Metronidazole belongs to the class of nitroimidazole molecules and has been considered as a potential radiosensitizer for radiation therapy. During the irradiation of biological tissue, secondary electrons are released that may interact with molecules of the surrounding environment. Here, we present a study of electron attachment to metronidazole that aims to investigate possible reactions in the molecule upon anion formation. Another purpose is to elucidate the effect of microhydration on electron-induced reactions in metronidazole. We use two crossed electron/molecular beam devices with the mass-spectrometric analysis of formed anions. The experiments are supported by quantum chemical calculations on thermodynamic properties such as electron affinities and thresholds of anion formation. For the single molecule, as well as the microhydrated condition, we observe the parent radical anion as the most abundant product anion upon electron attachment. A variety of fragment anions are observed for the isolated molecule, with NO2- as the most abundant fragment species. NO2- and all other fragment anions except weakly abundant OH- are quenched upon microhydration. The relative abundances suggest the parent radical anion of metronidazole as a biologically relevant species after the physicochemical stage of radiation damage. We also conclude from the present results that metronidazole is highly susceptible to low-energy electrons.
- Publikační typ
- časopisecké články MeSH
High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.
- MeSH
- 2-aminopurin analogy a deriváty farmakologie MeSH
- adenin MeSH
- DNA účinky léků účinky záření MeSH
- nukleotidy MeSH
- nukleové kyseliny MeSH
- oprava DNA účinky léků MeSH
- prebiotika * MeSH
- pyrimidinové dimery MeSH
- RNA chemie MeSH
- simulace molekulární dynamiky MeSH
- ultrafialové záření škodlivé účinky MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
- Publikační typ
- časopisecké články MeSH
- MeSH
- antikoagulancia * dějiny klasifikace terapeutické užití MeSH
- antithrombiny terapeutické užití MeSH
- aptamery nukleotidové terapeutické užití MeSH
- benzimidazoly terapeutické užití MeSH
- farmaceutická technologie * trendy MeSH
- geny helmintů genetika účinky léků MeSH
- heparin nízkomolekulární terapeutické užití MeSH
- heparin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kardiovaskulární nemoci * diagnóza prevence a kontrola MeSH
- léky zkušební MeSH
- lidé MeSH
- lipoproteiny terapeutické užití MeSH
- nežádoucí účinky léčiv MeSH
- peptidové fragmenty terapeutické užití MeSH
- polysacharidy terapeutické užití MeSH
- rekombinantní proteiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- adjuvantní chemoterapie metody využití MeSH
- benzensulfonáty terapeutické užití MeSH
- heparin nízkomolekulární analogy a deriváty terapeutické užití MeSH
- indoly terapeutické užití MeSH
- inhibitory angiogeneze * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie metody trendy využití MeSH
- léky zkušební MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- nádory * farmakoterapie terapie MeSH
- pyridiny terapeutické užití MeSH
- pyrroly terapeutické užití MeSH
- vaskulární endoteliální růstové faktory * antagonisté a inhibitory terapeutické užití MeSH
- Check Tag
- lidé MeSH
