Prostate cancer is the most commonly diagnosed tumor disease in men, and its treatment is still a big challenge in standard oncology therapy. Magnetically actuated microrobots represent the most promising technology in modern nanomedicine, offering the advantage of wireless guidance, effective cell penetration, and non-invasive actuation. Here, new biodegradable magnetically actuated zinc/cystine-based microrobots for in situ treatment of prostate cancer cells are reported. The microrobots are fabricated via metal-ion-mediated self-assembly of the amino acid cystine encapsulating superparamagnetic Fe3 O4 nanoparticles (NPs) during the synthesis, which allows their precise manipulation by a rotating magnetic field. Inside the cells, the typical enzymatic reducing environment favors the disassembly of the aminoacidic chemical structure due to the cleavage of cystine disulfide bonds and disruption of non-covalent interactions with the metal ions, as demonstrated by in vitro experiments with reduced nicotinamide adenine dinucleotide (NADH). In this way, the cystine microrobots served for site-specific delivery of Zn2+ ions responsible for tumor cell killing via a "Trojan horse effect". This work presents a new concept of cell internalization exploiting robotic systems' self-degradation, proposing a step forward in non-invasive cancer therapy.

• Klíčová slova
• cysteine, magnetic actuation, micromotors, nanorobots, self-propulsion, tumors,
• MeSH
• cystin * MeSH
• lidé MeSH
• nádory prostaty * MeSH
• zinek MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystin * MeSH
• zinek MeSH

Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure. The application of an untargeted approach, as described in this study, enabled the detection of 24 novel structurally unexpected metabolites. Several sulphur-containing compounds, probably originating after the reaction of reactive intermediates of imatinib with endogenous glutathione, were found and annotated as cysteine and cystine adducts. In the proposed mechanism, the cysteine adducts were formed after the rearrangement of piperazine moiety to imidazoline. On the contrary, in vivo S-N exchange occurred in the case of the cystine adducts. In addition, N-O exchange was observed in the collision cell in the course of the fragmentation of the cystine adducts. The presence of sulphur in the cysteine and cystine conjugates was proved by means of ultra-high resolution measurements using Orbitrap Elite. The detection of metabolites derived from glutathione might improve knowledge about the disposition of imatinib towards bioactivation and help to improve understanding of the mechanism of its hepatotoxicity or nephrotoxicity in humans.

• Klíčová slova
• Compound Discoverer™, Glutathione, Imatinib, LC-HRMS, Metabolization, Untargeted metabolite profiling,
• MeSH
• antitumorózní látky krev   metabolismus   moč   MeSH
• chromatografie kapalinová MeSH
• cystein metabolismus   MeSH
• cystin metabolismus   MeSH
• imatinib mesylát krev   metabolismus   moč   MeSH
• inhibitory proteinkinas krev   metabolismus   moč   MeSH
• lidé MeSH
• síra krev   metabolismus   moč   MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• cystein MeSH
• cystin MeSH
• imatinib mesylát MeSH
• inhibitory proteinkinas MeSH
• síra MeSH

A model small-scale field experiment was set up to investigate selenium (Se) uptake by four different varieties of broccoli plants, as well as the effect of Se foliar application on the uptake of essential elements for plants calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P), sulfur (S), and zinc (Zn). Foliar application of sodium selenate (Na2SeO4) was carried out at two rates (25 and 50 g Se/ha), and an untreated control variant was included. Analyses of individual parts of broccoli were performed, whereby it was found that Se in the plant accumulates mainly in the flower heads and slightly less in the leaves, stems, and roots, regardless of the Se rate and broccoli variety. In most cases, there was a statistically significant increase of Se content in all parts of the plant, while there was no confirmed systematic influence of the addition of Se on the changing intake of other monitored elements. Selenization of broccoli leads to an effective increase in the Se content at a rate of 25 g/ha, whereas the higher rate did not result in a substantial increase of Se content compared to the lower rate in all varieties. Therefore, the rate of 25 g/ha can be recommended as effective to produce broccoli with an increased Se content suitable for consumption. Moreover, Se application resulted in an adequate increase of the main organic compounds of Se, such as selenocystine (SeCys2), selenomethionine (SeMet), and Se-methylselenocysteine (Se-MeSeCys).

• Klíčová slova
• Se-methylselenocysteine, broccoli varieties, selenium, selenocystine, selenomethionine, supplementation,
• MeSH
• biologický transport MeSH
• Brassica účinky léků   metabolismus   MeSH
• cystin analogy a deriváty   izolace a purifikace   metabolismus   MeSH
• kationty dvojmocné metabolismus   MeSH
• kationty jednomocné metabolismus   MeSH
• kořeny rostlin účinky léků   metabolismus   MeSH
• květy účinky léků   metabolismus   MeSH
• listy rostlin účinky léků   metabolismus   MeSH
• organoselenové sloučeniny izolace a purifikace   metabolismus   MeSH
• selenocystein analogy a deriváty   izolace a purifikace   metabolismus   MeSH
• selenomethionin izolace a purifikace   metabolismus   MeSH
• sloučeniny selenu izolace a purifikace   metabolismus   farmakologie   MeSH
• spektrofotometrie atomová MeSH
• stonky rostlin účinky léků   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystin MeSH
• kationty dvojmocné MeSH
• kationty jednomocné MeSH
• organoselenové sloučeniny MeSH
• selenocystein MeSH
• selenocystine MeSH Prohlížeč
• selenomethionin MeSH
• selenomethylselenocysteine MeSH Prohlížeč
• sloučeniny selenu MeSH

Cysteine dioxygenase (CDO) is involved in regulation of intracellular cysteine levels by catabolising the cysteine to sulphite and sulphate. In keratinolytic fungi, sulphite is actively excreted to reduce disulphide bridges in keratin before its enzymatic degradation. The pathogenicity role of CDO was confirmed in cysteine-hypersensitive and growth-defective ΔCdo mutant of Arthroderma benhamiae on hair and nails. We analysed the CDO expression regulation in T. mentagrophytes (anamorph of A. benhamiae) mycelia by determining the Cdo mRNA and CDO protein levels and by analysing the proportion of two molecular forms of CDO in response to l-cystine exposure. Cdo mRNA levels in mycelia lysates were detected by reverse-transcription real-time polymerase chain reaction and CDO protein by western blot using mouse CDO-specific hyperimmune serum. The Cdo mRNA level increased gradually 2.5-4.5 h after exposure of the mycelium to l-cystine. The CDO protein, detected as two bands of different mobility, appeared earlier in comparison to mRNA (1 h) and culminated after 24 h. More mobile form prevailed after 4.5 h. The comparison of the dynamics in the Cdo mRNA and CDO protein levels indicates that T. mentagrophytes responds to l-cystine by increased transcription and apparently decreased degradation of the CDO and by changing towards higher mobility molecular form, similar to previous reports describing mammalian analogue.

• Klíčová slova
• Cysteine dioxygenase, dermatophytes, keratinolysis, vaccination,
• MeSH
• cysteindioxygenasa genetika   metabolismus   MeSH
• cystin metabolismus   MeSH
• fungální proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mycelium enzymologie   genetika   růst a vývoj   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• regulace genové exprese enzymů * MeSH
• tinea mikrobiologie   MeSH
• Trichophyton enzymologie   genetika   růst a vývoj   fyziologie   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cysteindioxygenasa MeSH
• cystin MeSH
• fungální proteiny MeSH

The CART (cocaine- and amphetamine-regulated transcript) peptide is an anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the mechanism of action of this peptide are still unknown. In our previous study, we showed that the CART peptide binds specifically to PC12 rat pheochromocytoma cells in both the native and differentiated into neuronal phenotype. Two biologically active forms, CART(55-102) and CART(61-102), with equal biological activity, contain three disulfide bridges. To clarify the importance of each of these disulfide bridges in maintaining the biological activity of CART(61-102), an Ala scan at particular S-S bridges forming cysteines was performed, and analogs with only one or two disulfide bridges were synthesized. In this study, a stabilized CART(61-102) analog with norleucine instead of methionine at position 67 was also prepared and was found to bind to PC12 cells with an anorexigenic potency similar to that of CART(61-102). The binding study revealed that out of all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide bridges (positions 74-94 and 88-101), preserved a high affinity to both native PC12 cells and those that had been differentiated into neurons. In food intake and behavioral tests with mice after intracerebroventricular administration, this analog showed strong and long-lasting anorexigenic potency. Therefore, the disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted without a loss of biological activity, but the preservation of two other disulfide bridges and the full-length peptide are essential for biological activity.

• MeSH
• anorektika chemie   farmakologie   MeSH
• buňky PC12 MeSH
• cystin chemie   MeSH
• kompetitivní vazba MeSH
• krysa rodu Rattus MeSH
• lokomoce účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nocicepce účinky léků   MeSH
• peptidové fragmenty chemie   farmakologie   MeSH
• přijímání potravy účinky léků   MeSH
• proteiny nervové tkáně chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anorektika MeSH
• cocaine- and amphetamine-regulated transcript peptide (62-102), human MeSH Prohlížeč
• cystin MeSH
• peptidové fragmenty MeSH
• proteiny nervové tkáně MeSH

In the venom of eusocial bee Lasioglossum laticeps, we identified a novel unique antimicrobial peptide named lasiocepsin consisting of 27 amino acid residues and two disulfide bridges. After identifying its primary structure, we synthesized lasiocepsin by solid-phase peptide synthesis using two different approaches for oxidative folding. The oxidative folding of fully deprotected linear peptide resulted in a mixture of three products differing in the pattern of disulfide bridges. Regioselective disulfide bond formation significantly improved the yield of desired product. The synthetic lasiocepsin possessed antimicrobial activity against both Gram-positive and -negative bacteria, antifungal activity against Candida albicans, and no hemolytic activity against human erythrocytes. We synthesized two lasiocepsin analogs cyclized through one native disulfide bridge in different positions and having the remaining two cysteines substituted by alanines. The analog cyclized through a Cys8-Cys25 disulfide bridge showed reduced antimicrobial activity compared to the native peptide while the second one (Cys17-Cys27) was almost inactive. Linear lasiocepsin having all four cysteine residues substituted by alanines or alkylated was also inactive. That was in contrast to the linear lasiocepsin with all four cysteine residues non-paired, which exhibited remarkable antimicrobial activity. The shortening of lasiocepsin by several amino acid residues either from the N- or C-terminal resulted in significant loss of antimicrobial activity. Study of Bacillus subtilis cells treated by lasiocepsin using transmission electron microscopy showed leakage of bacterial content mainly from the holes localized at the ends of the bacterial cells.

• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• Candida albicans účinky léků   MeSH
• cyklické peptidy chemická syntéza   chemie   farmakologie   MeSH
• cystin chemická syntéza   chemie   MeSH
• erytrocyty účinky léků   MeSH
• gramnegativní bakterie účinky léků   MeSH
• grampozitivní bakterie účinky léků   ultrastruktura   MeSH
• hemolýza MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární sekvence - údaje MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční analýza proteinů MeSH
• včelí jedy chemická syntéza   chemie   farmakologie   MeSH
• včely chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• cyklické peptidy MeSH
• cystin MeSH
• lasiocepsin MeSH Prohlížeč
• včelí jedy MeSH

HLA-G is a nonclassical class I MHC molecule with an unknown function and with unusual characteristics that distinguish it from other class I MHC molecules. Here, we demonstrate that HLA-G forms disulfide-linked dimers that are present on the cell surface. Immunoprecipitation of HLA-G from surface biotinylated transfectants using the anti-beta2-microglobulin mAb BBM.1 revealed the presence of an approximately equal 78-kDa form of HLA-G heavy chain that was reduced by using DTT to a 39-kDa form. Mutation of Cys-42 to a serine completely abrogated dimerization of HLA-G, suggesting that the disulfide linkage formed exclusively through this residue. A possible interaction between the HLA-G monomer or dimer and the KIR2DL4 receptor was also investigated, but no interaction between these molecules could be detected through several approaches. The cell-surface expression of dimerized HLA-G molecules may have implications for HLA-Greceptor interactions and for the search for specific receptors that bind HLA-G.

• MeSH
• antigeny povrchové chemie   MeSH
• choriokarcinom imunologie   patologie   MeSH
• cystein chemie   MeSH
• cystin chemie   MeSH
• dimerizace MeSH
• dithiothreitol farmakologie   MeSH
• geny MHC třídy II MeSH
• histokompatibilita - antigeny třídy I chemie   MeSH
• HLA antigeny chemie   MeSH
• HLA-G antigeny MeSH
• lidé MeSH
• mapování interakce mezi proteiny MeSH
• molekulová hmotnost MeSH
• nádorové buňky kultivované MeSH
• nádory dělohy imunologie   patologie   MeSH
• oxidace-redukce MeSH
• receptory imunologické genetika   metabolismus   MeSH
• receptory KIR MeSH
• receptory KIR2DL4 MeSH
• rekombinantní fúzní proteiny chemie   MeSH
• substituce aminokyselin MeSH
• těhotenství MeSH
• transfekce MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• antigeny povrchové MeSH
• cystein MeSH
• cystin MeSH
• dithiothreitol MeSH
• histokompatibilita - antigeny třídy I MeSH
• HLA antigeny MeSH
• HLA-G antigeny MeSH
• KIR2DL4 protein, human MeSH Prohlížeč
• receptory imunologické MeSH
• receptory KIR MeSH
• receptory KIR2DL4 MeSH
• rekombinantní fúzní proteiny MeSH

The compound L-cystine was determined using the method of capillary isotachophoresis in two electrolyte systems. Precision, correctness, linearity, robustness, and selectivity of ITP were evaluated. The results of ITP measurements were compared with the results obtained by means of the standard pharmacopoeial methods.

• MeSH
• cystin analýza   MeSH
• elektroforéza kapilární metody   MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystin MeSH

Vanadium was determined by radiochemical neutron activation analysis (RNAA) with proven accuracy in urine of workers occupationally exposed to vanadium-rich dust in a vanadium pentoxide production plant, and values in the range of 3.02-762 ng/mL (median 33.0 ng/mL) were found. In a control group consisting of administrative workers of the plant, urinary vanadium levels were found in the range of 1.05-53.4 ng/mL (median 2.53 ng/mL), whereas in an another control group of occupationally nonexposed persons, these values amounted to 0.066-0.489 ng/mL (median 0.212 ng/mL). Accuracy of the results was tested by analysis of reference material IAEA A-13 Animal Blood and NIST SRM-1515 Apple Leaves, and very good agreement was found with literature and the NIST certified values, respectively. Unlike urine, no significant differences were found for cystine levels in fingernails and hair of exposed and control persons.

• MeSH
• chemický průmysl * MeSH
• cystin analýza   krev   metabolismus   MeSH
• dospělí MeSH
• hutnictví * MeSH
• lidé středního věku MeSH
• lidé MeSH
• listy rostlin chemie   MeSH
• nehty chemie   metabolismus   MeSH
• neutronová aktivační analýza MeSH
• pracovní expozice analýza   MeSH
• vanad krev   moč   MeSH
• vlasy, chlupy chemie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystin MeSH
• vanad MeSH

We have observed a significantly increased content of fats and decreased content of proteins in the liver of experimental rats fed a diet supplemented with 25% casein proteins in comparison with the application of de-fatted soy flour. Casein proteins have a higher content of methionine in relation to cystine than baked soy flour. But the soy diet in contrast to the casein diet has a high content of free aminoacids which are not present in casein at all: aspartic acid, asparagine, alpha-aminoadipic acid, methionine, norleucine, lysine, phenylalanine, beta-alanine, ethanolamine, histidine, proline, gamma-aminobutyric acid, taurine. Differences in free valine, alanine, arginine, glycine, ornithine and cysteic acid are also significant. The content of free aminoacids in the liver of experimental animals fed a soy diet is high in the content of cystine, cystathionine, ornithine, beta-aminoisobutyric acid, beta-alanine, gamma-aminobutyric acid, leucine. We have also found accumulation of methionine, glycine, alpha-aminobutyric acid, taurine and citrulline in free aminoacids from the liver of animals fed a casein diet. Citrulline and glycine in free aminoacids from the liver of animals fed a soy protein supplement were not recorded. Our investigations have shown that the application of a soy diet enriched with cystine acts protectively on methionine and that methionine is preferentially utilized for protein synthesis. The catabolic pathway of methionine prevails in animals on a casein diet.

• MeSH
• alanin analýza   MeSH
• aminokyseliny analýza   metabolismus   MeSH
• asparagin analýza   MeSH
• cystin analýza   MeSH
• dietní proteiny analýza   farmakologie   MeSH
• fortifikované potraviny MeSH
• glycin analýza   MeSH
• játra chemie   metabolismus   MeSH
• kaseiny analýza   farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina aspartová analýza   MeSH
• methionin analýza   MeSH
• norleucin analýza   MeSH
• ornithin analýza   MeSH
• proteiny ze sójových bobů MeSH
• rostlinné proteiny ve výživě analýza   farmakologie   MeSH
• taurin analýza   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• alanin MeSH
• aminokyseliny MeSH
• asparagin MeSH
• cystin MeSH
• dietní proteiny MeSH
• glycin MeSH
• kaseiny MeSH
• kyselina aspartová MeSH
• methionin MeSH
• norleucin MeSH
• ornithin MeSH
• proteiny ze sójových bobů MeSH
• rostlinné proteiny ve výživě MeSH
• taurin MeSH