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1
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Contributions of the Hfq protein to translation regulation by small noncoding RNAs binding to the mRNA coding sequence

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Wroblewska Z., Olejniczak M.
Acta Biochimica Polonica
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2016
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vol. 63
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issue 4
701-707
EN
The bacterial Sm-like protein Hfq affects the regulation of translation by small noncoding RNAs (sRNAs). In this way, Hfq participates in the cell adaptation to environmental stress, regulation of cellular metabolism, and bacterial virulence. The majority of known sRNAs bind complementary sequences in the 5'-untranslated mRNA regions. However, recent studies have shown that sRNAs can also target the mRNA coding sequence, even far downstream of the AUG start codon. In this review, we discuss how Hfq contributes to the translation regulation by those sRNAs which bind to the mRNA coding sequence.
2
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Poly (ADP-ribose) polymerase 1 expression in fibroblasts of Down syndrome subjects

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Salemi M., Barone C., Romano C., Romano C., Scavuzzo C., Salluzzo M., Tirolo C., Cantarella R., Ragalmuto A., Paola S., Bosco P.
Open Medicine
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2013
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vol. 8
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issue 6
762-765
EN
Down syndrome (DS) is the most common chromosomal disorder. It is featured by intellectual disability and is caused by trisomy 21. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Poly (ADP-ribose) polymerase 1 is a mediator of programmed-necrotic cell death and appears to be also involved in the apoptosis. The aim of the present work was to detect the intracellular distribution of PARP-1 protein using immunofluorescence techniques and the expression of PARP-1 mRNA in culture of fibroblasts of DS subjects. The analysis of the intracellular distribution of PARP-1 show a signal at the nuclear level in about 75 % of the cells of DS subjects with a slight uniformly fluorescent cytoplasm. In contrast, in about 65% of the analyzed fibroblasts of the normal subjects only a slight fluorescent was found. These observations have been confirmed by PARP-1 gene mRNA expression evaluation. The data obtained from this study strengthen the hypothesis that the over-expression of PARP-1 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS.
3
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Zakażenia wirusem brodawczaka ludzkiego – współczesne metody diagnostyczne

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Skrajna A., Maździarz A., Reinholz-Jaskólska M.
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2010
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vol. 8
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issue 1
40-46
EN
Human papillomavirus (HPV) belongs to the family of DNA viruses. Infection by HPV is associated with the development of benign or malignant lesions within mucosal membrane and skin of the genitals, anus, head and neck. Presence of the virus, particularly of the highly oncogenic variants in epithelial cells of uterine cervix directly influences the development of cervical cancer. In a considerable proportion of cases, HPV infections are asymptomatic and this is probably associated with lack of proliferation phase of viral life cycle, or may be transient, which greatly complicates early detection of the virus. Diagnostic techniques enabling diagnosis of HPV infection include: cytological exam (PAP smear), colposcopy, histological study, as well as increasingly sophisticated molecular techniques, enabling detection of viral DNA when other indices of infection are lacking. These techniques include Southern Blot, Dot Blot, in situ hybridization, polymerase chain reaction (PCR) and Hybrid Capture System I and II (HCI, HCII). Increasingly often authors refer to tests based on isolation of viral mRNA (PreTect HPV-Proofer test). These techniques detect integrated form of HPV, the so-called episomal form of the virus. In general opinion, the presence of HPV in this form is directly associated with progression of lesions developing as a result of this infection. While the PreTect HPV-Proofer test detects a smaller number of cases of HPV infection, its use enables selection of patients most at risk of developing cervical cancer.
PL
Wirus brodawczaka ludzkiego (HPV) należy do grupy DNA wirusów. Infekcje wirusem brodawczaka ludzkiego wiążą się z występowaniem łagodnych lub złośliwych zmian w obrębie błon śluzowych i skóry narządów płciowych, odbytu, jak również głowy i szyi. Obecność wirusa, szczególnie typów wysokoonkogennych, w komórkach nabłonka szyjki macicy bezpośrednio wpływa na rozwój raka szyjki macicy. Zakażenia HPV w dużym odsetku przebiegają bezobjawowo i jest to najprawdopodobniej związane z niewystąpieniem fazy proliferacyjnej cyklu życiowego wirusa, a także mają charakter przejściowy, co znacznie utrudnia wczesną identyfikację wirusa. Wśród metod diagnostycznych umożliwiających rozpoznanie zakażenia wymienia się badanie cytologiczne, kolposkopię, badanie histologiczne, a także coraz doskonalsze metody molekularne, które pozwalają wykryć wirusowe DNA w przypadkach braku innych wykładników zakażenia. Do metod tych zalicza się: Southern Blot, Dot Blot, hybrydyzacje in situ, polymerase chain reaction (PCR), Hybrid Capture System I i II (HCI, HCII). Coraz częściej wspomina się o testach opartych na izolacji mRNA wirusa HPV (PreTect HPV-Proofer test). Metody te wykrywają zintegrowaną formę HPV, tzw. formę episomalną wirusa. Uważa się, że obecność wirusa HPV w tej postaci jest bezpośrednio związana z progresją zmian powstałych na podłożu tego zakażenia. Co prawda przy pomocy testu PreTect HPV-Proofer wykrywa się mniejszą liczbę zakażeń HPV, ale stosując go, można wyodrębnić grupę pacjentek najbardziej narażonych na raka szyjki macicy.
4
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The structure of fadL mRNA and its interactions with RybB sRNA

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Groszewska A., Wroblewska Z., Olejniczak M.
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EN
Small bacterial RNAs (sRNAs) regulate translation by pairing with complementary sequences in their target mRNAs, in a process which is often dependent on the Hfq protein. Here, the secondary structure of a 95-nt long fragment of Salmonella fadL mRNA containing RybB sRNA binding site in the coding region was analyzed. The data indicated local rearrangements in this mRNA structure after the annealing of RybB. The filter retention data had shown that Hfq bound both RybB and the fadL mRNA fragment with tight affinities. Moreover, Hfq increased the rate of RybB annealing to fadL mRNA. These data indicate that Hfq directly participates in RybB interactions with the fadL mRNA.
5
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The role of the 5' terminal region of p53 mRNA in the p53 gene expression

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Swiatkowska A., Zydowicz P., Sroka J., Ciesiołka J.
Acta Biochimica Polonica
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2016
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vol. 63
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issue 4
645-651
EN
The p53 tumour suppressor protein is one of the major factors responsible for cell cycle regulation and protection against cancer development. This is why it is often referred to as "the guardian of the genome". On the other hand, mutations in the p53 gene are connected with more than 50% of tumours of various types. The thirty-six years of extensive research on the p53 gene and its protein products have shown how sophisticated the p53-based cell system control is. An additional level of complexity of the p53 research is connected with at least twelve p53 isoforms which have been identified in the cell. Importantly, disturbance of the p53 isoforms' expression seems to play a key role in tumorigenesis, cell differentiation and cell response to pathogenic bacteria, and RNA and DNA viruses. Expression of various p53 isoforms results from the usage of different transcription promoters, alternative splicing events and translation initiation from alternative AUG codons. The importance of the 5'-terminal regions of different p53 mRNA transcripts in the multi-level regulation of the p53 gene has recently been documented. In this review we focus on the structural features of these regions and their specific role in the p53 translation initiation process.
6
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Wybrane czynniki prognostyczne w raku jajnika

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Markowska J., Bednarek W., Markowska A.
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2010
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vol. 8
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issue 1
8-20
EN
The authors discuss several predictive factors related to ovarian cancer, both those associated with prognosis and those potentially useful in targeted therapy thereof. Expression of mRNA BRCA1, VEGF and its receptors, CXCR4, HER-2, HIF-1α, COX-2, NM-23, KAI 1, IGF-1R, kisspeptin, neuropilin and Prox-1 gene are discussed. Expression of mRNA BRCA1 is associated not only with hereditary ovarian cancer, but also with its sporadic form. Higher expression correlates with a better response to taxanes. Hopefully, mRNA BRCA1 level in women with sporadic ovarian cancer will become a useful parameter, qualifying patients for a particular chemotherapy protocol. BRMS1 acts as a gene inhibiting development of metastases in ovarian cancer. Levels of mRNA for BRMS1 are lower in late than in early stage ovarian cancer. The VEFG family is involved in angio- and lymphangiogenesis and includes 5 glycoproteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D and VEGF-E), which acting upon receptors VEGFR1-3. Neuropilin 1 plays a role in angiogenesis, while neuropilin 2 modulates lymphangiogenesis, similar to the Prox-1 gene. COX-2 mediates the release of pro-angiogenic factors. HIF-1α expression is associated with resistance of hypoxic cancer cells against cytostatics and radiation. Expression of c-Met correlates with poorly differentiated cancer types. The SDF-1/CXCR4 complex plays a key role in the development of cancer metastases. Survivin is present in cancer cells only, where it inhibits apoptosis and promotes the development of cancer. Metastases suppressor gene (BRMS1) and receptors for VEGF, CXCR4, HER-2, HIF-1α and COX-2, may serve as targets for targeted therapy. At present, an increasing number of studies focus on VEGF receptors. Poor expression of NM-23 and KAI 1 correlate with tumor ability to form metastases. The authors discuss the role of biological markers for clear-cell ovarian cancer (IGF-1R and kisspeptin). Promising topics for future studies are survivin, neuropilin and the Prox-1 gene.
PL
W artykule omówiono szereg czynników prognostycznych związanych nie tylko z rokowaniem, ale również z możliwością zastosowania terapii tarczowej w raku jajnika. Przedstawiono ekspresję mRNA BRCA1, VEGF i jego receptorów, CXCR4, HER-2, HIF-1α, COX-2, NM-23, KAI 1, IGF-1R, kisspeptyny, neuropiliny i genu Prox-1. Ekspresja mRNA BRCA1 wiąże się nie tylko z dziedzicznym rakiem jajnika, ale również z rakiem sporadycznym. Wyższa ekspresja powoduje lepszą odpowiedź na taksany. Przypuszcza się, że zawartość mRNA BRCA1 u kobiet z rakiem sporadycznym może służyć do selekcji pacjentek do odpowiedniego typu chemioterapii. BRMS1 działa jako gen hamowania przerzutów w raku jajnika. Poziomy mRNA dla BRMS1 są niższe w zaawansowanych stadiach raka niż we wczesnych. Rodzina VEGF związana z angiogenezą i limfangiogenezą składająca się z 5 glikoprotein (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E) działa poprzez receptory VEGFR1-3. Neuropilina 1 odgrywa rolę w angiogenezie, a typ drugi moduluje proces limfangiogenezy, podobnie jak gen Prox-1. W uwalnianiu czynników proangiogennych bierze udział COX-2. Ekspresja HIF-1α związana jest z opornością niedotlenionych komórek raka na leczenie chemiczne i napromienianiem. Ekspresja c-Met wiąże się z niższym zróżnicowaniem raka. Kompleks SDF-1/CXCR4 odgrywa kluczową rolę w tworzeniu przerzutów komórek nowotworowych. Surwiwina występująca wyłącznie na komórkach nowotworowych poprzez hamowanie apoptozy promuje rozwój raka. Gen supresji przerzutów (BRMS1), podobnie jak receptory VEGF, CXCR4, HER-2, HIF-1α, COX-2, może być tarczą dla terapii celowanej. Obecnie coraz więcej badań dotyczy inhibitorów VEGF. Obniżona ekspresja NM-23 oraz KAI 1 koreluje ze zdolnością do przerzutowania. Omówiono markery biologiczne dla raka jasnokomórkowego jajnika (IGF-1R i kisspeptynę). Ciekawym obiektem badań może być surwiwina, neuropilina i gen Prox-1.
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