Monascus pigments having yellow, orange, and red colors are widely studied for their potential beneficial properties. Many different biological activities have been reported regarding Monascus pigments and their derivatives, but the usual method is to test complex extracts from the mycelium of the fungus or from a fungus-fermented substrate. However, this review is mainly concerned with the biological activities of purified Monascus pigments. Both yellow (ankaflavin, monascin) and red (rubropunctamine, monascorubramine) Monascus pigments are proven antioxidants if used in concentrations of 10 μg/mL or higher. Antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi has been observed with all Monascus pigments. However, the best antimicrobials are red Monascus pigments, and their amino acid derivatives (l-cysteine derivatives have MIC 4 μg/mL against Enterococcus faecalis). Yellow monaphilones and orange monaphilols seem to have the highest anti-inflammatory activity (IC50 1.7 μM of monaphilol D) and, together with red Monascus pigment derivatives, have mild antiobesity and antidiabetic activities. Further, monascin and ankaflavin in daily doses of 0.5 and 0.08 mg, respectively, lowered serum blood levels of low-density lipoprotein cholesterol complexes in rats on a high-fat diet. Orange Monascus pigments, rubropunctatin and monaphilols A and C, exhibit cytotoxic and antitumor activities (IC50 8-10 μM).
- MeSH
- antibakteriální látky farmakologie chemie izolace a purifikace MeSH
- antiflogistika farmakologie chemie izolace a purifikace MeSH
- antiinfekční látky farmakologie chemie izolace a purifikace MeSH
- antioxidancia farmakologie chemie izolace a purifikace MeSH
- biologické pigmenty * farmakologie chemie izolace a purifikace MeSH
- flaviny farmakologie chemie MeSH
- grampozitivní bakterie účinky léků MeSH
- heterocyklické sloučeniny tricyklické MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Monascus * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ankaflavin MeSH Prohlížeč
- antibakteriální látky MeSH
- antiflogistika MeSH
- antiinfekční látky MeSH
- antioxidancia MeSH
- biologické pigmenty * MeSH
- flaviny MeSH
- heterocyklické sloučeniny tricyklické MeSH
- monascin MeSH Prohlížeč
Bilirubin (BR) is a water-insoluble product of heme catabolism in mammals. Elevated blood concentrations of BR, especially in the neonatal period, are treated with blue-green light phototherapy. The major mechanism of BR elimination during phototherapy is photoisomerization, while a minor, less studied mechanism of degradation is oxidation. In this work, we studied the oxidation of the bilirubin model tetramethyl-dipyrrinone (Z-13) by singlet oxygen in methanol using UV-vis and ESI-MS spectroscopy, resulting in propentdyopents as the main oxidation products. We also identified two additional intermediates that were formed during the reaction (hydroperoxide 21a and imine 17). The structure of the hydroperoxide was confirmed by helium-tagging IR spectroscopy. Such reaction intermediates formed during the oxidation of BR or bilirubin models have not been described so far. We believe that this work can be used as a first step in studying the complex oxidation mechanism of BR during phototherapy.
- MeSH
- bilirubin chemie MeSH
- fotochemické procesy MeSH
- metamizol chemie MeSH
- molekulární struktura MeSH
- oxidace-redukce * MeSH
- singletový kyslík * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bilirubin MeSH
- metamizol MeSH
- singletový kyslík * MeSH
Carotenoids are crucial for photosynthesis, playing key roles in light harvesting and photoprotection. In this study, spheroidene and bacteriochlorophyll a (Bchl a) were reconstituted into the chromatophores of the carotenoidless mutant Rhodobacter sphaeroides R26.1, resulting in the preparation of high-quality LH2 complexes. Global and target analyses of transient absorption data revealed that incorporating B800 Bchl a significantly enhances excitation energy transfer (EET) efficiency from carotenoids to Bchl a. EET predominantly occurs from the carotenoid S2 state, with additional pathways from the S1 state observed in native LH2. Unique relaxation dynamics were identified, including the generation of the carotenoid S* state in reconstituted LH2 with both spheroidene and B800 Bchl a and the formation of the carotenoid T1 state in reconstituted LH2. These findings underscore the critical influence of pigment composition and spatial organization on energy transfer mechanisms. They provide valuable insights into the molecular interplay that governs excitation energy transfer in photosynthetic light-harvesting systems.
- Klíčová slova
- B800 bacteriochlorophyll a, carotenoid, light-harvesting, photoprotection, purple photosynthetic bacteria, reconstitution,
- MeSH
- bakteriální proteiny metabolismus genetika chemie MeSH
- bakteriochlorofyl A * metabolismus chemie MeSH
- fotosyntéza MeSH
- karotenoidy * metabolismus chemie MeSH
- přenos energie * MeSH
- Rhodobacter sphaeroides * metabolismus genetika MeSH
- světlosběrné proteinové komplexy * metabolismus chemie genetika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bakteriální proteiny MeSH
- bakteriochlorofyl A * MeSH
- karotenoidy * MeSH
- světlosběrné proteinové komplexy * MeSH
AIM: To evaluate the long-term impact of accelerated corneal cross-linking (A-CXL) on selected refractive and topographical parameters in eyes with progressive keratoconus. METHODS: 77 eyes with keratoconus in 54 patients treated with A-CXL (10 min "epi-off" protocol) were included in the analysis. Preoperative and postoperative (1, 3 and 5 years after A-CXL) values of the studied parameters were compared. RESULTS: In the cohort, there was an improvement in best corrected central visual acuity (BCCVA) 1 year (p = 0.004) and 3 years (p.
- Klíčová slova
- progressive keratoconus; accelerated corneal cross-linking; refractive and topographical parameters,
- MeSH
- dospělí MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky MeSH
- keratokonus * farmakoterapie diagnóza patofyziologie metabolismus MeSH
- kolagen metabolismus MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- reagencia zkříženě vázaná * MeSH
- refrakce oka MeSH
- riboflavin terapeutické užití MeSH
- rohovková topografie * MeSH
- zraková ostrost * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fotosenzibilizující látky MeSH
- kolagen MeSH
- reagencia zkříženě vázaná * MeSH
- riboflavin MeSH
The Monascus fungi have traditionally been used in Asia for food coloring. Unfortunately, the most well-known species, Monascus purpureus, very often produce mycotoxin citrinin in addition to pigments, which poses a significant problem for the use of pigments in foods. There is a step in pigment biosynthesis where a side chain of five or seven carbons is attached to the tetraketide, the product of polyketide synthase, resulting in the formation of pigments in pairs. Further, it is still unclear whether pigment and citrinin biosyntheses are related or independent. Therefore, this study is focused on the relationship between pigment and citrinin production and pigment analogues that differ in side chain length, all evaluated by the Spearman correlation test. To generate sufficient data, Monascus purpureus DBM 4360 was cultivated with different carbon and nitrogen sources and under osmotic stress induced by glucose and/or sodium chloride. The study reveals a very strong correlation between the production of five- and seven-carbon side chain pigments under all culture conditions tested for all three groups, yellow, orange, and red pigments. The correlation between pigments and citrinin depended on the group assessed and ranged from fair to very strong. While the coordinated synthesis of pigment analogues in pairs has been clearly confirmed, the relationship between pigment and citrinin production was unfortunately neither confirmed nor refuted and must be the subject of further research.
- Klíčová slova
- Monascus purpureus, citrinin, pigments, regulation of secondary metabolites biosynthesis, stress conditions,
- MeSH
- biologické pigmenty * chemická syntéza MeSH
- citrinin * biosyntéza chemie MeSH
- dusík metabolismus MeSH
- kultivační techniky MeSH
- Monascus * chemie růst a vývoj metabolismus MeSH
- osmotický tlak fyziologie MeSH
- uhlík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické pigmenty * MeSH
- citrinin * MeSH
- dusík MeSH
- uhlík MeSH
Biliary drainage is then one of the necessary procedures to help patients suffering from icterus to reduce serum bilirubin levels and relieve symptoms. The aim of this study was identifying risk factors for survival in patients with cholangiocarcinoma (CCA) treated with percutaneous transhepatic biliary drainage (PTBD) and to develop a simple scoring system predicting survival from PTBD insertion. This single-centre retrospective study included 175 consecutive patients undergoing PTBD for extrahepatic CCA (perihilar and distal). Prognostic factors affecting survival of patients with CCA treated with PTBD were analysed. A multivariate analysis showed that mass forming tumor with mass larger than 5 cm and presence of metastasis at the time of PTBD served as a negative prognostic factor (p = 0.002), better survival was associated with lower preprocedural bilirubin and lower CRP (p = 0.003). Multivariate analysis identified two significant risk factors for 3-month mortality: mass-forming tumors and bilirubin levels exceeding 185 µmol/L. A simple scoring system was developed to predict 3-month mortality after PTBD in patients with advanced CCA, demonstrating 86.3% negative predictive value and 43.2% positive predictive value.
- Klíčová slova
- Biliary malignancy, Biliary stenosis, Metal stent, Percutaneous transhepatic biliary drainage, Prognostic factors, Scoring system,
- MeSH
- bilirubin krev MeSH
- cholangiokarcinom * mortalita terapie patologie MeSH
- dospělí MeSH
- drenáž * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory žlučových cest * mortalita terapie patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bilirubin MeSH
The vertebrate visual cycle hinges on enzymatically converting all-trans-retinol (at-ROL) into 11-cis-retinal (11c-RAL), the chromophore that binds to opsins in photoreceptors, forming light-responsive pigments. When struck by a photon, these pigments activate the phototransduction pathway and initiate the process of vision. The enzymatic isomerization of at-ROL, crucial for restoring the visual pigments and preparing them to receive new light stimuli, relies on various enzymes found in both the photoreceptors and retinal pigment epithelium cells. To function effectively, retinoids must shuttle between these two cell types. Retinol-binding protein 3 (RBP3), located in the interphotoreceptor matrix, probably plays a pivotal role in this transport mechanism. Comprised of four retinoid-binding modules, RBP3 also binds fatty acids, potentially aiding retinal function by facilitating the loading and unloading of different retinoids at specific cell types thereby directing the cycle. In this study, we present a 3.67 Å cryoEM structure of porcine RBP3, along with molecular docking analysis and corroborative in-solution small-angle X-ray scattering data for titration of RBP3 with relevant ligands, that also give insights on RBP3 conformational adaptability.
- Klíčová slova
- RBP3, SAXS, conformational changes, cryoEM structure, molecular docking,
- MeSH
- difrakce rentgenového záření MeSH
- elektronová kryomikroskopie metody MeSH
- konformace proteinů MeSH
- maloúhlový rozptyl * MeSH
- molekulární modely MeSH
- oční proteiny MeSH
- prasata MeSH
- proteiny vázající retinol * chemie metabolismus MeSH
- simulace molekulového dockingu MeSH
- vazba proteinů MeSH
- vitamin A metabolismus chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- interstitial retinol-binding protein MeSH Prohlížeč
- oční proteiny MeSH
- proteiny vázající retinol * MeSH
- vitamin A MeSH
G-quadruplexes (G4 s), as non-canonical DNA structures, attract a great deal of research interest in the molecular biology as well as in the material science fields. The use of small molecules as ligands for G-quadruplexes has emerged as a tool to regulate gene expression and telomeres maintenance. Meso-tetrakis-(N-methyl-4-pyridyl) porphyrin (TMPyP4) was shown as one of the first ligands for G-quadruplexes and it is still widely used. We report an investigation comprising molecular docking and dynamics, synthesis and multiple spectroscopic and spectrometric determinations on simple cationic porphyrins and their interaction with different DNA sequences. This study enabled the synthesis of tetracationic porphyrin derivatives that exhibited binding and stabilizing capacity against G-quadruplex structures; the detailed characterization has shown that the presence of amide groups at the periphery improves selectivity for parallel G4 s binding over other structures. Taking into account the ease of synthesis, 5,10,15,20-tetrakis-(1-acetamido-4-pyridyl) porphyrin bromide could be considered a better alternative to TMPyP4 in studies involving G4 binding.
- Klíčová slova
- DNA, G-quadruplexes, Molecular dynamics, Molecular recognition, NMR,
- MeSH
- cirkulární dichroismus MeSH
- DNA * chemie MeSH
- G-kvadruplexy * MeSH
- ligandy MeSH
- porfyriny * chemie MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA * MeSH
- ligandy MeSH
- porfyriny * MeSH
- tetra(4-N-methylpyridyl)porphine MeSH Prohlížeč
INTRODUCTION: Pulsed electric field (PEF) has emerged as a promising energy source for catheter ablation of atrial fibrillation (AF). However, data regarding the in-vivo effect of PEF energy on erythrocytes during AF ablation procedures are scarce. This study aimed to quantify the impact of PEF energy on erythrocyte damage during AF ablation by assessing specific hemolytic biomarkers. METHODS: A total of 60 patients (age: 68 years, males: 72%, serum creatinine: 91 µmol/L) with AF underwent catheter ablation of AF using PEF energy delivered by a multipolar pentaspline Farawave catheter (Farapulse, Boston Scientific, Inc.). Ablation beyond pulmonary vein isolation was performed at the operator's discretion. Peripheral venous blood was sampled for assessing the plasma levels of free hemoglobin (fHb), direct (conjugated) bilirubin, lactate dehydrogenase (LDH), and creatinine before, immediately after the ablation, and on the next day. RESULTS: Following the PEF ablation with duration of [median (interquartile range)] 75 (58, 95) min, with 74 (52, 92) applications and PVI only in 27% of patients, fHb, LDH, and direct bilirubin significantly increased, from 40 (18, 65) to 493 (327, 848) mg/L, from 3.1 (2.6, 3.6) to 6.8 (5.0, 7.9) µkat/L, and from 12 (9, 17) to 28 (16, 44) µmol/L, respectively (all p < .0001). A strong linear correlation was found between the peak fHb and the number of PEF applications (R = 0.81, p < .001). The major hemolysis (defined as fHb >500 mg/L) was predicted by the number of PEF applications with the corresponding area under the receiver operating characteristic curve of 0.934. The optimum cut-off value of >74 PEF applications predicted the major hemolysis with 89% sensitivity and 87% specificity. CONCLUSION: Catheter ablation of AF using PEF energy delivered from a pentaspline catheter is associated with significant intravascular hemolysis. More than 74 PEF applications frequently resulted in major hemolysis. However, the critical amount of PEF energy that may cause kidney injury in susceptible patients remains to be investigated.
- Klíčová slova
- acute kidney injury, atrial fibrillation, hemolysis, pulsed field ablation,
- MeSH
- bilirubin krev MeSH
- biologické markery * krev MeSH
- časové faktory MeSH
- design vybavení MeSH
- erytrocyty MeSH
- fibrilace síní * chirurgie diagnóza patofyziologie krev MeSH
- hemoglobiny metabolismus MeSH
- hemolýza * MeSH
- katetrizační ablace * škodlivé účinky přístrojové vybavení MeSH
- kreatinin krev MeSH
- L-laktátdehydrogenasa krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- rizikové faktory MeSH
- senioři MeSH
- srdeční katétry MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bilirubin MeSH
- biologické markery * MeSH
- hemoglobiny MeSH
- kreatinin MeSH
- L-laktátdehydrogenasa MeSH
Recent research efforts in endocrine disruption have focused on evaluating non-EATS (estrogen, androgen, thyroid, and steroidogenesis) pathways. Retinoid signaling disruption is noteworthy because of its teratogenic effects and environmental relevance. However, current environmental risk assessments are limited in their ability to evaluate impacts on individuals and populations. This study characterizes an Adverse Outcome Pathway (AOP) network linking retinoid signaling disruption to teratogenicity and survival in zebrafish. We identified Retinoic Acid Receptor (RAR) overactivation as the molecular initiating event leading to key events including craniofacial (CFM) and tail (TM) malformations, posterior swim bladder (SB) non-inflation, impaired swimming performance, and reduced feeding, ultimately resulting in decreased survival. Our study (1) determines critical sensitivity windows for CFM, posterior SB non-inflation, and TM, (2) provides quantitative measurements for CFM and TM, and (3) defines impacts on higher biological levels including food ingestion, swimming, and survival. Results show that all-trans retinoic acid (ATRA) induces strong teratogenic effects with sensitivity windows between 4 and 48 h post fertilization (hpf) for CFM, TM, and posterior SB non-inflation. TM is the most sensitive indicator, with EC50 of 0.2 - 0.26 µg/L across exposure windows 4-48, 4-72, 4-96, and 4-120 hpf. Besides inducing known malformations, ATRA impaired posterior SB inflation with EC50 of 1 - 1.21 µg/L across the same exposure windows. ATRA exposure (1 µg/L) resulted in 50 % food ingestion inhibition at 7 days post fertilization (dpf) and 10 % survival at 14 dpf. This study provides a regulatory-relevant framework linking developmental effects to population outcomes, highlighting ecological risks and needs for improved risk assessments.
- Klíčová slova
- Adverse outcome pathway, Behavior toxicity, Developmental toxicity, Endocrine disruption, Retinoic acid, Retinoids, Survival/mortality, Teratogenicity,
- MeSH
- chemické látky znečišťující vodu * toxicita MeSH
- dánio pruhované * MeSH
- dráhy škodlivých účinků * MeSH
- embryo nesavčí * účinky léků MeSH
- receptory kyseliny retinové metabolismus genetika MeSH
- retinoidy metabolismus MeSH
- signální transdukce * účinky léků MeSH
- teratogeny * toxicita MeSH
- tretinoin * metabolismus toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chemické látky znečišťující vodu * MeSH
- receptory kyseliny retinové MeSH
- retinoidy MeSH
- teratogeny * MeSH
- tretinoin * MeSH