Nanodiamonds (ND) serve as RNA carriers with potential for in vivo application. ND coatings and their administration strategy significantly change their fate, toxicity, and effectivity within a multicellular system. Our goal was to develop multiple ND coating for effective RNA delivery in vivo. Our final complex (NDA135b) consisted of ND, polymer, antisense RNA, and transferrin. We aimed (i) to assess if a tumor-specific coating promotes NDA135b tumor accumulation and effective inhibition of oncogenic microRNA-135b and (ii) to outline off-targets and immune cell interactions. First, we tested NDA135b toxicity and effectivity in tumorospheres co-cultured with immune cells ex vivo. We found NDA135b to target tumor cells, but it binds also to granulocytes. Then, we followed with NDA135b intravenous and intratumoral applications in tumor-bearing animals in vivo. Application of NDA135b in vivo led to the effective knockdown of microRNA-135b in tumor tissue regardless administration. Only intravenous application resulted in NDA135b circulation in peripheral blood and urine and the decreased granularity of splenocytes. Our data show that localized intratumoral application of NDA135b represents a suitable and safe approach for in vivo application of nanodiamond-based constructs. Systemic intravenous application led to an interaction of NDA135b with bio-interface, and needs further examination regarding its safety.
- Publikační typ
- časopisecké články MeSH
MicroRNAs are short molecules of RNA regulating most cellular processes via the mechanism of RNA interference. Their dysregulation leads to a disease burden, making them important therapeutic targets. For the successful development of a therapeutic device, the uptake of a functionalized carrier by live cells and the sufficient release of effector therapeutic molecules are limiting factors. Here for the first time, the inhibition of oncogenic microRNA-21 in CT-26 colon cancer cells is achieved, using an advanced nanosystem consisting of fluorescent nanodiamond and antisense RNA. Stable nanocomplexes efficiently deliver antisense RNA into cell cytoplasm, encouraging further study of microRNA-21 function in target cells. Engaging the fluorescent nanoparticle enables monitoring of transfection and release of the antisense RNA load into cell cytoplasm. Importantly, the internalized antisense RNA effectively destroys target microRNA-21 in CT-26 cancer cells. The absence of oncogenic microRNA-21 liberates tumor suppressor genes Pdcd4 and Timp3 from silencing, and results in a decrease of cell invasion and migration, and in the induction of apoptotic cell death. This study uses a nanodiamond-based imaging and delivery system, and shows that the multidimensional performance of the presented device makes nanodiamond-based complexes promising therapeutic devices.
- MeSH
- cytomegalovirové infekce * komplikace patofyziologie přenos MeSH
- Cytomegalovirus MeSH
- kojenec MeSH
- kojení MeSH
- lidé MeSH
- mateřské mléko MeSH
- novorozenec nedonošený MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Glycan metabolism balance is critical for cell prosperity, and macromolecule glycosylation is essential for cell communication, signaling and survival. Thus, glycotherapy may be a potential cancer treatment. The aim of the present study was to determine whether combined synthetic glycoconjugates (GCs) induce changes in gene expression that alter the survival of colon cancer cells. The current study evaluated the effect of the GCs N‑acetyl‑D‑glucosamine modified polyamidoamine dendrimer and calix[4]arene scaffold on cancer cell proliferation, apoptosis, invasion and sensitivity to immune cell‑mediated killing. Using reverse transcription‑quantitative polymerase chain reaction, the expression of genes involved in the aforementioned processes was measured. It was determined that GCs reduce the expression of the glucosaminyltransferases Mgat3 and Mgat5 responsible for surface glycosylation and employed components of the Wnt signaling pathway Wnt2B and Wnt9B. In addition, the calix[4]arene‑based GC reduced cell colony formation; this was accompanied by the downregulation of the metalloproteinase Mmp3. By contrast, the dendrimer‑based GC affected the expression of the glucose transporter components Sglt1 and Egfr1. Therefore, to the best of our knowledge, the present study is the first to reveal that N‑acetyl‑D‑glucosamine‑dendrimer/calix[4]arene GCs alter mRNA expression in a comprehensive way, resulting in the reduced malignant phenotype of the colon cancer cell line HT‑29.
- MeSH
- apoptóza genetika MeSH
- buňky HT-29 MeSH
- glukosa metabolismus MeSH
- glykokonjugáty farmakologie MeSH
- lidé MeSH
- molekuly buněčné adheze genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky účinky léků metabolismus MeSH
- nádory tračníku genetika metabolismus MeSH
- proliferace buněk MeSH
- proteiny usnadňující transport glukosy genetika MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- stanovení celkové genové exprese MeSH
- testy nádorových kmenových buněk MeSH
- transkriptom MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Úkolem laktačních poradců a poradkyň je pomoci matkám s realizací kojení, doporučením nejvhodnějších strategií a řešení problémů vzniklých během kojení. Článek si klade za cíl upozornit na nejdůležitější negativní vlivy šidítka (dudlíku), mezi které patří negativní vliv na kojení (zkrácení celkové doby kojení), vyšší riziko zánětu středního ucha a vyšší procento malokluzí u dětí.
The primary role of a lactation consultant is to help mothers with breasfeeding, recommending the best strategies for nursing and solving any related problems that may arise in the duration of breastfeeding. The main aim of this article is to highlight the negative influence of soothers (dummies) on breastfeeding, resulting in a reduction in the total duration of breastfeeding; the increased risk of otitis and increased incidence of malocclusion in children.
Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p=0.039), to roll from supine to prone position (p=0.022) and were slightly later to begin crawling (p=0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed.
- MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- parazitární komplikace těhotenství * MeSH
- pohybová aktivita * MeSH
- průzkumy a dotazníky MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- toxoplazmóza * epidemiologie MeSH
- vývoj dítěte * MeSH
- vývoj plodu MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
N-Acetyl-D-glucosamine-substituted glycoconjugates (GCJs) with the polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold represent ligands for NKR-P1 molecule and induce NK cell-mediated cytotoxicity in vitro. The in vivo effect of these GCJs on mouse melanoma model was determined when administered either alone or in combination with non-specific immunostimulator keyhole limpet hemocyanin (KLH). All types of treatment significantly reduced the tumor growth on day 23, while GN4C as well as KLH were effective continuously (from day 14). The GN4C also induced the longest mean survival time (46.3 ± 11.1 d), followed by KLH+GN4C (36.4 ± 12.1), KLH (35.6 ± 6.5), KLH+GN8P (35.6 ± 6.7), and GN8P (32.4 ± 7.0), compared to controls (29.8 ± 3.6). The B16F10 specific cytotoxicity of peripheral blood cells was significantly elevated by both KLH and GN8P, whereas not by GN4C. KLH increased the effect of the GN4C, but did not influence that of GN8P. GN4C was proved to exert anticancer activity in mouse melanoma model. The combination of KLH with GCJs did not generate synergism.
- MeSH
- acetylglukosamin chemie MeSH
- adjuvancia imunologická terapeutické užití MeSH
- antitumorózní látky terapeutické užití MeSH
- financování organizované MeSH
- glykokonjugáty chemie terapeutické užití MeSH
- hemokyanin terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- melanom farmakoterapie patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory kůže farmakoterapie patologie MeSH
- synergismus léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
Latent toxoplasmosis has been previously found to cause behavioural and personality changes in humans, which are specific for each gender. Here we tested the stress hypothesis of these gender differences based on the assumption that latent toxoplasmosis causes long-term subliminal stress. In line with this hypothesis, the gender difference will appear specifically in situations with interpersonal context because in contrast to the typical individualistic coping style of men, women have a tendency to express elevated prosocial behaviour under stress. Altogether 295 biology students (29/191 females and 27/104 males infected by T. gondii) played a modified version of the Dictator Game and the Trust Game. As predicted, a gender difference in the effect of latent toxoplasmosis was found for the measure of reciprocal altruism in the Trust Game (p = 0.016), but both genders appeared less generous when infected in the Dictator Game modified to minimize social connotation (p = 0.048).
