Reversed-phase ultrahigh-performance liquid chromatography-mass spectrometry (RP-UHPLC/MS) method is optimized for the quantitation of a large number of lipid species in biological samples, primarily in human plasma and serum. The method uses a C18 bridged ethylene hybrid (BEH) column (150 × 2.1 mm; 1.7 μm) for the separation of lipids from 23 subclasses with a total run time of 25 min. Lipid species separation allows the resolution of isobaric and isomeric lipid forms. A triple quadrupole mass spectrometer is used for targeted lipidomic analysis using multiple reaction monitoring (MRM) in the positive ion mode. Data are evaluated by Skyline software, and the concentrations of analytes are determined using internal standards per each individual lipid class.
- Klíčová slova
- High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Reversed-phase, Serum, Ultrahigh-performance liquid chromatography,
- MeSH
- chromatografie s reverzní fází * metody MeSH
- hmotnostní spektrometrie metody MeSH
- kapalinová chromatografie-hmotnostní spektrometrie MeSH
- lidé MeSH
- lipidomika * metody MeSH
- lipidy * analýza MeSH
- rychlé screeningové testy metody MeSH
- software MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidy * MeSH
Spices are a rich source of vitamins, polyphenols, proteins, dietary fiber, and minerals such as calcium, magnesium, iron, and zinc, all of which play an important role in biological functions. Since ancient times, spices have been used in our kitchen as a food coloring agent. Spices like cinnamon and turmeric allegedly contain various functional ingredients, such as phenolic and volatile compounds. Therefore, this review aims to summarize the current knowledge about the nutritional profiles of cinnamon and turmeric, as well as to analyze the clinical studies on their extracts and essential oils in animals and humans. Furthermore, their enrichment applications for food products and animal feed have also been investigated in terms of safety and toxicity. Numerous studies have shown that cinnamon and turmeric have various health benefits, including the reduction of insulin resistance and insulin signaling pathways in diabetic patients, the reduction of inflammatory biomarkers, and the maintenance of gut microflora in both animals and humans. The food and animal feed industries have taken notice of these health benefits and have begun to promote cinnamon and turmeric as healthy foods. This has resulted in the development of new food products and animal feeds that contain cinnamon and turmeric as primary ingredients, which have been deemed an effective means of promoting cinnamon and turmeric's health benefits.
- Klíčová slova
- Cinnamon, enrichment, functional feed, functional food, turmeric,
- MeSH
- Curcuma * chemie MeSH
- funkční potraviny * MeSH
- inzulinová rezistence MeSH
- koření * analýza MeSH
- krmivo pro zvířata * analýza MeSH
- lidé MeSH
- oleje prchavé farmakologie MeSH
- rostlinné extrakty farmakologie MeSH
- skořicovník ceylonský * chemie MeSH
- střevní mikroflóra účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- oleje prchavé MeSH
- rostlinné extrakty MeSH
INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain. INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain.
- Klíčová slova
- Bacteroides, Dopamine, Metabolites, Serotonin, Tryptophan,
- MeSH
- agrese fyziologie MeSH
- dospělí MeSH
- feces * mikrobiologie chemie MeSH
- impulzivní chování * fyziologie MeSH
- kyseliny mastné těkavé analýza metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- střevní mikroflóra * fyziologie MeSH
- tryptofan krev metabolismus MeSH
- zločinci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyseliny mastné těkavé MeSH
- tryptofan MeSH
Ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC/MS) method is optimized for the high-throughput quantitation of lipids in human serum and plasma with an emphasis on robustness and accurate quantitation. Bridged ethylene hybrid (BEH) silica column (100 × 3 mm; 1.7 μm) is used for the separation of 17 nonpolar and polar lipid classes in 4.4 min using the positive ion electrospray ionization mode. The lipid class separation approach in UHPSFC/MS results in the coelution of all lipid species within one lipid class in one chromatographic peak, including two exogenous internal standards (IS) per lipid class, which provides the optimal conditions for robust quantitation. The method was validated according to European Medicines Agency and Food and Drug Administration recommendations. UHPSFC/MS combined with LipidQuant software allows a semiautomated process to determine lipid concentrations with a total run time of only 8 min including column equilibration, which enables the analysis of 160 samples per day.
- Klíčová slova
- High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Serum, Ultrahigh-performance supercritical fluid chromatography, Validation,
- MeSH
- hmotnostní spektrometrie metody MeSH
- lidé MeSH
- lipidomika * metody MeSH
- lipidy * analýza krev MeSH
- superkritická fluidní chromatografie * metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidy * MeSH
BACKGROUND: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class of endogenous bioactive lipids with promising therapeutic potential for diabetes and inflammation. They represent complex mixtures of different isomers whose biological functions are the subject of investigation. Highly selective methods are required to characterize the composition of enantiomers in biological samples composed of many isobars and regioisomers. We aimed to develop a method for characterizing the enantiomeric composition of FAHFAs in biological samples using supercritical fluid chromatography-mass spectrometry (SFC-MS). RESULTS: The influence of key chromatographic parameters, such as column chemistry, mobile phase composition, and gradient, on the separation efficiency of 21 commercially available FAHFA regioisomers without stated absolute configuration and 4 FAHFA enantiomers was assessed. The optimized SFC-MS method utilizes a chiral column based on a tris-(3-chloro-5-methylphenylcarbamate) derivative of amylose (Lux i-Amylose-3) and acetonitrile-methanol mobile phase modifier, enabling fast enantioseparation of most FAHFA racemic pairs in 5 min. However, the SFC separation of FAHFA regioisomers was less effective, limiting its applicability to complex biological samples. To address this, we propose an offline two-dimensional separation approach with reversed-phase liquid chromatography for isolating FAHFA regioisomers, followed by chiral SFC-MS analysis of fractions. The suitability of the method was demonstrated by characterizing the enantiomeric composition of FAHFA in white adipose tissue and rice samples. The chiral analysis revealed the presence of both R- and S-FAHFA isomers in the samples, with one enantiomer being predominant. SIGNIFICANCE: The developed approach represents a proof of concept for the use of SFC-MS with LC prefractionation for the characterization of FAHFA enantiomeric composition in complex biological samples, providing a valuable tool for future research on the biological roles of bioactive lipids in health and disease.
- Klíčová slova
- Chiral separation, FAHFA, Isomers, Lipids, Offline two-dimensional chromatography, Supercritical fluid chromatography,
- MeSH
- chromatografie kapalinová metody MeSH
- estery * chemie analýza izolace a purifikace MeSH
- hmotnostní spektrometrie * metody MeSH
- hydroxykyseliny chemie analýza izolace a purifikace MeSH
- mastné kyseliny * chemie analýza izolace a purifikace MeSH
- myši MeSH
- stereoizomerie MeSH
- superkritická fluidní chromatografie * metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- estery * MeSH
- hydroxykyseliny MeSH
- mastné kyseliny * MeSH
Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing. This review presents currently available computational methods for LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, with the focus on molecular dynamics simulations in all-atom and coarse-grained resolution. Their strengths and weaknesses are discussed, highlighting the aspects necessary for obtaining reliable results in the simulations. Furthermore, a machine learning, i.e., data-based learning, approach to the design of lipid-mediated API delivery is introduced. The data produced by the experimental and theoretical approaches provide valuable insights. Processing these data can help optimize the design of LNCs for better performance. In the final section of this Review, state-of-the-art of computer simulations of LNCs are reviewed, specifically addressing the compatibility of experimental and computational insights.
- Klíčová slova
- ionizable lipid, lipid nanocarrier, lipid nanoparticle, liposome, molecular simulation, vesicle,
- MeSH
- léčivé přípravky chemie MeSH
- lidé MeSH
- lipidy * chemie MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- počítačová simulace MeSH
- simulace molekulární dynamiky * MeSH
- strojové učení MeSH
- systémy cílené aplikace léků metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- léčivé přípravky MeSH
- lipidy * MeSH
- nosiče léků MeSH
The widespread use of hexachlorocyclohexanes (HCH) as pesticides has raised environmental concerns due to their persistence and toxicity. Addressing the pressing need for effective bioremediation strategies, this study explores the effects of α-, β-, δ-, and ε-HCH isomers on the growth, hormonal changes, physiological parameters and bioaccumulation in Alnus glutinosa saplings (1-year-old and 2-year-old) and bacterial communities in polluted soil. A. glutinosa saplings not only withstanded HCH exposure but also enhanced the remediation efficiency by 6.8-24.4%, suggesting an acceleration of pollutant breakdown likely mediated by root exudates positively affecting the soil microbiome. Interestingly, 1-year-old saplings demonstrated greater remediation efficiency post-pruning than unpruned 2-year-old saplings, despite the latter having a larger root biomass. The hormonal analysis indicated that HCH presence led to a reduction in abscisic acid (ABA) and an increase in jasmonic acid (JA), with the magnitude of changes being age-dependent. Salicylic acid (SA) levels increased 1-year-old and decreased in 2-year-old saplings under HCH stress. Moreover, a higher presence of lin-degrading genes in the rhizosphere of treated saplings compared to controls confirmed ongoing biodegradation processes. The outcomes help to better understand the processes involved in degradation of persistent pesticides in soil. The mechanism of in-plant isomerization and the identification of metabolites should be the focus of future research.
- Klíčová slova
- Alder tree, HCH, Pesticide, Phytoremediation, Rhizobiome,
- MeSH
- biodegradace * MeSH
- chlorované uhlovodíky metabolismus MeSH
- cyklopentany metabolismus MeSH
- hexachlorcyklohexan metabolismus MeSH
- kořeny rostlin metabolismus mikrobiologie MeSH
- kyselina abscisová metabolismus MeSH
- látky znečišťující půdu * metabolismus MeSH
- olše * mikrobiologie MeSH
- oxylipiny metabolismus MeSH
- pesticidy * metabolismus MeSH
- půda chemie MeSH
- půdní mikrobiologie * MeSH
- rhizosféra * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorované uhlovodíky MeSH
- cyklopentany MeSH
- hexachlorcyklohexan MeSH
- jasmonic acid MeSH Prohlížeč
- kyselina abscisová MeSH
- látky znečišťující půdu * MeSH
- oxylipiny MeSH
- pesticidy * MeSH
- půda MeSH
Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.
- Klíčová slova
- High-content imaging, In vitro testing, Lipid droplets, Metabolism-disrupting chemicals, NAFLD, NAMs,
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- buňky Hep G2 MeSH
- diacylglycerol-O-acyltransferasa genetika metabolismus MeSH
- diethylhexylftalát toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- viabilita buněk účinky léků MeSH
- ztučnělá játra * chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- Bisphenol A Compounds MeSH
- bisphenol A MeSH Prohlížeč
- DGAT1 protein, human MeSH Prohlížeč
- diacylglycerol-O-acyltransferasa MeSH
- diethylhexylftalát MeSH
- endokrinní disruptory * MeSH
- fenoly MeSH
- fluorokarbony MeSH
- kapryláty MeSH
- perfluorooctanoic acid MeSH Prohlížeč
The mitochondrial ADP/ATP carrier (AAC, ANT), a member of the SLC25 family of solute carriers, plays a critical role in transporting purine nucleotides (ATP and ADP) as well as protons across the inner mitochondrial membrane. However, the precise mechanism and physiological significance of proton transport by ADP/ATP carrier remain unclear. Notably, the presence of uncouplers-such as long-chain fatty acids (FA) or artificial compounds like dinitrophenol (DNP)-is essential for this process. We explore two potential mechanisms that describe ADP/ATP carrier as either (i) a proton carrier that functions in the presence of FA or DNP, or (ii) an anion transporter (FA- or DNP). In the latter case, the proton is translocated by the neutral form of FA, which carries it from the matrix to the intermembrane space (FA-cycling hypothesis). Our recent results support this hypothesis. We describe a four-step mechanism for the "sliding" of the FA anion from the matrix to the mitochondrial intermembrane space and discuss a possible generalization of this mechanism to other SLC25 carriers.
- Klíčová slova
- MD simulations, bilayer lipid membranes, membrane proteins, mitochondrial transporter, reconstituted protein, uncoupling protein,
- MeSH
- 2,4-dinitrofenol farmakologie metabolismus MeSH
- iontový transport MeSH
- lidé MeSH
- mastné kyseliny metabolismus MeSH
- mitochondriální ADP/ATP-translokasy * metabolismus chemie MeSH
- mitochondriální membrány metabolismus MeSH
- mitochondrie metabolismus MeSH
- protony * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- 2,4-dinitrofenol MeSH
- mastné kyseliny MeSH
- mitochondriální ADP/ATP-translokasy * MeSH
- protony * MeSH
The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.
- Klíčová slova
- 3D printing, Active pharmaceutical ingredient, Amorphous solid dispersion, COSMO-RS, PLA, Personalized medicine, Phase diagram, Plasticizers,
- MeSH
- 3D tisk * MeSH
- chemie farmaceutická metody MeSH
- citráty chemie MeSH
- diferenciální skenovací kalorimetrie metody MeSH
- farmaceutická technologie metody MeSH
- indomethacin * chemie MeSH
- krystalizace MeSH
- naproxen chemie MeSH
- polyestery * chemie MeSH
- rozpouštědla chemie MeSH
- rozpustnost * MeSH
- stabilita léku MeSH
- termodynamika MeSH
- tranzitní teplota MeSH
- triacetin chemie MeSH
- zvláčňovadla * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- citráty MeSH
- ethyl citrate MeSH Prohlížeč
- indomethacin * MeSH
- naproxen MeSH
- poly(lactide) MeSH Prohlížeč
- polyestery * MeSH
- rozpouštědla MeSH
- triacetin MeSH
- zvláčňovadla * MeSH
