Alginate lyases have countless potential for application in industries and medicine particularly as an appealing biocatalyst for the production of biofuels and bioactive oligosaccharides. Solid-state fermentation (SSF) allows improved production of enzymes and consumes less energy compared to submerged fermentation. Seaweeds can serve as the most promising biomass for the production of biochemicals. Alginate present in the seaweed can be used by alginate lyase-producing bacteria to support growth and can secrete alginate lyase. In this perspective, the current study was directed on the bioprocessing of brown seaweeds for the production of alginate lyase using marine bacterial isolate. A novel alginate-degrading marine bacterium Enterobacter tabaci RAU2C which was previously isolated in the laboratory was used for the production of alginate lyase using Sargassum swartzii as a low-cost solid substrate. Process parameters such as inoculum incubation period and moisture content were optimized for alginate lyase production. SSF resulted in 33.56 U/mL of alginate lyase under the static condition maintained with 75% moisture after 4 days. Further, the effect of different buffers, pH, and temperature on alginate lyase activity was also analyzed. An increase in alginate lyase activity was observed with an increase in moisture content from 60 to 75%. Maximum enzyme activity was perceived with phosphate buffer at pH 7 and 37 °C. Further, the residual biomass after SSF could be employed as biofertilizer for plant growth promotion based on the preliminary analysis. To our knowledge, this is the first report stating the usage of seaweed biomass as a substrate for the production of alginate lyase using solid-state fermentation.

• Klíčová slova
• Enterobacter tabaci RAU2C, Alginate lyase, Seaweeds, Solid-state fermentation,
• MeSH
• algináty * metabolismus   MeSH
• biomasa MeSH
• Enterobacter * metabolismus   enzymologie   izolace a purifikace   růst a vývoj   MeSH
• fermentace * MeSH
• koncentrace vodíkových iontů MeSH
• kyselina glukuronová metabolismus   MeSH
• mořské řasy * mikrobiologie   MeSH
• Phaeophyceae mikrobiologie   MeSH
• polysacharid-lyasy * metabolismus   MeSH
• Sargassum * mikrobiologie   metabolismus   MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• algináty * MeSH
• kyselina glukuronová MeSH
• poly(beta-D-mannuronate) lyase MeSH Prohlížeč
• polysacharid-lyasy * MeSH

The synthesis and antiproliferative evaluation of novel d-glucopyranuronamide-containing nucleosides is described. Based on our previously reported anticancer d-glucuronamide-based nucleosides, new analogues comprising N/O-dodecyl or N-propargyl substituents at the glucuronamide unit and anomerically-N-linked 2-acetamido-6-chloropurine, 6-chloropurine or 4-(6-chloropurinyl)methyl triazole motifs were synthesized in 4-6 steps starting from acetonide-protected glucofuranurono-6,3-lactone. The methodologies were based on the access to N-substituted glycopyranuronamide precursors, namely 1,2-O-acetyl derivatives or glucuronoamidyl azides for further nucleobase N-glycosylation or 1,3-dipolar cycloaddition with N9 - and N7 -propargyl-6-chloropurines, respectively. N-Propargyl glucuronamide-based N9 -purine nucleosides were converted into (triazolyl)methyl amide-6,6-linked pseudodisaccharide nucleosides via cycloaddition with methyl 6-azido-glucopyranoside. A CuI/Amberlyst A-21 catalytic system employed in the cycloaddition reactions also effected conversion into 6-dimethylaminopurine nucleosides. Antiproliferative evaluation in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells revealed significant effects exhibited by the synthesized monododecylated purine-containing nucleosides. A N-propargyl 3-O-dodecyl glucuronamide derivative comprising a N9 -β-linked 6-chloropurine moiety was the most active compound against MCF-7 cells (GI50 =11.9 μM) while a related α-(purinyl)methyltriazole nucleoside comprising a N7 -linked 6-chloropurine moiety exhibited the highest activity against K562 cells (GI50 =8.0 μM). Flow cytometry and immunoblotting analysis of apoptosis-related proteins in K562 cells treated with the N-propargyl 3-O-dodecyl glucuronamide-based N9 -linked 6-chloropurine nucleoside indicated that it acts via apoptosis induction.

• Klíčová slova
• N-glycosylation, antiproliferative activity, cycloaddition, d-glucuronamide, nucleoside analogs,
• MeSH
• amidy * farmakologie   MeSH
• glukuronáty MeSH
• lidé MeSH
• nukleosidy * farmakologie   MeSH
• purinové nukleosidy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amidy * MeSH
• glucuronamide MeSH Prohlížeč
• glukuronáty MeSH
• nukleosidy * MeSH
• purinové nukleosidy MeSH

Luteolin and naringenin are flavonoids found in various foods/beverages and present in certain dietary supplements. After a high intake of these flavonoids, their sulfate and glucuronide conjugates reach micromolar concentrations in the bloodstream. Some pharmacokinetic interactions of luteolin and naringenin have been investigated in previous studies; however, only limited data are available in regard to their metabolites. In this study, we aimed to investigate the interactions of the sulfate and glucuronic acid conjugates of luteolin and naringenin with human serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. Our main findings are as follows: (1) Sulfate conjugates formed more stable complexes with albumin than the parent flavonoids. (2) Luteolin and naringenin conjugates showed no or only weak inhibitory action on the CYP enzymes examined. (3) Certain conjugates of luteolin and naringenin are potent inhibitors of OATP1B1 and/or OATP2B1 enzymes. (4) Conjugated metabolites of luteolin and naringenin may play an important role in the pharmacokinetic interactions of these flavonoids.

• Klíčová slova
• Cytochrome P450 enzymes, Human serum albumin, Luteolin, Naringenin, OATP transporters, Sulfate/glucuronide metabolites,
• MeSH
• cytochrom P-450 CYP3A * metabolismus   MeSH
• cytochrom P450 CYP2C19 metabolismus   MeSH
• cytochrom P450 CYP2C9 metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• glukuronidy MeSH
• lidé MeSH
• lidský sérový albumin metabolismus   MeSH
• luteolin farmakologie   MeSH
• přenašeče organických aniontů * metabolismus   MeSH
• sírany metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CYP2C19 protein, human MeSH Prohlížeč
• CYP2C9 protein, human MeSH Prohlížeč
• CYP3A4 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A * MeSH
• cytochrom P450 CYP2C19 MeSH
• cytochrom P450 CYP2C9 MeSH
• flavonoidy MeSH
• glukuronidy MeSH
• lidský sérový albumin MeSH
• luteolin MeSH
• přenašeče organických aniontů * MeSH
• sírany MeSH
• systém (enzymů) cytochromů P-450 MeSH

Deoxynivalenol (DON) and its modified forms, including DON-3-glucoside (DON-3G), pose a major agricultural and food safety issue in the world. Their metabolites are relatively well-characterized; however, their metabolizing enzymes have not been fully explored. UDP-glucuronosyltransferases, 3-O-acetyltransferase, and glutathione S-transferase are involved in the formation of DON-glucuronides, 3-acetyl-DON, and DON-glutathione, respectively. There are interindividual differences in the metabolism of these toxins, including variation with respect to sex. Furthermore, interspecies differences in DON metabolism have been revealed, including differences in the major metabolites of DON, the role of de-acetylation, and the hydrolysis of DON-3G. In this review, we summarized the major enzymes involved in metabolizing DON to its modified forms, focusing on the differences in metabolism of DON and its modified forms between individuals and species. This work provides important insight into the toxicity of DON and its derivatives in humans and animals, and provides scientific basis for the development of safer and more efficient biological detoxification methods.

• Klíčová slova
• Deoxynivalenol, interspecies differences, metabolism, metabolizing enzymes, modified DON,
• MeSH
• glukuronidy metabolismus   MeSH
• glukuronosyltransferasa metabolismus   MeSH
• hydrolýza MeSH
• lidé MeSH
• metabolická inaktivace * MeSH
• trichotheceny * chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• deoxynivalenol MeSH Prohlížeč
• glukuronidy MeSH
• glukuronosyltransferasa MeSH
• trichotheceny * MeSH

Cyanobacteria produce a wide range of metabolites of interest for industrial or medical use. The cultivation of freshwater Nostoc cf. linckia yielded 5.4 g/L of a crude exopolysaccharide (cEPS) with a molecular weight of 1.31 × 105 g/mol. Ion-exchange chromatography of cEPS yielded two dominant fractions, EPS-1 and EPS-2, differing in molecular weight. The lower molecular weight fraction (EPS-1) was subjected to structural studies. Results of chemical and spectroscopic analyses showed that three of the four dominant sugars, glucose, galactose and xylose are 1,4-linked in the backbone in the following order: [→4)-β-D-Xylp-(1 → 4)-β-D-Glcp-(1 → 4)-α-D-Galp-(1 → 4)-β-D-Glcp-(1→]n. Terminal mannose residues were identified as side chains linked at C3 of every third backbone xylose and every second glucose is branched at C6 by 3-O-lactyl-β-D-glucuronic acid (nosturonic acid). Antioxidant properties of EPS were tested using two in vitro methods. Both assays showed that the cEPS was more active than purified EPS-1 and EPS-2 fractions and deproteinized EPS.

• Klíčová slova
• Acidic exopolysaccharide, Antioxidant activity, Nostoc cf. linckia, Nosturonic acid: 3-O-lactyl-β-D-glucuronic acid, Structure,
• MeSH
• antioxidancia chemie   MeSH
• bakteriální polysacharidy analýza   chemie   MeSH
• galaktosa chemie   MeSH
• glukosa chemie   MeSH
• kyselina glukuronová chemie   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• molekulární struktura MeSH
• molekulová hmotnost MeSH
• Nostoc chemie   MeSH
• xylosa chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• bakteriální polysacharidy MeSH
• galaktosa MeSH
• glukosa MeSH
• kyselina glukuronová MeSH
• xylosa MeSH

Mycophenolic acid (MPA) has become a cornerstone of immunosuppressive therapy, in particular for transplant patients. In the gastrointestinal tract, the liver and the kidney, MPA is mainly metabolized into phenyl-β-d glucuronide (MPAG). Knowledge about the interactions between MPA/MPAG and membrane transporters is still fragmented. The aim of the present study was to explore these interactions with the basolateral hepatic MRP4 transporter. The inhibition of the MRP4-driven transport by various drugs which can be concomitantly prescribed was also evaluated. In vitro experiments using vesicles overexpressing MRP4 showed an ATP-dependent transport of MPAG driven by MRP4 (Michaelis-Menten constant of 233.9 ± 32.8 µM). MPA was not effluxed by MRP4. MRP4-mediated transport of MPAG was inhibited (from -43% to -84%) by ibuprofen, cefazolin, cefotaxime and micafungin. An in silico approach based on molecular docking and molecular dynamics simulations rationalized the mode of binding of MPAG to MRP4. The presence of the glucuronide moiety in MPAG was highlighted as key, being prone to make electrostatic and H-bond interactions with specific residues of the MRP4 protein chamber. This explains why MPAG is a substrate of MRP4 whereas MPA is not.

• Klíčová slova
• MPA, MPAG, MRP4, drug–drug interactions, molecular docking,
• MeSH
• biologický transport MeSH
• glukuronidy metabolismus   MeSH
• hepatocyty metabolismus   MeSH
• játra metabolismus   MeSH
• kyselina mykofenolová analogy a deriváty   metabolismus   MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• membránové transportní proteiny metabolismus   MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům metabolismus   MeSH
• simulace molekulového dockingu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukuronidy MeSH
• kyselina mykofenolová MeSH
• membránové transportní proteiny MeSH
• mycophenolic acid glucuronide MeSH Prohlížeč
• proteiny spojené s mnohočetnou rezistencí k lékům MeSH

Complex structure of cyanobacterium Nostoc sp. exopolysaccharide (EPS), with apparent molecular weight 214 × 103 g/mol, can be deduced from its composition. Chemical and NMR analyses found four dominant sugar monomers, namely (1 → 4)-linked α-l-arabinopyranose, β-d-glucopyranose, β-d-xylopyranose and (1 → 3)-linked β-d-mannopyranose, two different uronic acids and a lactyl group, with (1 → 4,6)-linked β-d-glucopyranose as the only branch point suggest a complex structure of this polymer. The dominant uronic acid is α-linked, but it remained unidentified. β-d-Glucuronic acid was present in lower amount. Their position as well as that of lactyl remained undetermined too. Different doses of orally administered EPS in guinea pigs evoked a significant decrease in cough effort and a decrease in airway reactivity. The antitussive efficacy and bronchodilator effect of higher doses of EPS were found to be similar to that of the antitussive drug codeine and the antiasthmatic salbutamol. Without significant cytotoxicity on the RAW 264.7 cells, EPS stimulated the macrophage cells to produce pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and prostaglandins (PGs) and nitric oxide (NO) via induction of COX-2 and iNOS expression, respectively, suggesting that this biopolymer potentiates an early innate immune response and can therefore be used as a new immune modulator.

• Klíčová slova
• Biological activities, Cyanobacteria, Extracellular polysaccharide,
• MeSH
• albuterol farmakologie   MeSH
• bakteriální polysacharidy chemie   farmakologie   MeSH
• biopolymery chemie   MeSH
• bronchodilatancia farmakologie   MeSH
• buněčné linie MeSH
• cytokiny metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• kašel farmakoterapie   MeSH
• kodein farmakologie   MeSH
• kyselina glukuronová chemie   MeSH
• kyseliny uronové chemie   MeSH
• makrofágy účinky léků   metabolismus   MeSH
• morčata MeSH
• myši MeSH
• Nostoc metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• RAW 264.7 buňky MeSH
• sinice metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• albuterol MeSH
• bakteriální polysacharidy MeSH
• biopolymery MeSH
• bronchodilatancia MeSH
• cytokiny MeSH
• interleukin-6 MeSH
• kodein MeSH
• kyselina glukuronová MeSH
• kyseliny uronové MeSH
• oxid dusnatý MeSH
• TNF-alfa MeSH

Silybum marianum (milk thistle) is a medicinal plant used for producing the hepatoprotective remedy silymarin. Its main bioactive constituents, including silybin and related flavonolignans, can be metabolized directly by phase II conjugation reactions. This study was designed to identify UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of six silymarin flavonolignans, namely silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin. UHPLC-MS analyses showed that all of the tested compounds, both individually and in silymarin, were glucuronidated by human liver microsomes, and that glucuronidation was the main metabolic transformation in human hepatocytes. Further, each compound was glucuronidated by multiple recombinant human UGT enzymes. UGTs 1A1, 1A3, 1A8 and 1A9 were able to conjugate all of the tested flavonolignans, and some of them were also metabolized by UGTs 1A6, 1A7, 1A10, 2B7 and 2B15. In contrast, no glucuronides were produced by UGTs 1A4, 2B4, 2B10 and 2B17. With silymarin, we found that UGT1A1 and, to a lesser extent UGT1A9, were primarily responsible for the glucuronidation of the flavonolignan constituents. It is concluded that the metabolism of silymarin flavonolignans may involve multiple UGT enzymes, of which UGT1A1 appears to play the major role in the glucuronidation. These results may be relevant for future research on the metabolism of flavonolignans in humans.

• Klíčová slova
• Cytochrome P450, Glucuronidation, Metabolism, Microsomes, Silymarin, UGT,
• MeSH
• dospělí MeSH
• flavonolignany metabolismus   MeSH
• glukuronidy metabolismus   MeSH
• glukuronosyltransferasa metabolismus   MeSH
• hepatocyty metabolismus   MeSH
• jaterní mikrozomy metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• ostropestřec mariánský metabolismus   MeSH
• silibinin metabolismus   MeSH
• silymarin analogy a deriváty   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flavonolignany MeSH
• glukuronidy MeSH
• glukuronosyltransferasa MeSH
• isosilybin A MeSH Prohlížeč
• silibinin MeSH
• silidianin MeSH Prohlížeč
• silychristin MeSH Prohlížeč
• silymarin MeSH

The work is focused on the development of microspheres based on the combination of two polysaccharides; chitosan and alginic acid with the aim to allocate, hold, release and protect environmentally sensible molecules. The microspheres were prepared using a solvent-free, low cost and scalable approach and two enzymes; trypsin and protease from Aspergillus Oryzae have been used as a model to evaluate the microspheres peculiarities. The proteins were encapsulated during the microspheres preparation. The relationship between the polysaccharides weight ratio and the morphology, stability and ability of the carrier to allocate the enzymes has been evaluated. The enzymatic activity and the release kinetics were assessed in different conditions to assess the impact of the external environment. Obtained results demonstrate the efficacy of the prepared microspheres to preserve the activity of relevant bioactive compounds which are highly relevant in food, cosmetic and pharmaceutic, but the application is limited due to their high sensibility.

• Klíčová slova
• Controlled delivery, Microencapsulation, Microspheres, Polysaccharides, Protease,
• MeSH
• Aspergillus oryzae enzymologie   MeSH
• buňky NIH 3T3 MeSH
• chitosan chemie   toxicita   MeSH
• enzymy imobilizované chemie   metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina alginová chemie   toxicita   MeSH
• lidé MeSH
• mikrosféry * MeSH
• myši MeSH
• testování materiálů MeSH
• tobolky MeSH
• trypsin chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chitosan MeSH
• enzymy imobilizované MeSH
• kyselina alginová MeSH
• tobolky MeSH
• trypsin MeSH

BACKGROUND: The development of encapsulation technologies has played an important role in improving cryopreservation outcomes for many cell and tissue types over the past 20 years. Alginate encapsulation cryopreservation (AECryo) has been incorporated into a range of applications in biotechnology, species conservation and clinical therapies, using cells from many different phyla, including higher plants, animal and human cells. This review describes the background to the origins of AECryo, the development of AECryo in higher plant tissues, broadening to current applications in algal conservation, the roles for AECryo in preserving phytodiversity, fungal species and in animal and human cells. OBJECTIVE: The main aims are to provide information resources on AECryo in different areas of biology and to stimulate new ideas for wider applications and future improvement. The translation of this useful biopreservation strategy into new opportunities for cell cryopreservation and storage at non-freezing temperatures are also discussed.

• MeSH
• algináty farmakologie   MeSH
• houby účinky léků   fyziologie   MeSH
• kryoprezervace metody   MeSH
• kyselina glukuronová farmakologie   MeSH
• kyseliny hexuronové farmakologie   MeSH
• lidé MeSH
• PEG-DMA hydrogel farmakologie   MeSH
• rostliny účinky léků   MeSH
• zmrazování * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• algináty MeSH
• kyselina glukuronová MeSH
• kyseliny hexuronové MeSH
• PEG-DMA hydrogel MeSH