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Importance of genetic polymorphisms in liver transplantation outcomes

World Journal of Gastroenterology 2020年第12期26卷 1273-1285页

作者： Tomislav Kelava petra Turcic Antonio Markotic Ana Ostojic Dino Sisl Anna Mrzljak Laboratory for Molecular Immunology Croatian Institute for Brain ResearchUniversity of ZagrebSchool of MedicineZagreb 10000Croatia Department of Pharmacology Faculty of Pharmacy and Biochemistry of University of ZagrebZagreb 10000Croatia Center for Clinical Pharmacology University Clinical Hospital MostarMostar 88000Bosnia and Herzegovina Department of Medicine Merkur University HospitalZagreb 10000Croatia Department of Medicine Merkur University HospitalSchool of MedicineUniversity of ZagrebZagreb 10000Croatia

Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival *** addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the *** of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant *** provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration *** studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration *** also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant ***,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these ***,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association *** wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.

关键词： Single nucleotide polymorphisms Liver transplantation Acute rejection Non-alcoholic fatty liver disease New-onset diabetes mellitus Hepatocellular carcinoma Tacrolimus

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All Roads Lead to Susceptibility: The Many Modes of Action of Fungal and Oomycete Intracellular Effectors

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Plant Communications 2020年第4期1卷 1-12页

作者： Qin He Hazel McLellan petra C.Boevink Paul R.J.Birch Key Laboratory of Horticultural Plant Biology(HZAU) Ministry of EducationKey Laboratory of Potato Biology and Biotechnology(HZAU)Ministry of Agriculture and Rural AffairsHuazhong Agricultural UniversityWuhanHubei 430070China Division of Plant Sciences School of Life SciencesUniversity of Dundee(at JHI)InvergowrieDundee DD25DAUK Cell and Molecular Sciences James Hutton InstituteInvergowrieDundee DD25DAUK These authors contributed equally to this article.

The ability to secrete effector proteins that can enter plant cells and manipulate host processes is a key determinant of what makes a successful plant ***,we review intracellular effectors from filamentous(fungal and oomycete)phytopathogens and the host proteins and processes that are targeted to promote *** cover contrasting virulence strategies and effector modes of *** pathogen effectors alter the fates of host proteins that they target,changing their stability,their activity,their location,and the protein partners with which they *** effectors inhibit target activity,whereas others enhance or utilize it,and some target multiple host *** discuss the emerging topic of effectors that target negative regulators of immunity or other plant proteins with activities that support *** also highlight the commonly targeted host proteins that are manipulated by effectors from multiple pathogens,including those representing different kingdoms of life.

关键词： effectors fungi oomycete immunity defense susceptibility factor

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Interferon-α response in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment

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World Journal of Gastroenterology 2007年第2期13卷 228-235页

作者： Shi-He Guan Mengji Lu petra Grünewald Michael Roggendorf Guido Gerken Joerg F Schlaak Department of Gastroenterology and Hcpatology University Hospital of Esscn Esscn Germany Institute of Virology University Hospital of Essen Essen Germany Department of Laboratory Medicine the first Affiliated Hospital of Anhui Medical University China

AIM：To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS： HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-α 2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes （ISGs）. In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS： Two genes （MxA, CigS） with completely abolished and 4 genes （IFITM1, -2, -3, and 6-16） with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes （IFITM1, 6-16）, the response to IFN-α could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Statl activation and ISGF3 formation after stimulation with IFN-α in HepG2.2.15 compared to HepG2 cells. CONCLUSION： These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expressionby reducing HBV gene expression and replication.

关键词： Hepatitis B IFN-α Gene expression Larnivudine

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Non-invasive prediction of persistent villous atrophy in celiac disease

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World Journal of Gastroenterology 2020年第26期26卷 3780-3791页

作者： Barbora Packova petra Kovalcikova Zdenek Pavlovsky Daniel Bartusek Jitka Prokesova Jiri Dolina Radek Kroupa Department of Gastroenterology and Internal Medicine University Hospital BrnoFaculty of MedicineMasaryk UniversityBrno 62500Czech Republic Institute of Biostatistics and Analyses Faculty of MedicineMasaryk UniversityBrno 62500Czech Republic Department of Pathology University Hospital BrnoFaculty of MedicineMasaryk UniversityBrno 62500Czech Republic Department of Radiology and Nuclear Medicine University Hospital BrnoFaculty of MedicineMasaryk UniversityBrno 62500Czech Republic

BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the ***,duodenal biopsy is the only way to evaluate mucosal healing,and noninvasive markers are *** elevation of anti-tissue transglutaminase antibodies(aTTG)is not an ideal predictor of persistent villous atrophy(VA).Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies(aDGP)and abdominal ultrasonography are *** To evaluate the ability of aTTG,aDGP,small bowel ultrasonography,and clinical and laboratory parameters in predicting persistent VA determined using *** Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy,levels of aTTG and aDGP,and underwent small bowel ultrasonography were included in this retrospective cohort *** evaluated the sensitivity,specificity,and positive and negative predictive values of aTTG,aDGP,small bowel ultrasonography,laboratory and clinical parameters to predict persistent VA.A receiver operating characteristic(ROC)curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy *** Complete data were available for 82 patients who were followed up over a period of four years(2014-2018).Among patients included in the analysis,women(67,81.7%)were predominant and the mean age at diagnosis was 33.8 *** biopsy revealed persistent VA in 19 patients(23.2%).The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50%and 85.7%,respectively,while the sensitivity and specificity of aDGP(using the diagnostic cutoff value)was 77.8%and 75%,*** of an optimal cutoff value using ROC analysis(13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA)increased the accuracy and reached 72.2%[95%confidence interval(CI):46.5-90.3]sensitivity and 90%(9

关键词： Celiac disease Villous atrophy Anti-tissue transglutaminase antibodies Antideamidated gliadin peptide antibodies Abdominal ultrasound Gluten-free diet

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Therapeutic drug monitoring in inflammatory bowel disease:The dawn of reactive monitoring

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World Journal of Gastroenterology 2021年第37期27卷 6231-6247页

作者： Farah Albader petra Anna Golovics Lorant Gonczi Talat Bessissow Waqqas Afif Peter Laszlo Lakatos Department of Internal Medicine McGill UniversityMontreal H3G1A4QuebecCanada Division of Gastroenterology Hungarian Defence ForcesMedical CentreBudapest H-1062Hungar Division of Gastroenterology McGill UniversityMontreal H3G 1A4QuebecCanada First Department of Medicine Semmelweis UniversityBudapest H-1083Hungary Division of Gastroenterology McGill University Health CentreMontreal H3G 1A4QuebecCanada

Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its *** drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution,there remains a proportion of patients that do not respond or lose response to *** drug monitoring(TDM)involves measuring levels of serum drug concentrations and anti-drug *** of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory *** was then introduced in IBD to rationalize primary non-response or secondary loss of response,given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment *** aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment *** review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations,in everyday practice.A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management,through an electronic search using PubMed and *** has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in *** a trend towards an association between clinical outcomes and drug concentrations,proactive TDM based strategies have not been shown to achieve clear benefit in long-term *** the clinical setting,TDM has proven to be useful in managing IBD patients,and its use in the reactive setting,as an additional tool to help manage patients with treatment failure,is being promoted as newer guidelines and consensus groups implement

关键词： Therapeutic drug monitoring Inflammatory bowel disease Biologic therapies Loss of response Reactive Proactive

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Influence of COM-peptides/proteins on the properties of flocs formed at different shear rates

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Journal of Environmental Sciences 2019年第6期31卷 116-127页

作者： Monika Filipenska petra Vasatova Lenka Pivokonska Lenka Cermakova andrea Gonzalez-Torres Rita K.Henderson Jana Naceradska Martin Pivokonsky Institute of Hydrodynamics of the Czech Academy of Sciences Institute for Environmental Studies Faculty of Science Charles University The bioMASS Lab School of Chemical Engineering The University of New South Wales

Coagulation followed by floc separation is a key process for the removal of algal organic matter(AOM) in water treatment. Besides optimizing coagulation parameters,knowledge of the properties of AOM-flocs is essential to maximizing AOM ***, the impact of AOM on the floc properties remains unclear. This study investigated how peptides/proteins derived from the cellular organic matter(COM) of the cyanobacterium Microcystis aeruginosa influenced the size, structure, and shape of flocs formed at different shear rates(G). Flocs formed by kaolinite, COM-peptides/proteins and a mixture of the same were studied, and the effect of intermolecular interactions between floc components on floc properties was assessed. The coagulation experiments were performed in a Taylor–Couette reactor, with aluminum(Al) or ferric sulphate(Fe) utilized as coagulants. Image analysis was performed to gauge floc size and obtain data on fractal dimension. It was found that floc properties were affected by the presence of the COM-peptides/proteins and the coagulant used. COM-peptides/proteins increased floc size and porosity and widened floc size distributions. The Fe coagulant produced larger and less compact flocs than Al coagulant. Moreover, the decrease in floc size that occurred in parallel with increase in shear rate was not smooth in progress. A rapid change for the kaolinite-coagulant suspension and two rapid changes for the suspensions containing COM were observed. These were attributed to various intermolecular interactions between floc components participating in coagulation at different G. Based on the results obtained, shear rates suitable for efficient separation of flocs containing COM were suggested.

关键词： Algal organic matter Floc size Coagulation Image analysis Water treatment

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Viewpoints of the target population regarding barriers and facilitators of colorectal cancer screening in the Czech Republic

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World Journal of Gastroenterology 2019年第9期25卷 1132-1141页

作者： Radek Kroupa Monika Ondrackova petra Kovalcikova Milan Dastych Tomas Pavlik Lumir Kunovsky Jiri Dolina Department of Gastroenterology and Internal Medicine University Hospital Brno and Faculty of Medicine Masaryk University Department of Hematology Oncology and Internal Medicine University Hospital Brno and Faculty of Medicine Masaryk University Institute of Biostatistics and Analyses Faculty of MedicineMasaryk University

BACKGROUND Public awareness of colorectal cancer(CRC) and uptake of CRC screening remain challenges. The viewpoints of the target population(asymptomatic individuals older than 50) regarding CRC screening information sources and the reasons for and against participation in CRC screening are not well known in the Czech Republic. This study aimed to acquire independent opinions from the target population independently on the health *** To investigate the viewpoints of the target population regarding the source of information for and barriers and facilitators of CRC *** A survey among relatives(aged 50 and older) of university students was conducted. Participants answered a questionnaire about sources of awareness regarding CRC screening, reasons for and against participation, and suggestions for improvements in CRC screening. The effect of certain variables on participation in CRC screening was *** Of 498 participants, 478(96%) respondents had some information about CRC screening and 375(75.3%) had participated in a CRC screening test. General practitioners(GPs)(n = 319, 64.1%) and traditional media(n = 166, 33.3%) were the most common information sources regarding CRC screening. A lack of interest or time and a fear of colonoscopy or positive results were reported as reasons for non-participation. Individuals aged > 60 years [adjusted odds ratio(aOR) = 2.30, 95% confidence interval(CI)(1.42-3.71), P = 0.001], females(aOR =1.95, 95%CI(1.26-3.01) P = 0.003), and relatives of CRC patients(aOR = 4.17,95%CI(1.82-9.58) P = 0.001) were more likely to participate in *** regarding screening provided by physicians-GPs:(aOR = 8.11,95%CI(4.90-13.41), P < 0.001) and other specialists(aOR = 4.19, 95%CI(1.87-9.38),P = 0.001) increased participation in screening. Respondents suggested that providing better explanations regarding screening procedures and equipment for stool capturing could improve CRC screening *** GPs

关键词： Colorectal cancer Screening Colonoscopy General practitioner Patient compliance Fecal occult blood test

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Agriculture and Water Sources Protection Zones in the Czech Republic

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Journal of Agricultural Science and Technology(A) 2012年第10期2卷 1155-1161页

作者： petra Oppeltova Mendel University in Brno Zemedelska 1 Brno 61300 Czech Republic

The area of interest is located in the South Moravia Region at the confluence of the Jihlava, Oslava and Rokytn^i rivers. Ivan^ice spring area comprises a series of hydrologic boreholes, it is the main water source for water supply of Ivan^ice and Rosice towns and provides water for 30,000 inhabitants. The risk analysis was created on the basis of water quality monitoring, hydrogeological assessment and terrain exploration and a revision of protection zones was proposed. The spring area is situated in nitrate vulnerable zones and recently nitrate concentrations have been decreasing. Water quality evaluation results： high concentration of manganese and iron, sometimes higher concentration of ammonium and COD. This area is intensively used for agriculture and it is necessary to make a compromise solution during protection zones proposal, The regime in protection zones can not affect manganese and iron concentration （their origin is in the natural geological environment）. Therefore, water treatment plant is in operation and its modernization is proposed. Furthermore, the paper deals with spring area intensification construction of a new hydrologic borehole, and managed and unmanaged infiltration of surface water. The proposal of protection zones revision consists of reduction to a 2nd level protection zone.

关键词： Water quality ground water source of drinking water good agricultural practice nitrate vulnerable zones CzechRepublic.

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Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

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World Journal of Diabetes 2020年第7期11卷 269-279页

作者： petra Grubić Rotkvić Maja Cigrovski Berković Nikola Bulj Luka Rotkvić Ivana Ćelap Department of Cardiology University Hospital10000 ZagrebCroatia Department of Endocrinology DiabetesMetabolism and Clinical PharmacologyUniversity HospitalZagreb 10000Croatia Department for Medicine of Sports and Exercise Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Cardiology University Hospital CentreZagreb 10000Croatia Department of Cardiology Magdalena Clinic for Cardiovascular DiseaseKrapinske Toplice 49217Croatia Department of Clinical Chemistry University Hospital CentreZagreb 10000Croatia

Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 *** other CVOT to date has shown any significant benefit on heart failure *** more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes ***,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic *** time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal *** are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange *** most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure *** the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.

关键词： Sodium-glucose cotransporter 2 inhibitors Heart failure Cardiovascular outcomes Diabetes mellitus Physiological mechanisms Pleiotropic effects

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A cop1 spa Mutant Deficient in COP1 and SPA Proteins Reveals Partial Co-Action of COP1 and SPA during Arabidopsis Post-Embryonic Development and Photomorphogenesis

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Molecular Plant 2015年第3期8卷 479-481页

作者： Natalia Ordonez-Herrera petra Fackendahl Xu Yu Sabine Schaefer Csaba Koncz Ute Hoecker Botanical Institute and Cluster of Excellence on Plant Sciences (CEPLAS) Biocenter University of Cologne Zülpicher Strasse 47b 50674 Cologne Germany Max Planck Institute for Plant Breeding Research Carl-von-Linné Weg 10 50829 Cologne Germany Institute of Plant Biology Biological Research Center of Hungarian Academy of Sciences Temesvari krt. 62 H-6726 Szeged Hungary

Dear Editor,The Arabidopsis CONSTITUTIVELY PHOTOMORPHOGENIC1/ SUPPRESSOR OF PHYA-105 （COP1/SPA） complex is a key repressor of light signaling that inhibits light responses in dark- ness. It acts as an E3 ubiquitin ligase, which ubiquitinates posi- tively acting light-signaling intermediates, mainly transcription factors, thereby targeting them for proteolytic degradation by the 26S proteasome. In the light, photoreceptors directly interact with the COP1/SPA complex, leading to its inactivation, which subsequently allows the target transcription factors to accumu- late and initiate vast reprogramming of gene expression （Huang et al., 2014）.

关键词： COP1 SPA 蛋白质拟南芥光形态建成胚胎发育突变体 26S蛋白酶体

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