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.
- 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
Prezentujeme pětiletou pacientku s několikaměsíční anamnézou recidivujících infekcí dolních močových cest doprovázených častějším močením s hematurií. Na prostém rentgenovém snímku břicha byl v oblasti malé pánve prokázán oválný sytý stín, odpovídající konkrementu močového měchýře. Ultrazvukové vyšetření močového měchýře potvrdilo hyperechogenní útvar s mohutným dorzálním akustickým stínem, který odpovídal konkrementu. Cystinový kámen měl rozměry 4,5 × 3,6 cm. Otevřená cystolitotomie byla zvolena za nejlepší a nejbezpečnější chirurgickou léčbu.
A 5-year-old female patient with several months history of recurrent lower urinary tract infection presented with a complaint of frequency of micturition and hematuria. On plain abdominal radiography an elliptic opacified mass occupying the cavity of the small pelvis was detected. Ultrasonic bladder examination has shown a hyperechogenic formation with a massive dorsal acoustic shadow, which corresponds to the stones. The cystine bladder stone was oval-shaped 4,0 × 3,6 cm in size. Open cystolithotomy was therefore selected as the best and safest treatment choice.
- MeSH
- cystin MeSH
- kameny močového měchýře * terapie MeSH
- lidé MeSH
- močový měchýř patologie MeSH
- předškolní dítě MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Prezentujeme pětiletou pacientku s několikaměsíční anamnézou recidivujících infekcí dolních močových cest doprovázených častějším močením s hematurií. Na prostém rentgenovém snímku břicha byl v oblasti malé pánve prokázán oválný sytý stín, odpovídající konkrementu močového měchýře. Ultrazvukové vyšetření močového měchýře potvrdilo hyperechogenní útvar s mohutným dorzálním akustickým stínem, který odpovídal konkrementu. Cystinový kámen měl rozměry 4,5 × 3,6 cm. Otevřená cystolitotomie byla zvolena za nejlepší a nejbezpečnější chirurgickou léčbu.
A 5-year-old female patient with several months history of recurrent lower urinary tract infection presented with a complaint of frequency of micturition and hematuria. On plain abdominal radiography an elliptic opacified mass occupying the cavity of the small pelvis was detected. Ultrasonic bladder examination has shown a hyperechogenic formation with a massive dorsal acoustic shadow, which corresponds to the stones. The cystine bladder stone was oval-shaped 4,0 × 3,6 cm in size. Open cystolithotomy was therefore selected as the best and safest treatment choice.
- MeSH
- cystin izolace a purifikace škodlivé účinky MeSH
- cystinurie diagnóza genetika komplikace MeSH
- diagnostické techniky urologické MeSH
- hematurie diagnóza MeSH
- infekce močového ústrojí * diagnóza komplikace terapie MeSH
- kameny močového měchýře * diagnóza chirurgie komplikace MeSH
- lidé MeSH
- předškolní dítě MeSH
- urologické chirurgické výkony * metody MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem 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.
- 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
- MeSH
- citráty terapeutické užití MeSH
- cystin genetika metabolismus škodlivé účinky MeSH
- cystinurie * genetika moč patofyziologie MeSH
- dítě MeSH
- lidé MeSH
- mikrocefalie MeSH
- pití MeSH
- poruchy růstu MeSH
- svalová hypotonie MeSH
- urolitiáza epidemiologie etiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky 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).
- 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
Článek pojednává o současných trendech metafylaxe urolitiázy, laboratorních vyšetřeních krve a moči určených k prevenci recidivy močových kamenů. Podrobněji jsou rozebrány dietní a léková opatření (obecná a specifická), jakožto i nejčastější metabolické poruchy spojené s tvorbou jednotlivých typů konkrementů.
The article deals with the current trends in the metaphylaxis of urolithiasis and laboratory blood and urine tests intended to prevent the recurrence of urinary stones. Dietary and medical measures (general and specific) as well as the most common metabolic disorders associated with the formation of particular types of concrements are discussed in more detail.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- citráty terapeutické užití MeSH
- cystin metabolismus škodlivé účinky účinky léků MeSH
- dietoterapie metody využití MeSH
- farmakoterapie * metody využití MeSH
- hyperkalciurie etiologie prevence a kontrola terapie MeSH
- hyperoxalurie etiologie prevence a kontrola terapie MeSH
- kaménky diagnóza etiologie terapie MeSH
- kaptopril terapeutické užití MeSH
- klinické laboratorní techniky metody využití MeSH
- kyselina močová izolace a purifikace MeSH
- lidé MeSH
- metabolické nemoci diagnóza etiologie terapie MeSH
- methionin terapeutické užití MeSH
- močové kameny diagnóza etiologie terapie MeSH
- oxaláty MeSH
- urolitiáza * diagnóza prevence a kontrola terapie MeSH
- urologické chirurgické výkony * metody využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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.
- 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
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
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
