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EN
A causal association between inflammation and cancer has long been suspected. Multiple lines of compelling evidence from clinical, epidemiologic and laboratory studies support that inflammation plays a critical role in the promotion and progression stages of carcinogenesis. Recent progress in our understanding of the molecular biology of cancer highlights the intracellular signal transduction network, including that involved in mediating the inflammatory response, which often functions abnormally during carcinogenesis. One of the key players in inflammatory signaling is cyclooxygenase-2 (COX-2). Aberrant upregulation of COX-2 is frequently observed in various precancerous and malignant tissues. This seminar write-up highlights the cancer preventive effects of some anti-inflammatory phytochemicals derived from edible plants, and their underlying molecular mechanisms with a focus on representative transcription factors and upstream kinases responsible for COX-2 induction.
EN
Zinc is a microelement essential for the body. It has a great impact on the proper development and renewal of tissues, reproductive system, skin condition, or immune processes. Zincis involved practically in all aspects of the immune system and the production and activation of white blood cells. This work aimed to determine the effect of zinc oxide nanoparticles (ZnONP) on the expression of pro-inflammatory proteins in murine macrophages RAW 264.7, activated with lipopolysaccharide (LPS). Using the immunodetection technique the expression of cyclooxygenase 2 (COX-2), prostaglandin E2 synthase (cPGES), prostaglandin F2α receptor (FP receptor) and nuclear factor Nrf2 was determined. Statistically the highest expression of COX-2, cPGES, and FP receptor was observed in LPS-activated macrophages. RAW 264.7 cells supplementation with ZnONP 100 nmol and 500 nmol and LPS activation resulted in repression of COX-2 and cPGES, and an increased expression of Nrf2 protein when compared to control. The results suggest an anti-inflammatory effect and activation of the antioxidant system by ZnONP in RAW 264.7 macrophages. It seems appropriate to conduct further research on the molecular mechanism of action of ZnONP in eukaryotic cells.
EN
Introduction. High fat diet (HFD) intake induces obesity and adversely affects different body organs including liver and gallbladder. Aim. It was to clarify the effects of HFD on the liver and gallbladder structure using light microscopic (LM) examination. Material and methods. 16 healthy adult male mice were equally divided into 2 groups. Control group mice were fed normal diet. HFD group was fed using HFD. At the end of the 8-week experiment, mice were anesthetized. Liver and gallbladder were removed and prepared to histological processing. Sections were stained with hematoxylin and eosin (H&E) and immunostaining for cyclooxygenase-2 (COX-2) cellular localization. Oil Red O (ORO)-stained frozen liver sections were prepared. Results. H&E-stained sections of HFD group revealed rounded swollen hepatic cells with pale cytoplasm suggesting cellular ballooning. Dilated congested sinusoids and portal vein, cellular degeneration and collection of inflammatory cells were observed between hepatic cells and in portal region. Gallbladder sections showed epithelial stratification and cellular vacuolation. Strong immunoexpression of COX-2 was observed in Kupffer and hepatic cells of the liver and gallbladder mucosal epithelial cells. Conclusion. HFD is suggested to alter the normal histological features of liver and gallbladder represented by fatty liver and gallbladder epithelial hyperplasia and inflammatory reaction.
EN
Natural polyphenols and polyphenol-rich extracts have been found to possess preventive and therapeutic potential against several types of cancers, including colorectal cancer (CRC), which is an example of an inflammation-associated cancer. This study examines the chemopreventive effect of a Japanese quince (Chaenomeles japonica) fruit flavanol preparation (JQFFP) on colon cancer SW-480 cells. JQFFP, rich in procyanidin monomers and oligomers, was found to inhibit the SW-480 cell viability by 40% at 150 µM catechin equivalents (CE) after 72 h incubation when compared to control, but it was non-toxic to normal colon fibroblast CCD-18Co cells. Furthermore, 100 µM CE JQFFP suppressed COX-2 mRNA expression to 36.7% of control values and protein expression to 77%. In addition, JQFFP reduced the MMP-9 protein expression (to 24% vs. control at 100 µM CE) and caused inhibition of its enzymatic activity (to 35% vs. control at 100 µM CE). Not only did JQFFP inhibit the COX-2 and MMP-9 levels, but it also reduced the NF-κB protein expression (to 65% of control) and phosphorylation of its p65 subunit (to 51%) at 100 µM CE. These results provide the first evidence that JQFFP inhibits COX-2, MMP-9, and NF-κB expression, suggesting that it has cytotoxic, anti-inflammatory, and anti-metastatic activities towards the colon cancer SW-480 cells.
EN
Chronic inflammation is characterized by excessive production of cytokines and eicosanoids and is associated with unsufficient resolution. Supplementation with n-3 fatty acids may result in a lower incidence of many inflammatory diseases. The aim of this study was to determine the effect of α – linolenic acid (ALA) on the fatty acids profile of cell membranes and on the pro-inflammatory proteins cyclooxygenase – 2 (COX-2), prostaglandin E2 synthase (cPGES) and prostaglandin F2α receptor (FP) expression in murine RAW 264.7 macrophages, activated with lipopolysaccharide (LPS). It has been shown that COX-2, cPGES as well as FP receptor expression was highest in cells activated by LPS. In macrophages supplemented with ALA and activated with LPS a pro-inflammatory protein levels were significantly reduced, suggesting anti-inflammatory activity of α-linolenic acid. There were also statistically significant changes in the fatty acid profile after incubation of the RAW 264.7 cells for 48 hours with ALA. A deficiency or excess of specific fatty acids affect the cellular membrane fluidity, can also cause changes in cell morphology. Therefore it is appropriate to carry out further research on the ALA properties.
EN
Colorectal cancer (CRC) is still one of the unresolved issues in medicine. Despite constant improvements in diagnosis and treatment, the prognosis for CRC is unsatisfactory. In recent years, much attention has been paid to experiments concerning chemoprevention of CRC.The aim of the study was evaluation of the effectiveness of celecoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor of chemically-induced CRC carcinogenesis in Fisher F344 rats.Material and methods. Forty-five four-week old male F344 rats were randomized into four groups. In Groups 1, 2, and 3, we induced the CRC carcinogenesis through two subcutaneous injections of Azoxymethane in doses of 20 mg/kg. Rats from groups 1 and 2 were treated with celecoxib in doses of 10 and 30 mg/kg from the start of the experiment. Group 4 was a negative control. The experiment ended in the 26th week. We assessed the following parameters: the number of Aberrant Crypt Foci (premalignant lesions in colons) and the immunoexpression indexes: COX-2, Vascular Endothelial Growth Factor (VEGF), and c-myc.Results. Celecoxib reduced the ACF number. The ACF reduction was dose-dependent. The median ACF number per field of vision was as follows for each of the groups: 1.7, 0.75, 3.2, and 0.2. Celecoxib, irrespective of the dose, reduced the VEGF immunoexpression index. We did not observe a reduction of COX-2 or c-myc immunoexpression in the celecoxib groups.Conclusions. In this experiment, we proved that celecoxib possessed chemopreventive activity. Carcinogenesis inhibition by selective COX-2 inhibitor was dose-dependent. We demonstrated that celecoxib hidners angiogenesis, expressed as VEGF immunoexpression. We indirectly confirmed the hypothesis of a celecoxib COX-2 independent pathway mechanism of action.
EN
A novel ligand, N,N"-(4-methyl-1,2-phenylene)bis(2-(biphenyl-4-yl)-N'-hydroxy-2-oxoacetimidamide) (H₂L) with its Cu(II) and Mn(II) complexes were synthesized in this study. All compounds synthesized were also characterized by ¹H- and ¹³C-NMR, the Fourier transform infrared, elemental analysis, inductively coupled plasma optical emission spectrometry, molar conductivity, magnetic susceptibility measurements and thermogravimetric analysis. Vascular endothelial growth factor-2 (VEGFR-2) and cyclooxygenase-2 (COX-2) inhibition is often used as a parameter for being a potent anticancer agent in docking studies. For this purpose, synthesized and characterized ligand was investigated by molecular docking study to test its inhibitory effect against angiogenic factors VEGFR-2 and COX-2.
EN
INTRODUCTION Fibroids are the most common tumors of benign nature of the female reproductive organ. Before the age of 40 this problem aff ects nearly 30% of female Caucasian population. Diagnosis of fi broids is based on a gynecological examination and ultrasound. Additionally the diagnosis also applies histerosonography, CT scan and MRI scan. COX-2 is induced isoform synthesized in response to the physical, chemical or biological stimulation. Is expressed, inter alia, in tumor tissues. Stimulation of iNOS and NO separation occurring in the pathological changes play an important role in the development of cancer. AIM OF STUDY Therefore it seems to be justifi ed to determine the expression of COX-2 and iNOS in the benign tumor cells of uterine fi broids. For exact analysis of the expression of these factors also decided to get outskirts fragments of fi broids and shows a comparison of observed expressions with the results obtained with fi broids. MATERIAL AND METHODS Pure control comprised 20 patients in whom there were no fi broidal changes, both in the reproductive age and perimenopausal (10 patients each). To the research qualifi ed 20 women in childbearing age and 20 women in perimenopausal age all with fi broidal changes in uterus. In the studied biopsied tissue evaluated the optical density of cells with the expression of selected proteins like cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS). RESULTS AND CONCLUSIONS Expression of COX-2 and iNOS was higher in the myoma and in the surrounding myometrium fi broids compared with the expression of these proteins in healthy women uterus myometrium. Increased expression of COX-2 and iNOS at the periphery of uterine fi broids can decide the appearance of new tumors. Therefore, you should consider the use of the expression levels of COX-2 and iNOS as a prognostic factor.
PL
WSTĘP Mięśniaki macicy są najczęstszymi łagodnymi nowotworami żeńskiego narządu rodnego. Przed 40 rokiem życia problem ten dotyczy blisko 30% kobiet populacji kaukaskiej. Diagnostyka mięśniaków opiera się na badaniach ginekologicznym oraz ultrasonograficznym. Pomocniczo stosuje się również histerosonografi ę, tomografi ę komputerową oraz rezonans magnetyczny. Cyklooksygenaza 2 (COX-2) jest izoformą indukowalną, syntetyzowaną w odpowiedzi na stymulację fizyczną, chemiczną lub biologiczną. Ulega ekspresji m.in. w tkankach nowotworowych. Stymulacja indukowalnej syntazy tlenku azotu (iNOS) oraz wydzielanie NO zachodzące w zmianach patologicznych, odgrywają istotną rolę w rozwoju nowotworu. CEL PRACY Uzasadnione zatem wydaje się określenie ekspresji COX-2 i iNOS w niezłośliwych komórkach nowotworowych mięśniaków macicy. W celu dokładnej analizy ekspresji tych czynników zdecydowano się także na pobranie fragmentów obrzeża mięśniaków i porównanie zaobserwowanej ekspresji z wynikami otrzymanymi z mięśniaków. MATERIAŁ I METODY Kontrolę czystą stanowiło 20 pacjentek, u których nie stwierdzono zmian mięśniakowatych, zarówno w wieku reprodukcyjnym, jak i okołomenopauzalnym (po 10 pacjentek). Do badań zakwalifikowano po 20 kobiet w wieku rozrodczym ze zmianami mięśniakowymi w macicy oraz z mięśniakami w wieku okołomenopauzalnym. W badanych wycinkach tkankowych dokonano oceny gęstości optycznej komórek z ekspresją wybranych enzymów, tj. COX-2 oraz iNOS. WYNIKI I WNIOSKI Ekspresja COX-2 oraz iNOS była wyższa zarówno w mięśniaku, jak i w myometrium otaczającym mięśniak w porównaniu z ekspresją tych białek w myometrium macicy kobiet zdrowych. Zwiększona ekspresja COX-2 i iNOS na obrzeżu mięśniaków macicy może decydować o pojawieniu się nowych guzów. Dlatego też należy rozważyć wykorzystanie poziomu ekspresji COX-2 i iNOS jako czynników prognostycznych.
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