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Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

Neural Regeneration Research 2020年第4期15卷 586-596页

作者： Alisa A.Shaimardanova valeriya v.Solovyeva Daria S.Chulpanova victoria James kristina v.kitaeva Albert A.Rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry The Russian Academy of SciencesMoscowRussia School of veterinary Medicine and Science University of NottinghamSutton Bonington CampusLeicestershireUK

Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

关键词： biomarkers cell-mediated therapy central nervous system diseases diagnosis exosomes extracellular RNAs extracellular vesicles microRNAs microvesicles neurodegenerative diseases

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Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning

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神经科学通报:英文版 2023年第8期39卷 1309-1326页

作者： Qian Lv kristina Zeljic Shaoling Zhao Jiangtao Zhang Jianmin Zhang Zheng Wang School of Psychological and Cognitive Sciences Beijing Key Laboratory of Behavior and Mental HealthIDG/McGovern Institute for Brain ResearchPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China School of Health and Psychological Sciences CityUniversity of LondonLondon EC1V 0HBUK Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 101408China Tongde Hospital of Zhejiang Province(Zhejiang Mental Health Center) Zhejiang Ofce of Mental HealthHangzhou 310012China School of Biomedical Engineering Hainan UniversityHaikou 570228China

Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis.The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance,interpretability,and generalizability.Specifically,we argue that a core set of co-altered brain regions(namely‘core regions’)comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients.Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain.We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.

关键词： Psychiatric disorders Obsessive-compulsive disorder Core region Magnetic resonance imaging Machine learning Neuroimaging-based diagnosis

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Coulometric sizing of nanoparticles： Cathodic and anodic impact experiments open two independent routes to electrochemical sizing of Fez04 nanoparticles

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Nano Research 2013年第11期6卷 836-841页

作者： kristina Tschulik Baptiste Haddou Dario Omanovi Neil v. Rees Richard G. Compton Department of Chemistry Physical & Theoretical Chemistry Laboratory Oxford University South Parks Road Oxford OXI 3QZUnited Kingdom Center for Marine and Environmental Research Ruder Boskovic Institute P. O. Box 180 I0001 Zagreb Croatia

Anodic particle coulometry (APC) is a recently established method of sizing individual metal nanoparticles by oxidising them during their impact on a micro electrode. Here it is demonstrated that the application of APC can be extended to sizing of metal oxide nanoparticles, such as Fe3O4 magnetite nanoparticles. Additionally, a new route to electrochemical nanoparticle sizing is introduced—cathodic particle coulometry (CPC). This method uses the reduction of impacting nanoparticles, e.g., metal oxide nanoparticles, and is demonstrated to yield correct size information for Fe3O4 nanoparticles. The combination of these two independent electrochemical methods of nanoparticle sizing, allows for purely electrochemical sizing of single nanoparticles and simultaneous verification of the obtained results.

关键词：金属纳米粒子电化学方法库仑法影响实验路线阳极阴极金属氧化物

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Technosols on mining wastes in the subarctic: Efficiency of remediation under Cu-Ni atmospheric pollution

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International Soil and Water Conservation Research 2019年第3期7卷 297-307页

作者： Marina v.Slukovskaya viacheslav I.vasenev kristina v.Ivashchenko Dmitry v.Morev Svetlana v.Drogobuzhskaya Liubov A.Ivanova Irina P.Kremenetskaya I.v.Tananaev Institute of Chemistry and Technology of Rare Elements and Mineral Raw Materials Kola Science CentreRussian Academy of Sciences184209Academgorodok 26aApatityMurmansk RegionRussia Department of Landscape Design and Sustainable Ecosystems RUDN University117198Miklykho-Maklaya str.8MoscowRussia Institute of Physicochemical and Biological Problems in Soil Science Russian Academy of Sciences142290Institutskaya str.2PushchinoMoscow RegionRussia Department of Ecology Russian State Agrarian University-Moscow Timiryazev Agricultural Academy127550Timiryazevskaya str.49MoscowRussia N.A.Avrorin Polar-Alpine Botanical Garden-Institute Kola Science CentreRussian Academy of Sciences184209Academgorodok 18aApatityMurmansk RegionRussia

Tne copper-nickel factory's emissions in the Murmansk region,Russia,led to the degradanon of plant cover and topsoil with the subsequent formation of industrial barrens.In this study,the industrial barrens were remediated by means of Technosol engineering,when grasses were sown on the two different types of mining wastes (carbonatite and serpentinite-magnesite) covered by hydroponic vermiculite.The serpentinite-magnesite waste was significantly different from the carbonatite waste in the content of silicon (Si) and manganese (Mn),pH,and texture.Both wastes had an alkaline pH level and high content of calcium (Ca) and magnesium (Mg).The vegetation and Technosol properties at the remediated sites were analyzed in 2017 and compared to the initial state (2010 year) to assess the efficiency of the long-term remediation.The quality and sustainability of Technosols based on the serpentinite-magnesite wastes were substantially higher compared to the carbonatite-based Technosol.Biomass and a projective cover of the grass community depended on Si content in the original mining waste and were found to be higher in the serpentinite-magnesite Technosol.The content of organic carbon and its fractions,microbial biomass and basal respiration after seven years of Technosol evolution was comparable to natural values.These parameters were directly related to plant cover state and were inversely proportional to copper (Cu) content in Technosol.The Technosol development led to the reduction of nickel (Ni) and Cu migration in soil-plant ecosystems due to neutralization and adsorption properties of mining wastes and phytostabilization by underground parts of grass communities.The Technosol development in its early stage of pedogenesis indicates the efficiency of applied remediation technology to the degraded acidic soil under the conditions of industrial atmospheric pollution.

关键词： Industrial barrens Metals Phytostabilization Soil organic carbon Basal respiration Pedogenesis

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Bv(RI )c photometric study of three variable PMS stars in the field of v733 Cephei

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Research in Astronomy and Astrophysics 2020年第12期20卷 221-228页

作者： Sunay Ibryamov Evgeni Semkov Stoyanka Peneva kristina Gocheva Department of Physics and Astronomy University of Shumen115Universitetska Str.9700 ShumenBulgaria Institute of Astronomy and National Astronomical Observatory Bulgarian Academy of Sciences72Tsarigradsko Shose Blvd.1784 SofiaBulgaria

This paper reports results from the first long-term Bv(RI)c photometric CCD observations of three variable pre-main-sequence stars collected during the period from February 2007 to January 2020. The investigated stars are located in the field of the PMS star v733 Cep within the Cepheus OB3 association. All stars from our study show rapid photometric variability in all-optical passbands. In this paper, we describe and discuss the photometric behavior of these stars and the possible reasons for their variability. In the light variation of two of the stars, we found periodicity.

关键词： stars:pre-main sequence stars:variables:T Tauri,Herbig Ae/Be techniques:photometric methods:observational,data analysis stars:individual(2MASS J22534654+6234582,2MASS J22533629+6231446,2MASS J22531578+6235262)

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Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

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Cellular & Molecular Immunology 2011年第4期8卷 296-304页

作者： Cecilia Carnrot Kajsa E Prokopec kristina Rasbo Mikael CI Karlsson Sandra Kleinau Department of Cell and Molecular Biology Uppsala UniversityUppsalaSweden Department of Medicine Unit of Clinical Allergy ResearchThe Karolinska InstituteSolnaSweden

Antibodies against type II collagen(CII)are essential for development of collagen-induced arthritis(CIA),but how and where the B-cell response to CII is initiated is not fully known.We show here that naive DBA/1 mice display naturally reactive IgM and IgG anti-CII producing B cells prior to immunization.The CII-reactive B cells were observed in the spleen and recognized as marginal zone(MZ)B cells.After CII immunization,CII-specific B cells expanded rapidly in the spleen,in contrast to the lymph nodes,with the initial response derived from MZ B cells and later by follicular(FO)B cells.This was evident despite that the MZ B cells were subject to stringent tolerance mechanisms by having a greater Fc gamma receptor IIb expression than the FO B cells.Further,the MZ B cells migrated to the FO areas upon immunization,possibly providing antigen and activating FO T cells and subsequently FO B cells.Thus,around CIA onset increased numbers of IgG anti-CII producing FO B cells was seen in the spleen,which was dominated by IgG2a-and IgG2b-positive cells.These data demonstrate that CII-reactive MZ B cells are present before and expand after CII immunization,suggesting an initiating role of MZ B cells in the development of CIA.

关键词： arthritis B cells collagen type II ELISpot marginal zone mice

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Retrospective review of total neoadjuvant therapy

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 857-865页

作者： Laila Babar veli Bakalov Stephen Abel Obaid Ashraf Gene Grant Finley Moses S Raj kristina Lundeen Dulabh K Monga Alexander v Kirichenko Rodney E Wegner Department of Internal Medicine Allegheny General HospitalPittsburghPA 15212United States Department of Radiation Oncology Allegheny General HospitalPittsburghPA 15212United States Department of Medical Oncology Allegheny General HospitalPittsburghPA 15212United States

BACKGROUND Neoadjuvant chemoradiotherapy(nCRT)followed by resection and postoperative multi-agent chemotherapy(maChT)is the standard of care for locally advanced rectal cancer.Using this approach,maChT administration can be delayed for several months,leading to concern for distant metastases.To counteract this,a novel treatment approach known as total neoadjuvant therapy(TNT)has gained popularity,in which patients receive both maChT and nCRT prior to resection.We utilized the National Cancer Database to examine temporal trends in TNT usage,and any potential effect on survival.AIM To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation.METHODS We queried the National Cancer Database for patients with locally advanced rectal cancer,Stage II-III,from 2004-2015 treated with nCRT or TNT.TNT was defined as maChT initiated≥90 d prior to nCRT initiation.Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival,with logrank statistics to assess significance.Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias.RESULTS We identified 9066 eligible patients,with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT,respectively.Nodal involvement,stage III disease,and treatment in recent years were predictive of TNT use.There was greater use of TNT with more advanced stage,specifically>1 node involved(odds ratio[OR]=2.88,95%confidence interval[CI]:2.11-3.93,Pvant chemoradiation arms had a similar 5-year survival at 76%and 78%respectively.Multivariable analysis with propensity score demonstrated that increased age,high comorbidity s

关键词： Total neoadjuvant therapy Neoadjuvant chemoradiation Multi-agent chemotherapy Locally advanced rectal cancer National cancer database Colorectal cancer Retrospective review Gastrointestinal oncology Temporal trends Surgical excision

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

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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 system.Upon 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 antigen.In this paper,the curvature-dependence of the interaction between IgG and C1q is studied by surface plasmon resonance and quartz crystal microbalance.IgG 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 investigated.Nanoparticles 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 resonance.Interestingly antigen-bound IgG at the curved surface of nanoparticles showed 5.6 times lower binding of C1q compared to at matched flat surfaces.There was no significant difference between the binding at 100 and 200 nm polystyrene particles.These 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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Are neonatal morbidities associated with no prenatal care different from those associated with inadequate prenatal care?

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Open Journal of Obstetrics and Gynecology 2012年第2期2卷 89-97页

作者： Ekwutosi M. Okoroh Dean v. Coonrod kristina Chapple David Drachman Consultant 9239 E. Desert View Scottsdale USA Department of Obstetrics Gynecology & Women’s Health Maricopa Integrated Health System and University of Arizona College of Medicine Phoenix USA Department of Research Maricopa Integrated Health System Phoenix USA Division of Blood Disorders National Center for Birth Defects and Developmental Disorders Atlanta USA

Objective: Compare neonatal morbidities in women with no prenatal care, and women with inadequate prenatal care, to those with adequate prenatal care. Methods: Retrospective cohort study of neonatal morbidities of 3 exposure groups. Group 1: No prenatal care;Group 2: Inadequate prenatal care;Group 3: Intermediate/adequate prenatal care. Results: 2.5%, 23.3% and 74.1% of subjects (N = 264,138) were in Groups 1, 2 and 3 respectively. Severe neonatal morbidity was more common in Group 1, followed by Group 2, and least common in Group 3. After controlling for gestational age and birth weight, most of these differences were attenuated and not significant except for the following Group 1 vs Group 3 comparisons: meconium aspiration, odds ratio (OR) 2.15 and 95% confidence interval (CI) 1.39 - 3.33;suspected sepsis, OR 1.30 and CI 1.13 - 1.49;proven viral sepsis, OR 2.23 and CI 1.24 - 4.00. Conclusions: Severe neonatal morbidity was most common in those with no prenatal care followed by those with inadequate prenatal care. For most neonatal morbidities, this could largely be explained by gestational age and birth weight differences, but for some neonatal morbidities (meconium aspirations, viral sepsis and dysmorphic features) the impact of no prenatal care persisted after adjustment for these factors.

关键词： Prenatal Care Neonatal Outcomes Retrospective Cohort Study

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Understanding celiac disease monitoring patterns and outcomes after diagnosis:A multinational,retrospective chart review study

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World Journal of Gastroenterology 2021年第20期27卷 2603-2614页

作者： Knut EA Lundin Ciaran P Kelly David S Sanders kristina Chen Sheena Kayaniyil Sisi Wang Rajvi J Wani Caitlin Barrett Shakira Yoosuf Ellen S Pettersen Robert Sambrook Daniel A Leffler K.G.Jebsen Coeliac Disease Research Centre University of OsloOslo 0450Norway Department of Gastroenterology Oslo University Hospital RikshospitaletOslo 0372Norway Celiac Center Beth Israel Deaconess Medical Center Celiac Research Program Harvard Medical SchoolBostonMA 02115United States Royal Hallamshire Hospital University of SheffieldSheffield S102TNUnited Kingdom Takeda Pharmaceuticals International Co. CambridgeMA 02139United States Real World Evidence Strategy and Analytics ICON plc.TorontoON L7N 3G2Canada Real World Evidence Strategy and Analytics ICON plc.VancouverBC V6B 1P1Canada

BACKGROUND Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease.AIM To understand patterns of follow-up and management of patients with celiac disease,and to characterize symptoms and villous atrophy after diagnosis.METHODS A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease.Three gastroenterology referral centers,with substantial expertise in celiac disease,participated in the United Kingdom,United States,and Norway.Demographic and clinical data were collected from medical charts.Descriptive analyses were conducted on patients with biopsyconfirmed celiac disease,diagnosed between 2008 and 2012,with at least one follow-up visit before December 31,2017.Patient demographic and clinical characteristics,biopsy/serology tests and results,symptoms,and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period(i.e.,before the study end date of December 31,2017).RESULTS A total of 300 patients were included in this study[72%female;mean age at diagnosis:38.9 years,standard deviation(SD)17.2].Patients were followed-up for a mean of 29.9 mo(SD 22.1)and there were,on average,three follow-up visits per patient during the study period.Over two-thirds(68.4%)of patients were recorded as having ongoing gastrointestinal symptoms and 11.0%had ongoing symptoms and enteropathy during follow-up.Approximately 80%of patients were referred to a dietician at least once during the follow-up period.Half(50.0%)of the patients underwent at least one follow-up duodenal biopsy and 36.6%had continued villous atrophy.Patterns of monitoring varied between sites.Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration.CONCLUSION This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

关键词： Celiac disease Outcomes research Endoscopy Real-world General practice villous atrophy

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