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Proteolytic-antiproteolytic balance and its regulation in carcinogenesis

World Journal of Gastroenterology 2005年第9期11卷 1251-1266页

作者： elzbieta Skrzydlewska Mariola Sulkowska Mariusz Koda Stanislaw Sulkowski Department Department of Pathology

Cancer development is essentially a tissue remodeling process in which normal tissue is substituted with cancer tissue. A crucial role in this process is attributed to proteolytic degradation of the extracellular matrix (ECM). Degradation of ECM is initiated by proteases, secreted by different cell types, participating in tumor cell invasion and increased expression or activity of every known class of proteases (metallo-, serine-, aspartyl-, and cysteine) has been linked to malignancy and invasion of tumor cells. Proteolytic enzymes can act directly by degrading ECM or indirectly by activating other proteases, which then degrade the ECM. They act in a determined order, resulting from the order of their activation. When proteases exert their action on other proteases, the end result is a cascade leading to proteolysis. Presumable order of events in this complicated cascade is that aspartyl protease (cathepsin D) activates cysteine proteases (e.g. cathepsin B) that can activate pro-uPA. Then active uPA can convert plasminogen into plasmin. Cathepsin B as well as plasmin are capable of degrading several components of tumor stroma and may activate zymogens of matrix metalloproteinases, the main family of ECM degrading proteases. The activities of these proteases are regulated by a complex array of activators, inhibitors and cellular receptors. In physiological conditions the balance exists between proteases and their inhibitors. Proteolytic-antiproteolytic balance may be of major significance in the cancer development. One of the reasons for such a situation is enhanced generation of free radicals observed in many pathological states. Free radicals react with main cellular components like proteins and lipids and in this way modify proteolytic-antiproteolytic balance and enable penetration damaging cellular membrane. All these lead to enhancement of proteolysis and destruction of ECM proteins and in consequence to invasion and metastasis.

关键词： Proteases Protease inhibitors Reactive oxygen species

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Histological outcome of chronic hepatitis B in children treated with interferon alpha

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World Journal of Gastroenterology 2005年第45期11卷 7179-7182页

作者： Sobaniec-Lotowska Maria elzbieta Lebensztejn Dariusz Marek Department of Clinical Pathomorphology Ⅲrd Department of Pediatrics

AIM： To evaluate the effect of interferon alpha （IFN-α） treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients. METHODS： Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig, Ishak et al., and IETAVIR （only fibrosis stage） before and 12 mo after IFN-α treatment termination in 93 children aged 2-16 years with chronic hepatitis B. RESULTS： None of the three numerical scoring systems for liver fibrosis showed statistically significant differences in liver fibrosis, while evolution of inflammatory activity revealed statistically significant improvement in the whole group of children with chronic hepatitis B treated with IFN-α and in responders. Significantly positive correlations were found between fibrosis stage and inflammation grade in the respective scoring systems. CONCLUSION： Treatment with IFN-α did not improve histological fibrosis but decreased inflammatory activity in children with chronic hepatitis B. The three semiquantitative scoring systems seem to be comparable in the estimation of the inflammation grade and fibrosis stage in this group of children.

关键词： Children Chronic hepatitis B Interferonalpha Fibrosis stage, Inflammation grade Semiquantitative scoring systems

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Ultrastructure of Kupffer cells and hepatocytes in the Dubin-Johnson syndrome:A case report

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World Journal of Gastroenterology 2006年第6期12卷 987-989页

作者： Maria elzbieta Sobaniec-Lotowska Dariusz Marek Lebensztein Department of Clinical Pathomorphology Medical University of Bialystok Poland 3rd Department of Pediatrics Medical University of Bialystok Poland

Ultrastructure of Kupffer cells and hepatocytes in liver bioptate was evaluated in a 17-year-old boy with Dubin -Johnson syndrome （D.1S）. The liver tissue obtained by needle biopsy was fixed in glutaraldehyde and paraformaldehyde and routinely processed for electron microscopic analysis. The ultrastructural examinations of liver bioptate revealed the accumulation of membranebound, electron-dense lysosomal granules within the cytoplasm of hepatocytes, characteristic of D.1S. They were located mainly in the vicinity of the biliary pole, and preferentially in the centrilobular region that corresponded to the pigment deposits seen under light microscope. The presence of the granules was accompanied by dilated elements of the granular endoplasmic reticulum and paracrystalline mitochondrial inclusions as well as dilation of the bile canaliculi. The changes in hepatocytes coexisted with marked stimulation and enhanced phagocytic activity of Kupffer cells. This was manifested in the accumulation of pigment deposits within their cytoplasm that corresponded to those observed in hepatocytes. Hyperactive pericentral Kupffer cells which are involved in the response to pigmentary material originating from disintegrated hepatocytes may play an essential role in the development of DJS.

关键词： Liver biopsy Electron microscopic study Lysosomal granules Functional hyperbilirubinemia Dubin-Johnson syndrome

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Impact of cold on the immune system of burying beetle, Nicrophorus vespilloides （Coleoptera： Silphidae）

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Insect Science 2017年第3期24卷 443-454页

作者： Arkadiusz Urbanski elzbieta Czarniewska Edward Baraniak Grzegorz Rosinski Department of Systematic Zoology Department of Animal Physiology and Development Faculty of Biology Adam Mickiewicz University Poznan Poland

Insect overwintering is one of the most astonishing phases of the insect life cycle. Despite vast amounts of knowledge available about the physiological mechanisms of this phenomenon, the impact of stress factors on insect immune system functioning during the winter is still unknown. The aim of this study is to analyze how low temperatures influence the immune system of the beetle Nic＇rophorus vespilloides. The results show that the beetle＇s immune system is differently modulated by cold induced in laboratory settings than that which occurs in natural conditions, Among beetles cultured in conditions similar to summer, low temperatures, did not influence the number of circulating haemocytes, phenoloxidase activity, haemocytes morphology, and percentage ratio of haemocyte types. In these beetles, differences were noted only in the ability of haemocytes to perform phagocytosis. Individuals acclimated in natural conditions in autumn had a higher level of humoral response and a different percentage ratio of haemocyte types. During the winter period, the number of haemocytes in the beetles decreased, but the percentage ratio of phagocytic haemocytes increased. Furthermore, we noted an increase of phenoloxidase activity. Our study also showed mitotic divisions ofhaemocytes in haemolymph collected from burying beetles after cold exposure and from burying beetles collected from natural conditions during autumn and winter. Differences in response to low temperatures in laboratory conditions and the natural environment suggest that the simultaneous presence of other stress factors during winter such as desiccation and starvation have a significant influence on the activity of burying beetle＇s immune system.

关键词： burying beetles cold immune system overwintering phagocytosisphenoloxidase

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The long-term immunological effects of alloferon and its analogues in the mealworm Tenebrio mofitor

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Insect Science 2018年第3期25卷 429-438页

作者： elzbieta Czarniewska Arkadiusz Urbanski Szymon Chowanski Mariola Kuczer Department of Animal Physiology and Development Adam Mickiewicz University Umultowska 89 61-614 Poznan Poland Faculty of Chemistry Wroclaw University Joliot-Curie 14 50-383 Wroctaw Poland

The subject of this article is a search for the long-term immunological effects of alloferon and 3 structural analogues of alloferon, which were earlier characterized by the highest pro-apoptotic activity in Tenebrio molitor. The differences in the actions of these peptides on immune response were observed. Alloferon increased nodulation and significantly phenoloxidase activity in the hemolymph of experimentally infected T. molitor. However, [Phe（p-NH2）^1 ]- and [Phe（p-OMe） ^1 ]-alloferon strongly inhibited cellular and humoral defense of the mealworm against Staphylococcus aureus infection. One day after injection of these peptides, the specific biochemical and morphological hallmarks of apoptosis in bacteria-challenged hemocytes were visible; in contrast, 3 days after peptides injection in all hemocytes, caspase activation was not observed. However, these new, circulating hemocytes differed from the control and the peptide-untreated bacteria-challenged hemocytes. They had an increased adhesion that led to a separation of viable, anucleated fragments of hemocytes that retain the ability to adhere and to form long filopodia. The peptide-induced separation ofhemocyte fragments may resemble the formation ofplatelets in mammals and perhaps play a role in sealing wounds in insects. The results of in vivo studies may suggest a long half-life of studied peptides in the hemolymph of mealworm. Moreover, we showed the importance of the N-terminal histidine residues at position one of the alloferon molecule for its immunological properties in insects. The results obtained here show that alloferon plays pleiotropic functions in insects.

关键词： alloferon analogue hemocyte's apoptosis immune response nodulation phenoloxidase activity

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Drosophila melanogaster as a model system of aluminum toxicity and aging

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Insect Science 2014年第2期21卷 189-202页

作者： Ewelina Kijak Ezio Rosato Katarzyna Knapczyk elzbieta Pyza Department of Cell Biology and Imaging Institute of Zoology Jagiellonian University Krakow Poland Department of Genetics University of Leicester Leicester LE1 7RH United Kingdom

The aim of this study was to investigate the toxic effects of aluminum （A1） on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly＇s development, life span, and circadian rhythm in rest and activity. Flies were exposed to aluminum in concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on control medium. Moreover, the life span of insects exposed to aluminum containing 40, 120, or 240 mg/kg of A1 in the medium, only during their larval development, during the whole life cycle and only in their adult life was tested. To check if aluminum and aging cause changes in D. melanogaster behavior, the locomotor activity of flies at different ages was recorded. Results showed that aluminum is toxic in concentrations above 160 mg/kg in the rearing medium. Depending on A1 concentration and time of exposure, the life span of the flies was shortened. At intermediate concentrations （120 mg/kg）, however, A1 had a stimulating effect on males increasing their life span and level of locomotor activity. At higher concentration the aluminum exposure increased or decreased the level of locomotor activity ofD. melanogaster depending on age of flies. In addition, in the oldest insects reared on aluminum supplemented media and in mid-aged flies reared on the highest concentration of A1 the daily rhythm of activity was disrupted.

关键词： circadian rhythms development life-span locomotor activity rest/activity cycle survival

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Import Determinants of Organelle-Specific and Dual Targeting Peptides of Mitochondria and Chloroplasts in Arabidopsis thaliana

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Molecular Plant 2014年第1期7卷 121-136页

作者： Changrong Ge Erika Spanning elzbieta Glaser Ake Wieslander Department of Biochemistry and Biophysics Center for Biomembrane Research Stockholm University SE-106 91 Stockholm Sweden Medical Inflammation Research Department of Medical Biochemistry and Biophysics Karolinska Institute SE-171 77 Stockholm Sweden

Most of the mitochondrial and chloroplastic proteins are synthesized in the cytosol as precursor proteins carrying an N-terminal targeting peptide （TP） directing them specifically to a correct organelle. However, there is a group of proteins that are dually targeted to mitochondria and chloroplasts using an ambiguous N-terminal dual targeting peptide （dTP）. Here, we have investigated pattern properties of import determinants of organelle-specific TPs and dTPs combining mathematical multivariate data analysis （MVDA） with in vitro organellar import studies. We have used large datasets of mitochondrial and chloroplastic proteins found in organellar proteomes as well as manually selected data sets of experimentally confirmed organelle-specific TPs and dTPs from Arabidopsis thaliana. Two classes of organelle-specific TPs could be distinguished by MVDA and potential patterns or periodicity in the amino acid sequence contributing to the separation were revealed, dTPs were found to have intermediate sequence features between the organelle-specific TPs. Interestingly, introducing positively charged residues to the dTPs showed clustering towards the mitochondrial TPs in silico and resulted in inhibition of chloroplast, but not mitochondrial import in in vitro organellar import studies. These findings suggest that positive charges in the N-terminal region of TPs may function as an ＇avoidance signal＇ for the chloroplast import.

关键词： dual targeting ambiguous targeting signal mitochondria chloroplast protein import partial least square discriminant analysis Arabidopsis thaliana.

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Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

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Regenerative Biomaterials 2023年第1期10卷 218-248页

作者： Karolina Knap Konrad Kwiecien Katarzyna Reczynska-Kolman elzbieta Pamuła Department of Biomaterials and Composites Faculty of Materials Science and CeramicsAGH University of Science and Technology30-059 KrakowPoland

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary *** drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side *** the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a ***,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug *** summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural *** review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.

关键词： pulmonary therapies drug delivery systems to lungs microparticles inhalers dry powder inhalers

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Assessment of genetic effects on important breeding traits in reciprocal DH populations of winter oilseed rape (Brassica napus L.)

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Journal of Integrative Agriculture 2018年第1期17卷 76-85页

作者： Laurencja Szala Teresa Cegielska-Taras elzbieta Adamska Zygmunt Kaczmarek Plant Breeding and Acclimatization Institute National Research Institute Poznan 60-479 Poland Institute of Plant Genetics Polish Academy of Sciences Poznan 60-479 Poland

Here we present a study on the genetic effects of agronomic and seed quality traits in double haploid （DH） populations, which were developed by microspore culture from reciprocal F1 hybrids produced between cultivar Californium and DH W-15. Each of the populations consisted of 25 DH lines. The field experiments were conducted in a randomized complete block design with three replications during three growing seasons. Field observations were recorded on seed yield and its structure： the number of branches and pods per plant, the number of seeds per pod, the 1 000-seed weight, the content of fat in the seeds, and three unsaturated fatty acids （oleic, linoleic, linolenic） in the seed oil. In order to investigate the influence of cross direction on the studied traits, parental effects were evaluated on the basis of differences between reciprocal DH populations. The maternal effect was revealed on the number of seeds per pod and the effect of the paternal form on linolenic acid content. The occurrence of transgression effects also depended on the direction of crossing and this was particularly noticeable in terms of the number of seeds per pod. The use of multivariate statistical methods allowed for the simultaneous characterization and grouping of tested lines in terms of several traits. Graphic images of the distribution of DH lines in the space of the two first canonical variates showed a great variation between the two reciprocal populations, both in terms of yield and its components, as well as fat and those unsaturated fatty acids.

关键词： DH line reciprocal cross oilseed rape multivariate analysis transgression

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Determinants of disease-specific knowledge among children with inflammatory bowel disease and their parents:A multicentre study

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World Journal of Gastroenterology 2021年第27期27卷 4468-4480页

作者： Kinga Kowalska-Duplaga Anita Gawlik-Scislo elzbieta Krzesiek elzbieta Jarocka-Cyrta IzabellaŁazowska-Przeorek Mariusz Duplaga Aleksandra Banaszkiewicz Department of Pediatrics Gastroenterology and NutritionJagiellonian University Medical CollegeKraków 30-663Poland Children's Hospital of the Medical University of Warsaw Medical University of WarsawWarsaw 02-091Poland Department of Pediatrics Gastroenterology and NutritionWroclaw Medical UniversityWroclaw 50-369Poland Department of Pediatrics University of Warmia and MazuryOlsztyn 10-561Poland Department of Pediatric Gastroenterology and Nutrition Medical University of WarsawWarsaw 02-091Poland Department of Health Promotion and e-Health Jagiellonian University Medical CollegeKraków 31-066Poland

BACKGROUND Disease knowledge is associated with increased treatment compliance and improvement of symptoms in inflammatory bowel disease(IBD).IBD-knowledge inventory device(IBD-KID)was developed and validated specifically as a tool to measure disease-related knowledge in children with IBD and their *** To prospectively assess the determinants of disease-related knowledge regarding paediatric IBD patients and their parents,using the *** A questionnaire-based survey was carried out in paediatric patients and their *** determinants of patients’and parents’IBD-KID scores were assessed according to hierarchical linear regression *** The study group consisted of 269 IBD patients and 298 *** patients’mean(standard deviation,SD)IBD-KID score was 10.87(±3.97),while the parents’was 11.95(±3.97).Both groups exhibited poor knowledge of the side effects of steroid therapy,the role of surgical treatment in IBD,dietary restrictions and the risks associated with the use of herbal *** patients’IBD-KID scores were statistically associated with patient sex[B coefficient(standard error,SE)=1.03(0.44),P=0.021]and patient age[B(SE)=0.03(0.01),P<0.001].The parents’IBD-KID scores were significantly related to patient age[B(SE)=0.02(0.01),P=0.003],and treatment with immunosuppressive agent[B(SE)=1.85(0.48),P<0.001].The final models explained 26.9%of the variance of patients’IBD-KID scores and 18.5%of the variance of parents’*** The variables originating from parents’knowledge were significantly associated with patients’IBD-KID *** study results indicate the need to implement better education programmes for patients and parents.

关键词： Crohn’s disease Inflammatory bowel disease-knowledge inventory device Knowledge Parents Ulcerative colitis

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