BACKGROUND: Mechanistic data indicate the benefit of short-chain fatty acids (SCFA) produced by gut microbial fermentation of fiber on colorectal cancer, but direct epidemiologic evidence is limited. A recent study identified SNPs for two SCFA traits (fecal propionate and butyrate-producing microbiome pathway PWY-5022) in Europeans and showed metabolic benefits. METHODS: We conducted a two-sample Mendelian randomization analysis of the genetic instruments for the two SCFA traits (three SNPs for fecal propionate and nine for PWY-5022) in relation to colorectal cancer risk in three large European genetic consortia of 58,131 colorectal cancer cases and 67,347 controls. We estimated the risk of overall colorectal cancer and conducted subgroup analyses by sex, age, and anatomic subsites of colorectal cancer. RESULTS: We did not observe strong evidence for an association of the genetic predictors for fecal propionate levels and the abundance of PWY-5022 with the risk of overall colorectal cancer, colorectal cancer by sex, or early-onset colorectal cancer (diagnosed at <50 years), with no evidence of heterogeneity or pleiotropy. When assessed by tumor subsites, we found weak evidence for an association between PWY-5022 and risk of rectal cancer (OR per 1-SD, 0.95; 95% confidence intervals, 0.91-0.99; P = 0.03) but it did not surpass multiple testing of subgroup analysis. CONCLUSIONS: Genetic instruments for fecal propionate levels and the abundance of PWY-5022 were not associated with colorectal cancer risk. IMPACT: Fecal propionate and PWY-5022 may not have a substantial influence on colorectal cancer risk. Future research is warranted to comprehensively investigate the effects of SCFA-producing bacteria and SCFAs on colorectal cancer risk.
- MeSH
- butyráty * analýza metabolismus MeSH
- feces * chemie mikrobiologie MeSH
- kolorektální nádory * epidemiologie genetika metabolismus MeSH
- kyseliny mastné těkavé analýza genetika metabolismus MeSH
- lidé MeSH
- mendelovská randomizace MeSH
- propionáty * analýza metabolismus MeSH
- riziko MeSH
- střevní mikroflóra * genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Evropa MeSH
In this study, the ionic profile and pH of exhaled breath condensate (EBC) in a group of patients with acid and weakly acid reflux and no-reflux controls were compared. A portable sampler was used for non-invasive EBC collection from five exhalations. The ionic profile (anions, cations, organic acids) and pH of the collected EBC samples were measured by capillary electrophoresis with contactless conductivity detection and a pH microelectrode, respectively. Several ions were elevated in the patient groups. Sodium cation was elevated in weakly acid reflux (significance level p < 0.01) and acid reflux (p < 0.05) compared to no-reflux controls. Butyrate and propionate were elevated in both acid reflux and weakly acid reflux compared to no-reflux controls (butyrate: p < 0.01, propionate: p < 0.05). The median values of pH (after de-aeration with N2) were also significantly higher (p < 0.01) in groups with acid reflux and weakly acid reflux than in the control group with no reflux. The ionic analysis and simultaneous pH measurement offer a simple, cheap, fast, and non-invasive approach in gastroesophageal reflux disease diagnostics.
- MeSH
- butyráty analýza MeSH
- dechové testy metody MeSH
- dospělí MeSH
- elektroforéza kapilární metody MeSH
- gastroezofageální reflux diagnóza metabolismus MeSH
- ionty analýza metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- lidé středního věku MeSH
- lidé MeSH
- propionáty analýza MeSH
- senioři MeSH
- sodík analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Trilobolide (Tb) is a pharmacologically interesting sesquiterpene lactone isolated from Laser trilobum (L.) Borkh. Structural relation to a sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin bring promising prospects for Tb to be used in the development of new anti-cancer drugs. As long as there are still unanswered questions regarding its investigation, a need for novel analytical tools emerge. Since immunoassays serve as one of powerful tools within the investigation of natural products, the development of indirect competitive enzyme-linked immunosorbent assay (ELISA) utilizing coating based on avidin-biotin technology is described. In our set-up of ELISA, newly synthesized biotinylated Tb served as immobilized competitor. Tb-carboxymethyloxime-bovine serum albumin (BSA) and Tb-succinoyl-BSA conjugates were used separately for immunization of rabbits. Two sets of polyclonal antibodies (RAbs) were obtained. Antibodies against Tb-succinoyl-BSA conjugate (RAb No. 206) were chosen as the best. Under optimized conditions, limit of detection and 50% intercept of our ELISA were 849pg/mL and 8.89ng/mL, respectively. The cross-reactivity (CR) was tested on 10 structurally related compounds and CR did not exceed 6.1%. The reproducibility of the system is expressed as intra- and inter-assay coefficients of variation (9.7% and 11.4%, respectively). Based on conducted experiments, we proposed the use of ELISA for quantification of Tb in complex biological matrices such as plant extracts. A method was applied to analyze three extracts obtained from different parts of L. trilobum. Data obtained were compared to those acquired by UHPLC-MS/MS. The concordance between the methods (103-87%) showed the ability of ELISA to quantify Tb.
The analysis of an ionic profile of exhaled breath condensate (EBC) by capillary electrophoresis with contactless conductivity detection and double opposite end injection, is demonstrated. A miniature sampler made from a 2 ml syringe and an aluminium cooling cylinder was used for the fast collection of EBC (under one minute). Analysis of the collected EBC was performed in a 60 mM 2-(N-morpholino)ethanesulfonic acid, 60 mM L-histidine background electrolyte with 30 µM cetyltrimethylammonium bromide and 2 mM 18-crown-6 at pH 6, and excellent repeatability of migration times (RSD <1.3% (n = 7)) and peak areas (RSD < 7% (n = 7)) of 14 ions (inorganic anions, cations and organic acids) was obtained. It is demonstrated that the analysis of EBC samples obtained from patients with various respiratory diseases (chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, sarcoidosis, cystic fibrosis) is possible in less than five minutes and the ionic profile can be compared with the group of healthy individuals. The analysis of the ionic profile of EBC samples provides a set of data in which statistically significant differences among the groups of patients could be observed for several clinically relevant anions (nitrite, nitrate, acetate, lactate). The developed collection system and method provides a highly reproducible and fast way of collecting and analyzing EBC, with future applicability in point-of-care diagnostics.
- MeSH
- acetáty analýza metabolismus MeSH
- amoniové sloučeniny analýza metabolismus MeSH
- bronchiální astma metabolismus MeSH
- butyráty analýza metabolismus MeSH
- chloridy analýza metabolismus MeSH
- chronická obstrukční plicní nemoc metabolismus MeSH
- crown ethery MeSH
- cystická fibróza metabolismus MeSH
- dechové testy přístrojové vybavení metody MeSH
- dospělí MeSH
- draslík analýza metabolismus MeSH
- dusičnany analýza metabolismus MeSH
- dusitany analýza metabolismus MeSH
- elektroforéza kapilární MeSH
- hořčík analýza metabolismus MeSH
- ionty MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná analýza metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní fibróza metabolismus MeSH
- plicní sarkoidóza metabolismus MeSH
- propionáty analýza metabolismus MeSH
- senioři MeSH
- sírany analýza metabolismus MeSH
- sodík analýza metabolismus MeSH
- vápník analýza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Precursor-directed biogenetic approach was used to produce a range of nonactin homologues in a 50 l fermentor cultivation of strain Streptomyces griseus 34/249 obtained by UV mutagenesis. The production medium contained sodium propionate, isobutyrate and isovalerate as individual precursors, and 10 g l(-1) Diaion HP20 styrene-divinylbenzene resin that maintains suitable precursor concentration by reversibly adsorbing and releasing it. The produced nonactin homologues were separated on two C18 reversed-phase liquid chromatography columns in series and analyzed by MS with ESI source in the positive ion mode. Formation of doubly charged ions was suppressed by an excess of Na(+) ions throughout the process. The production of the homologues increased up to day 5 and then it leveled off. Cultivations with individual precursors yielded a total of 18 nonactin homologues whose spectrum depended on the precursor used. The total production of the homologues was lowered but their spectrum was shifted to higher-molecular-weight compounds.
- MeSH
- butyráty analýza MeSH
- chromatografie kapalinová metody MeSH
- fermentace MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- isobutyráty MeSH
- kultivační média chemie MeSH
- kyseliny pentanové analýza MeSH
- makrolidy chemie izolace a purifikace metabolismus MeSH
- propionáty analýza MeSH
- Streptomyces griseus růst a vývoj metabolismus účinky záření MeSH
- ultrafialové záření MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen and its major metabolite M17203 has been implicated as an important mechanism of flobufen elimination. To characterize flobufen metabolism by O-glucuronidation, new liquid chromatographic method (LC) coupled with ESI-MS was developed to detect the conjugates of flobufen and its metabolites formed in vitro in rat liver microsomes. Discovery DSC-18 LT cartridge columns were utilized for solid phase extraction (SPE) and Discovery C18 column (150 mm x 2.1 mm, 5 microm particle size) was used for LC separation. Chiral inversion of flobufen and its metabolites enantiomers was checked by special 1-allyl-(5R,8S,10R)-terguride column (150 mm x 4.6 mm). O-Glucuronidation of the S-enantiomer displayed a typical Michaelis-Menten kinetics, whereas the R-enantiomer exhibited a substrate inhibition type of kinetics. The study of glucuronidation of M17203 led to kinetics with sigmoidal characteristics.
- MeSH
- butyráty analýza MeSH
- financování organizované MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Výzkum a sledování metabolismu kyseliny máselné v Bacillus segetalis. Podařilo se zjistit tvorbu kyseliny octové při brzdění metabolismu kyseliny máselné As,2,O,3,. Za anaerobních podmínek byla prokázána tvorba kyseliny|vinyloctové jako meziproduktu
