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Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Protein & Cell 2014年第8期5卷 569-579页

作者： Jie Na Duncan Baker Jing Zhang Peter W. Andrews ivana Barbaric School of Medicine Tsinghua University Beijing 100084 China Sheffield Diagnostic Genetic Services Sheffield Children's Hospital Sheffield S10 2TH UK Centre for Stem Cell Biology Department of Biomedical Science The University of Sheffield Sheffield S10 2TN UK

Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.

关键词： human pluripotent stem cells (hPSCs),culture adaptation aneuploidy cancer genetic changes

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Melanoma in the ampulla of Vater

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Hepatobiliary & Pancreatic Diseases International 2013年第1期12卷 106-108页

作者： Antonia Bendic Merica Glavina Durdov Radoslav Stipic ivana Karaman Department of Pathology Forensic Medicine and CytologyClinical Hospital Center SplitUniversity School of MedicineSpinciceva 1Split 21000Croatia Department of Abdominal Surgery Clinical Hospital Center SplitUniversity School of MedicineSpinciceva 1Split 21000Croatia

BACKGROUND:The most common tumors in the ampulla of Vater are *** malignant melanoma usually occurs on the skin,it can also arise in the gastrointestinal and biliary ***:We present a case of a 52-year-old,previously healthy man who presented with painless ***:Clinical examination revealed dilated intrahepatic and extrahepatic bile ducts and pancreatic duct due to the obstructive mass in the ampulla of *** patient underwent pancreaticoduodenectomy and histopathological diagnosis of the resected tumor mass was malignant *** clinical examination was preformed,but no other primary or metastatic site of melanoma could be *** the next few months,the patient developed multiple liver metastases and ***:An isolated amelanotic lesion in the ampulla of Vater can be a potential diagnostic pitfall,especially in patients who have had melanoma.

关键词： malignant melanoma ampulla of Vater biliary tract

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Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols

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Asian Journal of Andrology 2010年第6期12卷 819-826页

作者： Rossella.Giuliani ivana Antonucci Isabella Torrente Paola Grammatico Giandomenico Palka Liborio Stuppia Department of Clinical Sciences and Bioimages ＇G. d＇Annunzio ＇University Chieti-Pescara 66013 Italy Department of Biomedical Sciences ＇G. d＇Annunzio＇ University Chieti-Pescara 66013 Italy IRCCS CSS-Mendel Institute Rome 00198 Italy Medical Genetics Laboratory Experimental Medicine Department Sapienza S. Camillo-Forlanini Hospital Universityof Rome Rome 00152 Italy Human Genetic Division Pescara Hospital Pescara 65100 Italy I.G.M. CNR c/o IOR Bologna 40136 Italy

Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach：（i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.

关键词： congenital bilateral absence of vas deferens cystic fibrosis transmembrane conductance regulator male infertility

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Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity

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Cellular & Molecular Immunology 2022年第2期19卷 260-275页

作者： Elena Hernández-García Francisco J.Cueto Emma C.L.Cook Ana Redondo-Urzainqui Sara Charro-Zanca Iñaki Robles-Vera Ruth Conde-Garrosa ivana Nikolić Guadalupe Sabio David Sancho Salvador Iborra Department of Immunology Ophthalmology and ENTSchool of MedicineUniversidad Complutense de MadridMadrid 28040Spain Centro Nacional de Investigaciones Cardiovasculares(CNIC) Madrid 28029Spain

Conventional dendritic cells(cDCs)scan and integrate environmental cues in almost every tissue,including exogenous metabolic *** cDCs are critical in maintaining immune balance,their role in preserving energy homeostasis is ***,we showed that Batf3-deficient mice lacking conventional type 1 DCs(cDC1s)had increased body weight and adiposity during *** led to impaired energy expenditure and glucose tolerance,insulin resistance,dyslipidemia,and liver ***1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+invariant NKT(iNKT)***,among antigen-presenting cells,cDC1s exhibited notable induction of IFN-γproduction by iNKT cells,which plays a metabolically protective role in lean adipose ***3L treatment,which expands the dendritic cell(DC)compartment,mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent *** effect was partially mediated by NK1.1+*** results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.

关键词： Dendritic Cells NKT Obesity ageing FLT3L

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Allergen specifi c sublingual immunotherapy in children with asthma and allergic rhinitis

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世界儿科杂志:英文版 2016年第3期12卷 283-290页

作者： ivana Duric-Filipovic Marco Caminati Gordana Kostic Dorde Filipovic Zorica Zivkovic Faculty of Medical Science Kragujevac Department of ImmunologySvetozara Markovica 6934000 KragujevacSerbia Unita di Allergologia Centro Regionale di riferimento per la prevenzione la diagnosi e la terapia delle malattie allergiche Ospedale Universitario Borgo TrentoPiazzale Stefani 1VeronaItaly Children's Hospital Clinical Centre KragujevacZmaj Jovina 3034000 KragujevacSerbia Institution for Emergency Medical Care Bulevar Fransa Depera 511000 BelgradeSerbia Children's Hospital for Lung Diseases and Tuberculosis Medical Center"Dr Dragisa Misovic"Heroja Mihajla Tepica 111000 BelgradeSerbia

Background:The incidence of asthma and allergic rhinitis(AR)is significantly increased,especially in younger *** treatment for children with asthma and allergic rhinitis include allergen avoidance,standard pharmacotherapy,and *** standard pharmacotherapy is prescribed for symptoms,immunotherapy at present plays an important role in the treatment of allergic *** article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and *** sources:PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms"asthma","allergic rhinitis","children",and"immune therapy".Additional articles were identified by hand searching of the references in the initial ***:Numerous studies have shown that sublingual application of allergen specifi c immunotherapy(SLIT)is an adequate,safe and effi cient substitution to subcutaneous route of allergens administration(SCIT)in the treatment of IgE-mediated respiratory tract allergies in *** to the literature,better clinical efficacy is connected with the duration of treatment and mono sensitized ***:At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of *** reduces the symptoms of allergic diseases and the use of medicaments,and improves the quality of life of children with the diseases.

关键词： allergic asthma allergic rhinitis allergic sensitization immunotherapy

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Advances in diagnosis of chronic liver diseases in pediatric patients

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World Journal of Pediatrics 2018年第6期14卷 541-547页

作者： Lucija Ruzman ivana Mikolasevic Kristina Baraba Dekanic Sandra Milic Goran Palcevski Pediatric Clinic UHC RijekaIstarska 4351000 RijekaCroatia Department of Gastroenterology UHC RijekaRijekaCroatia Pediatric Clinic Department of GastroenterologyUHC RijekaRijekaCroatia

Background Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recog-nition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. Methods A non-systematic literature search was performed to summarize the current knowledge about transient elastog-raphy (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. Results Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. Conclusions TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.

关键词： Child Liver disease Liver stiffness Pediatric Transient elastography

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How can probiotic improve irritable bowel syndrome symptoms?

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World Journal of Gastrointestinal Surgery 2021年第9期13卷 923-940页

作者： Indira Benjak Horvat ivana Gobin Andrea Kresović Goran Hauser Department of Gastroenterology Varaždin General HospitalVaražin 42000Croatia Department of Microbiology and Parasitology Faculty of MedicineUniversity of RijekaRijeka 51000Croatia Department of Gastroenterology Clinical Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology Faculty of MedicineClinical Hospital Center RijekaUniversity of RijekaRijeka 51000Croatia

The onset and manifestations of irritable bowel syndrome(IBS)is associated with several factors,and the pathophysiology involves various central and peripheral *** studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with *** clinical trials have assessed the efficacy of probiotics for IBS with controversial *** clinical trials have suggested that probiotics can improve global IBS symptoms,while others only improve individual IBS symptoms,such as bloating scores and abdominal pain *** a few clinical trials have found no apparent effect of probiotics on IBS ***,probiotics appear to be safe for patients with ***,the question of which probiotics should be used for certain IBS subtypes remains *** everyday practice,the dose of the recommended probiotic remains questionable,as well as how long the probiotic should be used in *** use of probiotics in the M subtype and non-classified IBS is particularly problematic,in which combination therapy should be recommended due to the change in ***,new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.

关键词： Irritable bowel syndrome Obstipation Diarrhoea Abdominal pain Probiotic Prebiotic Symbiotic Microbiota

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Effi ciency of phosphorus accumulation by plankton,periphyton developed on submerged artifi cial substrata and metaphyton:in-situ observation in two shallow ponds

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Journal of Oceanology and Limnology 2021年第3期39卷 928-945页

作者： Marija PEĆIĆ Slađana POPOVIĆ Vesna MILUTINOVIĆ Gordana SUBAKOV SIMIĆ ivana TRBOJEVIĆ Dragana PREDOJEVIĆ Institute of Botany and Botanical Garden‘Jevremovac’ Faculty of BiologyUniversity of BelgradeBelgrade 11000Serbia Institute of Chemistry Technology and MetallurgyScientific InstitutionNational InstituteCenter for Ecology and TechnoeconomicsUniversity of BelgradeBelgrade 11000Serbia Institute of Public Health of Belgrade Belgrade 11000Serbia

Phosphorus overenrichment of shallow ponds prevailing in wetlands leads to their eutrophication causing the collapse of those vulnerable *** potential of phosphorus accumulation by periphyton developed on artificial substrata has been investigated in two shallow ponds(Bara?ka and?iroki Rit)in northwest Serbia and compared to the same ability of plankton and *** periphyton substrate carrier has been submerged from May to *** continuously(CS)and monthly developed(MS)periphyton were *** component of all investigated communities has been qualitatively *** accumulation of only 14.7 mg TP/m^(2) was recorded in three-month exposed periphyton *** exposed from July to August reached maximal 12.7 mg TP/m^(2).Plankton community that was characterized by more diverse and abundantly developed algal component was more effective in phosphorus accumulation(0.7 mg/g dry weight)in comparison with dominantly inorganic and diatom-dominated periphyton in Bara?*** conditions caused by recent revitalization(dredging organic matter and mud from pond basin—redigging)as well as rapid desiccation of?iroki Rit disabled making an unambiguous conclusion about the efficiency of phosphorus accumulation among different communities,but suggested slight potential of phosphorus harvesting by metaphyton in this *** to the shorter exposure time that brings the reduced risk of unpredictable changes in the ecosystem,as well as the considerable amount of accumulated phosphorus,large-scale application of one-month exposed periphyton developed on artificial substrates would be more advisable for phosphorus harvesting in nutrient affected shallow ponds.

关键词： periphyton phosphorus accumulation shallow ponds (phyto)plankton metaphyton eutrophication

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Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium

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Biomedical and Environmental Sciences 2021年第3期34卷 192-202页

作者： KULAS Jelena TUCOVIC Dina ZELJKOVIC Milica POPOVIC Dusanka POPOV ALEKSANDROV Aleksandra KATARANOVSKI Milena MIRKOV ivana Immunotoxicology Group Department of EcologyInstitute for Biological Research‘Sinisa Stankovic'-National Institute of Republic of SerbiaUniversity of Belgrade142 Bulevar despota StefanaBelgrade 11000Serbia

Objective To investigate involvement of the aryl hydrocarbon receptor(Ah R)in the immunomodulatory effects of cadmium(Cd).Methods The effect of Cd on Ah R activation(CYP1 A1 and CYP1 B1 m RNA expression)was examined in lung leukocytes of Cd-exposed rats(5 and 50 mg/L,30 d orally)and by in vitro leukocyte *** involvement of Ah R signaling in the effects of Cd on the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)lung leukocyte response was investigated in vitro using the receptor antagonist *** Cd increased CYP1 B1(in vivo and in vitro)and CYP1 A1(in vitro)m RNA,indicating Ah R involvement in the action of *** response to Cd,lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels,but decreased IL-1βproduction due to reduced *** Ah R antagonist CH-223191 abrogated the observed effects of Cd on the cytokine *** absence of Ah R reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high Ah R repressor m RNA *** Ah R signaling is involved in the lung leukocyte proinflammatory cytokine response to *** relevance of the Ah R to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.

关键词： Cadmium Lung leukocytes Aryl hydrocarbon receptor Cytokine(IL-6,TNF,IL-1β)response

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Thermal stability and microstructure development of cast and powder metallurgy produced Mg-Y-Zn alloy during heat treatment

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Journal of Magnesium and Alloys 2017年第2期5卷 173-180页

作者： Tomas Kekule Bohumil Smola Martin Vlach Hana Kudrnova Veronika Kodetova ivana Stulikova Charles University in Prague Faculty of Mathematics and PhysicsKe Karlovu 3Praha 212116Czech Republic

Response to isochronal annealing up to 440 ℃ of squeeze cast Mg–Y–Zn alloy and of the same alloy prepared by powder metallurgy(PM)and extruded at 280 ℃ was studied by resistivity and microhardness measurement,differential scanning calorimetry(DSC)and microstructure *** resistivity was measured at 77 K and microhardness was measured at room temperature after each annealing *** measurement was performed at various heating *** and scanning electron microscopy and optical microscopy revealed ribbons of long-period ordered structure(LPSO)18R and planar defects within grain *** high density of planar defects was found in grain interiors of the cast alloy with the grain size approximately 50μ*** pronounced subgrains were observed in the PM prepared *** phase particles decorate grain boundaries in this *** precipitation processes were detected in the cast alloy during repeated isochronal annealing up to 440 ℃,whereas only one significant process was revealed in the PM *** processes were identified as embedding of stacking faults by solutes,development and rearrangement(18R→14H)of LPSO phase and development of grain boundary particles.A coarsening of grain boundary particles rich in Y and Zn only proceeds in the PM *** energies of the precipitation processes were *** exhibits good thermal stability against annealing up to 360 ℃ in the PM alloy.

关键词： Mg-Y-Zn alloys Powder metallurgy Microhardness Microstructure development Electrical resistivity

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