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Background: Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. Methods: Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. Results: Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5'-deoxy-5'-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4'-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). Conclusions: The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites. [ABSTRACT FROM AUTHOR]

Introduction: Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated. Methods: Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K. Results: Metabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity. Conclusion: These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Consumers are increasingly looking for healthier and sustainable diets. Plant-based diets rich in legumes satisfy this demand. Legumes contain protein, dietary fibers and starch. Technological processes can separate these fractions, which can be used as supplements, or as ingredients. Nonetheless, legumes are susceptible to fungal infection, causing a potential health concern, since some fungi can produce mycotoxins: toxic secondary metabolites. The aim of this work was to analyze the fate of mycotoxins during different stages of the production process of legume derived products from the raw materials to final products. An extraction followed by liquid chromatography-tandem mass spectrometry was used for the analysis, revealing the presence of enniatin B (ENN B), alternariol monomethyl ether (AME), deoxynivalenol, T2-toxin, nivalenol, fumonisin B1 and sterigmatocystin in raw materials, intermediate products and side streams. The alkaline solubilization steps, were effective in reducing ENN B; however, AME was found in one of the final products. [ABSTRACT FROM AUTHOR]

Maize grain samples collected from 129 small-scale farmers' stores in southern and southwestern Ethiopia were analysed by LC-MS/MS for a total of 218 mycotoxins and other fungal metabolites of which 15% were regulated mycotoxins. Mycotoxins produced by Penicillium, Aspergillus, and Fusarium accounted for 31%, 17%, and 12% of the metabolites, respectively. Most of the current samples were contaminated by masked and/or emerging mycotoxins with moniliformin being the most prevalent one, contaminating 93% of the samples. Each sample was co-contaminated by 3 to 114 mycotoxins/fungal metabolites. Zearalenone, fumonisin B1, and deoxynivalenol were the dominant mycotoxins, occurring in 78%, 61%, and 55% of the samples with mean concentrations of 243, 429, and 530 µg/kg, respectively. The widespread co-occurrence of several mycotoxins in the samples may pose serious health risks due to synergistic/additional effects. [ABSTRACT FROM AUTHOR]

The obesity epidemic among children has become a major public health issue, and the presence of childhood insulin resistance (IR) has been demonstrated prior to the onset of type 2 diabetes mellitus. However, it is unclear whether the metabolomic signature is associated with weight loss interventions in obese children with IR. Thirty-six obese children with IR were selected from the weight loss camp (Shenzhen Sunshine Xing Yada health Technology Co., LTD). Clinical parameters were collected before and after weight loss intervention. Targeted metabolomics of plasma samples was performed by ultra-performance liquid chromatography coupled to the tandem mass spectrometry, and principal component analysis, variable importance in projection, and orthogonal partial least squares discriminant analysis were used to obtain the differentially expressed metabolites. Pathway analysis was conducted with the Homo sapiens (HSA) sets in the Kyoto Encyclopedia of Genes and Genomes. We used machine learning algorithms to obtain the potential biomarkers and Spearman correlation analysis to clarify the association between potential biomarkers and clinical parameters. We found that clinical parameters and metabolite clusters were significantly changed in obese children with IR before and after weight loss intervention. Mechanistically, weight loss intervention significantly changed 61 metabolites in obese children with IR. Furthermore, 12 pathways were significantly changed. Moreover, the machine learning algorithm found 6 important potential biomarkers. In addition, these potential biomarkers were strongly associated with major clinical parameters. These data indicate different metabolomic profiles in obese children with IR after weight loss intervention, providing insights into the clinical parameters and metabolite mechanisms involved in weight loss programs. [ABSTRACT FROM AUTHOR]

Rationale: Spironolactone is a steroidal drug prescribed for a variety of medical conditions and is extensively metabolized quickly after administration. Measurement of spironolactone and its metabolites remains challenging using mass spectrometry (MS) due to in-source fragmentation and relatively poor ionization using electrospray ionization. Therefore, improved methods of measurements are needed, particularly in the case of small sample volumes. Methods: Girard's reagent P (GP) derivatization of spironolactone was employed to improve response and provide an MS-based solution to the measurement of spironolactone and its metabolites. We performed ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESIMS/MS) and ion mobility spectrometry (IMS)-high-resolution mass spectrometry (HRMS) to fully characterize the GP derivatization products. Analytes were studied in positive ionization mode, and MS/MS was performed using nonresonance and resonance excitation collision-induced dissociation. Results: We observed the successful GP derivatization of spironolactone and its metabolites using authentic chemical standards. A signal enhancement of 1-2 orders of magnitude was observed for GP-derivatized versions of spironolactone and its metabolites. Further, GP derivatization eliminated in-source fragmentation. Finally, we performed GP derivatization and ultra-high-performance liquid chromatography- high-resolution mass spectrometry (UHPLC-HRMS) in a small volume of murine serum (20 µL) from spironolactone-treated and control animals and observed multiple spironolactone metabolites only in the spironolactone-treated group. Conclusions: GP derivatization was proven to have advantageous mass spectral performance (e.g., limiting in-source fragmentation, enhancing signals, and eliminating isobaric analytes) for spironolactone and its metabolites. This work and the detailed characterization using ultra-high-performance liquid chromatography- high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) and IMS serve as the foundation for future developments in reaction optimization and/or quantitative assay development. [ABSTRACT FROM AUTHOR]

Importance and objective: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. Methods: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. Results: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3–5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3–5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. Conclusion: Self-reports of no or low caffeine consumption and consumption of more than 3–5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake. [ABSTRACT FROM AUTHOR]

• A literature survey revealed that information about antidiabetic activities of Typha domingensis is not available. • For the first time, in-vitro, in-silico , and in-vivo antidiabetic activities were performed. • Chemical profiling was done with UHPLC-MS and HPLC-PDA. • The study provides scientific evidence that n-butanol fraction of T. domingensis has strong antidiabetic effects and after evaluation it can be used for treating diabetes. Typha is one of the valuable plant genera in folklore use in diabetes, and it can be a good source of bioactive chemicals. The current project was planned to investigate the pharmaceutical potential of n -butanol fraction of Typha domingensis Pers. (TDBF), a less explored medicinal plant. The phytochemical composition of the TDBF was assessed through a comprehensive analysis, encompassing the quantification of total bioactive contents (including total tannins and HPLC-PDA quantification) and a thorough exploration of secondary metabolites through scanning with UHPLC-MS. The pharmacological assessment included the determination of antioxidant activity (Total Antioxidant Capacity and Metal Chelating Assay), hemolytic potential, in-vitro antidiabetic effects (α-glucosidase and α-amylase inhibition, and antiglycation activity), as well as in-vivo antidiabetic activities. Molecular docking and ADMET studies were also performed for UHPLC-MS identified compounds. The TDBF showed 134.76 ± 8.23 mg TAE/g total tannin contents. With HPLC-PDA, p -Hydroxy benzoic acid and p -Coumaric acid were quantified. During UHPLC-MS scanning, a total of five bioactive metabolites were identified in the negative mode, while 54 were detected in the positive mode. The in-vivo assessment of antidiabetic activity revealed a notable reduction in blood glucose levels in diabetic rats following treatment with the extract, demonstrating its efficacy compared to the control groups. Furthermore, the extract exhibited a positive impact on renal and liver function, evidenced by lowered levels of serum urea, ALT, ALP, creatinine, and a decrease in serum cholesterol levels. The results of this study showed that Typha domingensis Pers. possesses a variety of bioactive compounds and demonstrates notable potential in regulating diabetes. The study recommends further investigation into isolating these bioactive phytochemicals for their potential therapeutic applications across various diseases. [ABSTRACT FROM AUTHOR]

Trichoderma spp. are filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced have obtained special attention since they possess attractive chemical structures with a broad spectrum of biological activities. In Cuba, the species of Trichoderma have been commercially applied for the control of several phytopathogens to protect agricultural crops, but few studies have been carried out to detect and characterize the production of metabolites with biological activity. The strain Trichoderma harzianum LBAT-53 was subjected to an antifungal in vitro assay against Fusarium oxysporum f.sp. cubense by dual culture and volatile metabolite assays and fermented in PDB under constant agitation conditions. The ethyl acetate crude extract was obtained by liquid–liquid extraction. The fungal extract was investigated for the composition of secondary metabolites through chemical screening and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in negative ionization mode. As a result, LBAT-53 showed antagonistic activity in vitro (Class 2) against the pathogen evaluated in direct confrontation (76.9% of inhibition in 10 days) and by volatile metabolites (<40% in 7 days). Furthermore, seven low-molecular-weight phenolic compounds, including chrysophanol, phomarin, endocrocin, and trichophenol A, among others, were identified using UHPLC-ESI-MS/MS. This study is the first work on the characterization of secondary metabolites produced by the commercially applied strain LBAT-53, which is a promising source of bioactive compounds. These results provide a better understanding of the metabolism of this fungus, which is widely used in Cuba as biopesticides in agriculture pest control. [ABSTRACT FROM AUTHOR]

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC50 of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH• assay, the IC50 was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC50 of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC50 of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions. [ABSTRACT FROM AUTHOR]

mTORC1/2 dual inhibitors may be more effective than mTORC1 inhibitor rapamycin. However, their metabolic impacts on colon cancer cells remain unexplored. We conducted a comparative analysis of the anti-proliferative effects of rapamycin and the novel OSI-027 in colon cancer cells HCT-116, evaluating their metabolic influences through ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Our results demonstrate that OSI-027 more effectively inhibits colon cancer cell proliferation than rapamycin. Additionally, we identified nearly 600 metabolites from the spectra, revealing significant differences in metabolic patterns between cells treated with OSI-027 and rapamycin. Through VIP value screening, we pinpointed crucial metabolites contributing to these distinctions. For inhibiting glycolysis and reducing glucose consumption, OSI-027 was likely to be more potent than rapamycin. For amino acids metabolism, although OSI-027 has a broad effect as rapamycin, their effects in degrees were not exactly the same. These findings address the knowledge gap regarding mTORC1/2 dual inhibitors and lay a foundation for their further development and research. [ABSTRACT FROM AUTHOR]

Phthalates used in the industry penetrate the environment and negatively affect humans and animals. Hair samples seem to be the best matrix for studies on long-term exposure to phthalates, but till now they were used only in investigations on humans. Moreover, the knowledge of the wild terrestrial animal exposure to phthalates is extremely limited. This study aimed to establish of concentration levels of selected phthalate metabolites (i.e. monomethyl phthalate—MMP, monoethyl phthalate—MEP, mono-isobutyl phthalate—MiBP, monobutyl phthalate—MBP, monobenzyl phthalate—MBzP, mono-cyclohexyl phthalate—MCHP, mono(2-ethylhexyl) phthalate—MEHP and mono-n-octyl phthalate—MOP) in wild boar hair samples using liquid chromatography with mass spectrometry (LC–MS) analysis. MEHP was noted in 90.7% of samples with mean 66.17 ± 58.69 pg/mg (median 49.35 pg/mg), MMP in 59.3% with mean 145.1 ± 310.6 pg/mg (median 64.45 pg/mg), MiBP in 37.0% with mean 56.96 ± 119.4 pg/mg (median < limit of detection—LOD), MBP in 35.2% with mean 19.97 ± 34.38 pg/mg (median < LOD) and MBzP in 1.9% with concentration below limit of quantification. MEP, MCHP, and MOP have not been found in wild boar hair samples during this study. The results have shown that wild boars are exposed to phthalates and hair samples may be used as a matrix during studies on levels of phthalate metabolites in wild animals. [ABSTRACT FROM AUTHOR]

Background: Bletilla striata (Thunb.) Reichb.f. (B. striata) is a traditional Chinese medicinal herb. B. striata polysaccharides (BSP), stilbenes and 2-isobutyl malic acid glucosoxy-benzyl ester compounds are the main active ingredients in B. striata. However, there is limited report on the changes of medicinal components and their biosynthesis regulation mechanisms in the tubers of B. striata at different stages. Method: The tubers of B. striata were collected during the flowering period, fruiting period, and harvest period to determine the total polysaccharide content using the phenol sulfuric acid method. The changes in secondary metabolites in the tubers at these stages were analyzed by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS), and transcriptomics was conducted for further exploration of their biosynthetic pathways. Result: The BSP content gradually increases from the flowering period to the fruiting period as the tubers develop, reaching its peak, but subsequently decreases at harvest time, which may be associated with the germination of B. striata buds in later stage. A total of 294 compounds were identified in this study. Among them, a majority of the compounds, such as 2-isobutyl malate gluconoxy-benzyl ester, exhibited high content during the fruit stage, while stilbenes like coelonin, 3'-O-methylbatatasin III, and blestriarene A accumulated during the harvesting period. The transcriptome data also revealed a substantial number of differentially expressed genes at various stages, providing a partial explanation for the complex changes in metabolites. We observed a correspondence between the expression pattern of GDP-Man biosynthesis-related enzyme genes and cumulative changes in BSP. And identified a positive correlation between 9 transcription factors and genes associated with polysaccharide biosynthesis, while 5 transcription factors were positively correlated with accumulation of 2-isobutyl malate gluconoxy-benzyl ester compounds and 5 transcription factors exhibited negative correlated with stilbene accumulation. Conclusion: It is imperative to determine the appropriate harvesting period based on the specific requirements of different active ingredients and the accumulation patterns of their metabolites. Considering the involvement of multiple transcription factors in the biosynthesis and accumulation of its active ingredients, a comprehensive investigation into the specific regulatory mechanisms that facilitate high-quality cultivation of B. striata is imperative. [ABSTRACT FROM AUTHOR]

AbstractThe present study was undertaken to understand the dissipation behaviour/kinetics of fluoxapiprolin and its metabolites in cucumber and tomato under field conditions. A QuEChERS based extraction method followed by liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis showed that all method validation parameters were within the acceptable range as per international standards with a limit of quantitation (LOQ) of 0.01 mg kg−1 for all analytes. As significant matrix effects were observed with a few metabolites, matrix matched standards were used for the whole study. Residues of fluoxapiprolin in cucumber at standard dose were steady from 0 to 3 day after application and were below LOQ on the 5th day after application. In cucumber fruit at double dose and in tomato at both the doses the residues followed second-order kinetics and were respectively ≤ LOQ from days 7 and 14 onwards. Pre-harvest intervals (PHI) of 5 days and 14 days are proposed for cucumber and tomato fruits respectively. All the metabolites were ≤ LOQ from day 0 in all the matrices. The consumer risk, assessed as Hazard Quotient (HQ), showed that HQ was ≤1 in all the cases. The results of the present study and earlier studies on other similar fungicides suggest that the use of fluoxapiprolin in cucumber and tomato fruits may not pose health or environmental hazards provided that good agricultural practices are followed and the proposed waiting period is observed. The data from the present study can be used by regulatory bodies in establishing maximum residue limits. [ABSTRACT FROM AUTHOR]

The concern about the quality of medicinal herbs is becoming important due to the poor quality of commercial products like cosmetics, functional foods, and natural medicine produced from them. However, there is a lack of modern analytical methods to evaluate the constituents of P. macrophyllus until the moment. This paper reports an analytical method based on UHPLC-DAD and UHPLC-MS/MS MRM methods to evaluate the ethanolic extracts of P. macrophyllus leaves and twigs. 15 main constituents were identified using a UHPLC-DAD-ESI-MS/MS profiling. Subsequently, a reliable analytical method was established and successfully used to quantitate the constituent's content using four marker compounds in leaf and twig extracts of this plant. The result obtained from the current study demonstrated the secondary metabolites and the variety of their derivatives in this plant. The analytical method can help evaluate the quality of P. macrophyllus and develop high-value functional materials. [ABSTRACT FROM AUTHOR]

Tomato is the most important horticultural crop, and India is its second largest producer; however, the plant‐pathogenic nematode Meloidogyne incognita is a serious pest of tomato, causing detrimental losses in its production. This study is focused on the use of multistress‐tolerant Pseudomonas aeruginosa SSVP3 to control this devastating nematode and attempts to decipher the roles of its metabolites and volatile organic compounds (VOCs) during this interaction. The supernatant of P. aeruginosa SSVP3 caused 58% mortality in M. incognita J2 juveniles. The major nematicidal metabolites, identified using liquid chromatography‐mass spectrometry, were pyocyanin, pyoluteorin, pyochelin, benthocyanin and phenazines. The VOCs secreted by P. aeruginosa SSVP3, which were identified via gas chromatography–mass spectrometry (HS‐SPME‐GC–MS) in a mixture, caused 98% mortality in M. incognita J2 juveniles. In a pot experiment, seedling root treatment with P. aeruginosa SSVP3 activated the induced systemic response in tomato plants to M. incognita by increasing the activity of defence and antioxidant enzymes as well as the proline and phenolic contents. The malondialdehyde content in P. aeruginosa SSVP3‐treated plants decreased as compared to those in the other treatment groups. The number of galls formed and the number of endoparasitic stages of M. incognita in the untreated nematode control plants were much greater (19 and 35) than those in the P. aeruginosa SSVP3‐treated (0.33 and 1) and chemically treated groups (0.67 and 1.33). These results indicate that P. aeruginosa and its secreted metabolites and VOCs have a high potential for controlling nematodes. [ABSTRACT FROM AUTHOR]

Background: Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G. Don (ACGD) and Allium macrostemon Bunge (AMB) are it botanical sources. The aim of this study was to explore the cardioprotective effects, and decipher the visual spatial distribution and absolute content of primary metabolites derived from these two herbs. Methods: H9c2 cells were used to perform the hypoxia-reoxygenation (H/R)-induced myocardial injury model. Their protective effects were evaluated by apoptosis levels. Furthermore, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry imaging approach (MALDI-TOF MSI) was carried out to present the spatial location of primary metabolites including fatty acids, amino acids, carotenoids, and vitamins in these two Allium herbs. Multiple analytical methods were applied to perform quantitative analysis of these primary metabolites in AMB and ACGD bulbs by liquid chromatography tandem mass spectrometry (LC–MS). Results: First, AMB and ACGD extracts both could increase the cell viability in H9c2 cells, and attenuate H/R-induced injury. They markedly decreased apoptosis, accompanied by activating the BCL-2/BAX pathway. Further, MALDI-TOF MSI-based relative quantification results showed several amino acids, fatty acids, carotenoids, and vitamins were largely rich in the tunics and outside scales of fresh bulbs, while some primary metabolites were abundant in their developing flower buds. Absolute quantification results displayed total contents of amino acids in ACGD bulbs were higher than those in AMB, while total contents of fatty acids and vitamins provides opposite trends in these two Allium herbs. The total contents of carotenoids and trace elements showed no significant differences between AMB and ACGD samples. Conclusions: This study would be helpful to understand the myocardial injury protection effects of these two Allium herbs, and the spatial accumulation and quantitative content levels of their main nutrients. Highlights: Myocardial injury protection effects of two Allium extracts were characterized. Visual spatial distribution of main primary metabolites was performed. Absolute quantification was achieved by multiple conventional approaches. Similarities and differences of these two Allium extracts were summarized. [ABSTRACT FROM AUTHOR]

Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds. [ABSTRACT FROM AUTHOR]

A high‐performance liquid chromatography‐tandem mass spectrometry method has been developed for the determination of irinotecan, 7‐ethyl‐10‐hydroxycamptothecin (SN38), and SN38 glucuronide (SN38G) in rat plasma in the present study. The analytes were separated on a C18 column and a triple‐quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Irinotecan, SN38 and SN38G could be well retained in the C18 column after optimization of mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was above 90% and the matrix effect could be negligible. The method was linear over the concentration ranges of 3.46–3458.8 ng/mL for irinotecan, 2.53–2530.0 ng/mL for SN38 and 2.5–2500.0 ng/mL for SN38G. The precision and accuracy was within the acceptable limits. The simple and convenient method was validated and successfully applied to support the pharmacokinetic study and elucidate the mechanism of irinotecan‐induced diarrhea after irinotecan was intravenously injected to the Sprague‐Dawley rats. [ABSTRACT FROM AUTHOR]

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the plasma concentrations and determine the pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and orthohydroxyatorvastatin) after administration of a single oral dose in cockatiels (Nymphicus hollandicus). ANIMALS: 14 adult cockatiels (7 male, 7 female) around 2 years of age. METHODS: A compounded oral suspension of atorvastatin 10 mg/mL made with an oral suspending agent and an oral sweetener was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 7 different time points from 0.5 to 24 hours postadministration in a balanced incomplete block design with 3 blood samples per bird and 6 replicates per time point. Plasma concentrations of atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis. RESULTS: The estimated time to maximum concentration (tmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 3 hours for each. The estimated maximum plasma concentration (Cmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 152.6, 172.4, and 68.8 ng/mL, respectively. The terminal halflives were 4, 6.8, and 4.6 hours, respectively. CLINICAL RELEVANCE: These results support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. A starting dose of 20 mg/kg PO every 12 to 24 hours could be used to treat lipid disorders in cockatiels pending more data on multidose use and hypolipidemic efficacy. [ABSTRACT FROM AUTHOR]

Carbendazim, a common pesticide, has shown signs of causing cancer, infertility and toxicity to organisms. Due to its intense use, this fungicide has become a persistent compound in the environment, raising the importance of better understanding its behaviour, metabolic pathways and effects on organisms. Zebrafish is considered an excellent animal model, being able to rapidly absorb compounds in water, mimicking what occurs in the aquatic environment. Therefore, the aim of this work was to evaluate carbendazim metabolites in zebrafish water tank using liquid chromatography coupled to a high-resolution mass spectrometer (LC-HRMS) to highlight analytical targets in order to monitor carbendazim exposure in aquatic environments. For this purpose, treatment, negative and stability groups were defined. In addition, water samples were collected from the tanks and analyses were carried out by LC-HRMS. The results allowed the putative annotation of 7 target metabolites. This study applied the analysis of zebrafish water tank for evaluation of target metabolites of carbendazim as a promising approach, since it is a much cleaner matrix than the usual biological matrices. These metabolites can ensure detectability and further strengthen confidence in monitoring carbendazim exposure in aquatic environments. To the best of our knowledge, there is no one study that has evaluated carbendazim metabolites produced by zebrafish, neither in the animal's body nor in the water tank. This is the first report on the generation of carbendazim metabolites by zebrafish. [ABSTRACT FROM AUTHOR]

Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Proinflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. Five hundred and five men (85.0 ± 4.2 years) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein [CRP], alpha-1-acid glycoprotein [AGP] and a subsample [ n  = 305] with interleukin [IL-6, IL-1β, IL-17A] and tumor necrosis factor-α [TNF-α]) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23%–92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p  < .05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p  > .05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA, and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se. [ABSTRACT FROM AUTHOR]

Microfibrillated cellulose applications are vast and continue to grow across science disciplines. This growth increases exposures, including ingestion scenarios. Previous studies have shown that conventional cellulose is safe for consumption, while other studies indicate that microfibrillated cellulose has similar physicochemical properties to conventional cellulose. This new study compared microfibrillated cellulose with conventional cellulose after two simulated digestions to confirm that degradation patterns are the same between microfibrillated and conventional cellulose materials. Liquid chromatography-mass spectrometry results show that the conventional and microfibrillated cellulose spectra are strikingly similar for cellulase digestion and simulated human gastrointestinal digestion. No glucose, cellobiose, or other sugar monomers or dimers were seen in the standardized simulated gastrointestinal digestion, indicating that the degradation of sugars is not taking place. Further studies, which include the role of the gut microbiome, are needed to ensure the safety of the consumption of microfibrillated cellulose and to develop new microfibrillated materials. The data presented here demonstrates an efficient method to understand cellulose materials' degradation patterns using liquid chromatography-mass spectrometry. [ABSTRACT FROM AUTHOR]

Objective: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. Methods: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. Results: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. Conclusion: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism. [ABSTRACT FROM AUTHOR]

Paku gajah (Angiopteris evecta) is one of the largest ferns which has been used empirically by the Dayak tribe of Kalimantan, Indonesia as a traditional medicine to treat various diseases, one of which is tumors. This research aims to determine the potential utilization of A. evecta stem extract as an antitumor by secondary metabolites analysis, toxicity and antitumor assay. The methods used in this study were gradual maceration using three solvents ( n-hexane, ethyl acetate, and methanol), phytochemical screening, toxicity test, antitumor activity assay with the Alamarblue method, Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, and molecular docking analysis. This study indicated that A. evecta stem extract contained secondary metabolites such as flavonoids, saponins, tannins, and steroids. The ethyl acetate and methanol were found as toxic extracts with LC50 130.67 and 314.31 µg/mL, respectively. In line with the toxicity, the antitumor activity of the ethyl acetate extract was the highest with an IC50 of 240.94 µg/mL and phytochemical analysis revealed the presence of violanthin and angiopteroside in the extract. Molecular docking showed that the binding energy and inhibition constants of violanthin and angiopteroside against receptors were higher than standard ligand F82. The interaction between violanthin and the receptor results five hydrogen-bond (H-bond) with Lys920, Cys919, Asp1046, and Leu840, while the angiopteroside produces four H-bonds with Leu836, Leu834, and Arg831. [ABSTRACT FROM AUTHOR]

A method for the simultaneous determination of benzimidazoles and their metabolites in dairy products was established using ultra high performance liquid chromatography-tandem mass spectrometry (MS). After extracting the samples with acetonitrile containing 0.2% formic acid, the extracts were centrifuged and purified by solid phase extraction column, and then separated by UPLC HSS T3 chromatographic column, determined in multi reaction monitoring (MRM) method with a positive ESI mode. The results showed that the linear correlation coefficient (r) within the range of 1.0-50 μg/L was greater than 0.995 (except for triclabendazole, which was 0.9578). The method had a limit of detection (LOD) (S/N=3) of 0.002 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.003 mg/kg). The limit of quantitation (LOQ) (S/N=10) was 0.005 mg/kg (except for albendazole-2-aminosulfone, thiabendazole, and thiabendazole-5-hydroxy, which were 0.010 mg/kg). The recoveries at three spiked levels of 0.005, 0.01 and 0.05 mg/kg ranged from 62.5% to 117.6%, with relative standard deviations (RSD) between 1.92% and 12.17%. The method is simple to operate, highly sensitive, and suitable for the quantitative analysis of benzimidazoles and their metabolites in dairy products. [ABSTRACT FROM AUTHOR]

Trichothecenes (deoxynivalenol, 3- and 15-acetyl-deoxynivalenol) and zearalenone are toxic secondary metabolites produced by Fusarium species. Although managing these mycotoxins simultaneously is crucial, current analytical methods differ because of their distinct properties. In this study, food matrix extraction conditions were established and applied to cereal-based foods (n = 90). The optimal conditions were developed by utilizing fragment ions and precursors, following the guidelines established by the Association of Official Agricultural Chemists (AOAC). The developed method demonstrated high accuracy and reliability within 20 min, even for samples with low concentrations. Consequently, the recovery range of the fat-oil-processed products and cereal sirup improved from 27.0% to 98.3% and 27.6% to 97.8%, respectively. This improved extraction method offers a more convenient and rapid approach for the analysis of various matrices. Furthermore, these optimized methods can be extended to monitor the co-occurrence of mycotoxins in cereal-based foods, providing valuable assistance to the food industry and regulatory agencies for detecting and monitoring mycotoxins that may pose potential health risks. [ABSTRACT FROM AUTHOR]

Background: Different types of analytical methods, with different characteristics, are applied in metabolomics and lipidomics research and include untargeted, targeted and semi-targeted methods. Ultra High Performance Liquid Chromatography-Mass Spectrometry is one of the most frequently applied measurement instruments in metabolomics because of its ability to detect a large number of water-soluble and lipid metabolites over a wide range of concentrations in short analysis times. Methods applied for the detection and quantification of metabolites differ and can either report a (normalised) peak area or an absolute concentration. Aim of review: In this tutorial we aim to (1) define similarities and differences between different analytical approaches applied in metabolomics and (2) define how amounts or absolute concentrations of endogenous metabolites can be determined together with the advantages and limitations of each approach in relation to the accuracy and precision when concentrations are reported. Key scientific concepts of review: The pre-analysis knowledge of metabolites to be targeted, the requirement for (normalised) peak responses or absolute concentrations to be reported and the number of metabolites to be reported define whether an untargeted, targeted or semi-targeted method is applied. Fully untargeted methods can only provide (normalised) peak responses and fold changes which can be reported even when the structural identity of the metabolite is not known. Targeted methods, where the analytes are known prior to the analysis, can also report fold changes. Semi-targeted methods apply a mix of characteristics of both untargeted and targeted assays. For the reporting of absolute concentrations of metabolites, the analytes are not only predefined but optimized analytical methods should be developed and validated for each analyte so that the accuracy and precision of concentration data collected for biological samples can be reported as fit for purpose and be reviewed by the scientific community. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Kratom (Mitragyna speciosa) has a long history of traditional use. It contains various alkaloids and polyphenols. The properties of kratom's alkaloids have been well‐documented. However, the property of kratom's polyphenols in water‐soluble phase have been less frequently reported. This study assessed the effects of water‐soluble Mitragyna speciosa (kratom) extract (MSE) on gut microbiota and their metabolite production in fecal batch culture.The water‐soluble kratom extract (MSE0) and the water‐soluble kratom extract after partial sugar removal (MSE50) both contained polyphenols, with total phenolic levels of 2037.91 ± 51.13 and 3997.95 ± 27.90 mg GAE/g extract, respectively and total flavonoids of 81.10 ± 1.00 and 84.60 ± 1.43 mg CEQ/g extract. The gut microbiota in fecal batch culture was identified by 16S rRNA gene sequencing at 0 and 24 h of fermentation. After fermentation, MSE50 stimulated the growth of Bifidobacterium more than MSE0. MSE0 gave the highest total fatty acids level among the treatments. The phenolic metabolites produced by some intestinal microbiota during fecal fermentation at 24 h were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The major metabolite of biotransformation of both water‐soluble MSEs by intestinal microbiota was pyrocatechol (9.85–11.53%).The water‐soluble MSEs and their produced metabolites could potentially be used as ingredients for functional and medicinal food production that supports specific gut microbiota. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was utilized to develop a technique for the simultaneous quantification of icariin and its primary metabolites in mouse urine. The levels of icariin, icariside Ⅰ, icariside Ⅱ, baohuoside Ⅱ, wushanicaritin, icaritin, and desmethylicaritin in mouse urine were analyzed subsequent to the oral administration of an icariin suspension. This study aimed to preliminarily investigate the excretion profile of icariin in mice. Using an aqueous solution containing 0.1% formic acid (A) and an acetonitrile solution containing 0.1% formic acid (B) as the mobile phases, icariin and its major metabolites demonstrated satisfactory linearity over the concentration range of 0.25–800 ng·mL−1 . The precision and accuracy of intra-day and inter-day measurements were all found to be within 15%. Seventy-two hours after the intragastric administration of icariin suspension to a mouse, the cumulative urinary excretion of icariin, icariside Ⅰ, icariside Ⅱ, baohuoside Ⅱ, wushanicaritin, icaritin, and desmethylicaritin was quantified as 13.48, 18.70, 2,627.51, 2.04, 10.04, 3,420.44, and 735.13 ng, respectively. The UPLC-MS/MS method developed in this research is characterized by its simplicity, sensitivity, and speed, making it well-suited for the concurrent quantification of icariin and its associated metabolites in urine. Additionally, it is appropriate for analyzing urine samples that may contain multiple drugs in future investigations. [ABSTRACT FROM AUTHOR]

Hemerocallis citrina is an edible and medicinal homologous plant, which is rich in many nutrients and bioactive components. Terpenoids are a kind of important bioactive component in H. citrina. To understand the dominant terpenoid metabolites in H. citrina roots, stems, leaves, and flowers, respectively, this study analyzed the terpenoid metabolites in these 4 organs based on the ultra performance liquid chromatography-tandem mass spectrometry technology of widely targeted metabolomics. A total of 43 terpenoids were identified, including 7 kinds of monoterpenoids (16.2%), 18 kinds of ditepenoids (41.9%), 16 kinds of triterpene (37.2% ), and 2 kinds of triterpene saponin (4.7%). Principal component analysis and clustering analysis indicated that the mass spectrometry data were reliable, and the accumulation of terpenoids in different organs was significantly different. The dominant terpenoid metabolites in roots included isopimaradieneone, pimaradienone, abietic acid, scutebarbolide C, and isopimaric acid. The dominant terpenoid metabolites in stems included 3, 9-dihydroxy-13(14)-labden-16,15-olide and 9,19-cyclolanost-24-en-3-ol (cycloartenol). The dominant terpenoid metabolites in leaves included viteagnusin A and ent-3β-acetoxyisopimar-15-8β-ol. The dominant terpenoid metabolites in flowers included vitexilactone and 7-Ocoumaroyl- loganic acid. This study listed the relative contents of all terpenoids in roots, stems, leaves, and flowers of H. citrina in detail, which provided the foundation for further investigation of the different usages of various plant organs of H. citrina, and the information is important for the food industry and medical treatment. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis. [ABSTRACT FROM AUTHOR]

Due to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography–mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk's initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively. [ABSTRACT FROM AUTHOR]

Much more attention has been paid to the contamination of Alternaria toxins because of food contamination and the threat to human health. In this study, an ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed for the simultaneous detection of the prototypical alternariol, alternariol monomethylether, and the metabolites 4‐oxhydryl alternariol, and alternariol monomethylether 3‐sulfate ammonium salt of Alternaria toxins. The positive samples were used as matrix samples to optimize the different experimental conditions. 0.01% formic acid solution and acetonitrile were used as the mobile phase, and analytes were scanned in negative electron spray ionization under multiple reaction monitoring, and quantitative determination by isotope internal standard method. Application of this method to samples of human plasma and urine showed the detection of the above analytes. The results showed that the recoveries were from 80.40% to 116.4%, intra‐day accuracy was between 0.6% and 8.0%, and inter‐day accuracy was between 1.1% and 12.1%. The limit of detection of the four analytes ranged from 0.02 to 0.6 µg/L in urine, and 0.02 to 0.5 µg/L in plasma, respectively. Thus, the developed method was rapid and accurate for the simultaneous detection of analytes and provided a theoretical basis for the risk assessment of Alternaria toxins for human exposure. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is a neurodegenerative age-related disease that primarily affects the elderly population leading to progressive memory impairments and neural deficits. It is counted as a major cause of geriatric dependency and disability. The pathogenesis of Alzheimer's disease incidence is complex and involves various hypotheses, including the cholinergic hypothesis, deposition of β-amyloid plaques, neuroinflammation, oxidative stress, and apoptosis. Conventional treatments such as donepezil aim to delay the symptoms but do not affect the progression of the disease and may cause serious side effects like hepatoxicity. The use of natural candidates for Alzheimer's disease treatment has drawn the attention of many researchers as it offers a multitargeted approach. Methods: This current study investigates the metabolic profiles of total defatted methanolic extract of Vitex pubescens bark and its polar fractions, viz. ethyl acetate and n-butanol, using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry(UPLC-ESI-QTOF/MS/MS) technique as well as evaluate the antioxidant using free radical scavenging assays, viz. DPPH and ABTS assays and in-vitro acetylcholinesterase inhibitory activities using Ellman's microplate assay. Results: Metabolic profiling revealed a total of 71, 43, and 55 metabolites tentatively identified in the defatted methanolic extract, ethyl acetate, and n-butanol fractions, respectively. Phenolic acids were the most abundant class, viz. benzoic acids, and acyl quinic acid derivatives followed by flavonoids exemplified mainly by luteolin-C-glycosides and apigenin-C-glycosides. Quantification of the total phenolic and flavonoid contents in the total defatted methanolic extract confirmed its enrichment with phenolics and flavonoids equivalent to 138.61 ± 9.39 µg gallic acid/mg extract and 119.63 ± 4.62 µg rutin/mg extract, respectively. Moreover, the total defatted methanolic extract exhibited promising antioxidant activity confirmed through DPPH and ABTS assays with a 50% inhibitory concentration (IC50) value equivalent to 52.79 ± 2.16 µg/mL and 10.02 ± µg/mL, respectively. The inhibitory activity of acetylcholine esterase (AchE) was assessed using in-vitro Ellman's colorimetric assay, the total defatted methanolic extract, ethyl acetate, and n-butanol fractions exhibited IC50 values of 52.9, 15.1 and 108.8 µg/mL that they proved the significant inhibition of AchE activity. Conclusion: The results obtained herein unraveled the potential use of the total methanolic extract of Vitex pubescens bark and its polar fractions as natural candidates for controlling Alzheimer's disease progression. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). Methods: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. Results: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group (P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group (P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group (P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). Conclusions: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management. [ABSTRACT FROM AUTHOR]

Despite being protected by the blood–brain barrier and the blood–cerebrospinal fluid barrier, cerebrospinal fluids can contain contaminants that trigger neurotoxic effects, yet there are few effective methods to analyze metabolites of industrial additives. Here, we established a fast and robust analytical methodology, based on ultra-high performance liquid chromatography interfaced with triple quadrupole mass spectrometry, to quantitatively determine concentrations of metabolites of synthetic antioxidants, organophosphate esters, and phthalate esters in human cerebrospinal fluids. The developed method exhibited highly sensitive and stable instrumental performance, satisfactory recoveries, minimal matrix effects, and trace level detection limits. We identified and quantified thirty industrial additive metabolites in cerebrospinal fluid samples, at 0.58–13 ng/mL total concentrations. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) are often synthesized via small changes in the molecular structure, producing drugs whose effect and potency are not yet fully known. Ketamine is one of the oldest NPS, with therapeutic use in human and veterinary medicine authorized in several countries, being metabolized mainly into norketamine and 6-hydroxy-norketamine. Furthermore, two structural analogues of ketamine have recently been identified, deschloroketamine and 2-fluorodeschloroketamine, marketed as drugs of abuse. To comply with Green Analytical Toxicology (GAT) fundamentals, miniaturized techniques such as dispersive liquid–liquid microextraction (DLLME) were employed to determine toxicants in biological fluids. An analytical method for determining ketamine, its metabolites and its analogues in oral fluid was fully developed and validated by using DLLME and liquid chromatography–tandem mass spectrometry (LC-MS-MS). The extraction parameters were optimized by multivariate analysis, obtaining the best conditions with 200 μL of sample, 100 μL of methanol as dispersive solvent and 50 μL of chloroform as extractor solvent. Linearity was obtained from 10 to 1,000 ng/mL, with limit of detection (LOD) and lower limit of quantification (LLOQ) at 10 ng/mL. Imprecision (% relative standard deviation) and bias (%) were less than 8.2% and 9.5%, respectively. The matrix effect did not exceed 10.6%, and the recovery values varied from 24% to 42%. No matrix interference and good selectivity in the evaluation of 10 different sources of oral fluid and 42 drugs at 500 ng/mL, respectively, were observed. The method was applied in the analysis of 29 authentic oral fluid samples and had its green characteristic evaluated by three different tools: the Green Analytical Procedure Index (GAPI), the Analytical Eco-Scale and the Analytical GREEnness (AGREE) metrics. [ABSTRACT FROM AUTHOR]

Thiamethoxam, a systemic neonicotinoid insecticide, is widely accepted for use against various chewing and sucking insect pests. In this particular study, the authors examined the dissipation kinetics and metabolism of thiamethoxam in wheat using quick, easy, cheap, effective, rugged and safe (QuEChERS) methodology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) over two years during the same cropping season. Residues of thiamethoxam and its metabolites in wheat plants were investigated following foliar spray of thiamethoxam at recommended dose (12.5 g a.i. ha−1) and four times the recommended dose (50.0 g a.i. ha−1) at earhead formation stage. Total residues of thiamethoxam and its metabolites in leaves at 0 day (2 h after spray) ranged from 3.69 to 14.36 mg kg−1 for the two doses over the two years. Clothianidin was the only metabolite detected in leaves at 0 day (2 h after spray); however at 7 days after spray nitroguanidine, N-desmethyl-thiamethoxam and 1-methyl-3-nitroguanidine were also detected. Total residues of thiamethoxam and its metabolites in soil at 0 day (2 h after spray) ranged from 0.23 to 0.84 mg kg−1. Thiamethoxam residue in leaves and soil followed first order kinetics with half-life ranging from 9.04 to 15.50 days for the two doses over the two study years. Residues of thiamethoxam and its metabolites in leaves, straw and grain at harvest time for both the doses were below their limit of quantification (0.01 mg kg−1). This information could be helpful for evaluating both regulatory and food safety decisions regarding use of neonicotinoids. [ABSTRACT FROM AUTHOR]

Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total β-zearalenol (β-ZEL) and total zearalanone (ZAN), where 'total' refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total β-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 μg total DON/L, 0.0350 μg DOM-1/L, 0.0413 μg total ZEN/L, 0.0379 μg total α-ZEL/L, 0.0189 μg total β-ZEL/L, and 0.121 μg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 μg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study's findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population. [ABSTRACT FROM AUTHOR]

The stem base of alfalfa is a critical part for its overwintering, regeneration, and yield. To better understand the specificity and importance of the stem base, we analyzed the structure, metabolic substances, and transcriptome of the stem base using anatomical techniques, ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and RNA sequencing (RNA-seq), and compared it with stems and roots. The anatomical structure shows that the ratio of xylem to phloem changes at the base of the stem. A total of 801 compounds involved in 91 metabolic pathways were identified from the broadly targeted metabolome. Transcriptome analysis revealed 4974 differentially expressed genes (DEGs) at the stem base compared to the stem, and 5503 DEGs compared to the root. Comprehensive analyses of differentially accumulated compounds (DACs) and DEGs, in the stem base vs. stem, identified 10 valuable pathways, including plant hormone signal transduction, zeatin biosynthesis, α-Linolenic acid metabolism, histidine metabolism, carbon metabolism, carbon fixation in photosynthetic organisms, pentose phosphate pathway, galactose metabolism, and fructose and mannose metabolism. The pathways of plant hormone signal transduction and carbon metabolism were also identified by comparing the stem base with the roots. Taken together, the stem base of alfalfa is the transition region between the stem and root in morphology; in terms of material metabolism, its growth, development, and function are regulated through hormones and sugars. [ABSTRACT FROM AUTHOR]

Objective To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites. Results A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and Lisoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, Nacetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism. Conclusions Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS. [ABSTRACT FROM AUTHOR]

The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum—a factor with a high impact on all crops in Ecuador, representing one of the biggest phytosanitary problems. Four of the most common varieties of Musa spp. were tested to identify the metabolic reaction of plants facing Moko disease. The phenolic and flavonoid content has been evaluated as a defense system, and the α-diphenyl-α-picrylhydrazyl free-radical-scavenging method (DPPH), free-radical-scavenging activity (ABTS), ferric-reducing antioxidant power (FRAP) assays, and liquid chromatography and mass spectrometry (LC-MS) have been adapted to analyze the active compounds with the antioxidant capacity necessary to counteract the pathogenic attack. Our results indicate that all the studied varieties of Musa spp. react in the same way, such that the diseased samples showed a higher accumulation of secondary metabolites with antioxidant capacity compared with the healthy ones, with high active compound synthesis identified during the appearance of Moko disease symptoms. More than 40 compounds and their derivatives (from kaempferol and quercetin glycosides) with protective roles demonstrate the implication of the Musa spp. defense system against R. solanacearum infection. [ABSTRACT FROM AUTHOR]

Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC–MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework. [ABSTRACT FROM AUTHOR]

We previously conducted a systematic study on the metabolic process and products of hederasaponin B in rats. We hypothesized that the sugar chain structures play a key role in the metabolism of triterpenoid saponins. To verify this hypothesis, we conducted metabolic research on ciwujianoside B ascribed to the same sugar chains and a distinct aglycone and compared it with hederasaponin B. Specifically, we collected feces, urine, and plasma of rats after gavage with ciwujianoside B and identified 42 metabolites by UPLC-Fusion Lumos Orbitrap mass spectrometry. Finally, ciwujianoside B metabolism and hederasaponin B metabolism were compared, reaching the following conclusions: (i) more than 40 metabolites were identified in both, with the majority of metabolites identified in feces; (ii) the corresponding metabolic pathways in vivo were basically similar, including deglycosylation, acetylation, hydroxylation, glucuronidation, oxidation, and glycosylation; and (iii) deglycosylation was considered the main metabolic reaction, and its metabolites accounted for approximately 50% of all metabolites. Overall, this study provides a foundation for further research on the metabolism of triterpenoid saponins. [ABSTRACT FROM AUTHOR]

Background: Imbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated. Methods: We investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. Results: The results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum. Conclusions: These findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism-gut-metabolite axis. [ABSTRACT FROM AUTHOR]

Curcumin, the fat-soluble active ingredient and major compound of curcuminoids contained in the curcuma root, is known for its physiological low absorption and bioavailability. Various formulations and galenic technologies are currently available on the market. In this study, the product tested was provided as a soft gelatin capsule containing curcuminoids in an oily matrix mixed with phospholipids (oil/phospholipids [PL]-based, no new technologies applied or artificial excipients added). This was intended to improve bioavailability of curcuminoids as well as to mimic the natural digestion process of fat-soluble substances. In particular, the oral bioavailability of curcuminoids in the oil/PL-based formulation was compared with the pure curcuminoids extract alone (reference product), in a randomized, cross-over, single oral dose study design. Twelve healthy subjects were administered 200 mg curcuminoids under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration–time curves of total curcuminoids, as well as the curcumin metabolite tetrahydrocurcumin (THC). Results showed significantly higher AUC0-8h levels after the intake of the oil/PL-based formulation for total curcuminoids (205.60 vs. 112.50 ng/mL*h, P =.0001) as well as for THC (347.30 vs. 118.90 ng/mL*h, P <.0001) in comparison to the pure curcuminoids extract. Cmax was also significantly higher for both parameters analyzed (total curcuminoids: 47.54 vs. 21.16 ng/mL, P =.0001; THC: 96.69 vs. 29.83 ng/mL, P <.0001). In addition, the uptake kinetic of total curcuminoids was significantly fastened with the oil/PL-based curcuminoids formulation compared with the pure curcuminoids extract (P =.0446). These data suggest an improved impact on curcuminoids uptake of the oil/PL-based formulation and confirms its good tolerability. [ABSTRACT FROM AUTHOR]

Prompted by the need for related analytical reference material in the frame of the fight against doping in sports, synthetic efforts towards the main long‐term bishydroxylated metabolite (LGD‐LTM1) of the nonsteroidal selective androgen receptor modulator (SARM) ligandrol have produced related derivatives that were exploited for a targeted metabolite analysis of urine samples obtained in the course of previous excretion studies of this SARM. Further clarifying ligandrol's metabolic profile, the availability of synthetic reference material permitted the structural elucidation of a previously reported pyrrolidinone‐type metabolite and revealed its potential analytical utility as an additional long‐term marker. Moreover, synthetic reference material enabled the comparison and validation of liquid chromatography coupled with mass spectrometry (LC‐MS)‐based and gas chromatography coupled with mass spectrometry (GC‐MS)‐based detection and identification methods focusing on the LGD‐LTM1 marker. [ABSTRACT FROM AUTHOR]