Wyniki wyszukiwania - Biblioteka Nauki

1

Targeting BACE with small inhibitory nucleic acids - a future for Alzheimer's disease therapy?

100%

Nawrot B.

Acta Biochimica Polonica

|

2004

|

tom 51

|

nr 2

EN

ß-Secretase, a ß-site amyloid precursor protein (APP) cleaving enzyme (BACE), participates in the secretion of ß-amyloid peptides (Aß), the major components of the toxic amyloid plaques found in the brains of patients with Alzheimer's disease (AD). According to the amyloid hypothesis, accumulation of Aß is the primary influence driving AD pathogenesis. Lowering of Aß secretion can be achieved by decreasing BACE activity rather than by down-regulation of the APP substrate protein. Therefore, ß-secretase is a primary target for anti-amyloid therapeutic drug design. Several approaches have been undertaken to find an effective inhibitor of human ß-secretase activity, mostly in the field of peptidomimetic, non-cleavable substrate analogues. This review describes strategies targeting BACE mRNA recognition and its down-regulation based on the antisense action of small inhibitory nucleic acids (siNAs). These include antisense oligonucleotides, catalytic nucleic acids — ribozymes and deoxyribozymes — as well as small interfering RNAs (siRNAs). While antisense oligonucleotides were first used to identify an aspartyl protease with S-secretase activity, all the strategies now demonstrate that siNAs are able to inhibit BACE gene expression in a sequence-specific manner, measured both at the level of its mRNA and at the level of protein. Moreover, knock-down of BACE reduces the intra- and extracellular population of Aß40 and Aß42 peptides. An anti-amyloid effect of siNAs is observed in a wide spectrum of cell lines as well as in primary cortical neurons. Thus targeting BACE with small inhibitory nucleic acids may be beneficial for the treatment of Alzheimer’s disease and for future drug design.

2

Katalityczne DNA - deoksyrybozymy.

88%

Nawrot B.

Postępy Biochemii

|

2002

|

tom 48

|

nr 1

20-33

3

FHIT - białko supresowe zaangażowane w indukcję apoptozy i regulację cyklu komórkowego

63%

Pecherzewska R. , Nawrot B.

Postępy Biochemii

|

2009

|

tom 55

|

nr 1

4

Charakterystyka zjawiska interferencji RNA : podstawy strukturalne i właściwości siRNA

63%

Sierant M. , Nawrot B.

Wiadomości Chemiczne

|

2003

|

tom [Z] 57, 7-8

569--585

EN

RNA interference (RNAi) is a natural biological mechanism for sequence-specific posttranscriptional gene silencing triggered by double-stranded RNA (dsRNA) homologous to a silenced gene. RNAi is found in a wide range of eukaryotes including human cells. The natural function of RNAi appears to be protection of a genome against invasion by mobile genetic elements such as transposons and viruses which produce aberrant RNA or dsRNA in a host cell. Specific mRNA degradation prevents transposon and virus replication. The majority of studies on the molecular mechanism underlying RNAi activity has been conducted in vivo using Drosophila melanogaster and Caenorhabditis elegans or in selected mammalian cell cultures. It has been demonstrated that long dsRNA is cleaved to 21–23 nucleotide long fragments by RNase III-like nuclease Dicer. These short interfering RNAs (siRNAs) are essential sequence–specific mediators of RNAi. They are bound by RNAi specific enzymes of nuclease complex RISC that targets mRNA for degradation. In this complex siRNA recognises, binds and cleaves the target mRNA. Cleavage occurs in the middle of the mRNA region recognized by the siRNA. The second model, which has been proposed for RNAi to explain the mechanism by which siRNA direct target mRNA destruction, requires RNA-dependent RNA polymerase (RdRP) to convert the target mRNA into dsRNA. RdRP is hypothesized to use antisense strand of siRNA as a primer in mRNA templated synthesis of complementary chain RNA. The resulting dsRNA is proposed to be cleaved then by Dicer for generation of secondary siRNA. Short interfering RNAs can be synthesized chemicaly or by in vitro transcription with T7 RNA polymerase, or expressed from siRNA coding vectors in the cells. These 21-nt siRNA duplexes cause efficent inhibition of exogenous and endogenous genes expression in a sequence-specific manner. Detailed analysis of potential modifications, that can be introduced into siRNA strands shows, that chemical modifications of sense strand are tolerated without loss of RNAi activity. However, some modification of antisense strand of siRNA (especially in the middle of the chain as well as modification of the 5’end) completely abolish RNAi. These results indicate that two strands of siRNA have different function in RNAi. RNAi approach can be broadly used for analysis of gene functions, and, what is even more important, this phenomenon can be used for searching new agents for therapeutic applications.

5

RNAi w terapii

63%

Kubiak K. , Nawrot B.

Biotechnologia

|

2009

|

nr 1

132-151

6

Rybozymy w medycynie

63%

Antoszczyk S. , Nawrot B.

Biotechnologia

|

2003

|

nr 2

7

Krótkie interferujące RNA jako narzędzia do sekwencyjno-specyficznego wyciszania ekspresji genów

63%

Sierant M. , Nawrot B.

Biotechnologia

|

2003

|

nr 2

8

RNAi mediated silencing of cyclin-dependent kinases of G1 phase slows down the cell-cycle progression and reduces apoptosis

51%

Sierant M. , Piotrzkowska D. , Nawrot B.

Acta Neurobiologiae Experimentalis

|

2015

|

tom 75

|

nr 1

EN

One of the hypotheses on the origin of Alzheimer's disease (AD) stems from a close relation between a re-activation of a cell-cycle in post-mitotic neurons and a neural cells death observed in pathologically affected parts of AD brains. In the normal, healthy brain almost all neural cells are terminally differentiated and "locked" in the GO phase of the cell-cycle. For these cells, the consequence of the re-entry to the cell-cycle is targeting them towards cellular divisions and turning on the apoptotic pathway. We used an RNA interference (RNAi) methodology in neural cells to switch-off genes for two cyclin- dependent kinases 4 and 6 (cdk4, cdk6), which control the activation of the initial steps of the cell-cycle. As a result, some evidences are delivered that silencing these genes, which are expressed during cell proliferation but inhibited at mature neurons, prevents the stimulation of apoptotic pathways in the neural cells cultured in a oxidative stress conditions and may have a neuroprotective effect. We demonstrate that down-regulation of genes important in the G1 phase of the cell-cycle may play the protective function on the neuronal cells, and can be considered as the promising approach for the potential gene therapy of neurodegenerative diseases.

9

Deposition of particulate matter on tree and shrub leaves in a city and a clean site in Norway

51%

Saebo A. , Nawrot B. , Gawronski S.

Acta Physiologiae Plantarum

|

2009

|

tom 31

|

nr 1 Suppl.

10

Ocena znajomosci i przestrzegania zasad diety srodziemnomorskiej u pacjentow przychodni kardiologicznych

45%

Bogacka A. , Nawrot B. , Gryza M. , Balejko E. , Kucharska E.

Żywność Nauka Technologia Jakość

|

2008

|

tom 15

|

nr 2

128-139

PL

Celem pracy była ocena sposobu żywienia oraz znajomości i zastosowania zasad diety śródziemnomorskiej wśród pacjentów leczących się w przychodniach kardiologicznych na terenie Szczecina. Badania przeprowadzono wykorzystując metodę wywiadu 24-godzinnego. Grupę ankietowaną stanowili mężczyźni (67 osób) i kobiety (88 osób) powyżej 26 roku życia. Wyliczono zawartość i odsetek realizacji normy na składniki odżywcze i energię dostarczoną z posiłkami. Otrzymane wartości porównano z normami żywienia na poziomie bezpiecznym. Ponadto określono częstość spożycia produktów według piramidy zdrowego żywienia. Uwzględniono współczynniki strat związane z procesami technologicznymi i kulinarnymi. Posługiwano się programem „Dietetyk 2” i Excel. Ponadto oceniono wpływ żywienia na parametry biochemiczne krwi (stężenie cholesterolu całkowitego, frakcji HDL i LDL oraz triacylogliceroli). Badania wykazały, że znajomość i zastosowanie zasad diety śródziemnomorskiej wśród ankietowanych były niewielkie. Średnie stężenie cholesterolu całkowitego i frakcji LDL były podwyższone w stosunku do przyjętych norm. U znacznej liczby osób stwierdzono występowanie chorób dietozależnych i zaburzeń lipidowych. Wynikało to prawdopodobnie ze złych nawyków żywieniowych, a więc spożywania posiłków obfitujących w cukry proste i nasycone kwasy tłuszczowe, a ubogich w owoce i warzywa. W całodziennych racjach pokarmowych stwierdzono zbyt małą zawartość pieczywa ciemnego, mleka i jego przetworów, kaszy, ryżu co wiązało się z niedoborami witamin z grupy B, C, D oraz wapnia. Spożycie ryb również było małe. Ponadto w badanej grupie osób zaobserwowano niską aktywność fizyczną.

EN

The objective of this research was to evaluate dietary behaviours of the patients from cardiologic clinics in Szczecin and to estimate their knowledge of the Mediterranean diet principles. The research was conducted using a method of 24-hour anamnesis. The polled group consisted of men (67 persons) and women (88 persons) aged above 26 years. Referring to the regular meals eaten by the polled, three factors were computed: content of nutrients contained in their meals, percentage rate of realizing the relevant nourishment norm, and energy provided with their meals. The received values were compared with the safe levels of nutrients as indicated by the relevant norms on proper nourishment. Additionally, the frequency of consuming certain products by the polled, according to the pyramid of healthy diet, was determined. Coefficients of losses occurring owing to technological and culinary processing procedures were also included. A “Dietetyk 2” software and ‘Exel’ package were applied. Furthermore, the impact of the diet applied on the biochemical parameters of the patients’ blood (total cholesterol concentration, HDL and LDL fractions, as well as triacylglycerols) was estimated. The research proved that the knowledge and use of Mediterranean diet principles among the polled was little. Average concentration levels of total cholesterol and LDL fractions in their blood were increased compared to the generally approved norms. A considerable number of patients suffered from dietdepending diseases and lipid disorders. Quite probably, it resulted from their improper dietary behaviours, i.e. from the fact that they usually ate meals rich in monosaccharides and in saturated fatty acids, but poor in fruit and vegetables. According to the research results, it was also found that their meals contained too little amounts of dark bread, milk and milk products, cereals, and rice; thus, their daily meals provided too little amounts of vitamins from the B, C, and D groups, and of calcium per day. The level of fish consumption was low, too. Moreover, it was found that all the polled showed a low physical activity level.

11

Targetic BACE1 mRNA with chemically synthesized and plasmid coded siRNAs

45%

Sipa K. , Kazmierczak-Baranska J. , Goss W. , Nawrot B. , Strec W. J.

Acta Biochimica Polonica

|

2006

|

tom 53

|

nr Supplement 1

12

A mutational study of individual functional groups on the G6 base of the 10-23 deoxyribozyme core

38%

Nawrot B. , Widera K. , Wojcik M. , Rebowska B. , Goss W. , Mikolajczyk B. , Stec W. J.

Acta Biochimica Polonica

|

2006

|

tom 53

|

nr Supplement 1

13

Mapping of the function phosphate groups in the catalytic core of DNAzyme 10-23

38%

Nawrot B. , Winder K. , Wojcik M. , Rebowska B. , Goss W. , Stec W. J.

Acta Biochimica Polonica

|

2006

|

tom 53

|

nr Supplement 1

14

Studies on the oxidative damage of wobble 5-methylcarboxymethyl-2-thiouridine in transfer RNAs

38%

Sierant M. , Komar P. , Szewczyk R. , Dziergowska A. , Sochacka E. , Nawrot B.

Acta Biochimica Polonica

|

2018

|

tom 65

|

nr S2

15

Decrease of the somatostatin receptor subtype 3 (SSTR3) expression in gastric mucosa of patients with familiar gastric cancer and infected with Helicobacter pylori

32%

Peczek L. , Stec-Michalska K. , Krakowiak A. , Michalski B. , Chojnacki J. , Knopik-Dabrowicz A. , Glupinska G. , Nawrot B.

Acta Biochimica Polonica

|

2006

|

tom 53

|

nr Supplement 1

16

Thermodynamic characterization and functional studies of chemically modified siRNAs

26%

Sipa K.-A. , Kazmierczak-Branska J. , Sochacka E. , Janicka M. , Nowak G. , Sierant M. , Brzuska K. , Sobczak M. , Deka M. , Okruszek A. , Kierzek R. , Nawrot B.

Acta Biochimica Polonica

|

2007

|

tom 54

|

nr Supplement 4