TiO2 nanoparticles are highly produced nanomaterials from industry and commonly found in the air we breathe, but their interactions with lung surfactants and impairing lung functions have not well understood. In this study, effects of two crystalline structures of TiO2 nanoparticles, i.e., anatase and rutile, with their various sizes, shapes, surface charges and concentrations, interacting with a single-component model of pulmonary surfactant, were studied. Nonlinear interfacial rheology was used to quantitatively distinguish effects of nanoparticles at different stages of breathing cycles. Oscillation studies which simulated the breathing cycles in different human ages showed that both crystalline structures of TiO2 nanoparticles made nanoparticles-dipalmitoyl phosphatidylcholine (DPPC) system more viscous, dissipative and irreversible during the oscillations, thus affecting the normal operation of lung surfactant. At the least concentration of nanoparticles studied, i.e., 0.01 wt%, the anatase ones significantly affected the expansion part of the cycle, whereas the rutile ones affected both expansion and compression phases. Interactions between DPPC and TiO2 nanoparticles under dynamic conditions of breathing cycles were affected by the crystalline structures and concentrations of nanoparticles and breathing conditions, with key factors including physical properties, such as sizes, shapes, and zeta potentials of nanoparticles. These results are crucial for understanding the adverse effects of nanosized pollutants in the lungs and applying drug delivery into lungs.
- Klíčová slova
- Air-liquid interface, DPPC, Lung Surfactant, Surface tension, Titanium dioxide nanoparticles,
- MeSH
- 1,2-dipalmitoylfosfatidylcholin chemie MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- plicní surfaktanty * chemie MeSH
- reologie MeSH
- titan * chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1,2-dipalmitoylfosfatidylcholin MeSH
- plicní surfaktanty * MeSH
- titan * MeSH
- titanium dioxide MeSH Prohlížeč
Alterations in the excitability of dorsal root ganglion (DRG) neurons are critical in the pathogenesis of acute and chronic pain. Neurotransmitter release from the terminals of DRG neurons is regulated by cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both activated by anandamide (AEA). In our experiments, the AEA precursor N-arachidonoylphosphatidylethanolamine (20:4-NAPE) was used to study the modulation of nociceptive DRG neurons excitability using K+-evoked Ca2+ transients. Intrathecal administration was used to evaluate in vivo effects. Application of 20:4-NAPE at lower concentrations (10 nM - 1 µM) decreased the excitability of DRG neurons, whereas the higher (10 µM) increased it. Both effects of 20:4-NAPE were blocked by the N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. Similarly, lower concentrations of externally applied AEA (1 nM - 10 nM) inhibited DRG neurons, whereas higher concentration (100 nM) did not change it. High AEA concentration (10 µM) evoked Ca2+ transients dependent on TRPV1 activation in separate experiments. Inhibition of the CB1 receptor by PF514273 (400 nM) prevented the 20:4-NAPE- and AEA-induced inhibition, whereas TRPV1 inhibition by SB366791 (1 µM) prevented the increased DRG neuron excitability. In behavioral tests, lower 20:4-NAPE concentration caused hyposensitivity, while higher evoked mechanical allodynia. Intrathecal LEI-401 prevented both in vivo effects of 20:4-NAPE. These results highlight anti- and pro-nociceptive effects of 20:4-NAPE mediated by CB1 and TRPV1 in concentration-dependent manner. Our study underscores the complexity of endocannabinoid signaling in pain transmission modulation and highlights 20:4-NAPE as a potential therapeutic target, offering new insights for developing analgesic strategies.
- Klíčová slova
- 20:4-NAPE, Anandamide, CB1, DRG neurons, NAPE-PLD, TRPV1,
- MeSH
- endokanabinoidy farmakologie metabolismus MeSH
- fosfatidylethanolaminy * farmakologie MeSH
- fosfolipasa D * metabolismus antagonisté a inhibitory MeSH
- kationtové kanály TRPV metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny arachidonové * farmakologie MeSH
- neurony * účinky léků metabolismus MeSH
- polynenasycené alkamidy farmakologie MeSH
- potkani Sprague-Dawley MeSH
- receptor kanabinoidní CB1 metabolismus MeSH
- spinální ganglia * účinky léků metabolismus cytologie MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anandamide MeSH Prohlížeč
- endokanabinoidy MeSH
- fosfatidylethanolaminy * MeSH
- fosfolipasa D * MeSH
- kationtové kanály TRPV MeSH
- kyseliny arachidonové * MeSH
- polynenasycené alkamidy MeSH
- receptor kanabinoidní CB1 MeSH
- Trpv1 protein, rat MeSH Prohlížeč
- vápník MeSH
The light reactions of oxygenic photosynthesis are performed by protein complexes embedded in the lipid bilayer of thylakoid membranes (TMs). Bilayers provide optimal conditions for the build-up of the proton motive force (pmf) and ATP synthesis. However, functional plant TMs, besides the bilayer, contain an inverted hexagonal (HII) phase and isotropic phases, a lipid polymorphism due to their major, non-bilayer lipid species, monogalactosyldiacylglycerol (MGDG). The lipid phase behavior of TMs is explained within the framework of the Dynamic Exchange Model (DEM), an extension of the fluid-mosaic model. DEM portrays the bilayer phase as inclusions between photosynthetic supercomplexes - characterized by compromised membrane impermeability and restricted sizes inflicted by the segregation propensity of lipid molecules, safe-guarding the high protein density of TMs. Isotropic phases mediate membrane fusions and are associated with the lumenal lipocalin-like enzyme, violaxanthin de-epoxidase. Stromal-side proteins surrounded by lipids give rise to the HII phase. These features instigate experimentally testable hypotheses: (i) non-bilayer phases mediate functional sub-compartmentalization of plant chloroplasts - a quasi-autonomous energization and ATP synthesis of each granum-stroma TM assembly; and (ii) the generation and utilization of pmf depend on hydrated protein networks and proton-conducting pathways along membrane surfaces - rather than on strict impermeability of the bilayer.
Brassinosteroid hormones are positive regulators of plant organ growth, yet their function in proliferating tissues remains unclear. Here, through integrating single-cell RNA sequencing with long-term live-cell imaging of the Arabidopsis root, we reveal that brassinosteroid activity fluctuates throughout the cell cycle, decreasing during mitotic divisions and increasing during the G1 phase. The post-mitotic recovery of brassinosteroid activity is driven by the intrinsic polarity of the mother cell, resulting in one daughter cell with enhanced brassinosteroid signaling, while the other supports brassinosteroid biosynthesis. The coexistence of these distinct daughter cell states during the G1 phase circumvents a negative feedback loop to facilitate brassinosteroid production while signaling increases. Our findings uncover polarity-guided, uneven mitotic divisions in the meristem, which control brassinosteroid hormone activity to ensure optimal root growth.
- Klíčová slova
- brassinosteroids, cell cycle, cell division, cell polarity, live-cell imaging, root meristem, single-cell RNA sequencing,
- MeSH
- Arabidopsis * metabolismus cytologie růst a vývoj MeSH
- brassinosteroidy * metabolismus MeSH
- kořeny rostlin * cytologie metabolismus růst a vývoj MeSH
- meristém metabolismus cytologie MeSH
- mitóza * MeSH
- polarita buněk * MeSH
- proliferace buněk MeSH
- proteiny huseníčku metabolismus genetika MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin metabolismus MeSH
- signální transdukce MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- brassinosteroidy * MeSH
- proteiny huseníčku MeSH
- regulátory růstu rostlin MeSH
Chemical derivatization involves the reaction of an analyte with a derivatization agent to modify its structure, improving the peak shape, chromatographic performance, structural analysis, ionization efficiency, and sensitivity. A novel derivatization method using 3-(chlorosulfonyl)benzoic acid is developed for the determination of monoacylglycerols, diacylglycerols, free sterols, and tocopherols using the reversed-phase ultra-high-performance liquid chromatography-tandem mass spectrometry (RP-UHPLC/MS/MS) method in the negative ion mode. The chromatographic and mass spectrometric properties of derivatized lipids are investigated by using 29 lipid standards spanning four lipid classes. The derivatization process is optimized using pooled plasma spiked by 9 internal standards, achieving an optimal yield with a reaction time of 40 min at 60 °C. The stability of the derivatives is confirmed, with short-term stability maintained for 10 h at 4 °C and long-term stability preserved for 5 days at -80 °C. The repeatability and reproducibility are verified by one/two operator(s), which underscores the simplicity and robustness of the method, and calibration curves with high linear regression coefficients illustrate the accuracy of the method. The derivatization approach, which combines RP-UHPLC/MS/MS and the use of specific fragmentation patterns, significantly reduces limits of detection, reaching 15-25 pmol/mL for free sterols in plasma. The optimized method is applied to the analysis of human plasma, leading to the identification of 92 lipid species in the targeted lipid classes. This represents a substantial improvement in sensitivity and detection capabilities compared to those of previously reported methods.
Developing novel anticancer agents requires understanding their interactions with biological systems at both the cellular and molecular levels. Enantiomeric lactones have demonstrated notable cytotoxic activities against various cancer cell lines. Building on this foundation, we investigated enantiomeric piperonal-derived trans-β-aryl-δ-iodo-γ-lactones ((-)-(4S,5R,6S) and (+)-(4R,5S,6R)), focusing on their impact on cancer cells membrane (Jurkat and GL-1), model membranes, and biomacromolecules such as human serum albumin (HSA) and DNA. Also, the cytotoxicity toward red blood cells and the antitumor activity of the compounds were evaluated against a set of canine lymphoma and/or leukemia cell lines. Membrane interaction studies revealed that both enantiomers interact with the hydrophobic core of lipid bilayers, enhancing lipid acyl chain packing, with the (-)-(4S,5R,6S) isomer showing a stronger impact on membrane fluidity. Comprehensive spectroscopic and theoretical studies revealed distinct stereochemical differences in binding affinities to HSA, where the (-)-(4S,5R,6S) isomer showed higher binding affinity and significant hydrophobic interactions. Detailed biological studies demonstrated that both enantiomers exhibit antiproliferative and proapoptotic activities, with the (-)-(4S,5R,6S) enantiomer showing higher activity. This study underscores the biological activity and interactions of enantiomeric iodolactones derived from piperonal with biomacromolecules, providing comprehensive insights into their biophysical behavior and potential anticancer properties.
- Klíčová slova
- DNA, Enantiomeric iodolactones, HSA, Single-molecule fluorescence spectroscopy, cancer cell membrane,
- MeSH
- buněčná membrána * účinky léků metabolismus MeSH
- DNA * metabolismus chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- laktony chemie farmakologie MeSH
- lidé MeSH
- lidský sérový albumin chemie MeSH
- lipidové dvojvrstvy chemie MeSH
- nádorové buněčné linie MeSH
- protinádorové látky * farmakologie chemie MeSH
- psi MeSH
- stereoizomerie MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA * MeSH
- laktony MeSH
- lidský sérový albumin MeSH
- lipidové dvojvrstvy MeSH
- protinádorové látky * MeSH
Brassinosteroids (BRs) are phytohormones which regulate various developmental processes in plants. They are exceptional phytohormones, as they do not undergo long-distance transport between plant organs. However, knowledge about the function of the enzymes that catalyse BR biosynthesis (particularly its early stages) in cereal crops remains limited. Therefore, this study identifies and analyses the function of the HvDWARF5 (HvDWF5) gene, involved in the early stage of BR biosynthesis in barley (Hordeum vulgare), an important cereal crop, using the TILLING (Targeting Induced Local Lesions IN Genomes) approach. The detailed functional analysis allowed for the identification of various mutations in different gene fragments. The influence of these mutations on plant architecture, reproduction, and yield was characterised. Moreover, effects of the missense and intron retention mutations on sequence and splicing of the HvDWF5 transcript, sequence and predicted structure of the encoded HvDWF5 enzyme, and accumulation of endogenous BR were determined. Some of the barley mutants identified in this study showed semi-dwarfism, a trait of particular importance for cereal breeding and yield. However, unlike other BR mutants in cereals, this did not negatively affect grain size or weight. It indicated that mutations in this gene allow for a balance between plant height reduction and maintenance of grain size. Thus, the results of this study provide a novel insight into the role of the HvDWF5 gene in the BR biosynthesis-dependent regulation of architecture and reproduction of the important cereal crop - barley.
- MeSH
- brassinosteroidy * metabolismus biosyntéza MeSH
- fenotyp MeSH
- ječmen (rod) * genetika metabolismus růst a vývoj MeSH
- jedlá semena genetika metabolismus růst a vývoj MeSH
- mutace * genetika MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin metabolismus MeSH
- rostlinné geny MeSH
- rostlinné proteiny * genetika metabolismus MeSH
- semena rostlinná genetika růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- brassinosteroidy * MeSH
- regulátory růstu rostlin MeSH
- rostlinné proteiny * MeSH
BACKGROUND AND AIMS: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. METHODS: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD. RESULTS: Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77-48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10-2.63 and odds ratio 1.65, 95% confidence interval 1.27-2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations. CONCLUSIONS: Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.
- Klíčová slova
- Adiposity, Atherosclerosis, Dyslipidaemia, Insulin resistance,
- MeSH
- dítě MeSH
- dospělí MeSH
- heterozygot MeSH
- hyperlipoproteinemie typ II * epidemiologie komplikace MeSH
- index tělesné hmotnosti MeSH
- kardiovaskulární nemoci epidemiologie etiologie MeSH
- LDL-cholesterol krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nadváha * epidemiologie komplikace MeSH
- obezita * komplikace epidemiologie MeSH
- prevalence MeSH
- průřezové studie MeSH
- registrace * MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- LDL-cholesterol MeSH
The study focused on the changes in C-peptide, glycemia, insulin concentration, and insulin resistance according to LDL-cholesterol concentration ranges. The metabolic profile of individuals in the Czech Republic (n = 1840) was classified by quartiles of LDL-cholesterol into four groups with the following ranges: 0.46-2.45 (n = 445), 2.46-3.00 (n = 474), 3.01-3.59 (n = 459), and 3.60-7.18 mmol/l (n = 462). The level of glucose, C-peptide, insulin, and area of parameters during OGTT and HOMA IR were compared with a relevant LDL-cholesterol range. The evaluation involved correlations between LDL-cholesterol and the above parameters, F-test and t-test. Generally, mean values of glucose homeostasis-related parameters were higher with increasing LDL-cholesterol levels, except for mean HOMA IR values which rapidly increased (2.7-3.4) between LDL-cholesterol ranges of 3.00-3.59 and 3.60-7.18 mmol/l. Glucose, C-peptide, insulin concentrations, and the area of parameters reached greater changes especially after glucose load during OGTT (p ≤ 0.001). Considerable changes were already observed for the above parameters between groups with LDL-cholesterol ranges of 2.46-3.00 and 3.01-3.59 mmol/l. HOMA IR increased with higher LDL-cholesterol concentrations, but the differences in mean values were not statistically significant. Most important differences appeared in glucose metabolism at LDL-cholesterol concentrations of 3.60-7.18 mmol/l in comparison to LDL-cholesterol lower ranges. In particular, the areas of C-peptide, glucose, and insulin ranges showed statistically significant differences between all groups with growing LDL-cholesterol ranges. The variances of HOMA IR statistically differed between groups created according to LDL-cholesterol concentrations ranges.
- Klíčová slova
- C-peptide, Glucose, HOMA IR, Insulin, LDL-cholesterol,
- MeSH
- C-peptid * krev MeSH
- dospělí MeSH
- glukózový toleranční test MeSH
- inzulin * krev MeSH
- inzulinová rezistence * MeSH
- krevní glukóza * analýza metabolismus MeSH
- LDL-cholesterol * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- C-peptid * MeSH
- inzulin * MeSH
- krevní glukóza * MeSH
- LDL-cholesterol * MeSH
Artificial anion transporters offer a potential way to treat deficiencies in cellular anion transport of genetic origins. In contrast to the large variety of mobile anion carriers and self-assembled anion channels reported, unimolecular anion channels are less investigated. Herein, we present a unique example of a unimolecular anion channel based on a bambusuril (BU) macrocycle, a well-established anion receptor. The BU structure was expanded by appending various bile acid residues allowing a single molecule to span the membrane. Chloride transport mediated by BUs through lipid bilayers was investigated in liposomes and these studies revealed a surprisingly high dependence of the anion transport activity on the cholesterol content in the liposomal membrane.
- Klíčová slova
- Anion Channels, Anion transport, Bambusurils, Macrocycles, Supramolecular Chemistry,
- MeSH
- anionty * chemie MeSH
- cholesterol * chemie metabolismus MeSH
- iontový transport MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- liposomy chemie metabolismus MeSH
- molekulární struktura MeSH
- žlučové kyseliny a soli * chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anionty * MeSH
- cholesterol * MeSH
- lipidové dvojvrstvy MeSH
- liposomy MeSH
- žlučové kyseliny a soli * MeSH
