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Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing

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World Journal of Stem Cells 2024年第3期16卷 305-323页

作者： Jian-Jing Lin Tong Ning Shi-Cheng Jia Ke-Jia Li Yong-Can Huang Qiang Liu Jian-Hao Lin Xin-Tao Zhang Department of Sports Medicine and Rehabilitation Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina Institute of Medical Science The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033Shandong ProvinceChina Department of Biomedical Engineering Institute of Future TechnologyPeking UniversityBeijing 100871China Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina arthritis Clinical and research center Peking University People’s HospitalBeijing 100044China

BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine ***,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple ***,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs *** To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with *** The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome *** were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA *** transcript was normalized by fragments per kilobase per *** change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction *** In total,263 DEGs were discovered,with 92 upregulated and 171 *** were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound *** cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and *** aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid *** real-time polymerase chain reaction confirmed targeted transcript *** Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 26

关键词： Nanosecond pulsed electric fields Whole transcriptome sequencing Mesenchymal stem cells Genetic response Stem cell engineering

Initial host-pathogen interactions explained by the Organism Prearranged Recognition Theory: fundamental role of saccharides

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Life research 2024年第3期7卷 9-23页

作者： Luz P.Blanco Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of HealthBethesdaUSA

Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment *** hypothesis asserts that:"recognition and interaction that occur between organisms is *** are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like *** receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular *** in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell *** lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular *** scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are *** is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes.

关键词： Species-specificity saccharides extracellular-matrix host-pathogen antibodies

Long noncoding nuclear enriched abundant transcript 1_2 is a promising biomarker for childhood-onset systemic lupus erythematosus

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Pediatric Investigation 2024年第2期8卷 101-107页

作者： Shipeng Li Xia Wang Xiaozhen Zhao Jianghong Deng Weiying Kuang Junmei Zhang Xiaohua Tan Chao Li Caifeng Li Department of Rheumatology Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina center for Infectious Diseases Beijing Youan HospitalCapital Medical UniversityBeijing Key Laboratory for HIV/AIDS ResearchBeijingChina

Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged *** early diagnosis and condition monitoring of SLE are crucial to disease ***:To assess the diagnostic value of long noncoding RNA(lncRNA)nuclear enriched abundant transcript 1(NEAT1)in childhood-onset SLE(cSLE).Methods:Fifty-seven children diagnosed with SLE,40 children diagnosed with juvenile idiopathic arthritis(JIA),and 40 healthy children were *** blood samples from each patient were collected.A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral *** among parameters were analyzed using the Mann-Whitney U test or independent sample ***:The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with *** operating characteristic curves revealed an area under the curve(AUC)of 0.633(95%confidence interval[CI],0.524-0.742;P=0.024)for lncNEAT1_*** AUC of lncNEAT1_2 was 0.812(95%CI,0.727-0.897;P<0.0001)to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of ***,lncNEAT1_2 expression was higher in patients with cSLE presenting with fever,lupus nephritis,elevated erythrocyte sedimentation rate,active disease activity,and decreased C3 level,compared with those without these ***,no similar correlation was observed for lncNEAT1_***:The expression of lncNEAT1_2 was significantly elevated in children with SLE,especially those with fever,renal involvement,and low C3 *** findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.

关键词： Biomarker Children LncRNA SLE NEAT1

Contributions of neutrophils to the adaptive immune response in autoimmune disease

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World Journal of Translational Medicine 2015年第3期4卷 60-68页

作者： Kathryn M Pietrosimone Peng Liu thurston arthritis research center University of North Carolina at Chapel Hill Department of Medicine and thurston arthritis research center University of North Carolina at Chapel Hill

Neutrophils are granulocytic cytotoxic leukocytes of the innate immune system that activate during acute inflammation. Neutrophils can also persist beyond the acute phase of inflammation to impact the adaptive immune response during chronic inflammation. In the context of the autoimmune disease, neutrophils modulating T and B cell functions by producing cytokines and chemokines, forming neutrophil extracellular traps, and acting as or priming antigen presentation cells. Thus, neutrophils are actively involved in chronic inflammation and tissue damage in autoimmune disease. Using rheumatoid arthritis as an example, this review focuses on functions of neutrophils in adaptive immunity and the therapeutic potential of these cells in the treatment of autoimmune disease and chronic inflammation.

关键词： Neutrophils Chronic inflammation Autoimmune disease Rheumatoid arthritis Collagen-induced arthritis

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis:potential implications for systemic nitric oxide availability

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International Journal of Oral Science 2024年第1期16卷 52-61页

作者： Bob T.Rosier William Johnston Miguel Carda-Diéguez Annabel Simpson Elena Cabello-Yeves Krystyna Piela Robert Reilly Alejandro Artacho Chris Easton Mia Burleigh Shauna Culshaw Alex Mira Department of Genomics and Health FISABIO FoundationCenter for Advanced Research in Public HealthValenciaSpain Department of Biological and Biomedical Sciences Glasgow Caledonian UniversityGlasgowUK Oral Sciences University of Glasgow Dental SchoolSchool of MedicineDentistry and NursingCollege of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowUK Sport and Physical Activity research Institute University of the West of ScotlandBlantyreScotland Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Científicas(IBV-CSIC)ValenciaSpain CIBER center for Epidemiology and Public Health MadridSpain

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity(NRC)and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitratereducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals(P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate(a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment(P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria(P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

关键词： impaired intake nitrate

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

The role of botanical triterpenoids and steroids in bile acid metabolism,transport,and signaling:Pharmacological and toxicological implications

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3385-3415页

作者： Zichen Luo Wei Zhou Tong Xie Weichen Xu Chen Shi Zihan Xiao Yu Si Yan Ma Qingling Ren Liuqing Di Jinjun Shan Medical Metabolomics center Institute of PediatricsJiangsu Key Laboratory of Children’s Health and Chinese MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu CM Clinical Medicine Innovation center for Obstetrics Gynecologyand ReproductionAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210001China National Institute of Biological Sciences Beijing 102206China Jiangsu Engineering research center for Efficient Delivery System of TCM School of PharmacyNanjing University of Chinese MedicineNanjing 210023China

Bile acids(BAs)are synthesized by the host liver from cholesterol and are delivered to the intestine,where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various *** serve to emulsify dietary lipids and act as signaling molecules,regulating the host’s metabolism and immune homeostasis through specific ***,disruptions in BA metabolism,transport,and signaling are closely associated with cholestasis,metabolic disorders,autoimmune diseases,and *** triterpenoids and steroids share structural similarities with BAs,and they have been found to modulate BA metabolism,transport,and signaling,potentially exerting pharmacological ortoxicological ***,we have updated the research progress on BA,with a particular emphasis on new-found microbial ***,the latest advancements in targeting BA metabolism and signaling for disease treatment are ***,the roles of botanical triterpenoids in BA metabolism,transport,and signaling are examined,analyzing their potential pharmacological,toxicological,or drug interaction effects through these ***,a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

关键词： Bile acid Triterpenoid Phytosterol Saponin Gut microbes Cholestasis Metabolic disorders Rheumatoid arthritis

Diagnostic issue on spontaneous osteonecrosis of medial tibial plateau

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Chinese Medical Journal 2019年第6期132卷 755-756页

作者： Jun Jiang Jian Chen arthritis Clinic and research center Peking University People Hospital Beijing 100044 China

To the Editor: I read with great interest the recent report of Yang et al[1],“Clinical Characteristics and Treatment of Spontaneous Osteonecrosis of Medial Tibial Plateau: A retrospective case study”(published on November 5, 2018, Chin Med J, page 2544-2550), because there have been very few reports on isolated spontaneous medial tibial plateau osteonecrosis and little is known about osteonecrosis of the tibial plateau. I would like to comment on diagnostic issues in this letter.

关键词： Diagnostic issue spontaneous osteonecrosis medial tibial plateau

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer:Integrating Bioinformatics Analysis with Experimental Confirmation

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Current Medical Science 2024年第3期44卷 529-544页

作者： Yan-min LIU Tie-cheng YANG Xiao-chang FANG Li-jie YANG Li-wen SHI Hua-qiao WANG Ting-ting DOU Lin SHU Tian-Liang CHEN Jun HU Xiao-ming YU Xuan-fei LI Department of Gastroenterology the Central Hospital of WuhanKey Laboratory for Molecular Diagnosis of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430014China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan430071China Clinical Medical research center of Peritoneal Cancer of Wuhan Wuhan430071China Hubei Provincial Clinical research center for Cancer Hubei Key Laboratory of Tumor Biological Behavi Wuhan430071China Department of General Surgery Taihe HospitalHubei University of MedicineShiyan442000China Department of Gastrointestinal Surgery Huangshi Central HospitalAffiliated Hospital of Hubei Polytechnic UniversityWuhan435001China

Objective To uncover the mechanisms underlying the development of colorectal cancer(CRC),we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and *** We performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on differentially expressed genes(DEGs),constructed a protein-protein interaction(PPI)network to find the top 10 hub genes,and analyzed their expression in colon adenocarcinoma(COAD)and rectum adenocarcinoma(READ).We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western *** experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and *** We found 130 DEGs,with 45 up-regulated and 85 down-regulated in *** analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH,zymogen granules,and transmembrane transporter *** pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion,rheumatoid arthritis,and the IL-17 signaling *** identified 10 hub genes:CXCL1,SLC26A3,CXCL2,MMP7,MMP1,SLC9A2,SLC4A4,CLCA1,CLCA4,and *** enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of *** expression analysis revealed that CXCL1,CXCL2,MMP1,and MMP7 were highly expressed in CRC,whereas CLCA1,CLCA4,SLC4A4,SLC9A2,SLC26A3,and ZG16 were expressed at lower *** analysis revealed that 5 key genes were significantly associated with the prognosis of *** mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell ***,SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation,migration,and *** blotting analysis revealed tha

关键词： SLC9A2 colorectal cancer bioinformatic analysis biomarkers immune infiltrate