Plasmalogens (vinyl-ether phospholipids) are an emergent class of lipid drugs against various diseases involving neuro-inflammation, oxidative stress, mitochondrial dysfunction, and altered lipid metabolism. They can activate neurotrophic and neuroprotective signaling pathways but low bioavailabilities limit their efficiency in curing neurodegeneration. Here, liquid crystalline lipid nanoparticles (LNPs) are created for the protection and non-invasive intranasal delivery of purified scallop-derived plasmalogens. The in vivo results with a transgenic mouse Parkinson's disease (PD) model (characterized by motor impairments and α-synuclein deposition) demonstrate the crucial importance of LNP composition, which determines the self-assembled nanostructure type. Vesicle and hexosome nanostructures (characterized by small-angle X-ray scattering) display different efficacy of the nanomedicine-mediated recovery of motor function, lipid balance, and transcriptional regulation (e.g., reduced neuro-inflammation and PD pathogenic gene expression). Intranasal vesicular and hexosomal plasmalogen-based LNP treatment leads to improvement of the behavioral PD symptoms and downregulation of the Il6, Il33, and Tnfa genes. Moreover, RNA-sequencing and lipidomic analyses establish a dramatic effect of hexosomal nanomedicines on PD amelioration, lipid metabolism, and the type and number of responsive transcripts that may be implicated in neuroregeneration.
- MeSH
- aplikace intranazální * MeSH
- liposomy MeSH
- metabolismus lipidů účinky léků MeSH
- modely nemocí na zvířatech * MeSH
- myši transgenní MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nanomedicína * metody MeSH
- Parkinsonova nemoc * metabolismus farmakoterapie MeSH
- plasmalogeny * chemie farmakologie MeSH
- regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The main bottleneck in the return of industrial butanol production from renewable feedstock through acetone-butanol-ethanol (ABE) fermentation by clostridia, such as Clostridium beijerinckii, is the low final butanol concentration. The problem is caused by the high toxicity of butanol to the production cells, and therefore, understanding the mechanisms by which clostridia react to butanol shock is of key importance. Detailed analyses of transcriptome data that were obtained after butanol shock and their comparison with data from standard ABE fermentation have resulted in new findings, while confirmed expected population responses. Although butanol shock resulted in upregulation of heat shock protein genes, their regulation is different than was assumed based on standard ABE fermentation transcriptome data. While glucose uptake, glycolysis, and acidogenesis genes were downregulated after butanol shock, solventogenesis genes were upregulated. Cyclopropanation of fatty acids and formation of plasmalogens seem to be significant processes involved in cell membrane stabilization in the presence of butanol. Surprisingly, one of the three identified Agr quorum-sensing system genes was upregulated. Upregulation of several putative butanol efflux pumps was described after butanol addition and a large putative polyketide gene cluster was found, the transcription of which seemed to depend on the concentration of butanol.
- MeSH
- biologický transport genetika MeSH
- bioreaktory mikrobiologie MeSH
- buněčná membrána metabolismus MeSH
- butanoly toxicita MeSH
- Clostridium beijerinckii účinky léků genetika metabolismus MeSH
- fyziologický stres genetika MeSH
- glukosa metabolismus MeSH
- glykolýza genetika fyziologie MeSH
- mastné kyseliny metabolismus MeSH
- plasmalogeny biosyntéza MeSH
- proteiny teplotního šoku metabolismus MeSH
- quorum sensing genetika MeSH
- stanovení celkové genové exprese MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Plasmalogens are a group of lipids mainly found in the cell membranes. They occur in anaerobic bacteria and in some protozoa, invertebrates and vertebrates, including humans. Their occurrence in plants and fungi is controversial. They can protect cells from damage by reactive oxygen species, protect other phospholipids or lipoprotein particles against oxidative stress, and have been implicated as signaling molecules and modulators of membrane dynamics. Biosynthesis in anaerobic and aerobic organisms occurs by different pathways, and the main biosynthetic pathway in anaerobic bacteria was clarified only this year (2021). Many different analytical techniques have been used for plasmalogen analysis, some of which are detailed below. These can be divided into two groups: shotgun lipidomics, or electrospray ionization mass spectrometry in combination with high performance liquid chromatography (LC-MS). The advantages and limitations of both techniques are discussed here, using examples from anaerobic bacteria to specialized mammalian (human) organs.
- MeSH
- aktivace komplementu * imunologie MeSH
- anafylaxe * imunologie metabolismus MeSH
- bazofily imunologie MeSH
- biologické markery * metabolismus MeSH
- bradykinin imunologie metabolismus MeSH
- chymasy imunologie metabolismus MeSH
- cytokiny * imunologie metabolismus MeSH
- faktor aktivující destičky imunologie metabolismus MeSH
- fenotyp * MeSH
- histamin imunologie metabolismus MeSH
- imunoglobulin E imunologie MeSH
- imunoglobulin G imunologie MeSH
- individualizovaná medicína MeSH
- interleukin-6 imunologie metabolismus MeSH
- karboxypeptidasy A imunologie metabolismus MeSH
- lidé MeSH
- mastocyty imunologie MeSH
- tryptasy imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The oxidized phospholipids (oxPl) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) are cytotoxic components of oxidized LDL (oxLDL). Sustained exposure to oxLDL or isolated oxPl induces apoptotic signaling in vascular cells, which is a hallmark of the late phase of atherosclerosis. Activation of sphingomyelinase, the coordinate formation of ceramide and activation of caspase 3/7 as well as the activation of stress-associated kinases are causally involved in this process. Here, we provide evidence for a role of PKCδ in oxPl cytotoxicity. Silencing of the enzyme by siRNA significantly reduced caspase 3/7 activation in RAW 264.7 macrophages under the influence of oxPl. Concomitantly, PKCδ was phosphorylated as a consequence of cell exposure to PGPC or POVPC. Single molecule fluorescence microscopy provided direct evidence for oxPl-protein interaction. Both oxPl recruited an RFP-tagged PKCδ to the plasma membrane in a concentration-dependent manner. In addition, two color cross-correlation number and brightness (ccN&B) analysis of the molecular motions revealed that fluorescently labeled PGPC or POVPC analogs co-diffuse and are associated with the fluorescent protein kinase in live cells. The underlying lipid-protein interactions may be due to chemical bonding (imine formation between the phospholipid aldehyde POVPC with protein amino groups) and physical association (with POVPC or PGPC). In summary, our data supports the assumption that PKCδ acts as a proapototic kinase in oxPl-included apoptosis of RAW 264.7 macrophages. The direct association of the bioactive lipids with this enzyme seems to be an important step in the early phase of apoptotic signaling.
- MeSH
- aktivace enzymů MeSH
- apoptóza účinky léků MeSH
- časové faktory MeSH
- fosfolipidethery toxicita MeSH
- fosforylace MeSH
- kaspasa 3 metabolismus MeSH
- kaspasa 7 metabolismus MeSH
- makrofágy účinky léků enzymologie patologie MeSH
- myši MeSH
- oxidace-redukce MeSH
- proteinkinasa C-delta genetika metabolismus MeSH
- RAW 264.7 buňky MeSH
- regulace genové exprese enzymů MeSH
- reportérové geny MeSH
- RNA interference MeSH
- signální transdukce účinky léků MeSH
- transfekce MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antikoagulancia kontraindikace MeSH
- Aspirin MeSH
- balení výrobků normy zákonodárství a právo MeSH
- česnek účinky léků MeSH
- faktor aktivující destičky antagonisté a inhibitory farmakologie kontraindikace účinky léků MeSH
- farmaceutický průmysl metody normy organizace a řízení MeSH
- Ginkgo biloba MeSH
- ginkgolidy kontraindikace krev MeSH
- heparin MeSH
- hygiena normy MeSH
- informační služby o lécích * MeSH
- internet využití zákonodárství a právo MeSH
- káva MeSH
- lékové interakce MeSH
- lidé MeSH
- nápoje MeSH
- ovoce MeSH
- P-glykoprotein MeSH
- potravní doplňky * klasifikace normy využití zásobování a distribuce MeSH
- potravní vláknina MeSH
- systém (enzymů) cytochromů P-450 MeSH
- ženšen účinky léků MeSH
- Check Tag
- lidé MeSH
- MeSH
- benzodiazepiny MeSH
- bilobalidy farmakologie MeSH
- faktor aktivující destičky antagonisté a inhibitory MeSH
- Ginkgo biloba * toxicita MeSH
- ginkgolidy farmakologie MeSH
- glykosidy farmakologie MeSH
- ibuprofen MeSH
- inhibitory fosfodiesteras farmakologie MeSH
- krvácení MeSH
- lékové interakce * MeSH
- lidé MeSH
- nežádoucí účinky léčiv MeSH
- systém (enzymů) cytochromů P-450 farmakologie MeSH
- výzkum MeSH
- warfarin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Anafylaxe je akutní, potencionálně fatální multiorgánová alergická reakce. Mů že se vyskytnout i u nejmenších dětí. Reakce u dětí do 3 let věku má specifický průběh a př íznaky. V časná a správná diagnóza a léčba anafylaxe mnohdy zachrání život. Důležitá jsou následná vyšetření, která verifikují spouštěč reakce. Laboratorní diagnostika anafylaxe u dětí má svá úskalí. Úspěšná léčba zahrnuje komplex medikamentózních a nemedikamentózních opatření. Akutní intervence spočívá v podání adrenalinu a v dalších postupech, které jsou přiměřené vě ku dítěte. Léčbu úvodních projevů anafylaxe má ovládat zdravotník i laik. Dítě s prodělanou anafylaxí č i rizikový potravinový alergik musí být vybaven balíčkem první pomoci, jeho opatrovníci mají mít informace jak a kdy ho použít.
Anaphylaxis is an acute, potentionally fatal, multi-organ system, allergic reaction. It may happen even to the youngest childre n. The reaction has specific symptoms and course for children up to 3 years old. The early and proper diagnosis and treatment of anaphys is often l ife saving. The subsequent tests are important for identification of the reaction trigger. The laboratory diagnosis of anaphylaxis of children has certain obstacles. The successful treatment comprises of set of medical and non-medical measures. The acute management is based on intramuscular a dmission of adrenaline and other procedures depending on childs age. Both healthcare professionals and children caregivers should be famili ar with initial anaphylaxis management. The child dispensed after the anaphylaxis treatment or a patient with a food allergy and a risk of anap hylaxis must be equipped with an emergency package. The caregivers must be educated to know when and how to use it.
- MeSH
- adrenalin * škodlivé účinky terapeutické užití MeSH
- alergeny imunologie izolace a purifikace škodlivé účinky MeSH
- anafylaxe * diagnóza etiologie terapie MeSH
- antihistaminika terapeutické užití MeSH
- faktor aktivující destičky izolace a purifikace škodlivé účinky MeSH
- glukagon terapeutické užití MeSH
- glukokortikoidy terapeutické užití MeSH
- histamin imunologie izolace a purifikace škodlivé účinky MeSH
- imunoglobuliny izolace a purifikace terapeutické užití MeSH
- klinické laboratorní techniky metody využití MeSH
- kojenec * MeSH
- lidé MeSH
- potrava pro kojence škodlivé účinky využití MeSH
- předškolní dítě MeSH
- první pomoc * metody ošetřování využití MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tryptasy imunologie izolace a purifikace škodlivé účinky MeSH
- Check Tag
- kojenec * MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- kazuistiky MeSH
Alergická rýma je počtem pacientů na prvním místě mezi všemi alergickými projevy. Poznání základních mechanismů vzniku a průběhu potvrdilo, že je systémovým onemocněním. Nepodaří-li se dosáhnout kontroly nad eozinofilním zánětem, řadí se k nepřenosným chronickým onemocněním dýchacích cest s výraznými dopady na kvalitu života. Alergická rýma je rizikem pro vznik astmatu a z komorbidit jsou významné rinosinusitida a nosní polypóza. Novou strategií péče je výzva evropských alergologů k „integrované péči o respirační nemoci“ (Integrated Care Pathways for Airway Diseases) včetně alergické rýmy.
Allergic rhinitis is the most common one among all allergic disorders. It is a systemic disease with local symptoms. Management of eosinophilic inflammation is influential in the prognosis. Allergic rhinitis represents a social and economic problem and with its high prevalence it belongs among the most significant chronic non-communicable diseases in terms of their impact. Allergic rhinitis is a risk factor for asthma development. The persisting nasal inflammation is connected with risk of chronic rhinosinusitis or nasal polyposis. This comorbidity has a significant impact on the patient’s quality of life. Treatment of AR must be complex, the forms of pharmacotherapy need to be combined with specific allergen immunotherapy. A new strategy of care is offered by the Integrated Care Pathways for all Airways Diseases project.
- MeSH
- alergická rýma * diagnóza farmakoterapie imunologie klasifikace MeSH
- antihistaminika farmakologie terapeutické užití MeSH
- aplikace intranazální MeSH
- desenzibilizace imunologická metody MeSH
- faktor aktivující destičky terapeutické užití MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- kromoglykát dvojsodný terapeutické užití MeSH
- lidé MeSH
- mezioborová komunikace MeSH
- zánět imunologie krev MeSH
- Check Tag
- lidé MeSH
Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was used for characterizing intact plasmalogen phospholipid molecules in beer-spoilage bacteria. Identification of intact plasmalogens was carried out using collision-induced dissociation and the presence of suitable marker molecular species, both qualitative and quantitative, was determined in samples containing the anaerobic bacteria Megasphaera and Pectinatus. Using selected ion monitoring (SIM), this method had a limit of detection at 1 pg for the standard, i.e. 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphoethanolamine and be linear in the range of four orders of magnitude from 2 pg to 20 ng. This technique was applied to intact plasmalogen extracts from the samples of contaminated and uncontaminated beer without derivatization and resulted in the identification of contamination of beer by Megasphaera and Pectinatus bacteria. The limit of detection was about 830 cells of anaerobic bacteria, i.e. bacteria containing natural cyclopropane plasmalogenes (c-p-19:0/15:0), which is the majority plasmalogen located in both Megasphaera and Pectinatus. The SIM ESI-MS method has been shown to be useful for the analysis of low concentration of plasmalogens in all biological samples, which were contaminated with anaerobic bacteria, e.g. juice, not only in beer. Significance and impact of the study: Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) using collision-induced dissociation was used to characterize intact plasmalogen phospholipid molecules in beer-spoilage anaerobic bacteria Megasphaera and Pectinatus. Using selected ion monitoring (SIM), this method has a detection limit of 1 pg for the standard 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphoethanolamine and is linear within four orders of magnitude (2 pg to 20 ng). The limit of detection was about 830 cells of bacteria containing natural cyclopropane plasmalogen (c-p-19:0/15:0). SIM ESI-MS method is useful for analyzing low concentrations of plasmalogens in biological samples contaminated with anaerobic bacteria, e.g. beer or juice.
- MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- limita detekce MeSH
- Megasphaera klasifikace izolace a purifikace metabolismus MeSH
- Pectinatus klasifikace izolace a purifikace metabolismus MeSH
- pivo mikrobiologie MeSH
- plasmalogeny analýza MeSH
- potravinářská mikrobiologie metody MeSH
- tandemová hmotnostní spektrometrie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
