provides a clear anatomical *** is associated with a low incidence of postoperative complications and favorable pathological outcomes,making it worth further research and application.

关键词： Intersphincteric resection Transanal Rectal cancer Complications Endoscopic

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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu Jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal Tumor Surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Cardiothoracic Surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

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