In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.
We used quantitative real-time PCR method to analyse mtDNA copy number in a random subsample (n=996; 358 men aged 66,31±7,24 years; 468 women aged 67,62±7,1 years) selected from a population cohort (n=9 630) examined at baseline in international project HAPIEE in Novosibirsk, Russia, in 2003-2005. The participants were re-examined after 12 years in 2015-2017. The average relative number of mtDNA copies in peripheral blood leukocytes was greater in women than in men, independently of age and smoking (p=0,001). mtDNA copy number was inversely correlated with age both in men (p=0,005) and women (p<0,001). In age adjusted analysis, mtDNA copy number was inversely associated with waist, hip and heart rate in both sexes. In addition, mtDNA copy number in women was inversely associated with triglycerides and glucose, aterogenity index and positively with HDL cholesterol. In men, mtDNA copy number was positively associated with physical activity. The age-adjusted mean of mtDNA copy number among male never-smokers was greater than in smokers (p=0,003), and the mean mtDNA copy number was lower in women with diabetes than in women without diabetes (p=0,005). In both sexes, subjects with baseline history of hypertension had lower mtDNA copy number after 12-year follow-up than those without hypertension (p=0,05). This broadly supports the hypothesis that mtDNA copy number may act as biomarker of ageing.
- MeSH
- biologické markery * analýza MeSH
- diagnóza * MeSH
- leukocyty * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondriální DNA * MeSH
- rizikové faktory MeSH
- senioři MeSH
- sexuální faktory MeSH
- stárnutí * genetika MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Rusko MeSH
The effective drug delivery systems for cancer treatment are currently on high demand. In this paper, biological behavior of the novel hybrid copolymers based on polysaccharide glycogen were characterized. The copolymers were modified by fluorescent dyes for flow cytometry, confocal microscopy, and in vivo fluorescence imaging. Moreover, the effect of oxazoline grafts on degradation rate was examined. Intracellular localization, cytotoxicity, and internalization route of the modified copolymers were examined on HepG2 cell line. Biodistribution of copolymers was addressed by in vivo fluorescence imaging in C57BL/6 mice. Our results indicate biocompatibility, biodegradability, and non-toxicity of the glycogen-based hybrid copolymers. Copolymers were endocyted into the cytoplasm, most probably via caveolae-mediated endocytosis. Higher content of oxazoline in polymers slowed down cellular uptake. No strong colocalization of the glycogen-based probe with lysosomes was observed; thus, it seems that the modified externally administered glycogen is degraded in the same way as an endogenous glycogen. In vivo experiment showed relatively fast biodistribution and biodegradation. In conclusion, this novel nanoprobe offers unique chemical and biological attributes for its use as a novel drug delivery system that might serve as an efficient carrier for cancer therapeutics with multimodal imaging properties.
- MeSH
- buňky Hep G2 MeSH
- endocytóza MeSH
- fluorescein-5-isothiokyanát aplikace a dávkování farmakokinetika MeSH
- fluorescenční barviva aplikace a dávkování farmakokinetika MeSH
- glykogen aplikace a dávkování farmakokinetika MeSH
- heterocyklické sloučeniny aplikace a dávkování farmakokinetika MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- nosiče léků aplikace a dávkování farmakokinetika MeSH
- organokovové sloučeniny aplikace a dávkování farmakokinetika MeSH
- polyaminy aplikace a dávkování farmakokinetika MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The activity of the Wnt pathway undergoes complex regulation to ensure proper functioning of this principal signaling mechanism during development of adult tissues. The regulation may occur at several levels and includes both positive and negative feedback loops. In the present study we employed one of such negative feedback regulators, naked cuticle homolog 1 (Nkd1), to follow the Wnt pathway activity in the intestine and liver and in neoplasia originated in these organs. Using lineage tracing in transgenic mice we localized Nkd1 mRNA to the bottom parts of the small intestinal crypts and hepatocytes surrounding the central vein of the hepatic lobule. Furthermore, in two mouse models of intestinal tumorigenesis, Nkd1 expression levels were elevated in tumors when compared to healthy tissue. We utilized a collection of human intestinal polyps and carcinomas to confirm that NKD1 represents a robust marker of neoplastic growth. In addition, expression analysis of NKD1 in liver cancer showed that high expression levels of the gene distinguish a subclass of hepatocellular carcinomas related to aberrant Wnt signaling. Finally, our results were confirmed by bioinformatic analysis of large publicly available datasets that included gene expression profiling and high-throughput sequencing data of human colon and liver cancer specimens.
- MeSH
- beta-katenin genetika metabolismus MeSH
- genetická transkripce MeSH
- hepatocelulární karcinom metabolismus patologie MeSH
- hepatocyty metabolismus patologie MeSH
- kolorektální nádory metabolismus patologie MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- mutace MeSH
- myši transgenní MeSH
- myši MeSH
- nádory jater metabolismus patologie MeSH
- protein familiární adenomatózní polypózy nedostatek genetika metabolismus MeSH
- proteiny Wnt metabolismus MeSH
- signální transdukce MeSH
- střevní nádory metabolismus patologie MeSH
- transportní proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: To assess the impact of a quadrivalent human papillomavirus vaccine (4HPV) in women at increased risk of genital warts (GWs) acquisition. METHODS: The study was conducted using a population-based cross-sectional survey of 19,199 women aged 16 to 40 years randomly chosen from the general population in the Czech Republic between January 2013 and March 2014. A total of 1086 women reported having received the 4HPV vaccine. The vaccine's effectiveness was estimated not only in the general population of women but also in those at increased risk due to having a sexual partner with GWs or prior GWs history. RESULTS: The acquisition of GWs was dramatically reduced by 90.6% (80.1-95.6%) in immunised women at least one year after the completion of the 4HPV vaccination in comparison with unimmunised women. Recurrent GWs prevalences of 1.1% (95% CI, 0.0-5.9) and 10.9% (95% CI, 9.1-12.9) in immunised and unimmunised women with prior GWs history, respectively, resulted in a vaccine effectiveness of 89.0% (38.6-98.0%). The notably strong protective effect of 4HPV immunisation in women who had a sexual partner with GWs was demonstrated by a very low age-adjusted odds ratio of 0.02 (95% CI 0.01-0.10) in contrast to unimmunised women. CONCLUSIONS: To lower the chance of genital warts acquisition in the general population and in populations at increased risk, only current 4HPV or incoming 9HPV vaccination should be recommended to provide effective protection.
- MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- kondylomata akuminata epidemiologie prevence a kontrola MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- průřezové studie MeSH
- rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND/OBJECTIVES: Alcoholic chronic pancreatitis (ACP) and liver cirrhosis (ALC) are sequels of excessive alcohol intake. They develop in a minority of long-term alcohol consumers. Their concomitant occurrence is rare and the organ selection remains unknown. The aim of study was to compare patients with ACP and ALC with respect to their lifestyle. METHODS: Sixty-six patients with ACP and 80 with ALC were personally interviewed about their lifestyle, drinking, and eating habits. RESULTS: The groups of ACP (60 males, 6 females) and ALC (64 males, 16 females) did not differ in the amount of alcohol intake (58 g/day vs. 64 g/day). Significantly more patients with ACP reported first alcohol contact before the age of 15 (28.5% vs. 88%; p=0.03). ACP patients had the highest alcohol intake between 20 and 30 years of age (43.6% vs. 20.3%; p<0.01), were more likely to smoke (92.4% vs. 78.7%; p=0.02) and more likely to start smoking before the age of 15 (16.7% vs. 3.7%; p=0.04). Patients with ACP had a lower level of education (p<0.01). We did not observe significant differences between the dietary habits of the groups. The incidence of cirrhosis in ACP patients was 16.7%. The incidence of pancreatitis in the ACL group was 2.5%. CONCLUSION: The socio-behavioral factors affecting development of either ACP or ALC differed. ACP was associated with an early onset of drinking and smoking, highest alcohol intake at a young age, and a lower level of education. Simultaneous occurrence was unusual. Supported by grant IGAMZ NS/10527-3.
- MeSH
- alkoholická cirhóza jater komplikace epidemiologie MeSH
- alkoholická pankreatitida komplikace epidemiologie MeSH
- chronická pankreatitida komplikace epidemiologie MeSH
- dospělí MeSH
- ethanol aplikace a dávkování MeSH
- kouření škodlivé účinky epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- prospektivní studie MeSH
- stupeň vzdělání MeSH
- věkové faktory MeSH
- životní styl * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
The main complication of aortocoronary reconstruction with vein grafts is restenosis in the course of time. The aim was to assess the effect of a periadventitial polyester mesh releasing sirolimus on intimal hyperplasia of autologous grafts. We implanted v. jugularis ext. into a. carotis communis in rabbits. The vein graft was either intact, or was wrapped with a pure polyester mesh, or with a sirolimus-releasing mesh. Three and six weeks after surgery, the veins were subjected to standard histological staining and the thicknesses of the tunica intima, the media and the intima-media complex were measured. Wrapping the vein with a mesh releasing sirolimus or with a pure mesh decreased the thickness of the intima in comparison with a vein graft by 73 ± 11% or 73 ± 8% after 3 weeks, and by 73 ± 9% or 59 ± 12% after 6 weeks, respectively. Sirolimus-releasing meshes reduced the thickness of the media by 65 ± 9% and 20 ± 12% after 3 and 6 weeks. The thickness of the intima-media complex in grafts with sirolimus-releasing meshes decreased by 60 ± 6% and 30 ± 13% in comparison with pure PES meshes, after 3 and 6 weeks, respectively. A periadventitial polyester mesh releasing sirolimus has the potential to become an effective device in preventing vein graft restenosis.
- MeSH
- chirurgické síťky MeSH
- činčila MeSH
- fixace tkání MeSH
- hyperplazie patologie MeSH
- imunohistochemie MeSH
- imunosupresiva aplikace a dávkování terapeutické užití MeSH
- králíci MeSH
- léky implantované MeSH
- okluze cévního štěpu patologie prevence a kontrola MeSH
- počet buněk MeSH
- polyestery MeSH
- proliferace buněk MeSH
- proliferační antigen buněčného jádra metabolismus MeSH
- sirolimus aplikace a dávkování terapeutické užití MeSH
- svaly hladké cévní účinky léků MeSH
- tunica intima patologie MeSH
- tunica media patologie MeSH
- vény transplantace MeSH
- zalévání tkání do parafínu MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
