Stilbenoids are important components of foods (e.g., peanuts, grapes, various edible berries), beverages (wine, white tea), and medicinal plants. Many publications have described the anti-inflammatory potential of stilbenoids, including the widely known trans-resveratrol and its analogues. However, comparatively little information is available regarding the activity of their prenylated derivatives. One new prenylated stilbenoid (2) was isolated from Artocarpus altilis and characterized structurally based on 1D and 2D NMR analysis and HRMS. Three other prenylated stilbenoids were prepared synthetically (9-11). Their antiphlogistic potential was determined by testing them together with known natural prenylated stilbenoids from Macaranga siamensis and Artocarpus heterophyllus in both cell-free and cell assays. The inhibition of 5-lipoxygenase (5-LOX) was also shown by simulated molecular docking for the most active stilbenoids in order to elucidate the mode of interaction between these compounds and the enzyme. Their effects on the pro-inflammatory nuclear factor-κB (NF-κB) and the activator protein 1 (AP-1) signaling pathway were also analyzed. The THP1-XBlue-MD2-CD14 cell line was used as a model for determining their anti-inflammatory potential, and lipopolysaccharide (LPS) stimulation of Toll-like receptor 4 induced a signaling cascade leading to the activation of NF-κB/AP-1. The ability of prenylated stilbenoids to attenuate the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was further evaluated using LPS-stimulated THP-1 macrophages.
- MeSH
- buněčné linie MeSH
- cyklooxygenasy metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- lidé MeSH
- lipoxygenasy metabolismus MeSH
- NF-kappa B antagonisté a inhibitory MeSH
- prenylace * MeSH
- signální transdukce účinky léků MeSH
- stilbeny farmakologie MeSH
- transkripční faktor AP-1 antagonisté a inhibitory MeSH
- zánět prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy.
- MeSH
- 2-aminopurin analýza MeSH
- amilorid analýza MeSH
- denaturace nukleových kyselin MeSH
- DNA footprinting MeSH
- DNA-lyasa (apurinová nebo apyrimidinová) antagonisté a inhibitory MeSH
- DNA chemie MeSH
- inhibitory enzymů chemie MeSH
- kalorimetrie MeSH
- poškození DNA * MeSH
- protinádorové látky chemie MeSH
- vazebná místa MeSH
- železnaté sloučeniny chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.
- MeSH
- aflatoxin B1 * metabolismus MeSH
- aktivace transkripce MeSH
- cytochrom P-450 CYP1A1 * genetika metabolismus MeSH
- cytochrom P450 CYP2A6 * metabolismus genetika MeSH
- játra * metabolismus MeSH
- kur domácí * metabolismus MeSH
- promotorové oblasti (genetika) * MeSH
- transkripční faktor AP-1 * metabolismus genetika MeSH
- transkripční faktor Sp1 * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF THE STUDY This study aims to ascertain whether a high anteversion of the femoral neck can influence the measurement of the caputcollum-diaphyseal (CCD) angle on a plain anteroposterior (AP) radiograph of the proximal femur. MATERIAL AND METHODS We developed a new method of measuring the CCD angle and femoral neck version of the femur. This was done with the use of a computer program that utilised the measurement of the entire visualised area of femoral neck and shaft to calculate their long axis. Using this method, we measured the CCD angle and femoral neck version (FNV) of 100 photographed cadaveric femurs in two projections: The condylar line (CL) projection and the femoral neck (FN) projection. The same method was applied to 50 radiographs of the same femurs. The femurs were divided into three groups depending on the femoral neck version: Retro (FNV of <0°), Normal (FNV of 0-15°) and Ante (FNV of >15°) RESULTS We found a statistically significant difference in the CCD angle measured in the FN and CL projections in the Normal and Ante groups but not in the Retro group. There is a significant correlation between the increase in FNV and the difference between the measured CCD values in the FL and CL projections. The femoral neck version of our cadaveric femurs varied from -14. 4° to 31. 5° which is a range of more than 35°. CONCLUSIONS From the results, it is clear that with an increase in femoral neck anteversion, there is a statistically significant difference in the CCD angle measured between the two projections. This difference can be up to almost 10°. Surgeons should be aware of the limitation of the AP projection when planning for surgery on the hip. Key words: femoral neck anteversion, CCD angle, templating, preoperative planning.
- MeSH
- diafýzy MeSH
- femur * diagnostické zobrazování MeSH
- krček femuru diagnostické zobrazování MeSH
- lidé MeSH
- počítačová rentgenová tomografie * MeSH
- radiografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
