The cyanobacterial dialkylresorcinol bartolosides were initially reported to feature glycosylated and halogenated moieties. Later, biosynthetic and in vitro studies showed that the chlorinated alkyl chains are utilized for a nucleophilic substitution with free fatty acid carboxylates from primary metabolism, generating bartoloside esters. Here, we applied a workflow based on PCR screening coupled to LC-HRESIMS and molecular network analysis with the aim of discovering additional bartoloside diversity. We report the annotation of 27 bartoloside and bartoloside ester derivatives, including the characterization of two new bartolosides, underlining the breadth of structures generated by bartoloside biosynthetic pathways. Some of the herein reported bartolosides feature hydroxylation in their side chains, a modification that has not been associated with this metabolite family.
- MeSH
- molekulární struktura MeSH
- resorcinoly * chemie MeSH
- sinice * chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
The mycotoxin zearalenone (ZEA) in food and feed seriously harms human and animal health. How to reduce its toxicity is an important direction of current research on food safety. This study aim to assess the effects of procyanidins (PC) on cell apoptosis caused by ZEA and to clarify the role of Nrf2 in the process. Swine testicle (ST) cells were treated with ZEA (57.5 μmol/L) and/or PC (10 mg/L) for 24 h. Cell viability was detected by CCK-8 assay. Cell apoptosis and the level of ROS were detected by flow cytometry. The expression levels of mRNA and protein was detected by qRT-PCR and western blotting. Our results showed that ZEA reduced the antioxidant capacity of the ST cells, induced the cell apoptosis and inhibited the gene and protein expression of Nrf2 and its downstream genes (ho-1,nqo1), while PC improved the cell antioxidant capacity, reduced the degree of ZEA-induced cell apoptosis and promoted the gene and protein expression of Nrf2 and its downstream genes. However, when the Nrf2 small molecule inhibitor ML385 was added, the ability of PC to inhibit ZEA-induced cell apoptosis and promote the expression of Nrf2 and its downstream genes were decreased. Our results demonstrated that ZEA induced oxidative stress and apoptosis of ST cells, which were alleviated by PC intervention via activating Nrf2 signaling pathway. This finding of this study provided a molecular basis for the clinical application of PC to prevent ZEN-caused reproductive toxicity.
- MeSH
- antioxidancia metabolismus farmakologie MeSH
- apoptóza MeSH
- faktor 2 související s NF-E2 genetika metabolismus MeSH
- oxidační stres MeSH
- prasata MeSH
- proantokyanidiny * farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce MeSH
- testis metabolismus MeSH
- zearalenon * metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Zearalenone (ZEN) is a toxic secondary metabolite of Fusarium sp. commonly found in wheat, corn, and other crops. In addition to economic losses, ZEN can seriously endanger the health of both humans and livestock, thus presenting an urgent need for ZEN-detoxifying enzymes that function in the extreme heat or pH conditions of industrial fermenters. Here, we identify and characterize the activity of the ZEN-degrading enzyme from Exophiala spinifera, ZHD_LD, which shares 60.15% amino acid identity and a conserved catalytic triad with the well-characterized ZEN-detoxifying protein ZHD101 from Clonostachys rosea. Biochemical activity and stability assays indicated that purified recombinant ZHD_LD exhibited high activity against ZEN with optimal reaction conditions of 50 °C and pH 7.0-10.0. Structural modeling of the ZHD_LD active site and comparison with ZHD101 revealed its likely mechanism of ZEN degradation. This research provides an industrially valuable candidate enzyme for ZEN detoxification in food and livestock feed.
- MeSH
- Fusarium * metabolismus MeSH
- hydrolasy metabolismus MeSH
- lidé MeSH
- pšenice metabolismus MeSH
- zearalenon * chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Due to increasing food safety standards, the analysis of mycotoxins has become essential in the food industry. In this work, we have developed a competitive upconversion-linked immunosorbent assay (ULISA) for the analysis of zearalenone (ZEA), one of the most frequently encountered mycotoxins in food worldwide. Instead of a toxin-conjugate conventionally used in competitive immunoassays, we designed a ZEA mimicking peptide extended by a biotin-linker and confirmed its excellent suitability to mimic ZEA by nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) analysis. Upconversion nanoparticles (UCNP, type NaYF4:Yb,Tm) served as background-free optical label for the detection of the peptide mimetic in the competitive ULISA. Streptavidin-conjugated UCNPs were prepared by click reaction using an alkyne-PEG-neridronate linker. The UCNP conjugate clearly outperformed conventional labels such as enzymes or fluorescent dyes. With a limit of detection of 20 pg mL-1 (63 pM), the competitive ULISA is well applicable to the detection of ZEA at the levels set by the European legislation. Moreover, the ULISA is specific for ZEA and its metabolites (α- and β-zearalenol) without significant cross-reactivity with other related mycotoxins. We detected ZEA in spiked and naturally contaminated maize samples using liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) as a reference method to demonstrate food analysis in real samples.
Mycotoxin management in agriculture is an essential challenge for maintaining the health of both animals and humans. Choosing the right adsorbent is still a question for many breeders and an important criterion for feed manufacturers. New adsorbents are still being sought. Graphene oxide is a promising material in the field of nanotechnology, which excels in its adsorption properties. Presented in vitro study investigates graphene oxide for the binding of mycotoxins from crushed wheat. The results show that graphene oxide has an adsorption capacity for aflatoxin 0.045 mg/g, zearalenone 0.53 mg/g and deoxynivalenol 1.69 mg/g at 37° C. In vitro simulation of crushed wheat digestion showed rapid adsorption during the gastric phase. Of the minerals, Mg, Cu and Zn were the most adsorbed. The applied dose of graphene oxide of 10 mg/g caused only a slight inhibition of the digestive enzymes α-amylase and trypsin compared to pepsin and gastric lipase. In vitro results indicated the suitability of graphene oxide in the adsorption of the aflatoxin, zearalenone and deoxynivalenol.
- MeSH
- adsorpce MeSH
- aflatoxin B1 izolace a purifikace toxicita MeSH
- gastrointestinální absorpce MeSH
- grafit chemie MeSH
- kontaminace potravin analýza prevence a kontrola MeSH
- krmivo pro zvířata analýza toxicita MeSH
- lidé MeSH
- mykotoxiny izolace a purifikace toxicita MeSH
- nanostruktury chemie MeSH
- pšenice chemie toxicita MeSH
- techniky in vitro MeSH
- trávení MeSH
- trichotheceny izolace a purifikace toxicita MeSH
- zearalenon izolace a purifikace toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prior to 1985 the Food and Agriculture Organization (FAO) estimated global food crop contamination with mycotoxins to be 25%. The origin of this statement is largely unknown. To assess the rationale for it, the relevant literature was reviewed and data of around 500,000 analyses from the European Food Safety Authority and large global survey for aflatoxins, fumonisins, deoxynivalenol, T-2 and HT-2 toxins, zearalenone and ochratoxin A in cereals and nuts were examined. Using different thresholds, i.e. limit of detection, the lower and upper regulatory limits of European Union (EU) legislation and Codex Alimentarius standards, the mycotoxin occurrence was estimated. Impact of different aspects on uncertainty of the occurrence estimates presented in literature and related to our results are critically discussed. Current mycotoxin occurrence above the EU and Codex limits appears to confirm the FAO 25% estimate, while this figure greatly underestimates the occurrence above the detectable levels (up to 60-80%). The high occurrence is likely explained by a combination of the improved sensitivity of analytical methods and impact of climate change. It is of immense importance that the detectable levels are not overlooked as through diets, humans are exposed to mycotoxin mixtures which can induce combined adverse health effects.
- MeSH
- aflatoxiny analýza MeSH
- Evropská unie MeSH
- fumonisiny analýza MeSH
- klimatické změny MeSH
- kontaminace potravin analýza statistika a číselné údaje MeSH
- lidé MeSH
- mykotoxiny analýza MeSH
- reprodukovatelnost výsledků MeSH
- zearalenon analýza MeSH
- zemědělské plodiny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Based on the significant anti-inflammatory activity of natural quinone primin (5a), series of 1,4-benzoquinones, hydroquinones, and related resorcinols were designed, synthesized, characterized and tested for their ability to inhibit the activity of cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) enzymes. Structural modifications resulted in the identification of two compounds 5b (2-methoxy-6-undecyl-1,4-benzoquinone) and 6b (2-methoxy-6-undecyl-1,4-hydroquinone) as potent dual COX/5-LOX inhibitors. The IC50 values evaluated in vitro using enzymatic assay were for compound 5b IC50 = 1.07, 0.57, and 0.34 μM and for compound 6b IC50 = 1.07, 0.55, and 0.28 μM for COX-1, COX-2, and 5-LOX enzyme, respectively. In addition, compound 6d was identified as the most potent 5-LOX inhibitor (IC50 = 0.14 μM; reference inhibitor zileuton IC50 = 0.66 μM) from the tested compounds while its inhibitory potential against COX enzymes (IC50 = 2.65 and 2.71 μM for COX-1 and COX-2, respectively) was comparable with the reference inhibitor ibuprofen (IC50 = 4.50 and 2.46 μM, respectively). The most important structural modification leading to increased inhibitory activity towards both COXs and 5-LOX was the elongation of alkyl chain in position 6 from 5 to 11 carbons. Moreover, the monoacetylation in ortho position of bromo-hydroquinone 13 led to the discovery of potent (IC50 = 0.17 μM) 5-LOX inhibitor 17 (2-bromo-6-methoxy-1,4-benzoquinone) while bromination stabilized the hydroquinone form. Docking analysis revealed the interaction of compounds with Tyr355 and Arg120 in the catalytic site of COX enzymes, while the hydrophobic parts of the molecules filled the hydrophobic substrate channel leading up to Tyr385. In the allosteric catalytic site of 5-LOX, compounds bound to Tyr142 and formed aromatic interactions with Arg138. Taken together, we identified optimal alkyl chain length for dual COX/5-LOX inhibition and investigated other structural modifications influencing COX and 5-LOX inhibitory activity.
- MeSH
- benzochinony chemie MeSH
- inhibitory cyklooxygenasy chemická syntéza chemie farmakologie MeSH
- inhibitory lipoxygenas chemická syntéza chemie farmakologie MeSH
- katalytická doména MeSH
- oxidace-redukce MeSH
- počítačová simulace MeSH
- resorcinoly chemie MeSH
- simulace molekulového dockingu MeSH
- spektrální analýza metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
The goal of this study was to observe the effect of resorcinol on motility, viability and morphology of bovine spermatozoa. The semen was used from six randomly chosen breeding bulls. Ejaculate was diluted by different solutions of resorcinol in 1:40 ratio. Samples were divided into 7 groups with different concentrations of resorcinol (Control, RES1 - 4 mg/ml, RES2 - 2 mg/ml, RES3 - 1 mg/ml, RES4 - 0.5 mg/ml, RES5 - 0.25 mg/ml and RES6 - 0.125 mg/ml). Motility of spermatozoa was detected using CASA method at temperature of 37 °C in time periods 0, 1, 2, 3, 4 hours from the start of the experiment. Significant motility differences between all groups except control and RES6 with difference of 5.58 %, as well as between RES1 and RES2 groups with difference of 2.17 % were found. Progressive motility had the same significant differences. Spermatozoa viability (MTT test) decreased compared to control in all experimental groups during the entire duration of experiment. Observing morphologically changed spermatozoa, no significant changes were observed and a higher percentage of spermatozoa with separated flagellum in all experimental resorcinol groups compared to control were detected. Also, increased number of spermatozoa with broken flagellum, acrosomal changes and other morphological forms in the group with the highest concentration of resorcinol (RES1) were found. Results of our study clearly show negative effects on motility parameters of spermatozoa which depend on concentration, cultivation temperature and time period.
- MeSH
- motilita spermií účinky léků MeSH
- resorcinoly farmakologie MeSH
- skot MeSH
- sperma účinky léků fyziologie MeSH
- spermie účinky léků MeSH
- techniky in vitro MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A dietary exposure assessment to sum of deoxynivalenol (DON) forms, sum of T-2/HT-2 toxins (T2/HT2) and zearalenone (ZEA) was conducted for Czech children 4-6 years and Czech men and women 18-59 years. Retail foods (25 different commodities, n = 336) were assessed by LC-MS/MS methods. The 95th percentile chronic exposure to sum of DON forms was determined in children from 648 to 1030 ng/kg bw/day (LB/lower bound/and UB/upper bound/), in men from 362 to 923 ng/kg bw/day and in women from 272 to 490 ng/kg bw/day. The 95th percentile chronic exposure to sum T2/HT2 was determined in children from 6.5 to 31 ng/kg bw/day, in men from 1.9 to 11.2 ng/kg bw/day and in women from 2.5 to 11.5 ng/kg bw/day. The 95th percentile chronic exposure to ZEA was determined in children from 11.9 to 24.9 ng/kg bw/day, in men from 5.9 to 27.5 ng/kg bw/day and in women from 4.8 to 12.6 ng/kg bw/day. The risk linked with the mean and the 95th percentile chronic exposure (LB scenario) to the sum of DON forms, sum of T2/HT2 and ZEA is considered to be out of health concern for the selected population groups.
- MeSH
- dietární expozice * MeSH
- dítě MeSH
- dospělí MeSH
- jedlá semena chemie MeSH
- kontaminace potravin analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mykotoxiny analýza MeSH
- pivo analýza MeSH
- předškolní dítě MeSH
- T-2 toxin analogy a deriváty toxicita MeSH
- trichotheceny toxicita MeSH
- zearalenon toxicita MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hidradenitis suppurativa (acne inversa) je chronické, zánětlivé, recidivující, vysilující kožní onemocnění, které se projevuje postpubertálně bolestivými, hluboko uloženými, zánětlivými lézemi v oblastech, kde jsou lokalizovány apokrinní potní žlázy, nejčastěji v axilách, inguinách a anogenitálně (Dessau definice, 1st International Conference on Hidradenitis suppurativa, 30. 3.–1. 4. 2006, Dessau, Německo). Hidradenitis suppurativa je velmi závažné onemocnění s četnými komplikacemi, komorbiditami a s refrakterními následky pro pacienta, ale bývá bohužel často chybně nebo velmi pozdě diagnostikováno. Postiženo je 1 % populace, projevuje se nejčastěji od puberty do 50. roku věku a častěji jsou postiženy ženy. Primární patologický proces je lokalizován do oblasti terminálního vlasového folikulu s následným postižením apokrinních potních žláz. Klinicky nacházíme komedony (jedno/vícepórové), bolestivé hluboce uložené zánětlivé noduly, abscesy, drénující sinusy, jizvení a sekundární lymfedém. Dle tíže klinického obrazu dělíme pacienty do tří stupňů Hurleyho klasifikace, dále se používají k hodnocení léčby dynamické skórovací systémy. V roce 2015 byly vydány Evropské S1 doporučené postupy pro léčbu hidradenitis suppurativa/acne inversa a následně terapeutický algoritmus pro léčbu onemocnění, který dělí terapii na první linii (lokální klindamycin 1%; systémová antibiotika: tetracyklin – doxycyklin, rifampicin + klindamycin; adalimumab), druhou linii (infliximab, acitretin, glukonát zinku, resorcinol, intralezionální glukokortikoidy) a třetí linii léčby (kolchicin, botulotoxin, isotretinoin, dapson, cyclosporin, hormonální terapie – antiandrogeny). Dále má nezastupitelnou roli v léčbě chirurgie a adjuvantní terapie. Mezioborová spolupráce je důležitá v celostním přístupu k hidradenitis suppurativa.
Hidradenitis suppurativa or acne inversa is a chronic, inflammatory, reccurent, debilitating skin disease that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillaries, inguinal and anogenital regions (Dessau definiton, 1st International Conference on Hidradenitis suppurativa, March 30-April1, 2006, Dessau, Germany). Hidradenitis suppurativa is very serious illness with certain complications and comorbidities and refractory results for the patients, but unfortunatelly it is still either lately or misdiagnosed. Prevalence is 1% of population. It starts after puberty and the incidence declines after fifth decade. Women are more prone to hidradenitis suppurativa. Primary patological proces is localised to the terminal hair follicle with ongoing apocrine gland involvement. Clinically we see comedones, painfull deep-seated inflamed nodules, abscesses, draining sinuses, scarring, secondary lymphedema. Hurley scale devides the patients into three stages according to the clinical picture. Other dynamic scaling systems are used. In 2015 were printed European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa, followed by therapeutical algorithm, which devides therapeutical options into three lines: 1st line (topical clindamycin 1%; systemic anibiotics: tetracyclin - doxycyclin, clindamycin + rifampicin; adalimumab), 2nd line (infliximab, acitretin/etretinate, zinc gluconate, resorcinol, intralesional glucocorticoids) and 3rd line (colchicine, botulinum toxinum, isotretinoin, dapson, cyclosporin, hormonal therapy – antiandrogens). Adjuvant therapy and surgery is necessary. Multidisciplinary attititude is important for the therapeutical outcome.
- MeSH
- acitretin aplikace a dávkování MeSH
- adalimumab aplikace a dávkování MeSH
- bolest etiologie farmakoterapie MeSH
- botulotoxiny typ A terapeutické užití MeSH
- cyklosporin terapeutické užití MeSH
- dapson terapeutické užití MeSH
- dermatochirurgické výkony metody MeSH
- dítě MeSH
- dospělí MeSH
- hidradenitis suppurativa * diagnóza farmakoterapie klasifikace MeSH
- klindamycin aplikace a dávkování farmakologie MeSH
- kolchicin terapeutické užití MeSH
- lasery plynové terapeutické užití MeSH
- lidé MeSH
- resorcinoly aplikace a dávkování farmakologie MeSH
- rifampin aplikace a dávkování farmakologie MeSH
- sloučeniny zinku aplikace a dávkování MeSH
- stupeň závažnosti nemoci MeSH
- terciární zdravotní péče organizace a řízení statistika a číselné údaje MeSH
- triamcinolon aplikace a dávkování MeSH
- týmová péče o pacienty MeSH
- způsoby aplikace léků MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
