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Maternal nutrition during the critical period of pregnancy increases the susceptibility of offspring to the development of diseases later in life. This study aimed to analyze metabolite profiles to investigate the effect of maternal diet during pregnancy on changes in offspring plasma metabolites and to identify correlations with metabolic parameters. Pregnant Sprague-Dawley rats were exposed to under- and overnutrition compared to controls, and their offspring were fed a standard diet after birth. Plasma metabolism was profiled in offspring at 16 weeks of age using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS). We analyzed 80 metabolites to identify distinct metabolites and metabolic and neurodegenerative disease-associated metabolites that were sex-differentially altered in each group compared to controls (p < 0.05, VIP score > 1.0). Specifically, changes in 3-indolepropionic acid, anthranilic acid, linoleic acid, and arachidonic acid, which are involved in tryptophan and linoleic acid metabolism, were observed in male offspring and correlated with plasma leptin levels in male offspring. Our results suggest that fatty acids involved in tryptophan and linoleic acid metabolism, which are altered by the maternal diet during pregnancy, may lead to an increased risk of metabolic and neurodegenerative diseases in the early life of male offspring. [ABSTRACT FROM AUTHOR]

Bovine digital dermatitis (BDD) is a cattle infection causing hoof lesions and lameness, with treponemes as key pathogens. We analyzed the metabolic activity of Treponema phagedenis and Treponema pedis using gas chromatography–mass spectrometry for organic acids (OAs), amino acids (AAs), and fatty acids (FAs), and high-performance liquid chromatography for short-chain fatty acids (SCFAs). Key findings include a 61.5% reduction in pyruvic acid in T. pedis and 81.0% in T. phagedenis. 2-hydroxybutyric acid increased by 493.8% in T. pedis, while succinic acid increased by 31.3%, potentially supporting T. phagedenis. Among AAs, glycine was reduced by 97.4% in T. pedis but increased by 64.1% in T. phagedenis. Proline increased by 76.6% in T. pedis but decreased by 13.6% in T. phagedenis. Methionine and glutamic acid were competitively utilized, with methionine reduced by 41.8% in T. pedis and 11.9% in T. phagedenis. Both species showed significant utilization of palmitic acid (reduced by 82.8% in T. pedis and 87.2% in T. phagedenis). Butyric acid production increased by 620.2% in T. phagedenis, and propionic acid increased by 932.8% in T. pedis and 395.6% in T. phagedenis. These reveal metabolic interactions between the pathogens, contributing to disease progression and offering insights to BDD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival. Methods: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex. Results: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites. Conclusion: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex. [ABSTRACT FROM AUTHOR]

Considering the greater pharmaceutical and clinical interest of triiodothyronine (T3) thyroid hormone, an effective D/L‐T3 enantiomer separation was performed on a crown ether‐based chiral stationary phase by LC–MS/MS. In optimal analytical condition and selected reaction monitoring mode, the two enantiomers of T3 were baseline separated within 10 min. The limit of detection and limit of quantitation were found to be 0.05 and 0.10 ng/μl; 0.20 and 0.50 ng/μl for D‐ and L‐T3, respectively. During validation, this method proved to be feasible, accurate as well as enantioselective and sensitive for the resolution of T3 enantiomers. For commercial D‐ and L‐T3 chemicals, the enantiomeric impurities as the other enantiomer were 0.11% and 4.61%. On the other hand, the impurity as D‐T3 for commercial pharmaceutical products (liothyronine sodium tablets, two suppliers) was 0.68% and 6.57%. [ABSTRACT FROM AUTHOR]

Cryopreservation in liquid nitrogen (LN, −196 °C) is a unique option for the long-term conservation of threatened plant species with non-orthodox or limitedly available seeds. In previous studies, a systematic approach was used to develop a droplet-vitrification (DV) cryopreservation protocol for Postemon yatabeanus shoot tips that includes preculture with 10% sucrose, osmoprotection with C4-35%, cryoprotection with A3-80% vitrification solution, and a three-step regrowth starting with the ammonium-free medium. The tricarboxylic acid (TCA) cycle is a crucial component of plant cell metabolism as it is involved in redox state regulation and energy provision. We hypothesized that organic acids (OAs) associated with the TCA and its side reactions indirectly indicate metabolism intensity and oxidative stress development in shoot tips under the cryopreservation procedure. In this study, the contents of 14 OAs were analyzed using gas chromatography–tandem mass spectrometry (GC-MS/MS) in P. yatabeanus shoot tips in a series of treatments including individual steps of the DV procedure, additional stress imposed by non-optimum protocol conditions (no preculture, no osmoprotection, various vitrification solution composition, using vials instead of aluminum foils, etc.) and regrowth on different media with or without ammonium or growth regulators. The possible relation of OA content with the total cryoprotectant (CPA) concentration and shoot tips regeneration percentage was also explored. Regeneration of cryopreserved shoot tips reduced in descending order as follows: standard protocol condition (91%) > non-optimum vitrification solution (ca. 68%) > non-optimum preculture (60–62%) > regrowth medium (40–64%) > no osmoprotection, cryopreservation in vials (28–30%). Five OAs (glycolic, malic, citric, malonic, and lactic) were the most abundant in the fresh (control) shoot tips. The dynamic pattern of OAs during the DV procedure highly correlated (r = 0.951) with the total CPA concentration employed: it gradually increased through the preculture, osmoprotection, and cryoprotection, peaked at cooling/rewarming (6.38-fold above control level), and returned to the fresh control level after 5 days of regrowth (0.89-fold). The contents of four OAs (2-hydroxybutyric, 3-hydroxypropionic, lactic, and glycolic) showed the most significant (10-209-fold) increase at the cooling/rewarming step. Lactic and glycolic acids were the major OAs at cooling/rewarming, accounting for 81% of the total OAs content. The OAs were categorized into three groups based on their dynamics during the cryopreservation protocol, and these groups were differently affected by protocol step modifications. However, there was no straightforward relationship between the dynamics of OAs and shoot tip regeneration. The results suggest that active modulation of OAs metabolism may help shoot tips to cope with osmotic stress and the chemical cytotoxicity\ of CPAs. Further intensive studies are needed to investigate the effect of cryopreservation on cell primarily metabolism and identify oxidative stress-related biomarkers in plant materials. [ABSTRACT FROM AUTHOR]

This study describes the enantioseparation of three chiral amines as naphthaldimine derivatives, using normal phase HPLC with amylose and cellulose tris(3,5‐dimethylphenylcarbamate) chiral stationary phases (CSPs). Three chiral amines were derivatized using three structurally similar naphthaldehyde derivatizing agents, and the enantioselectivity of the CSPs toward the derivatives was examined. The degree of enantioseparation and resolution was affected by the amylose or cellulose‐derived CSPs and aromatic moieties as well as a kind of chiral amine. Especially, efficient enantiomer separation was observed for 2‐hydroxynapthaldimine derivatives on cellulose‐derived CSPs. Molecular docking studies of three naphthaldimine derivatives of leucinol on cellulose tris(3,5‐dimethylphenylcarbamate) were performed to estimate the binding energies and conformations of the CSP–analyte complexes. The obtained binding energies were in good agreement with the experimentally determined enantioseparation and elution order. [ABSTRACT FROM AUTHOR]

Simple Summary: Heat stress has a negative effect on feed intake, growth, and metabolic disorders of ruminants that cause oxidative stress by the overproduction of free radicals and disturbance of the redox balance. Different breeds have different abilities to adapt to heat stress; thus, feeding them with antioxidants such as minerals can help build up an antioxidant defense system that prevents oxidative damage in the body. This study investigated the effects of recommended and high mineral concentrations on antioxidant enzymes, heat shock proteins, and metabolites in the blood of Holstein and Jersey steers during heat stress. Our results showed that animals supplemented with high mineral concentrations prevent oxidative stress and metabolite changes related to heat stress in the blood. Therefore, increasing mineral supplementation during high temperatures is an effective strategy for reducing heat stress. This study investigated the influence of high concentrations of dietary minerals on reducing heat stress (HS)-associated oxidative stress and metabolic alterations in the blood of Holstein and Jersey steers. Holstein steers and Jersey steers were separately maintained under a 3 × 3 Latin square design during the summer conditions. For each trial, the treatments included Control (Con; fed basal TMR without additional mineral supplementation), NM (NRC recommended mineral supplementation group; [basal TMR + (Se 0.1 ppm + Zn 30 ppm + Cu 10 ppm) as DM basis]), and HM (higher than NRC recommended mineral supplementation group; [basal TMR + (Se 3.5 ppm + Zn 350 ppm + Cu 28 ppm) as DM basis]). Blood samples were collected at the end of each 20-day feeding trial. In both breeds, a higher superoxide dismutase concentration (U/mL) along with lower HSP27 (μg/L) and HSP70 (μg/L) concentrations were observed in both mineral-supplemented groups compared to the Con group (p < 0.05). The HM group had significantly higher lactic acid levels in Jersey steers (p < 0.05), and tended to have higher alanine levels in Holstein steers (p = 0.051). Based on star pattern recognition analysis, the levels of succinic acid, malic acid, γ-linolenic acid, 13-methyltetradecanoic acid, and tyrosine decreased, whereas palmitoleic acid increased with increasing mineral concentrations in both breeds. Different treatment groups of both breeds were separated according to the VIP scores of the top 15 metabolites through PLS–DA analysis; however, their metabolic trend was mostly associated with the glucose homeostasis. Overall, the results suggested that supplementation with a higher-than-recommended concentration of dietary minerals rich in organic Se, as was the case in the HM group, would help to prevent HS-associated oxidative stress and metabolic alterations in Holstein and Jersey steers. [ABSTRACT FROM AUTHOR]

Nanoparticles have garnered significant interest in neurological research in recent years owing to their efficient penetration of the blood–brain barrier (BBB). However, significant concerns are associated with their harmful effects, including those related to the immune response mediated by microglia, the resident immune cells in the brain, which are exposed to nanoparticles. We analysed the cytotoxic effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] in a BV2 microglial cell line using systems toxicological analysis. We performed the invasion assay and the exocytosis assay and transcriptomics, proteomics, metabolomics, and integrated triple-omics analysis, generating a single network using a machine learning algorithm. The results highlight alteration in the mechanisms of the nanotoxic effects of nanoparticles using integrated omics analysis. [ABSTRACT FROM AUTHOR]

We performed targeted metabolomics with machine learning (ML)-based interpretation to identify metabolites that distinguish the progression of nonalcoholic fatty liver disease (NAFLD) in a cohort. Plasma metabolomics analysis was conducted in healthy control subjects (n = 25) and patients with NAFL (n = 42) and nonalcoholic steatohepatitis (NASH, n = 19) by gas chromatography-tandem mass spectrometry (MS/MS) and liquid chromatography-MS/MS as well as RNA sequencing (RNA-seq) analyses on liver tissues from patients with varying stages of NAFLD (n = 12). The resulting metabolomic data were subjected to routine statistical and ML-based analyses and multi-omics interpretation with RNA-seq data. We found 6 metabolites that were significantly altered in NAFLD among 79 detected metabolites. Random-forest and multinomial logistic regression analyses showed that eight metabolites (glutamic acid, cis-aconitic acid, aspartic acid, isocitric acid, α-ketoglutaric acid, oxaloacetic acid, myristoleic acid, and tyrosine) could distinguish the three groups. Then, the recursive partitioning and regression tree algorithm selected three metabolites (glutamic acid, isocitric acid, and aspartic acid) from these eight metabolites. With these three metabolites, we formulated an equation, the MetaNASH score that distinguished NASH with excellent performance. In addition, metabolic map construction and correlation assays integrating metabolomics data into the transcriptome datasets of the liver showed correlations between the concentration of plasma metabolites and the expression of enzymes governing metabolism and specific alterations of these correlations in NASH. Therefore, these findings will be useful for evaluation of altered metabolism in NASH and understanding of pathophysiologic implications from metabolite profiles in relation to NAFLD progression. [ABSTRACT FROM AUTHOR]

This is a metabolomics study for monitoring altered amino acid (AA) and organic acid (OA) metabolism of in eyes from aging an mouse model at 8 and 18 weeks and 18 months. Simultaneous metabolic profiling analysis of OAs and AAs was performed as ethoxycarbonyl/methoxime/tert‐butyldimethylsilyl derivatives by gas chromatography–tandem mass spectrometry. A total of 42 metabolites—24 AAs and 18 OAs—were determined and their composition values were normalized to the corresponding mean values of 8‐week‐old mice as the control group. Then their normalized values were plotted as star graphs, which were distorted and readily distinguishable for each age‐related group. Among the 42 metabolites, 18 AAs and 11 OAs were age dependent and significantly different (p < 0.05). Principal component analysis and partial least squares discriminant analysis showed unclear separation between 8‐ and 18‐week‐old mice but clear separation between these and 18‐month‐old mice. In particular, the variable importance in projection scores of 4‐hydroxyproline, cis‐aconitic acid, glycine, isocitric acid, leucine, pipecolic acid and lysine from partial least‐squares–discriminant analysis were higher than 1.3. A heatmap for the classification and visualization of 42 metabolites showed differences in metabolite changes with aging. Altered AA and OA profiles were monitored, which may explain the metabolic disturbance of AA and OA. These findings are related to mitochondrial dysfunctions related to energy metabolism and the impaired antioxidant system in the aging eye. Therefore, the present metabolomics results of the association between physiological states and altered metabolism of AA and OA will be useful for understanding the aging eye and related diseases. [ABSTRACT FROM AUTHOR]

An efficient gas chromatography‐tandem mass spectrometry‐based method using tert‐butyldimethylsilyl derivative was developed for the simultaneous analysis of 10 phenolic acids. Under optimal conditions, linearity in the range of 2–100 ng/ml exhibited correlation coefficient (r) of ≥0.999. Repeatability showed low relative standard deviation of <16.7%, and accuracy (% relative error) varied from −9.8 to 3.4. New mass spectra data sets of 10 phenolic acids were constructed in multiple reaction monitoring mode. When applied to Orostachys japonica (Maxim.) A. Berger, the 10 phenolic acids of salicylic, 4‐hydroxybenzoic, vanillic, m‐coumaric, syringic, p‐coumaric, protocatechuic, ferulic, gallic, and caffeic acids were positively identified. We believe that the devised method will be found useful for profiling phenolic acids in various plant samples. [ABSTRACT FROM AUTHOR]

Background: Plants in nature interact with other species, among which are mutualistic microorganisms that affect plant health. The co-existence of microbial symbionts with the host contributes to host fitness in a natural context. In turn, the composition of the plant microbiota responds to the environment and the state of the host, raising the possibility that it can be engineered to benefit the plant. However, technology for engineering the structure of the plant microbiome is not yet available. Results: The loss of diversity and reduction in population density of Streptomyces globisporus SP6C4, a core microbe, was observed coincident with the aging of strawberry plants. Here, we show that glutamic acid reshapes the plant microbial community and enriches populations of Streptomyces, a functional core microbe in the strawberry anthosphere. Similarly, in the tomato rhizosphere, treatment with glutamic acid increased the population sizes of Streptomyces as well as those of Bacillaceae and Burkholderiaceae. At the same time, diseases caused by species of Botrytis and Fusarium were significantly reduced in both habitats. We suggest that glutamic acid directly modulates the composition of the microbiome community. Conclusions: Much is known about the structure of plant-associated microbial communities, but less is understood about how the community composition and complexity are controlled. Our results demonstrate that the intrinsic level of glutamic acid in planta is associated with the composition of the microbiota, which can be modulated by an external supply of a biostimulant. Cg3iRbBtvJ_v2-WLHm3hSU Video Abstract [ABSTRACT FROM AUTHOR]

Background: Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods: Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results: Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions: Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods: Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results: Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions: Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods: Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results: Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions: Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due to their small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, the resident macrophages of the central nervous system, and indirect toxicity on neuronal cells exerted by silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]. Methods: We investigated MNPs@SiO2(RITC)-induced biological changes in BV2 murine microglial cells via RNA-sequencing-based transcriptome analysis and gas chromatography-mass spectrometry-based intracellular and extracellular amino acid profiling. Morphological changes were analyzed by transmission electron microscopy. Indirect effects of MNPs@SiO2(RITC) on neuronal cells were assessed by Transwell-based coculture with MNPs@SiO2(RITC)-treated microglia. MNPs@SiO2(RITC)-induced biological changes in the mouse brain in vivo were examined by immunohistochemical analysis. Results: BV2 murine microglial cells were morphologically activated and the expression of Iba1, an activation marker protein, was increased after MNPs@SiO2(RITC) treatment. Transmission electron microscopy analysis revealed lysosomal accumulation of MNPs@SiO2(RITC) and the formation of vesicle-like structures in MNPs@SiO2(RITC)-treated BV2 cells. The expression of several genes related to metabolism and inflammation were altered in 100 µg/ml MNPs@SiO2(RITC)-treated microglia when compared with that in non-treated (control) and 10 µg/ml MNPs@SiO2(RITC)-treated microglia. Combined transcriptome and amino acid profiling analyses revealed that the transport of serine family amino acids, including glycine, cysteine, and serine, was enhanced. However, only serine was increased in the growth medium of activated microglia; especially, excitotoxic D-serine secretion from primary rat microglia was the most strongly enhanced. Activated primary microglia reduced intracellular ATP levels and proteasome activity in cocultured neuronal cells, especially in primary cortical neurons, via D-serine secretion. Moreover, ubiquitinated proteins accumulated and inclusion bodies were increased in primary dopaminergic and cortical neurons cocultured with activated primary microglia. In vivo, MNPs@SiO2(RITC), D-serine, and ubiquitin aggresomes were distributed in the MNPs@SiO2(RITC)-treated mouse brain. Conclusions: MNPs@SiO2(RITC)-induced activation of microglia triggers excitotoxicity in neurons via D-serine secretion, highlighting the importance of neurotoxicity mechanisms incurred by nanoparticle-induced microglial activation. [ABSTRACT FROM AUTHOR]

Endogenous normal and modified nucleosides have been studied as potential biomarkers of various inflammatory diseases including sepsis. However, no systematic nucleoside profiling and pattern analysis study has been performed in sepsis. In this study, simultaneous liquid chromatography–mass spectrometry profiling of normal and modified nucleosides was performed to characterize altered nucleoside metabolism in sepsis mice. [ABSTRACT FROM AUTHOR]

The influences of radiofrequency electromagnetic exposure on animal health, particularly on serotonin metabolism, are not well-elucidated. In this in vivo study, we studied the influences of exposure to radiofrequency identification (RFID) signals on serotonin metabolism. Twenty-two male Sprague–Dawley rats were assigned to sham (n = 10) and RFID-exposed (n = 12) groups. Rats in the RFID-exposed group were exposed to RFID signals at an average whole-body specific absorption rate of 2 W/kg for 8 h/day, 5 days/week for 2 weeks. Before and after RFID exposure, 24-h urine was collected from each rat. Urinary tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and 5-methoxyindole-3-acetic acid concentrations were examined using gas chromatography-mass spectrometry, and changes in the patterns of values were compared between the two groups. Urinary levels of serotonin decreased by 20% (p =.041, Student's t-test) and 40% (p =.024, Student's t-test) in both the sham and RFID-exposed groups, respectively. The level of 5-methoxyindole-3-acetic acid decreased by 30% in the RFID-exposed group (p =.039, Student's t-test). Our results indicate that exposure to RFID signals at a specific absorption rate of 2 W/kg is sufficient to alter serotonin metabolism in rats regardless of whether the exposure level is considered biohazardous. [ABSTRACT FROM AUTHOR]

The antidepressant-like activity of ethanol extract of Ziziphus jujuba Mill var. spinosa seeds (Semen Ziziphi Spinosae, SZS) was investigated by behavioral tests, such as a forced swimming test (FST), a tail-suspension test (TST), and an open field test (OFT), using mice exposed to chronic unpredictable mild stress (CUMS). In the TST, immobility times of the extract-treated groups E100 and E300 (CUMS + 100 and 300 mg/kg extract, respectively) were significantly decreased in a dose-dependent manner compared with the negative control (CUMS; p < 0.01, though those of E100 and E300 were higher than those of the positive control (CUMS + 15 mg/kg fluoxetine). In the FST, immobility times of E100 and E300 were decreased compared to the normal control. In the OFT, total and zone distances of E100 and E300 were significantly higher than those of negative controls (p < 0.01) with a dose dependency. In liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis after behavioral tests, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the hippocampus tissues of E100 and E300 were significantly higher than those of negative controls. Brain-derived neurotrophic factor (BDNF) levels in the hippocampus tissues of E100 and E300 were higher than those of negative controls. From these results, the SZS ethanol extract exhibited significant antidepressant-like effects via immobility decrease, distance increase, hippocampal NE and 5-HT increase, and BDNF expression. These results suggest that the extract could be a potential antidepressant agent. [ABSTRACT FROM AUTHOR]

Background: Acetyl octapeptide-3 (SNAP-8) is an antiaging peptide that is more effective than acetyl hexapeptide-3, which is more stable than botulinum toxin and effectively relieves facial wrinkles. Products containing SNAP-8 such as patch are producing, but analytical method has not been reported to determination of SNAP-8. Method: Mobile phase, collision energy, and desolvation line temperature were optimized, and mass spectral data set for SNAP-8 was newly constructed by liquid chromatography-triple quadrupole mass spectrometer in multiple reaction monitoring mode. Results: The developed method showed good linearity (r ≥ 0.9971) with limit of quantification of 0.0125 ng/mL, repeatability (% relative standard deviation = 0.02 to 0.12) and accuracy (% relative error = − 1.68 to 1.44) under optimal conditions. This method was successfully applied to a biodegradable microneedle patch loaded with SNAP-8. Conclusion: The present method for the quantification of SNAP-8 may be useful for quality control in the cosmetic fields. [ABSTRACT FROM AUTHOR]

The antidepressant activities of hispidol and decursin (both potent monoamine oxidase A (MAO-A) inhibitors) were evaluated using the forced swimming test (FST) and the tail suspension test (TST) in mice, and thereafter, levels of neurotransmitter monoamines and metabolites in brain tissues were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Hispidol (15 mg/kg) caused less or comparable immobility than fluoxetine (15 mg/kg; the positive control) in immobility time, as determined by FST (9.6 vs 32.0 s) and TST (53.1 vs 48.7 s), respectively, and its effects were dose-dependent and significant. Decursin (15 mg/kg) also produced immobility comparable to that of fluoxetine as determined by FST (47.0 vs 43.4 s) and TST (55.6 vs 63.4 s), and its effects were also dose-dependent and significant. LC–MS/MS analysis after FST showed that hispidol (15 mg/kg) greatly increased dopamine (DA) and serotonin levels dose-dependently in brain tissues as compared with the positive control. Decursin (15 mg/kg) dose-dependently increased DA level after TST. Slight changes in norepinephrine and 3,4-dihydroxyphenylacetic acid levels were observed after FST and TST in hispidol- or decursin-treated animals. It was observed that hispidol and decursin were effective and comparable to fluoxetine in immobility tests. These immobility and monoamine level results suggest that hispidol and decursin are potential antidepressant agents for the treatment of depression, and that they act mainly through serotonergic and/or dopaminergic systems. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TA) as a synthetic derivative of lysine is a potent antifibrinolytic drug used to reduce bleeding during surgeries including dental extraction. The efficacy of TA administration in ovarian cancer and melasma has also been reported in a previous study. In this study, the mass spectral data set of TA as ethoxycarbonyl‐tert‐butyldimethylsilyl derivatives was newly constructed by gas chromatography‐tandem mass spectrometry in multiple reaction‐monitoring mode. This analytical method was validated with good linearity (r > 0.9988), limit of detection (LOD, 0.22 ng/mL), limit of quantification (LOQ, 0.72 ng/mL), relative standard deviation (1.3 to 4.8%), and relative error (−6.8 to 3.5%) under optimal conditions. The LOD and LOQ were assessed to be lower than other reported methods. Therefore, the present method will be useful for monitoring of TA in the pharmacological and cosmetic fields. [ABSTRACT FROM AUTHOR]

A simple and rapid method for the simultaneous determination of 35 non-derivatized metabolites was developed using liquid chromatography – tandem mass spectrometry. Under the optimal conditions, linearity was achieved in the range from 0.05 to 10.0 ng (R2 ≥ 0.989). The repeatability provided percentage relative standard deviations ≤11.2 and a trueness expressed as percentage relative error from −10.7% to 12%. The recoveries ranged from 87.3% to 109.8% with good repeatability. When applied to mouse lung tissue, plasma, and urine samples, 30 amino acids, creatine, creatinine, and oxidized glutathione were positively identified and quantified. The described present method was useful for the simultaneous determination of amino acids, creatine, creatinine, and oxidized glutathione in biological samples, including tissue, plasma, and urine. [ABSTRACT FROM AUTHOR]

Flavonoids are secondary metabolites with antioxidant, anticancer, and anti‐inflammatory properties. However, no method has yet been reported for the simultaneous profiling analysis for flavonoids of various types. Thus, simultaneous profiling analysis of various flavonoids was performed in this study. Under optimal conditions, the developed method showed good linearity (r ≥ 0.9973) in the range 25–1000 ng/μL with a limit of detection (LOD) of 0.9–12.1 pg. and a limit of quantification (LOQ) of 2.6–36.5 pg., respectively. The repeatability as a percentage of relative standard deviation (% RSD) varied from 0.5 to 5.9 (% RSD). And accuracy as a percentage of relative error (% RE) was from −11.8 to 10.5 (% RE). The validated method was applied to a solid phase extraction fraction of Orostachys japonicus (Maxim.) A. Berger. Six flavonoids of catechin, rutin, quercitrin, quercetin, luteolin, and kaempferol were positively identified and quantified. Therefore, the present method will be useful for the monitoring and screening of flavonoids in natural products. [ABSTRACT FROM AUTHOR]

Bananas are a well-known healthy food that contain various functional amino acids (AAs) whose concentrations may vary during ripening. Thus, amino acid profiling analysis was performed at different stages of ripeness in bananas by gas chromatography–mass spectrometry (GC-MS) using selected ion monitoring (SIM) with ethoxycarbonyl/tert-butyldimethylsilyl (EOC/TBDMS) derivatives. The variability of the amino acids in ripening was subsequently explored by star pattern analysis after normalization to the corresponding mean values of the unripe bananas. Significant alterations of amino acids were found in ripe bananas following 1, 6, and 10 days of storage. The star graphic patterns were different in the unripe and ripe bananas. In particular, glutamine and asparagine were present as two major components making up 65.68 to 71.75% and 10.86 to 14.94% of the total amino acids. The compositions (%) of valine, leucine, γ-aminobutyric acid, and glutamic acid were significantly increased by 65–210% in ripe bananas following 10 days of storage. In addition, the total composition (%) of essential amino acids was significantly increased at 10 days by comparison with those of 1 and 6 days. Therefore, the present amino acid profiling protocol combined with star pattern analysis has been shown to be useful for the monitoring of the ripening of bananas. [ABSTRACT FROM AUTHOR]

meta‐Xylene (m‐xylene) is one of three isomers of xylene, which is widely used as a solvent and detergent in various industries and medical technology. Exposure to volatile organic compounds, such as m‐xylene, causes pulmonary inflammation and airway inflammation, thereby contributing to the onset of asthma. Exposure to m‐xylene increases acute wheezing and intensity of asthma symptom. However, the mechanism of the onset of asthma by m‐xylene has not been studied yet. C57BL/6 mice were sensitized and challenged by m‐xylene at 100 or 300 mg/kg. The mice were then sacrificed after the last challenge. Exposure to m‐xylene increased the total number of inflammatory cells and the production of interleukin (IL)‐4, IL‐5, IL‐13, and immunoglobulin E related to the Th2 immune response. In contrast, the production of interferon‐γ related to the Th1 immune response was decreased. In addition, the airway resistance increased according to the airway hyper‐responsiveness measurements. Finally, a histological analysis revealed infiltration of inflammatory cells, mucus production, and lung fibrosis. These results suggest that m‐xylene is a potential risk factor for asthma and the onset of asthma is caused by TH2 cytokines. [ABSTRACT FROM AUTHOR]

We studied the effects of high mobility group box chromosomal protein 1 (HMGB1) and toll-like receptor (TLR4) in diisonoyl phthalate (DINP)-induced asthma. Mice with DINP-induced asthma were treated with a TLR4-signaling inhibitor or anti-HMGB1 antibody, and various markers of asthma were measured 24 h later. DINP increased airway hyperresponsiveness, numbers of cells in BALF, numbers of inflammatory cells (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils) in blood, mucus production, pulmonary fibrosis, Th2 type cytokine levels in BALF, and lung cell apoptosis. On the other hand, administrations of TLR4-signaling inhibitors (TAK-242) or anti-HMGB1 antibodies to a mouse model of DINP-induced asthma reduced biological markers of asthma. These results show TLR4 and HMGB1 both contribute to DINP-induced asthma, and that the inhibitions of TLR4 or HMGB1 offer potential means of treating asthma induced by phthalates like DINP. [ABSTRACT FROM AUTHOR]

The skin is a very suitable organ for the induction of immune responses to vaccine antigens. Antigen delivery systems to the skin by needle and syringe directly deposit the antigen into the epidermal-dermal compartment, one of the most immunocompetent sites due to the presence of professional antigen-presenting cells aimed at the induction of antigen-specific T cells. In this study, we analyzed the amount of ovalbumin as an antigen delivered to the skin by a microneedle. When ovalbumin protein as an antigen was delivered to the skin of mice using a dissolving microneedle, it induced an immune response through the enhanced proliferation and cytokines production by the splenocytes and lymph nodes. Also, it effectively increased the ovalbumin-specific CD8+ T cell and CD4+ T cell population and induced an ovalbumin-specific CTL response against the graft of ovalbumin-expressing EG7 tumor cells in the immunized mice. Also, we identified the inhibition of tumor growth and prevention of tumor formation in the context of the therapeutic and prophylactic vaccine, respectively through EG-7 tumor mouse model. Finally, these data show the potential of patches as attractive antigen delivery vehicles. [ABSTRACT FROM AUTHOR]

Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Using gas chromatography–tandem mass spectrometry, we analysed the metabolite profiles of 14 organic acids (OAs), 20 amino acids (AAs), and 13 fatty acids (FAs) after treatment with 0.1 or 1.0 µg/µl MNPs@SiO2(RITC) for 12 h. The metabolic changes were highly related to reactive oxygen species (ROS) generation and glucose metabolism. Additionally, effects on the combined metabolome and transcriptome or "metabotranscriptomic network" indicated a relationship between ROS generation and glucose metabolic dysfunction. In the experimental validation, MNPs@SiO2(RITC) treatment significantly decreased the amount of glucose in cells and was associated with a reduction in glucose uptake efficiency. Decreased glucose uptake efficiency was also related to ROS generation and impaired glucose metabolism in the metabotranscriptomic network. Our results suggest that exposure to high concentrations of MNPs@SiO2(RITC) produces maladaptive alterations in glucose metabolism and specifically glucose uptake as well as related metabolomic and transcriptomic disturbances via increased ROS generation. These findings further indicate that an integrated metabotranscriptomics approach provides useful and sensitive toxicological assessment for nanoparticles. [ABSTRACT FROM AUTHOR]

Liquid chromatographic enantiomer separation and simultaneous determination of chemical and enantiomeric purity of α‐amino acids and their methyl esters as N‐fluorenylmethoxycarbonyl (FMOC) derivatives was performed on three covalently bonded type chiral stationary phases (CSPs) derived from amylose derivatives. The enantiomer separation of α‐amino acid esters as N‐FMOC derivatives was better than that of the corresponding acids, especially for CSP 1 and 2. Chemical impurities as the corresponding racemic acids present in several commercially available racemic amino acid methyl esters were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L‐amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α‐amino acids and/or esters as N‐FMOC derivatives using amylose‐derived CSPs. [ABSTRACT FROM AUTHOR]

Metabolomic analysis of organic acids has not been performed for evaluation whether ginseng has been cultivated using conventional or environmental‐friendly farming methods. In this study, profiling analysis was conducted for organic acids (OAs) in ginseng roots produced using conventional or environment‐friendly farming methods at five locations in each of five regions. In OA profiles, lactic acid was the most abundant OA in all regions, with the exception for environmentally friendly farmed ginseng in two of the five regions, in which glycolic acid was most abundant OA. OA profiles in all regions showed isocitric acid levels were increased by environment‐friendly cultivation, which suggests metabolic differences associated from farming method, and that isocitric acid might be a useful discriminatory biomarker of environmental‐friendly and conventional cultivation. The results of the present study suggest metabolomic studies of OAs in ginseng roots might be useful for monitoring whether ginseng has been cultivated using conventional or environmentally friendly farming methods. [ABSTRACT FROM AUTHOR]

Abstract: A new liquid chromatographic enantiomer separation of chiral amines as 2-hydroxynaphthaldimine derivatives on several coated and immobilized chiral stationary phases (CSPs) derived from polysaccharides is described. 2-Hydroxynaphthaldehyde was introduced as a derivatizing agent for the enantiomeric separation of chiral aliphatic amines under the normal phase conditions, and was found to both enhance detection sensitivity and provide suitable interaction sites for enantiodiscrimination. Cellulose-derived CSPs, in general, exhibited better enantiomeric separation than amylose-derived CSPs. Amongst the examined six covalently bonded and four coated-type CSPs, covalently bonded Chiralpak IC, which contains a cellulose-based chiral selector, showed the best enantioseparation. The method was applied to the determination of the enantiomeric purity of commercially available (R)- and (S)-leucinol. The enantiomeric impurities of the investigated analytes procured from two suppliers were found to be 0.06-1.20%. The developed analytical method was also validated in accordance with ICH guidelines and proved to be enantioselective, sensitive and effective for the enantiomeric separation of chiral aliphatic amines as 2-hydroxynaphthaldimine derivatives under ultraviolet detection.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Epidermal growth factor (EGF) has an anti‐aging effect of skin. In this study, a HPLC method was developed to monitor of EGF degradation products from pure EGF as a cosmetic raw material. The optimized mobile phase was 7.5 mM sodium phosphate buffer (pH 6.8) at flow rate of 0.6 mL/min. In the method validation of pure EGF, it showed good linearity (r ≥ 0.999) with a detection limit of 0.5 ng/mL. Intra‐ and inter‐day repeatability as a percentage of relative standard deviation (%RSD) varied from 0.01‐2.1, and accuracy was 1.1 as the percentage of relative error (%RE). Under optimized conditions, four peaks of pure EGF and three degradation products were observed after storage at room temperature for 12 days. Pure EGF represented as 97.78 ± 0.03% from the total area of the four peaks, whereas the three unknown peaks showed as 0.53 ± 0.01%, 0.61 ± 0.01%, and 1.08 ± 0.01%, respectively. The present method will be useful for the purity and stability tests of EGF in cosmetic materials and products. [ABSTRACT FROM AUTHOR]

An efficient method for the simultaneous profiling analysis of 44 fatty acids including 24 aliphatic, 12 hydroxyl, and eight methyl-branched fatty acids astert-butyldimethylsilyl (TBDMS) derivatives was developed by gas chromatography–mass spectrometry. In this study, new mass spectral databases of isolauric, 11-methyllauric, isomyristic, isopentadecylic, isopalmitic, isostearic, 17-methylstearic, and 19-methylarachidic acids were constructed as TBDMS derivatives. Under the optimal conditions, linearity in the range of 0.1–10.0 µg/mL (24 aliphatic fatty acids) and 0.01–1.0 µg/mL (eight methyl-branched and 12 hydroxy fatty acids) showed good correlation coefficients (r ≥ 0.997). The repeatability showed relative standard deviation of less than 11.2% and accuracy (percent relative error) varied from −11.0 to 7.8 for the 44 fatty acids studied. The recoveries ranged from 61.7 to 90.1% with good repeatability. When applied to human plasma sample, 18 aliphatic, three 2-hydroxy, three 3-hydroxy, and five methyl-branched fatty acids were positively identified and quantified. Therefore, the present method will be useful for profiling analysis of various fatty acids in biological samples including plasma. [ABSTRACT FROM AUTHOR]

Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and selective detection of loxoprofen. Under optimal conditions, this method showed good linearity (r ≥ 0.999) in the range of 10-500 ng/mL, repeatability (% relative standard deviation = 5.6-8.5), and accuracy (% relative error = − 0.3-0.9) with a detection limit of 1.0 ng. When applied to the analysis of loxoprofen in tablet and patch products, loxoprofen was positively identified as TBDMS derivative by GC-MS. The present method provided rapid and accurate determination of loxoprofen in patch and tablet products. Levels of loxoprofen were highest in equine urine at 0.5 and 1 h after oral administration with single dose (3 mg/kg) to three horses, and then rapidly reduced to below the lower limit of quantification at 24 h. Therefore, the present method will be useful for the pharmacokinetic study and doping tests for loxoprofen and other similar acidic drugs in horses. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with heterogeneous clinical manifestations mediated by immune dysregulation. Objectives: We aimed to analyze the metabolomic differences in free fatty acids (FFAs) between patients with SLE and healthy controls (HCs). Methods: In this study, the levels of 24 FFAs, as their tert-butyldimethylsilyl derivatives, in the plasma of 41 patients with SLE and 41 HCs, were investigated using gas chromatography with mass spectrometry in selected-ion monitoring mode. Results: The results showed that patients with SLE and HCs had significantly different levels of 13 of the 24 FFAs. The levels of myristic, palmitoleic, oleic, and eicosenoic acids were significantly higher, whereas the levels of caproic, caprylic, linoleic, stearic, arachidonic, eicosanoic, behenic, lignoceric, and hexacosanoic acids were significantly lower in patients with SLE, than in the HCs. In the partial-correlation analysis of the FFA profiles and markers of disease activity of SLE, several metabolic markers correlated with SLE disease activity. Conclusions: Our results provide a comprehensive understanding of the relationship between FFAs and markers of SLE disease activity. Thus, this approach has promising potential for the discovery of metabolic biomarkers of SLE. [ABSTRACT FROM AUTHOR]

Asthma is a long term inflammatory disease of the airway of lungs characterized by variable airflow obstruction and bronchospasm. Asthma is caused by a complex combination of environmental and genetic interactions. In this study, we conducted proteomic analysis of samples derived from control and OVA challenged mice for environmental respiratory disease by using 2-D gel electrophoresis. In addition, we explored the genes associated with the environmental substances that cause respiratory disease and conducted RNA-seq by next-generation sequencing. Proteomic analysis revealed 7 up-regulated (keratin KB40, CRP, HSP27, chaperonin containing TCP-1, TCP-10, keratin, and albumin) and 3 down-regulated proteins (PLC-α, PLA2, and precursor ApoA-1). The expression diversity of many genes was found in the lung tissue of OVA challenged moue by RNA-seq. 146 genes were identified as significantly differentially expressed by OVA treatment, and 118 genes of the 146 differentially expressed genes were up-regulated and 28 genes were downregulated. These genes were related to inflammation, mucin production, and airway remodeling. The results presented herein enable diagnosis and the identification of quantitative markers to monitor the progression of environmental respiratory disease using proteomics and genomic approaches. [ABSTRACT FROM AUTHOR]

The liquid chromatographic enantiomer separation of various chiral acids as 1-naphthylamides was performed using several chiral stationary phases (CSPs). The CSPs used in this study were six covalently bonded and four coated type CSPs derived from amylose and cellulose derivatives as chiral selectors. The degree of enantioseparation is affected by the structure of chiral acids and the CSPs used, which have different chiral selectors and types of immobilization. For the enantiomer resolution of chiral acids as 1-naphthylamide derivatives, the performance of the coated type Lux Cellulose-1 was superior to those of the other CSPs, except for 2-aryloxypropionic acid derivatives. Owing to the strong ultraviolet absorbance of the 1-naphthyl group, the convenient analytical method developed and validated in this study could be expected to be very useful for the enantiomer separation of various chiral acids as 1-naphthylamide derivatives using polysaccharide-derived CSPs. [ABSTRACT FROM AUTHOR]

We investigated changes in PA levels by the treatment of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS-treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM-MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In the in vivo MCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In the in vitro OGD system, N1-acetylspermidine, spermidine, N1-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group. [ABSTRACT FROM AUTHOR]

Metabolomic analysis of urinary polyamines (PAs) from rat exposed to 915 MHz radiofrequency identification (RFID) signal for 8 h/day for 2 weeks was performed by gas chromatography-mass spectrometry as N-ethoxycarbonyl/ N-pentafluoropropionyl derivatives. Large alterations in nine PA levels including four aliphatic and five acetylated PAs were monitored in sham-exposed and RFID-exposed groups. Total PA and urinary levels of N-acetylputrescine, N-acetylcadaverine, putrescine, cadaverine, N-acetylspermidine, N-acetylspermidine, spermidine and spermine were reduced, whereas N-acetylspermine was significantly increased after sham and RFID exposure compared with those before exposure. Their levels were normalized to the corresponding group means before exposure and then plotted into star symbol patterns. N-Acetylspermine after RFID exposure was 54 % higher compared to the level before RFID exposure, while it was elevated by only 17 % in the sham group. The results suggest that 915 MHz RFID exposure may induce metabolic disturbance of PA. It may also elevate spermidine/spermine acetyltransferase (SSAT) activity. Thus, the present metabolic profiling combined with star pattern recognition method might be useful for understanding the complexity of biochemical events after exposure to RFID signal. [ABSTRACT FROM AUTHOR]

Purpose:We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on mela-tonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Materials and methods:Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Uri-nary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Results:Eight hours of nocturnal RFID exposure caused a sig-nificant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expres-sion of AANAT were suppressed by exposure to RFID (p < 0. 05). Conclusions:Our results suggest that nocturnal RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression ofAanatgene transcription in the rat pineal gland. [ABSTRACT FROM AUTHOR]

Simultaneous analysis of several β-blockers using a novel dual chiral selector system was achieved for their accurate chiral discrimination by chiral capillary electrophoresis ( CE) in normal polarity mode. The CE system was operated using heptakis(2,6-di- O-methyl)-β-cyclodextrin ( DM-β-CD) dissolved in 100 mM phosphoric acid-triethanolamine buffer ( pH 3) and (+)- or (−)-18-crown-6-tetracarboxylic acid (18-C-6- TA) as a co-chiral selector in DM-β- CD solution. All eight investigated analytes were resolved using (+)-18-C-6- TA as a co-chiral selector in the presence of DM-β-CD solution, whereas the other β-blockers, except propranolol, were resolved using (−)-18-C-6- TA as the second chiral selector in DM-β-CD solution. Also, DM-β-CD had a major effect on chiral discrimination compared with 18-C-6- TA as a co-chiral selector. Relative migration times to that of ( S)-pindolol as an internal standard were characteristic of each enantiomer with good precision. The method showed good linearity with a correlation coefficient ( r ≥ 0.993). The precision as a percentage of relative standard deviation (% RSD) and accuracy as a percentage of relative error (% RE) ranged from 0.5 to 9.6 and from −5.7 to 9.1, respectively. These were adequate for the chiral assay of the β-blockers investigated. Thus, the present chiral profiling method is expected to be useful for accurate chiral discrimination and optical purity tests of chiral β-blockers and their related drugs. [ABSTRACT FROM AUTHOR]

An efficient method for the simultaneous analysis of seven 2-hydroxy fatty acids (2-HFAs) as tert-butyldimethylsilyl (TBDMS) derivative was developed by gas chromatography-mass spectrometry in selected ion monitoring mode. New mass spectral data on 2-hydroxycapric, 2-hydroxypalmitic, 2-hydroxystearic and 2-hydroxybehenic acids as di-TBDMS derivatives for hydroxyl and carboxyl groups were built. Under the optimal conditions, the present method showed a good correlation coefficient ( r ≥ 0.999) in the range of 0.01-0.5 µg. The precision showed low relative standard deviation of <10%, and the accuracy (percentage relative error) varied from −5.2 to 0.3 for the seven 2-HFAs studied. Recovery rates of all 2-HFAs were ≥ 93.2% with good precision. When applied to normal human plasma, seven 2-HFAs were positively identified. Therefore, the present efficient method will be useful for simultaneous analysis of 2-HFAs in plasma. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effect of whole-body exposure to 915-MHz radiofrequency identification (RFID) on rat cortical glucose metabolism by using 18F-deoxyglucose positron emission tomography (FDG-PET). Materials and methods: Male Sprague-Dawley rats were divided into three groups: Cage-control, sham-exposed and RFID-exposed groups. Rats were exposed to the 915-MHz RFID for 8 h daily, 5 days per week, for 2 or 16 weeks. The whole-body average specific absorption rate (SAR) was 4 W/kg for the field of the 915 MHz RFID signal. FDG-PET images were obtained the day after RFID exposure, using micro-PET with a FDG tracer. With a Xeleris functional imaging workstation, absolute values in regions of interest (ROI) in the frontal, temporal and parietal cortexes and cerebellum were measured. Cortical ROI values were normalized to the cerebellar value and compared. Results: The data showed that the relative cerebral glucose metabolic rate was unchanged in the frontal, temporal and parietal cortexes of the 915 MHz RFID-exposed rats, compared with rats in cage-control and sham-exposed groups. Conclusion: Our results suggest that 915 MHz RFID radiation exposure did not cause a significant long lasting effect on glucose metabolism in the rat brain. [ABSTRACT FROM AUTHOR]

ABSTRACT A novel derivatization method was developed for the simultaneous determination of six acidic metabolites of catecholamine and serotonin by gas chromatography-mass spectrometry (GC-MS). The metabolites were converted to O-ethoxycarbonyl/ tert-butyldimethylsilyl (EOC/TBDMS) derivatives for the direct GC-MS analysis in selected ion monitoring mode. Their mass spectral pattern as EOC/TBDMS derivatives showed characteristic fragment ions of [M - 15]+ and [M - 57]+, which permitted rapid and accurate structural confirmation of acidic metabolites. The present method was linear ( r ≥ 0.998), reproducible (percentage relative standard deviation = 1.0-10.0) and accurate (% relative error = −9.7-9.8) with detection limits of 0.001-4.7 ng/mL. When applied to human urine samples, the method allowed simultaneous determination of six acidic metabolites of catecholamine and serotonin. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]