Kostní dysplazie jsou širokou, heterogenní skupinou chorob. Thanatoforická dysplazie patří mezi nejčastější letální kostní dysplazie. Základem diagnostiky je kvalitní ultrazvukové vyšetření ve II. trimestru a nejnovější metody genetického testování vč. vyšetření klinického exomu. Znalost správné diagnózy je klíčová pro budoucnost plodu i páru.
Bone dysplasias are a broad, heterogeneous group of diseases. Thanatophoric dysplasia is a rare bone dysplasia, but it is the most common lethal skeletal dysplasias. The major role in diagnostics plays a high-quality ultrasound examination in the 2nd trimester and the latest methods of genetic testing, including clinical exome testing. Knowing the correct diagnosis is crucial for the future of the fetus and the couple.
- MeSH
- dospělí MeSH
- indukovaný potrat MeSH
- lidé MeSH
- nemoci plodu diagnostické zobrazování genetika patologie MeSH
- progrese nemoci MeSH
- sekvenování exomu * MeSH
- těhotenství MeSH
- thanatoforní dysplazie * diagnostické zobrazování genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis. The increasing incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has created a need for new antiTB agents with new chemical scaffolds to combat the disease. Thus, the key question is: how to search for new antiTB and where to look for them? One of the possibilities is to search among natural products (NPs). In order to search for new antiTB drugs, the detailed phytochemical study of the whole Dicranostigma franchetianum plant was performed isolating wide spectrum of isoquinoline alkaloids (IAs). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. Alkaloids were screened against Mycobacterium tuberculosis H37Ra and four other mycobacterial strains (M. aurum, M. avium, M. kansasii, and M. smegmatis). Alkaloids 3 and 5 showed moderate antimycobacterial activity against all tested strains (MICs 15.625-31.25 μg/mL). Furthermore, ten semisynthetic berberine (16a-16k) derivatives were developed and tested for antimycobacterial activity. In general, the derivatization of berberine was connected with a significant increase in antimycobacterial activity against all tested strains (MICs 0.39-7.81 μg/mL). Two derivatives (16e, 16k) were identified as compounds with micromolar MICs against M. tuberculosis H37Ra (MIC 2.96 and 2.78 μM). All compounds were also evaluated for their in vitro hepatotoxicity on a hepatocellular carcinoma cell line (HepG2), exerting lower cytotoxicity profile than their MIC values, thereby potentially reaching an effective concentration without revealing toxic side effects.
Berberine, a naturally occurring compound, possesses an interesting multipotent pharmacological profile potentially applicable for Alzheimer's disease (AD) treatment. In this study, a series of novel 22 berberine derivatives was developed and tested in vitro. Berberine core was substituted at position 9-O of its aromatic ring region. All the hybrids under the study revealed multi-targeted profile inhibiting prolyl oligopeptidase, acetylcholinesterase and butyrylcholinesterase highlighting 4a, 4g, 4j, 4l and 4s possessing balanced activities in the micromolar range. The top-ranked candidates in terms of the most pronounced potency against POP, AChE and BChE can be classified as 4d, 4u and 4v, bearing 4-methylbenzyl, (naphthalen-2-yl)methylene and 1-phenoxyethyl moieties, respectively. In vitro data were corroborated by detailed kinetic analysis of the selected lead molecules. 4d, 4u and 4v were also inspected for their potential to inhibit aggregation of two abberant proteins in AD, namely amyloid beta and tau, indicating their potential disease-modifying properties. To explain the results of our study, we carried out docking simulation to the active sites of the respective enzyme with the best berberine derivatives, along with QSAR study. We also investigated compounds' potential permeability through blood-brain barrier by applying parallel artificial membrane permeation assay and addressed their cytotoxicity profile.
- MeSH
- berberin chemie metabolismus farmakologie MeSH
- cholinesterasové inhibitory chemie metabolismus farmakologie MeSH
- cholinesterasy metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- prolyloligopeptidasy antagonisté a inhibitory MeSH
- racionální návrh léčiv * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
