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
- Administration, Intranasal * MeSH
- Liposomes MeSH
- Lipid Metabolism drug effects MeSH
- Disease Models, Animal * MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Nanomedicine * methods MeSH
- Parkinson Disease * metabolism drug therapy MeSH
- Plasmalogens * chemistry pharmacology MeSH
- Gene Expression Regulation drug effects MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- Biological Transport genetics MeSH
- Bioreactors microbiology MeSH
- Cell Membrane metabolism MeSH
- Butanols toxicity MeSH
- Clostridium beijerinckii drug effects genetics metabolism MeSH
- Stress, Physiological genetics MeSH
- Glucose metabolism MeSH
- Glycolysis genetics physiology MeSH
- Fatty Acids metabolism MeSH
- Plasmalogens biosynthesis MeSH
- Heat-Shock Proteins metabolism MeSH
- Quorum Sensing genetics MeSH
- Gene Expression Profiling MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- Complement Activation * immunology MeSH
- Anaphylaxis * immunology metabolism MeSH
- Basophils immunology MeSH
- Biomarkers * metabolism MeSH
- Bradykinin immunology metabolism MeSH
- Chymases immunology metabolism MeSH
- Cytokines * immunology metabolism MeSH
- Platelet Activating Factor immunology metabolism MeSH
- Phenotype * MeSH
- Histamine immunology metabolism MeSH
- Immunoglobulin E immunology MeSH
- Immunoglobulin G immunology MeSH
- Precision Medicine MeSH
- Interleukin-6 immunology metabolism MeSH
- Carboxypeptidases A immunology metabolism MeSH
- Humans MeSH
- Mast Cells immunology MeSH
- Tryptases immunology metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review 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
- Enzyme Activation MeSH
- Apoptosis drug effects MeSH
- Time Factors MeSH
- Phospholipid Ethers toxicity MeSH
- Phosphorylation MeSH
- Caspase 3 metabolism MeSH
- Caspase 7 metabolism MeSH
- Macrophages drug effects enzymology pathology MeSH
- Mice MeSH
- Oxidation-Reduction MeSH
- Protein Kinase C-delta genetics metabolism MeSH
- RAW 264.7 Cells MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Genes, Reporter MeSH
- RNA Interference MeSH
- Signal Transduction drug effects MeSH
- Transfection MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Anticoagulants contraindications MeSH
- Aspirin MeSH
- Product Packaging standards legislation & jurisprudence MeSH
- Garlic drug effects MeSH
- Platelet Activating Factor antagonists & inhibitors pharmacology contraindications drug effects MeSH
- Drug Industry methods standards organization & administration MeSH
- Ginkgo biloba MeSH
- Ginkgolides contraindications blood MeSH
- Heparin MeSH
- Hygiene standards MeSH
- Drug Information Services * MeSH
- Internet utilization legislation & jurisprudence MeSH
- Coffee MeSH
- Drug Interactions MeSH
- Humans MeSH
- Beverages MeSH
- Fruit MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- Dietary Supplements * classification standards utilization supply & distribution MeSH
- Dietary Fiber MeSH
- Cytochrome P-450 Enzyme System MeSH
- Panax drug effects MeSH
- Check Tag
- Humans MeSH
- MeSH
- Benzodiazepines MeSH
- Bilobalides pharmacology MeSH
- Platelet Activating Factor antagonists & inhibitors MeSH
- Ginkgo biloba * toxicity MeSH
- Ginkgolides pharmacology MeSH
- Glycosides pharmacology MeSH
- Ibuprofen MeSH
- Phosphodiesterase Inhibitors pharmacology MeSH
- Hemorrhage MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Cytochrome P-450 Enzyme System pharmacology MeSH
- Research MeSH
- Warfarin MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline 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
- Epinephrine * adverse effects therapeutic use MeSH
- Allergens immunology isolation & purification adverse effects MeSH
- Anaphylaxis * diagnosis etiology therapy MeSH
- Histamine Antagonists therapeutic use MeSH
- Platelet Activating Factor isolation & purification adverse effects MeSH
- Glucagon therapeutic use MeSH
- Glucocorticoids therapeutic use MeSH
- Histamine immunology isolation & purification adverse effects MeSH
- Immunoglobulins isolation & purification therapeutic use MeSH
- Clinical Laboratory Techniques methods utilization MeSH
- Infant * MeSH
- Humans MeSH
- Infant Food adverse effects utilization MeSH
- Child, Preschool MeSH
- First Aid * methods nursing utilization MeSH
- Practice Guidelines as Topic MeSH
- Tryptases immunology isolation & purification adverse effects MeSH
- Check Tag
- Infant * MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Case Reports 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
- Rhinitis, Allergic * diagnosis drug therapy immunology classification MeSH
- Histamine Antagonists pharmacology therapeutic use MeSH
- Administration, Intranasal MeSH
- Desensitization, Immunologic methods MeSH
- Platelet Activating Factor therapeutic use MeSH
- Adrenal Cortex Hormones administration & dosage MeSH
- Cromolyn Sodium therapeutic use MeSH
- Humans MeSH
- Interdisciplinary Communication MeSH
- Inflammation immunology blood MeSH
- Check Tag
- Humans 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
- Spectrometry, Mass, Electrospray Ionization MeSH
- Limit of Detection MeSH
- Megasphaera classification isolation & purification metabolism MeSH
- Pectinatus classification isolation & purification metabolism MeSH
- Beer microbiology MeSH
- Plasmalogens analysis MeSH
- Food Microbiology methods MeSH
- Tandem Mass Spectrometry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
