Overcoming the skin barrier properties efficiently, temporarily, and safely for successful transdermal drug delivery remains a challenge. We synthesized three series of potential skin permeation enhancers derived from natural amino acid derivatives proline, 4-hydroxyproline, and pyrrolidone carboxylic acid, which is a component of natural moisturizing factor. Permeation studies using in vitro human skin identified dodecyl prolinates with N-acetyl, propionyl, and butyryl chains (Pro2, Pro3, and Pro4, respectively) as potent enhancers for model drugs theophylline and diclofenac. The proline derivatives were generally more active than 4-hydroxyprolines and pyrrolidone carboxylic acid derivatives. Pro2-4 had acceptable in vitro toxicities on 3T3 fibroblast and HaCaT cell lines with IC50 values in tens of μM. Infrared spectroscopy using the human stratum corneum revealed that these enhancers preferentially interacted with the skin barrier lipids and decreased the overall chain order without causing lipid extraction, while their effects on the stratum corneum protein structures were negligible. The impacts of Pro3 and Pro4 on an in vitro transepidermal water loss and skin electrical impedance were fully reversible. Thus, proline derivatives Pro3 and Pro4 have an advantageous combination of high enhancing potency, low cellular toxicity, and reversible action, which is important for their potential in vivo use as the skin barrier would quickly recover after the drug/enhancer administration is terminated.

• MeSH
• aplikace kožní MeSH
• hydroxyprolin metabolismus   MeSH
• kožní absorpce * MeSH
• kůže metabolismus   MeSH
• kyseliny karboxylové metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• organické látky metabolismus   MeSH
• permeabilita MeSH
• prolin * metabolismus   MeSH
• pyrrolidinony farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Due to insufficient amount of soluble phosphate and poor persistence of traditional chemical phosphate fertilizers in agricultural soils, the eco-friendly and sustainable phosphorus sources for crops are urgently required. The efficient phosphate-releasing fungal strain designated y2 was isolated and identified by the internal transcribed spacer of rDNA as Penicillium oxalicum y2. When lecithin, Ca3(PO4)2, or ground phosphate rock were separately used as sole phosphorus source, different phosphate-releasing modes were observed. The strain y2 was able to release as high as 2090 mg/L soluble phosphate within 12 days of incubation with Ca3(PO4)2 as sole phosphorus source. In the culture solution, high concentration of oxalic, citric, and malic acids and high phosphatase activity were detected. The organic acids contributed to solubilizing inorganic phosphate sources, while phosphatase was in charge of the mineralization of organic phosphorus lecithin. Afterwards, the fungus culture was applied to the soil with rape growing. During 50 days of incubation, the soil's available phosphate concentration increased by three times compared with the control, the dry weight of rape increased by 78.73%, and the root length increased by 38.79%. The results illustrated that P. oxalicum y2 possessed both abilities of solubilizing inorganic phosphorus and mineralizing organic phosphorus, which have great potential application in providing biofertilizer for modern agriculture.

• MeSH
• biologická dostupnost MeSH
• Brassica napus růst a vývoj   MeSH
• dusík metabolismus   MeSH
• fosfatasy metabolismus   MeSH
• fosfáty metabolismus   farmakokinetika   MeSH
• fosfor metabolismus   MeSH
• fylogeneze MeSH
• kyseliny karboxylové metabolismus   MeSH
• mezerníky ribozomální DNA genetika   MeSH
• Penicillium klasifikace   genetika   izolace a purifikace   metabolismus   MeSH
• půda chemie   MeSH
• půdní mikrobiologie * MeSH
• uhlík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.

• MeSH
• dobytek MeSH
• karboxypeptidasy metabolismus   MeSH
• kyseliny karboxylové metabolismus   MeSH
• léková rezistence MeSH
• myši MeSH
• parazitemie veterinární   MeSH
• prekurzory léčiv metabolismus   MeSH
• protozoální proteiny metabolismus   MeSH
• sloučeniny boru metabolismus   MeSH
• trypanocidální látky metabolismus   MeSH
• Trypanosoma brucei brucei účinky léků   enzymologie   MeSH
• Trypanosoma congolense účinky léků   enzymologie   MeSH
• Trypanosoma vivax účinky léků   enzymologie   MeSH
• trypanozomóza africká farmakoterapie   parazitologie   veterinární   MeSH
• valin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Biological membranes are tricky to investigate. They are complex in terms of molecular composition and structure, functional over a wide range of time scales, and characterized by nonequilibrium conditions. Because of all of these features, simulations are a great technique to study biomembrane behavior. A significant part of the functional processes in biological membranes takes place at the molecular level; thus computer simulations are the method of choice to explore how their properties emerge from specific molecular features and how the interplay among the numerous molecules gives rise to function over spatial and time scales larger than the molecular ones. In this review, we focus on this broad theme. We discuss the current state-of-the-art of biomembrane simulations that, until now, have largely focused on a rather narrow picture of the complexity of the membranes. Given this, we also discuss the challenges that we should unravel in the foreseeable future. Numerous features such as the actin-cytoskeleton network, the glycocalyx network, and nonequilibrium transport under ATP-driven conditions have so far received very little attention; however, the potential of simulations to solve them would be exceptionally high. A major milestone for this research would be that one day we could say that computer simulations genuinely research biological membranes, not just lipid bilayers.

• MeSH
• biologické modely * MeSH
• fosfolipidy chemie   metabolismus   MeSH
• kyseliny karboxylové chemie   metabolismus   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• membránové lipidy chemie   metabolismus   MeSH
• membrány chemie   metabolismus   fyziologie   MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Microbial ecology has been recognized as useful in archaeological studies. At Archaic Monte Iato in Western Sicily, a native (indigenous) building was discovered. The objective of this study was the first examination of soil microbial communities related to this building. Soil samples were collected from archaeological layers at a ritual deposit (food waste disposal) in the main room and above the fireplace in the annex. Microbial soil characterization included abundance (cellular phospholipid fatty acids (PLFA), viable bacterial counts), activity (physiological profiles, enzyme activities of viable bacteria), diversity, and community structure (bacterial and fungal Illumina amplicon sequencing, identification of viable bacteria). PLFA-derived microbial abundance was lower in soils from the fireplace than in soils from the deposit; the opposite was observed with culturable bacteria. Microbial communities in soils from the fireplace had a higher ability to metabolize carboxylic and acetic acids, while those in soils from the deposit metabolized preferentially carbohydrates. The lower deposit layer was characterized by higher total microbial and bacterial abundance and bacterial richness and by a different carbohydrate metabolization profile compared to the upper deposit layer. Microbial community structures in the fireplace were similar and could be distinguished from those in the two deposit layers, which had different microbial communities. Our data confirmed our hypothesis that human consumption habits left traces on microbiota in the archaeological evidence; therefore, microbiological residues as part of the so-called ecofacts are, like artifacts, key indicators of consumer behavior in the past.

• MeSH
• acetáty metabolismus   MeSH
• archeologie * MeSH
• Bacteria klasifikace   genetika   izolace a purifikace   metabolismus   MeSH
• bakteriální nálož MeSH
• biodiverzita MeSH
• biomasa MeSH
• dějiny starověku MeSH
• DNA bakterií MeSH
• DNA fungální MeSH
• enzymatické testy MeSH
• fosfolipidy metabolismus   MeSH
• heterotrofní procesy MeSH
• houby klasifikace   genetika   metabolismus   MeSH
• kyseliny karboxylové metabolismus   MeSH
• lidské činnosti dějiny   MeSH
• mastné kyseliny metabolismus   MeSH
• mikrobiální společenstva genetika   fyziologie   MeSH
• půda chemie   MeSH
• půdní mikrobiologie * MeSH
• RNA ribozomální 16S genetika   MeSH
• shluková analýza MeSH
• Check Tag
• dějiny starověku MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH

Responses of Scenedesmus quadricauda grown in vitro and differing in age (old culture-13 months, young culture-1 month) to short-term cadmium (Cd) or nickel (Ni) excess (24h) were compared. Higher age of the culture led to lower amount of chlorophylls, ascorbic acid and glutathione but higher signal of ROS. Surprisingly, sucrose was detected using DART-Orbitrap MS in both old and young culture and subsequent quantification confirmed its higher amount (ca. 3-times) in the old culture. Cd affected viability and ROS amount more negatively than Ni that could arise from excessive Cd uptake which was also higher in all treatments than in respective Ni counterparts. Surprisingly, nitric oxide was not extensively different in response to age or metals. Strong induction of phytochelatin 2 is certainly Cd-specific response while Ni also elevated ascorbate content. Krebs cycle acids were more accumulated in the young culture but they were rather elevated in the old culture (citric acid under Ni excess). We conclude that organic solid 'Milieu Bristol' medium we tested is suitable for long-term storage of unicellular green algae (also successfully tested for Coccomyxa sp. and Parachlorella sp.) and the impact of age on metal uptake may be useful for bioremediation purposes.

• MeSH
• fytochelatiny metabolismus   MeSH
• kadmium farmakokinetika   toxicita   MeSH
• kyseliny karboxylové metabolismus   MeSH
• metabolom účinky léků   MeSH
• nikl farmakokinetika   toxicita   MeSH
• oxid dusnatý metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Scenedesmus účinky léků   růst a vývoj   metabolismus   MeSH
• sulfhydrylové sloučeniny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A novel 1,1,1,2,2,3,3-heptafluorobutyl chloroformate reagent (HFBCF) was examined for in-situ derivatization of amino-carboxylic metabolites in human urine. The arising reaction products exhibit greatly reduced polarity which facilitates combining the derivatization and liquid-liquid microextraction (LLME) from an aqueous urine into an isooctane phase and immediate gas chromatographic-mas spectrometric analysis (GC-MS). The sample preparation protocol is simple, proceeds without an alcohol excess and provides cleaner extracts than other urinary GC-MS based methods. Moreover, thiol metabolites bound in disulfide bonds can be released by reduction with tris(3-hydroxypropyl)phosphine (THP) prior to the developed derivatization and LLME step. In order to evaluate potential of the novel method for GC-MS metabolomics, reaction products of 153 urinary metabolites with HFBCF, particularly those possessing amino and carboxyl groups (56 amino acids and their conjugates, 84 organic acids, 9 biogenic amines, 4 other polar analytes) and two internal standards were investigated in detail by GC-MS and liquid chromatography-mass spectrometry (LC-MS). One hundred and twenty metabolites (78%) yielded a single product, 25 (16%) and 2 metabolites (2-methylcitrate, citrate) generated two and more derivatives. From the examined set, analytically applicable products of 5 metabolites were not detected; the derivatives of 3 metabolites were only suitable for LC-MS analysis. Electron ionization (EI) of the examined analytes contained characteristic, diagnostic ions enabling to distinguish related and isomeric structures. The new method was validated for 132 metabolites using two internal standards in artificial urine and with special attention to potential disease biomarker candidates. The developed sample preparation protocol was finally evaluated by means of a certified organic acid standard mixture in urine and by GC-MS analysis of 100 morning urines obtained from healthy patients (50 males and 50 females), where 112 physiological metabolites were quantified in a 25 μL sample aliquot. The quantification data for the set were satisfactory, most metabolites were found within the range reported in the reference human metabolome (HMDB) database and literature. The reported results suggest that the described method has been a novel promising tool for targeted GC-MS based metabolomic analysis in urine.

• MeSH
• aminokyseliny analýza   chemie   metabolismus   MeSH
• analýza moči metody   MeSH
• fluorokarbony chemie   MeSH
• formiáty chemie   MeSH
• indikátory a reagencie MeSH
• kyseliny karboxylové analýza   chemie   metabolismus   MeSH
• lidé MeSH
• metabolomika metody   MeSH
• mikroextrakce kapalné fáze MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Ginkgo biloba has long been used in traditional Chinese medicine. In this study, ginkgoneolic acid, a kind of compound extracted from G. biloba, was investigated for its effects on growth, acid production, adherence, biofilm formation, and biofilm morphology of Streptococcus mutans. The results showed that ginkgoneolic acid inhibited not only the growth of S. mutans planktonic cells at minimum inhibitory concentration (MIC) of 4 μg/mL and minimum bactericidal concentration (MBC) of 8 μg/mL but also the acid production and adherence to saliva-coated hydroxyapatite of S. mutans at sub-MIC concentration. In addition, this agent was effective in inhibiting the biofilm formation of S. mutans (MBIC(50) = 4 μg/mL), and it reduced 1-day-developed biofilm of S. mutans by 50 % or more at low concentration (MBRC(50) = 32 μg/mL). Furthermore, the present study demonstrated that ginkgoneolic acid disrupted biofilm integrity effectively. These findings suggest that ginkgoneolic acid is a natural anticariogenic agent in that it exhibits antimicrobial activity against S. mutans and suppresses the specific virulence factors associated with its cariogenicity.

• MeSH
• antibakteriální látky izolace a purifikace   farmakologie   MeSH
• bakteriální adheze účinky léků   MeSH
• biofilmy růst a vývoj   MeSH
• Ginkgo biloba chemie   MeSH
• kyseliny karboxylové metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• mikrobiální viabilita účinky léků   MeSH
• rostlinné extrakty izolace a purifikace   farmakologie   MeSH
• sliny mikrobiologie   MeSH
• Streptococcus mutans účinky léků   růst a vývoj   metabolismus   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH

The use of natural chelates to enhance risk element mobility combined with rhizofiltration by free floating macrophytes have not been thoroughly studied in recent years. The aim of this study was to investigate the efficiency of organic acids in soil by conducting flushing experiments to enhance the mobility of Cd, Pb, and Zn from soil to solution. In addition, the bioaccumulation of Cd, Pb, and Zn, in water lettuce (Pistia stratiotes L.) will be studied as they affect the biomass in the rhizofiltration process. The results revealed that citric and tartaric acids mobilised the highest amount of all risk elements. In comparison to control, citric acid mobilised 71%, 181%, and 112% of Cd, Pb, and Zn while tartaric acid mobilised 70%, 155%, and 135% of Cd, Pb, and Zn respectively. The bioconcentration factor was approximately 2-5 times higher for juvenile plants than mature plants for all treatments as well as for both parts (leaves and roots). The risk element translocation into aerial parts decreased with increased time. Juvenile and mature plants proved a high accumulation potential and a 3 week growth period was observed as a sufficient time period to remove more than 80% of Cd, Pb, and Zn.

• MeSH
• Araceae růst a vývoj   metabolismus   MeSH
• biodegradace MeSH
• biologický transport MeSH
• biomasa MeSH
• časové faktory MeSH
• chemické látky znečišťující vodu metabolismus   MeSH
• kadmium metabolismus   MeSH
• kořeny rostlin růst a vývoj   metabolismus   MeSH
• kyselina citronová metabolismus   MeSH
• kyseliny karboxylové metabolismus   MeSH
• látky znečišťující půdu metabolismus   MeSH
• listy rostlin růst a vývoj   metabolismus   MeSH
• olovo metabolismus   MeSH
• půda chemie   MeSH
• tartaráty metabolismus   MeSH
• těžké kovy metabolismus   MeSH
• zinek metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• alkaloidy izolace a purifikace   metabolismus   MeSH
• aminokyseliny cyklické izolace a purifikace   metabolismus   MeSH
• aminokyseliny farmakologie   izolace a purifikace   metabolismus   MeSH
• antibakteriální látky izolace a purifikace   MeSH
• Bacteria MeSH
• farmakologické účinky MeSH
• houby MeSH
• isomerasy aminokyselin farmakologie   izolace a purifikace   metabolismus   MeSH
• kyseliny karboxylové farmakologie   izolace a purifikace   metabolismus   MeSH
• peptidy farmakologie   izolace a purifikace   metabolismus   MeSH
• rostliny MeSH
• Publikační typ
• přehledy MeSH