Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. Mitochondrial gene expression is essential for OXPHOS biogenesis since core subunits of the complexes are mitochondrial-encoded. COX14 is required for translation of COX1, the central mitochondrial-encoded subunit of complex IV. Here we describe a COX14 mutant mouse corresponding to a patient with complex IV deficiency. COX14M19I mice display broad tissue-specific pathologies. A hallmark phenotype is severe liver inflammation linked to release of mitochondrial RNA into the cytosol sensed by RIG-1 pathway. We find that mitochondrial RNA release is triggered by increased reactive oxygen species production in the deficiency of complex IV. Additionally, we describe a COA3Y72C mouse, affected in an assembly factor that cooperates with COX14 in early COX1 biogenesis, which displays a similar yet milder inflammatory phenotype. Our study provides insight into a link between defective mitochondrial gene expression and tissue-specific inflammation.
- MeSH
- cyklooxygenasa 1 * MeSH
- DEAD box protein 58 MeSH
- DEAD-box RNA-helikasy metabolismus genetika MeSH
- játra * metabolismus patologie MeSH
- lidé MeSH
- membránové proteiny MeSH
- mitochondriální proteiny metabolismus genetika MeSH
- mitochondrie metabolismus MeSH
- mutace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oxidativní fosforylace * MeSH
- proteosyntéza MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- respirační komplex IV * metabolismus genetika MeSH
- RNA mitochondriální genetika metabolismus MeSH
- zánět * metabolismus genetika patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Dirofilaria repens and Dirofilaria immitis are the most common filarial species affecting humans in Europe. Dirofilaria repens causes subcutaneous or ocular infection, whereas D. immitis is responsible mainly for the pulmonary form. In this report, we present the first human case of periorbital dirofilariasis in the Czech Republic. A 58-year-old woman suffered from an eyelid oedema, redness and pain in the left eye. After excising the parasite from her eyelid, all clinical symptoms disappeared. Based on the morphology and cytochrome oxidase I sequencing, the parasite was identified as D. repens. Histology revealed that the excised worm was female with absent microfilariae in uteri. With respect to the length of the incubation period and the sequence identity with a known Czech isolate, we concluded that D. repens was most likely of autochthonous origin.
- MeSH
- cyklooxygenasa 1 genetika MeSH
- Dirofilaria repens cytologie genetika izolace a purifikace MeSH
- dirofilarióza parazitologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrofilárie izolace a purifikace MeSH
- oční infekce parazitární parazitologie patologie MeSH
- proteiny červů genetika MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
Free ranging ungulates, represented in Europe mostly by several deer species, are important hosts for ticks and reservoirs of tick-borne infections. A number of studies have focused on the prevalence of tick borne pathogens in deer chiefly with the aim to determine their potential role as reservoir hosts for important human and livestock pathogens. However, genetic similarity of Babesia spp. forming a group commonly termed as a clade VI that accommodates the deer piroplasms, complicates this task and has led to the description of a bewildering array of poorly characterised strains. This study aims to resolve this issue by using two independent genetic loci, nuclear 18S rRNA and mitochondrial cytochrome c oxidase subunit I genes, used in parallel to identify Babesia isolates in free-ranging red, sika, and roe deer in two areas of their co-occurrence in the Czech Republic. The COX1 loci, in contrast to 18S rRNA gene, shows a clear difference between interspecific and intraspecific variation at the nucleotide level. The findings confirm B. divergens, Babesia sp. EU1 and B. capreoli in studied deer species as well as common presence of another unnamed species that matches a taxon previously referred to as Babesia sp. or Babesia cf. odocoilei or Babesia CH1 group in several other sites throughout Europe. The invasive sika deers enter the life cycle of at least three piroplasmid species detected in native deer fauna. The presence of B. divergens in both sika and red deer in an area where bovine babesiosis is apparently absent raises important questions regarding the epidemiology, host specificity and taxonomic status of the parasite.
- MeSH
- Babesia klasifikace genetika MeSH
- babezióza parazitologie virologie MeSH
- cyklooxygenasa 1 genetika MeSH
- fylogeneze MeSH
- molekulární evoluce MeSH
- protozoální DNA genetika MeSH
- protozoální proteiny genetika MeSH
- ribozomální DNA genetika MeSH
- RNA ribozomální 18S genetika MeSH
- sekvenční analýza DNA metody MeSH
- vysoká zvěř parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.
- MeSH
- benz(a)anthraceny toxicita MeSH
- benzopyren toxicita MeSH
- buňky A549 MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- lidé MeSH
- mutageny toxicita MeSH
- nádorové buněčné linie MeSH
- NF-kappa B metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- pevné částice toxicita MeSH
- pneumocyty účinky léků MeSH
- polycyklické aromatické uhlovodíky toxicita MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- transkripční faktory bHLH metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prostaglandins and inhibitors of their synthesis (cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs) were shown to play a significant role in the regulation of hematopoiesis. Partly due to their hematopoiesis-modulating effects, both prostaglandins and COX inhibitors were reported to act positively in radiation-exposed mammalian organisms at various pre- and post-irradiation therapeutical settings. Experimental efforts were targeted at finding pharmacological procedures leading to optimization of therapeutical outcomes by minimizing undesirable side effects of the treatments. Progress in these efforts was obtained after discovery of selective inhibitors of inducible selective cyclooxygenase-2 (COX-2) inhibitors. Recent studies have been able to suggest the possibility to find combined therapeutical approaches utilizing joint administration of prostaglandins and inhibitors of their synthesis at optimized timing and dosing of the drugs which could be incorporated into the therapy of patients with acute radiation syndrome.
- MeSH
- akutní radiační syndrom krev farmakoterapie etiologie metabolismus MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- hematopoéza účinky léků MeSH
- inhibitory cyklooxygenasy 2 farmakologie terapeutické užití MeSH
- lidé MeSH
- metabolické sítě a dráhy účinky léků MeSH
- modely nemocí na zvířatech MeSH
- prostaglandiny biosyntéza farmakologie MeSH
- radioprotektivní látky farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The Moluccan net-winged beetle fauna remains poorly studied and here, new species of Schizotrichalus Kleine, 1926 and Eniclases Waterhouse, 1879 are reported from Halmahera. Using morphological traits and cox1 mitochondrial DNA sequences, we propose two new species, Eniclases kusyi sp. nov. and Schizotrichalus halmaherensis sp. nov., and redescribe E. moluccanus Kleine, 1930. New molecular data confirm morphology-based sister relationships between Schizotrichalus and Eniclases and the analysis identifies the combined area of the present-day Halmahera and New Guinea as an ancestral area of these genera. Now, Halmahera and New Guinea are quite similar in respect of the number of trichaline genera. Concerning the size of islands and the recent origin of the nowadays northern Moluccas, these results are unexpected and thus the general validity of this distribution pattern should be confirmed with other groups of beetles.
- MeSH
- brouci * MeSH
- cyklooxygenasa 1 MeSH
- fylogeneze MeSH
- mitochondriální DNA MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Nová Guinea MeSH
BACKGROUND: Rats (Rattus spp.) invaded most of the world as stowaways including some that carried the rat lungworm, Angiostrongylus cantonensis, the cause of eosinophilic meningoencephalitis in humans and other warm-blooded animals. A high genetic diversity of A. cantonensis based on short mitochondrial DNA regions is reported from Southeast Asia. However, the identity of invasive A. cantonensis is known for only a minority of countries. The affordability of next-generation sequencing for characterisation of A. cantonensis genomes should enable new insights into rat lung worm invasion and parasite identification in experimental studies. METHODS: Genomic DNA from morphologically verified A. cantonensis (two laboratory-maintained strains and two field isolates) was sequenced using low coverage whole genome sequencing. The complete mitochondrial genome was assembled and compared to published A. cantonensis and Angiostrongylus malaysiensis sequences. To determine if the commonly sequenced partial cox1 can unequivocally identify A. cantonensis genetic lineages, the diversity of cox1 was re-evaluated in the context of the publicly available cox1 sequences and the entire mitochondrial genomes. Published experimental studies available in Web of Science were systematically reviewed to reveal published identities of A. cantonensis used in experimental studies. RESULTS: New A. cantonensis mitochondrial genomes from Sydney (Australia), Hawaii (USA), Canary Islands (Spain) and Fatu Hiva (French Polynesia), were assembled from next-generation sequencing data. Comparison of A. cantonensis mitochondrial genomes from outside of Southeast Asia showed low genetic diversity (0.02-1.03%) within a single lineage of A. cantonensis. Both cox1 and cox2 were considered the preferred markers for A. cantonensis haplotype identification. Systematic review revealed that unequivocal A. cantonensis identification of strains used in experimental studies is hindered by absence of their genetic and geographical identity. CONCLUSIONS: Low coverage whole genome sequencing provides data enabling standardised identification of A. cantonensis laboratory strains and field isolates. The phenotype of invasive A. cantonensis, such as the capacity to establish in new territories, has a strong genetic component, as the A. cantonensis found outside of the original endemic area are genetically uniform. It is imperative that the genotype of A. cantonensis strains maintained in laboratories and used in experimental studies is unequivocally characterised.
- MeSH
- Angiostrongylus cantonensis genetika MeSH
- cyklooxygenasa 1 genetika MeSH
- fylogeneze MeSH
- genetická variace * MeSH
- genom mitochondriální * MeSH
- genom u helmintů MeSH
- infekce hlísticemi řádu Strongylida parazitologie MeSH
- krysa rodu rattus MeSH
- mitochondriální DNA * MeSH
- sekvenční analýza DNA MeSH
- sekvenování celého genomu MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Austrálie MeSH
- Havajské ostrovy MeSH
- Polynésie MeSH
- Španělsko MeSH
BACKGROUND: One reason for the lower incidence of cardiovascular diseases in Asian countries may be the high intake of isoflavonoids and their antiplatelet effects may be an important factor. To date, there is limited comparison of a range of isoflavonoids and knowledge of their effects at different levels of platelet aggregation. PURPOSE: To screen the antiplatelet effects of a number of isoflavonoids on the arachidonic acid based aggregation pathway and investigate how the antiplatelet activity might occur. METHODS: The antiplatelet effects were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. RESULTS: Thirteen of the eighteen tested isoflavonoids had significant inhibitory effect on platelet aggregation in whole human blood. Genistein had the same potency as clinically used acetylsalicylic acid (ASA) while tectorigenin was clearly stronger than ASA. Further analyses showed that the effect of tectorigenin was not based on inhibition of cyclooxygenase-1 in contrast to ASA or thromboxane synthase but by competitive antagonism at thromboxane receptors. CONCLUSION: Tectorigenin is a more potent antiplatelet compound than ASA and thus an interesting substance for further testing.
Kyselina acetylsalicylová (aspirin, ASA) v sekundární prevenci kardiovaskulárních příhod u pacientů s aterosklerotickým postižením koronárních i periferních tepen snižuje výskyt úmrtí a závažných ischemických cévních příhod o 22 %. Pokud je však laboratorně měřena účinnost antiagregační terapie aspirinem, neodpovídá kolem jedné třetiny pacientů adekvátním způsobem. Pro tento fenomén se vžil název aspirinová rezistence. Většina studií a metaanalýzy, které se zabývaly aspirinovou rezistencí, potvrdily korelaci různými metodami zjištěné aspirinové rezistence s horšími klinickými výsledky. V metaanalýze dvaceti studií s témě? 3?000 pacienty ?inil pom?r ?anc? (pooled odds ratio) pro kardiovaskul?rn? p??hodu u?pacient? rezistentn?ch na terapii ASA 3,8. Frekvence v?skytu aspirinov? rezistence se v?jednotliv?ch studi?ch ?asto dramaticky li?? od?t?m?? nulov?ch hodnot po?hodnoty p?es 70?%. K?t?mto markantn?m rozd?l?m doch?z? p?edev??m v?z?vislosti na?pou?it? laboratorn? metod?, klinick? situaci (stabiln?, nebo akutn? onemocn?n?, p??padn? zdrav? dobrovoln?ci) a?dal??ch aspektech, jako jsou l?kov? interakce atd. V?n?sleduj?c?m textu se pokus?me nazna?it, jak? klinick? a?laboratorn? aspekty ovliv?uj? v?skyt aspirinov? rezistence a?jak?m zp?sobem naopak aspirinov? rezistence ovliv?uje progn?zu pacienta. V?sou?asn? dob? nen? dostupn? p?esv?d?iv? d?kaz o?efektivit? ?pravy medikace na?z?klad? laboratorn? zji?t?n? aspirinov? rezistence, uv?d?me v?ak postupy, kter? byly pou?ity v?klinick?ch studi?ch za???elem zv??en? laboratorn? odpov?di na?antiagrega?n? terapii. ř 3 000 pacienty činil poměr šancí (pooled odds ratio) pro kardiovaskulární příhodu u pacientů rezistentních na terapii ASA 3,8. Frekvence výskytu aspirinové rezistence se v jednotlivých studiích často dramaticky liší od téměř nulových hodnot po hodnoty přes 70 %. K těmto markantním rozdílům dochází především v závislosti na použité laboratorní metodě, klinické situaci (stabilní, nebo akutní onemocnění, případně zdraví dobrovolníci) a dalších aspektech, jako jsou lékové interakce atd. V následujícím textu se pokusíme naznačit, jaké klinické a laboratorní aspekty ovlivňují výskyt aspirinové rezistence a jakým způsobem naopak aspirinová rezistence ovlivňuje prognózu pacienta. V současné době není dostupný přesvědčivý důkaz o efektivitě úpravy medikace na základě laboratorně zjištěné aspirinové rezistence, uvádíme však postupy, které byly použity v klinických studiích za účelem zvýšení laboratorní odpovědi na antiagregační terapii.
Acetylsalicylic acid (aspirin, ASA) reduces mortality and major adverse cardiovascular events by 22% when used in coronary and peripheral artery disease secondary prevention. Laboratory assessed aspirin antiplatelet therapy effectiveness showed an inadequate response to the ASA treatment in about one third of patients. This phenomenon is often called “aspirin resistance”. Most of the studies and metaanalyses regarding the aspirin resistance proved a certain correlation between the ASA resistance assessed by various laboratory methods and the worst clinical outcomes. In the metaanalysis with nearly 3,000 patients the pooled odds ratio of cardiovascular events in ASA resistant patients was 3.8. The ASA resistance frequency shown in various clinical studies varies from almost zero values to as much as 70% of resistant patients. The distinct differences in the ASA resistance frequency are caused by variability in used laboratory methods, different clinical situations in particular studies (stable or acute cardiovascular disease or healthy volunteers) and other aspects as drug interactions etc. In the text as follows, we describe the clinical and laboratory aspects influencing the ASA resistance incidence and the influence of the ASA resistance on patient prognosis. Nowadays, there is no solid proof available which would confirm the fact that the ASA resistance guided treatment modification is associated with better clinical outcomes. Nevertheless, herein we describe various methods of therapy modification used in clinical studies for improving the laboratory ASA treatment response.
- Klíčová slova
- aspirinová rezistence, agregometrie,
- MeSH
- antiflogistika nesteroidní MeSH
- Aspirin * farmakologie terapeutické užití MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- inhibitory agregace trombocytů farmakologie MeSH
- inhibitory protonové pumpy MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- léková rezistence * MeSH
- lékové interakce * MeSH
- lidé MeSH
- monitorování léčiv MeSH
- thromboxan B2 metabolismus MeSH
- vyšetření funkce trombocytů metody MeSH
- Check Tag
- lidé MeSH
Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.
- MeSH
- antiflogistika chemie izolace a purifikace farmakologie MeSH
- arachidonát-5-lipoxygenasa metabolismus MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemie izolace a purifikace farmakologie MeSH
- inhibitory lipoxygenas chemie izolace a purifikace farmakologie MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- ovoce chemie MeSH
- proteomika * MeSH
- Publikační typ
- časopisecké články MeSH
