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C1q recognizes antigen-bound IgG in a curvature-dependent manner

Nano research 2020年第6期13卷 1651-1658页

作者： Christina M.Zeuthen Ali Shahrokhtash Karin Fromell Kristina Nilsson Ekdahl Hossein Mohammad-Beigi Duncan S.Sutherland interdisciplinary Nanoscience Center Aarhus UniversityGustav Wieds vej 148000Aarhus CDenmark Department of Immunology Genetics and PathologyUppsala UniversityDag Hammarskjölds väg 2075185UppsalaSweden Linnaeus Center of Biomaterials Chemistry Linnaeus University39182KalmarSweden Sino-Danish Center for Education and research Niels Jensens Vej 2Building 11908000Aarhus CDenmark The centre for Cellular Signal Patterns(CellPAT) Gustav Wieds vej 148000Aarhus CDenmark

Nano research volume 13,pages1651–1658(2020)Cite this article 109 Accesses Metrics details Abstract C1q is an important recognition protein in the complement system,which is a major protein cascade in the innate immune *** recognition of a target by C1q,the target is marked for opsonization and destruction.C1q recognizes many pathogenic patterns directly,but an important target is the Fc domain of antibodies binding to their *** this paper,the curvature-dependence of the interaction between IgG and C1q is studied by surface plasmon resonance and quartz crystal *** is organized in similar surface coverage densities on flat polystyrene surfaces and polystyrene nanoparticles of different sizes,and the amount of C1q binding to the IgG is *** in solution were found to aggregate upon incubation with IgG,and therefore a new technique utilizing nanoparticles binding to antifouling polymer brush functionalized surfaces was used to prepare surfaces with nanoparticles for measurements with surface plasmon *** antigen-bound IgG at the curved surface of nanoparticles showed 5.6 times lower binding of C1q compared to at matched flat *** was no significant difference between the binding at 100 and 200 nm polystyrene *** findings are important for designing drug delivery systems to evade the complement system.

关键词： C1q complement system antibodies curvature nanoparticles

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Making Use of Plant uORFs to Control Transgene Translation in Response to Pathogen Attack

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BioDesign research 2022年第1期2022卷 381-394页

作者： Gan Ai Jin Liu Xiaowei Fu Tianli Li Hai Zhu Ying Zhai Chuyan Xia Weiye Pan Jialu Li Maofeng Jing Danyu Shen Ai Xia Daolong Dou College of Plant Protection Academy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China Department of Plant pathology Washington State UniversityPullmanWA 99164USA

Reducing crop loss to diseases is urgently needed to meet increasing food production challenges caused by the expanding world population and the negative impact of climate change on crop ***-resistant crops can be created by expressing endogenous or exogenous genes of interest through transgenic ***,enhanced resistance by overexpressing resistance-produced genes often results in adverse developmental *** open reading frames(uORFs)are translational control elements located in the 5′untranslated region(UTR)of eukaryotic mRNAs and may repress the translation of downstream *** investigate the function of three uORFs from the 5′-UTR of ACCELERATED CELL 11(uORFsACD11),we develop a fluorescent reporter system and find uORFsACD11 function in repressing downstream gene *** or simultaneous mutations of the three uORFsACD11 lead to repression of downstream translation efficiency at different ***,uORFsACD11-mediated translational inhibition is impaired upon recognition of pathogen attack of plant *** coupled with the PATHOGENESIS-RELATED GENE 1(PR1)promoter,the uORFsACD11 cassettes can upregulate accumulation of Arabidopsis thaliana LECTIN RECEPTOR KINASE-VI.2(AtLecRKVI.2)during pathogen attack and enhance plant resistance to Phytophthora *** findings indicate that the uORFsACD11 cassettes can be a useful toolkit that enables a high level of protein expression during pathogen attack,while for ensuring lower levels of protein expression at normal conditions.

关键词： expressing crops impaired

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Impact of microbiota-immunity axis in pancreatic cancer management

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World Journal of Gastroenterology 2022年第32期28卷 4527-4539页

作者： Ilenia Bartolini Giulia Nannini Matteo Risaliti Francesco Matarazzo Luca Moraldi Maria Novella Ringressi Antonio Taddei Amedeo Amedei Department of Experimental and Clinical Medicine HPB Surgery UnitAzienda Ospedaliero-Universitaria CareggiFlorence 50134Italy Department of Experimental and Clinical Medicine SOD of Interdisciplinary Internal MedicineAzienda Ospedaliera-Universitaria CareggiFlorence 50134Italy Division of Oncologic surgery Department of OncologyCareggi University HospitalFirenze 50134Italy

The microbiota impact on human diseases is well-known,and a growing body of literature is providing evidence about the complex interplay between microbiotaimmune system-human physiology/pathology,including *** with the defined risk factors(e.g.,smoke habits,diet,diabetes,and obesity),the oral,gut,biliary,and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune ***,a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially *** the poor pancreatic cancer prognosis,complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential noninvasive biomarkers,new therapeutic targets,and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.

关键词： Gastrointestinal tumors Hepatopancreatobiliary tumors Pancreatic cancer Gut microbiota Dysbiosis Cancer development Carcinogenesis

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Current understanding of osteoarthritis pathogenesis and relevant new approaches

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Bone research 2022年第4期10卷 627-643页

作者： Liping Tong Huan Yu Xingyun Huang Jie Shen Guozhi Xiao Lin Chen Huaiyu Wang Lianping Xing Di Chen research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518005China Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Orthopedic surgery School of MedicineWashington University in St.LouisSt.LouisMO 63110USA School of Medicine Southern University of Science and TechnologyShenzhen 518055China Department of Wound Repair and Rehabilitation State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China research Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of pathology and Laboratory of Medicine Center for Musculoskeletal ResearchUniversity of Rochester Medical CenterRochesterNY 14642USA

Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the *** molecular mechanisms of OA are currently *** is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA *** better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA *** this review,we first focus on the epigenetic regulation of OA,with a particular focus on DNA methylation,histone modification,and microRNA regulation,followed by a summary of several key mediators in OA-associated *** then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain,such as CRISPR,scRNA sequencing,and lineage ***,we discuss the timely updates concerning cell death regulation in OA pathology,including pyroptosis,ferroptosis,and autophagy,as well as their individual roles in OA and potential molecular targets in treating ***,our review highlights new directions on the role of the synovial lymphatic system in *** improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

关键词： pathogenesis swelling concerning

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Human CD34loCD133lo fetal liver cells support the expansion of human CD34hiCD133hi hematopoietic stem cells

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Cellular & Molecular Immunology 2016年第5期13卷 605-614页

作者： Kylie Su Mei Yong Choong Tat Keng Shu Qi Tan Eva Loh Kenneth TE Chang Thiam Chye Tan Wanjin Hong Qingfeng Chen Humanized Mouse Unit Institute of Molecular and Cell Biology Agency for Science Technology and Research (A＊STAR) Singapore 138673 Singapore Department of Obstetrics & Gynaecology KK Women's and Children's Hospital Singapore 229899 Singapore Department of pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore 229899 Singapore Duke-NUS Graduate Medical School Singapore 169857 Singapore interdisciplinary research Group in Infectious Diseases Singapore-Massachusetts Institute of Technology Alliance for Research and Technology Singapore 138602 Singapore Department of Microbiology Yong Loo Lin School of Medicine National University of Singapore Singapore 119228 Singapore

We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver （FL） that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD341~CD133~~ cells. Our findings show that these CD341~CD133I~ cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34~~CD 133I~ cel Is express growth factors that are important for human hematopoietic stem cell （HSC） expansion： stem cell factor （SCF）, insulin-like growth factor 2 （IGF2）, C-X-C motif chemokine 12 （CXCL12）, and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34loCD133lo cells supports and expands both types of *** findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together,CD34loCD133lo cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.

关键词： epithelial-mesenchymal transition fetal liver niche hematopoietic cell expansion hematopoietic celltransplantation

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Microbiota revolution:How gut microbes regulate our lives

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World Journal of Gastroenterology 2023年第28期29卷 4368-4383页

作者： Marica Colella Ioannis Alexandros Charitos Andrea Ballini Concetta Cafiero Skender Topi Raffaele Palmirotta Luigi Santacroce interdisciplinary Department of Medicine Section of Microbiology and VirologyUniversity of Bari“Aldo Moro”Bari 70124Italy Maugeri Clinical Scientific research Institutes(IRCCS)of Pavia-Division of Pneumology and Respiratory Rehabilitation Scientific Institute of BariBari 70124Italy Department of Clinical and Experimental Medicine University of FoggiaFoggia 71122Italy Department of Precision Medicine University of Campania“Luigi Vanvitelli”Naples 80138Italy Area of Molecular pathology Anatomic Pathology UnitFabrizio Spaziani HospitalFrosinone 03100Italy Department of Clinical Disciplines School of Technical Medical SciencesUniversity of Elbasan“A.Xhuvani”Elbasan 3001Albania

The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during *** intestinal microorganisms called microbiota and are involved in a variety of mechanisms of the organism,they interact with the host and therefore are in contact with the organs of the various ***,they play a crucial role in maintaining host homeostasis,also influencing its ***,microorganisms perform a series of biological functions important for human *** host provides the microorganisms with the environment and nutrients,simultaneously drawing many benefits such as their contribution to metabolic,trophic,immunological,and other *** these reasons it has been reported that its quantitative and qualitative composition can play a protective or harmful role on the host ***,a dysbiosis can lead to an association of unfavourable factors which lead to a dysregulation of the physiological processes of ***,it has previously noted that the gut microbiota can participate in the pathogenesis of autoimmune diseases,chronic intestinal inflammation,diabetes mellitus,obesity and atherosclerosis,neurological disorders(e.g.,neurological diseases,autism,etc.)colorectal cancer,and more.

关键词： Microbiology Human microbiota Intestinal microbiota Immune system Metabolites Dysbiosis Probiotics Diseases Cancer

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Nanoparticle–Cartilage Interaction: pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

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Nano-Micro Letters 2021年第10期13卷 29-76页

作者： Xu Li Bingyang Dai Jiaxin Guo Lizhen Zheng Quanyi Guo Jiang Peng Jiankun Xu Ling Qin musculoskeletal research Laboratory Department of Orthopedics and TraumatologyThe Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials The Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLAInstitute of OrthopedicsChinese PLA General HospitalBeijingPeople’s Republic of China Innovative Orthopedic Biomaterial and Drug Translational research Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China

Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic ***-articular administration of agents is clinically used for pain ***,the effectiveness is inapparent caused by the rapid clearance of *** overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic *** the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of *** this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug ***,we review the interactions of nanoparticles with cartilage microenvironment and the rational ***,we highlight advances in the therapeutic schemes according to the pathology ***,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological *** anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.

关键词： Nanoparticle Drug delivery Osteoarthritis Articular cartilage Nanomedicine

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Ectopic Tcf1 expression instills a stem-like program in exhausted CD8^(+) T cells to enhance viral and tumor immunity

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Cellular & Molecular Immunology 2021年第5期18卷 1262-1277页

作者： Qiang Shan Sheng’en Hu Xia Chen Derek B.Danahy Vladimir P.Badovinac Chongzhi Zang Hai-Hui Xue Center for Discovery and Innovation Hackensack Meridian HealthNutleyNJ07110USA Department of Microbiology and Immunology Carver College of MedicineUniversity of IowaIowa CityIA52242USA Center for Public Health Genomics University of Virginia School of MedicineCharlottesvilleVA22908USA Department of pathology Carver College of MedicineUniversity of IowaIowa CityIA52242USA interdisciplinary Immunology Graduate Program Carver College of MedicineUniversity of IowaIowa CityIA52242USA Iowa City Veterans Affairs Health Care system Iowa CityIA52246USA

Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exhausted(Tex-term)***,we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor ***1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade,leading to enhanced viral and tumor ***,ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells,such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes,including Mx1,Tox2,and *** findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.

关键词： T cell exhaustion Tcf1 Stem cell features

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IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss

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Bone research 2023年第1期11卷 215-227页

作者： Hyunsoo Kim Noriko Takegahara Yongwon Choi Department of pathology and Laboratory Medicine University of Pennsylvania Perelman School of MedicinePhiladelphiaPA19104USA

Osteoclasts are primary bone-resorbing cells,and receptor-activated NF-k B ligand(RANKL)stimulation is the key driver of osteoclast *** late-stage differentiation,osteoclasts become multinucleated and enlarged(so-called“maturation”),suggesting their need to adapt to changing metabolic demands and a substantial increase in ***,we demonstrate that immunoglobulin superfamily 11(Ig SF11),which is required for osteoclast differentiation through an association with the postsynaptic scaffolding protein PSD-95,regulates osteoclast differentiation by controlling the activity of pyruvate kinase M isoform2(PKM2).By using a system that directly induces the activation of Ig SF11 in a controlled manner,we identified PKM2 as a major Ig SF11-induced tyrosine-phosphorylated *** SF11 activates multiple Src family tyrosine kinases(SFKs),including c-Src,Fyn,and Hc K,which phosphorylate PKM2 and thereby inhibit PKM2 ***,Ig SF11-deficient cells show higher PKM2activity and defective osteoclast ***,inhibiting PKM2 activities with the specific inhibitor Shikonin rescues the impaired osteoclast differentiation in Ig SF11-deficient cells,and activating PKM2 with the specific activator TEPP46 suppresses osteoclast differentiation in wild-type ***,PKM2 activation further suppresses osteoclastic bone loss without affecting bone formation in *** together,these results show that Ig SF11 controls osteoclast differentiation through PKM2 activity,which is a metabolic switch necessary for optimal osteoclast maturation.

关键词： SF11 osteoclast impaired

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Oxygen-driven cuproptosis synergizes with radiotherapy to potentiate tumor immunotherapy

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Aggregate 2024年第3期5卷 219-231页

作者： Pei Pei Yuhong Wang Wenhao Shen Qing He Xiangming Han Chonghai Zhang Yuyuan Xie Guangming Zhou Ye Zhao Lin Hu Kai Yang Teaching and research Section of Nuclear Medicine School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhuiChina State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection&School for Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhouJiangsuChina Department of pathology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsuChina Department of Oncology Taizhou People’s Hospital Affiliated to Nanjing Medical UniversityNanjingJiangsuChina

The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor ***,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics ***,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor ***,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory *** work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.

关键词： cuproptosis immune response oxygen generator radio-immunotherapy RNA-seq analysis

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