The aim of our study was to analyse the possible protective effect of quercetin application during the jejunal ischemia-reperfusion injury (IRI) in rats. Quercetin was administered intraperitoneally 30min before 1h ischemia of superior mesenteric artery with following 24h lasting reperfusion period. The male specific pathogen-free (SPF) Charles River Wistar rats were used. In the group with applied quercetin, the significantly increased (p<0.001) levels of anti-inflammatory cytokine IL10 were observed both in the blood serum and jejunal tissue. The improvement of the mucosal tissue morphology and proliferating and DNA repairing cell number measured by PCNA activity were recorded by more than 30% higher in the quercetin group. Simultaneously, significant elongation of the intestinal glands (p<0.001) and increase in the number of CD68-positive cells in the lamina propria mucosae (p<0.001) in comparison with control group were found. Based on our results, the preventive application of quercetin before induction of jejunal IRI stimulates faster jejunal mucosa restoration and it seems to have immunomodulatory and anti-inflammatory effects as well. CD68-positive macrophages could have crucial role in this process since they work as both growth factor and cytokine producers.
- MeSH
- antiflogistika farmakologie MeSH
- antigeny diferenciační myelomonocytární metabolismus MeSH
- CD antigeny metabolismus MeSH
- jejunum účinky léků MeSH
- krysa rodu rattus MeSH
- quercetin farmakologie MeSH
- reperfuzní poškození patofyziologie MeSH
- žaludeční sliznice účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
CYP2C and CYP2 J enzymes, commonly named as cytochrome P450 (CYP) epoxygenases, convert arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active eicosanoids with many functions in organism. EETs are rapidly hydrolysed to less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). We investigated spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2 J2 and sEH in normal human placenta by immunohistochemical method. In the villous trophoblast, CYP2C8 was the most abundant protein. Its expression is higher than the CYP2C9 and CYP2 J2 in the cytotrophoblast in the embryonic stage of development and remains higher in syncytiotrophoblast of term placenta. Unlike to CYP2C8, CYP2C9 and CYP2 J2 expression decrease in term placenta. sEH expression increases with gestation age and is strictly limited to cytotrophoblast in embryonic and foetal stages of the development. Moreover, CYP2C8 shows more intensive staining than the other protein monitored in Hofbauer cells in villous stroma. Specific information regarding the exact role of EETs and DHETs functions in a normal placenta is still unknown. Based on CYP epoxygenases and sEH localization and well known information about the functions of placental structures during development, we suggest that these enzymes could play different roles in various cell populations in the placenta. As the placenta is absolutely crucial for prenatal development, arachidonic acid is essential part of human nutrient and CYP epoxygenases expression can be affected by xenobiotics, further investigation of the exact role of CYP epoxygenases, sEH, and their metabolites in normal pregnancy and under pathological conditions is needed.
- MeSH
- cytochrom P450 CYP2C8 biosyntéza MeSH
- cytochrom P450 CYP2C9 biosyntéza MeSH
- lidé MeSH
- placenta cytologie enzymologie MeSH
- regulace genové exprese enzymů fyziologie MeSH
- systém (enzymů) cytochromů P-450 biosyntéza MeSH
- těhotenské proteiny biosyntéza MeSH
- těhotenství metabolismus MeSH
- Check Tag
- lidé MeSH
- těhotenství metabolismus MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: Regression of atherosclerosis is a key aspect of preventing further coronary artery disease and understanding which cell type forms smooth muscle cells in atherosclerotic fibrous caps will aid in reducing CAD. Atherogenesis is a complex interplay of cells migrating and proliferating into the vascular wall. CD34 positive hemapoetic stem cells are believed to not transform into vascular smooth muscle cells (SMC). The current study hypothesised that there would be no evidence for CD34(+)/α SMC actin(+) cells in atherosclerotic coronary arteries. AIMS: To identify CD34+/α actin positive cells in the fibrous cap and wall of atherosclerotic plaques in the coronary artery. METHODS: Male New Zealand White rabbits were fed a diet containing 0.5% cholesterol and 1% methionine for 4 weeks, then 9 weeks of normal diet to induce regression. Immunohistochemistry was used to detect CD34(+) haematopoietic progenitor cells and α SMC actin. RESULTS: In the fibrous cap, the majority of cells were CD34(-)/α SMC actin(+) spindle shaped cells. However very rare populations of CD34(+)/α SMC actin(+) and CD34(+)/α SMC actin(-) cells were also present but these cells were not spindle shaped. CONCLUSION: Our study found that CD34(+)/α SMC actin(-) spindle shaped cells were absent from the fibrous cap. Moreover, the predominant cell population were the vascular smooth muscle cells (CD34(-)/α SMC actin(+)) but (CD34(+)/α SMC actin(+)) cells were also present. This model could be used to understand the role of each SMC population subtype to hasten atherosclerotic regression in the coronary artery.
- MeSH
- aktiny metabolismus MeSH
- antigeny CD3 metabolismus MeSH
- aterosklerotický plát patologie MeSH
- ateroskleróza patologie MeSH
- hematopoetické kmenové buňky metabolismus MeSH
- koronární cévy metabolismus patologie MeSH
- králíci MeSH
- myocyty hladké svaloviny metabolismus MeSH
- nemoci koronárních tepen metabolismus patologie MeSH
- svaly hladké cévní patologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tripolar mitosis is a specific case of cell division driven by typical molecular mechanisms of mitosis, but resulting in three daughter cells instead of the usual count of two. Other variants of multipolar mitosis show even more mitotic poles and are relatively rare. In nature, this phenomenon was frequently observed or suspected in multiple common cancers, infected cells, the placenta, and in early human embryos with impaired pregnancy-yielding potential. Artificial causes include radiation and various toxins. Here we combine several pieces of the most recent evidence for the existence of different types of multipolar mitosis in preimplantation embryos together with a detailed review of the literature. The related molecular and cellular mechanisms are discussed, including the regulation of centriole duplication, mitotic spindle biology, centromere functions, cell cycle checkpoints, mitotic autocorrection mechanisms, and the related complicating factors in healthy and affected cells, including post-mitotic cell-cell fusion often associated with multipolar cell division. Clinical relevance for oncology and embryo selection in assisted reproduction is also briefly discussed in this context.
- MeSH
- blastocysta metabolismus MeSH
- centrioly metabolismus MeSH
- kontrolní body buněčného cyklu * MeSH
- lidé MeSH
- nádory metabolismus MeSH
- placenta metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
We examined immunohistochemically the expression pattern of a potential tumor biomarker survivin in a panel of 116 tubular adenomatous polyps to determine its association with clinicomorphological parameters such as age of patients, size of polyps, degree of dysplasia and polyp localization. In each section, the subcellular localization of survivin antigen and the intensity of staining were assessed. Overall, survivin was expressed in 90 cases (77.6%). Cytoplasmic positivity was observed in 46/116 cases (39.7%), while nuclear and combined nuclear and cytoplasmic reaction in 44/116 cases (37.9%). High grade dysplasia was diagnosed in 52 cases (44.8%) and low grade dysplasia in 64 cases (55.2%). Statistical analysis revealed a significant correlation between subcellular survivin localization and the degree of dysplasia, size of polyps and colon localization. On the other hand, survivin expression pattern did not correlate with the age of patients. Statistically significant trend was confirmed between intensity of survivin immunoreaction and tumor size and dysplasia grade, and also the trend between negative/strong survivin intensity and polyp localization. Another statistically significant association was found between the degree of dysplasia and the size of polyps. Our findings revealed that survivin is frequently expressed in different subcellular compartments of adenoma cells. Our recent results suggest that the nuclear and combined nuclear and cytoplasmic survivin localizations are strongly associated with poor prognostic parameters in the assessment of colon adenomas. Thus, survivin may represent a promising biomarker in immunohistochemical evaluation of these lesions.
- MeSH
- adenom MeSH
- imunohistochemie MeSH
- inhibitory apoptózy metabolismus MeSH
- kolon metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory tračníku metabolismus patologie MeSH
- prognóza MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A histological study was designed to determine the influence of flaxseed and/or lactobacilli inclusion in the diet of piglets from 10 days before to 21 days after weaning. The selected inflammatory cell population incidence in the piglet jejunal mucosa was investigated. Significantly higher numbers of myeloperoxidase-positive (P<0.01) and CD163-positive (P<0.001) cells in the jejunal mucosa were recorded on the weaning day and for 7 days after (P<0.001 and P<0.01, respectively) in the flaxseed group compared with the basal diet. The number of intraepithelial lymphocytes was also significantly increased until 3 days after weaning (P<0.001). A prolonged significant increase in the myeloperoxidase-positive cells and intraepithelial lymphocyte numbers in the flaxseed+lactobacilli group was detected. In contrast, the number of CD163-positive cells in the flaxseed+lactobacilli group was significantly lower on the day of weaning (P<0.05) and 3 days after (P<0.01). The same effect was observed in the group with lactobacilli alone during the first 3 days after weaning (P<0.05 and P<0.01, respectively) and these findings indicate down-regulation of CD163 expression in the jejunal mucosa by lactobacilli. The presence of lactobacilli in the diet had a stimulatory effect on goblet cell quantity in the epithelium (P<0.001) and a distinct 50% reduction in the flaxseed group (P<0.01) compared with the basal diet was observed on the weaning day. A significant increase in myeloperoxidase-positive cell number in the jejunal mucosa in the flaxseed+lactobacilli group was the only significant difference (P<0.05 and P<0.01, respectively) found 21 days after weaning in comparison with all the other groups, indicating the pro-inflammatory effect of this feed additive combination. We conclude that dietary supplementation with flaxseed and lactobacilli on the cells of local innate immunity response in the jejunal mucosa in piglets after weaning might be linked with significant anti-inflammatory effects in the jejunal mucosa.
- MeSH
- jejunum mikrobiologie MeSH
- Lactobacillus * MeSH
- len * MeSH
- odstavení * MeSH
- potravní doplňky mikrobiologie MeSH
- prasata MeSH
- střevní sliznice mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Our previous results indicated significant tumor-suppressive effects of different statins in rat mammary carcinogenesis. The purpose of this experiment was to examine the chemopreventive effects of Pitavastatin alone and in combination with the pineal hormone melatonin in the model of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats. Pitavastatin was administered dietary (10mg/kg) and melatonin in an aqueous solution (20μg/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Compared to controls, Pitavastatin alone reduced average tumor volume by 58% and lengthened latency by 8 days; on the other hand, the drug increased tumor frequency by 23%. Combined administration of Pitavastatin with melatonin decreased tumor frequency by 23%, tumor volume by 44% and lengthened tumor latency by 5.5 days compared to control animals. The analysis of carcinoma cells showed significant increase in caspase-3 expression in both treated groups and a tendency of increased caspase-7 expression after Pitavastatin treatment alone. Significant expression decrease of Ki67 was found in carcinoma cells from both treated groups. Compared to control carcinoma cells, Pitavastatin alone increased VEGF expression by 41%, however melatonin totally reversed its undesirable effect. Pitavastatin combined with melatonin significantly increased femur compact bone thickness in animals. Pitavastatin alone decreased plasma triglycerides and total cholesterol levels, however it significantly increased levels of glucose. In summary, our results show a partial antineoplastic effect of Pitavastatin combined with melatonin in the rat mammary gland carcinoma model.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- chinoliny terapeutické užití MeSH
- experimentální nádory mléčných žláz farmakoterapie MeSH
- krysa rodu rattus MeSH
- melatonin terapeutické užití MeSH
- nádory mléčné žlázy u zvířat farmakoterapie MeSH
- nádory prsu farmakoterapie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the production of abnormally short or inactivated proteins. The antiapoptotic protein survivin functions in the inhibition of apoptosis, regulation of cell division and also enhances angiogenesis. Both MMRP and survivin are considered to be powerful prognostic parameters. This study was designed to determine the relationship between MMRP and survivin in colon lesions. The study included 113 cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and MMRP status were assessed by immunohistochemistry. In each section, expression, intensity of immunostaining and percentage of labeled cells were analyzed. In carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%), 112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical analysis confirmed a significant correlation between the expression of MMRP and survivin in the assessed parameters. All 51 polyp samples were positive for MLH1, MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin. Statistically significant differences were observed between the expression of MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the antiapoptotic function of survivin through p53 inactivation of its promoter in grade 1 and grade 2 colon carcinomas.
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- adenokarcinom enzymologie MeSH
- adenosintrifosfatasy metabolismus MeSH
- DNA vazebné proteiny metabolismus MeSH
- enzymy opravy DNA metabolismus MeSH
- homolog 2 proteinu MutS metabolismus MeSH
- inhibitory apoptózy metabolismus MeSH
- jaderné proteiny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové proteiny metabolismus MeSH
- nádory tračníku enzymologie MeSH
- oprava chybného párování bází DNA MeSH
- polypy tlustého střeva enzymologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We examined the expression of carbonic anhydrase IX (CA IX) by immunohistochemical staining using monoclonal antibody M75 (Institute of Virology, Slovak Academy of Sciences, Bratislava) in a group of 38 fibroadenomas and 55 carcinomas of the breast. In each case, the intensity of staining, percentage of labeled cells and subcellular localization of CA IX were assessed. CA IX was detected in 11/38 fibroadenomas (28.9%). Weak cytoplasmic positivity was dominant in these positive cases. Immunohistochemical analysis of 55 carcinomas showed CA IX expression in 34 cases (61.8%). Membrane staining alone was observed in 27/55 carcinomas (49.1%), while cytoplasmic positivity was found in 4/55 cases (7.3%). Combined membrane and cytoplasmic immunostaining of CA IX was detected in 3/55 carcinomas (5.4%). The intensity of immunoreactivity varied from weak to strong. Under 50% of reactive cells were found in 9/38 fibroadenomas (23.6%) and in 29/55 carcinomas (52.7%). More than 50% of reactive cells were found in 2/38 fibroadenomas (5.3%) and in 5/55 carcinomas (9.1%). Statistical analysis confirmed significant differences in the subcellular localization, intensity of immunoreactivity and percentage of labeled cells in fibroadenomas and carcinomas (p<0.05). Our results confirmed the hypothesis that expression of CA IX may represent a valuable tumor biomarker as well as a promising diagnostic and prognostic parameter in breast cancer.
- MeSH
- antigeny nádorové metabolismus MeSH
- fibroadenom enzymologie patologie MeSH
- karboanhydrasy metabolismus MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory prsu enzymologie patologie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in tissue remodeling and wound healing. These enzymes degrade and also synthesize components of the extracellular matrix. Overexpression of MMPs results in excessive extracellular matrix degradation and tissue destruction. In the cornea, destructive processes may lead to scarring and loss of vision. In this study MMPs (types 1, 2, 7, 8, 9 and 14) were examined immunohistochemically in the normal rabbit corneal epithelium and in epithelium irradiated in vivo with similar doses of UVB or UVA radiation (UVB rays 312 nm, UVA rays 365 nm, daily dose 1.01 J/cm(2) for four days). Results show that MMPs studied revealed low expression in the normal corneal epithelium, whereas after repeated UVB irradiation the expression of MMPs was significantly increased in the corneal epithelium, in ascending order: MMP-2, MMP-9, MMP-1, and MMP-7 with MMP-8. In contrast, compared to normal corneas, repeated UVA radiation did not significantly change the expression of MMPs in the irradiated corneal epithelium. MMP-14 was expressed at very low levels in all studied corneas, whereas no significant changes were detected upon UV exposure. In conclusion, UV radiation of shorter wavelength (UVB) induced an increase in expression of all MMPs except MMP-14. It is suggested that overexpression of MMPs in the corneal epithelium contributes to the damaging effect of UVB radiation to the cornea.
- MeSH
- imunohistochemie MeSH
- králíci MeSH
- matrixové metaloproteinasy analýza biosyntéza MeSH
- regulace genové exprese enzymů účinky záření MeSH
- rohovkový epitel enzymologie účinky záření MeSH
- ultrafialové záření * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH