PubMed

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jul 17;1228:123831. doi: 10.1016/j.jchromb.2023.123831. Online ahead of print.ABSTRACTTraditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.PMID:37515912 | DOI:10.1016/j.jchromb.2023.123831

Food Chem. 2023 Jul 17;430:136915. doi: 10.1016/j.foodchem.2023.136915. Online ahead of print.ABSTRACTAs a natural sweetener produced by honey bees, honey was recognized as being healthier for consumption than table sugar. Our previous study also indicated thatmetaboliteprofiles in mice fed honey and mixedsugardiets aredifferent. However, it is still noteworthy about the batch-to-batch consistency of the metabolic differences between two diet types. Here, the machine learning (ML) algorithms were applied to complement and calibrate HPLC-QTOF/MS-based untargeted metabolomics data. Data were generated from three batches of mice that had the same treatment, which can further mine the metabolite biomarkers. Random Forest and Extra-Trees models could better discriminate between honey and mixed sugar dietary patterns under five-fold cross-validation. Finally, SHapley Additive exPlanations tool identified phosphatidylethanolamine and phosphatidylcholine as reliable metabolic biomarkers to discriminate the honey diet from the mixed sugar diet. This study provides us new ideas for metabolomic analysis of larger data sets.PMID:37515908 | DOI:10.1016/j.foodchem.2023.136915

Mol Biotechnol. 2023 Jul 29. doi: 10.1007/s12033-023-00809-9. Online ahead of print.ABSTRACTThis study aims to reveal the metabolic differences between SDC-1 knockout mice and wild-type mice and the metabolic differences caused by shock in SDC-1 knockout mice by integrating transcriptomics and metabolomics. A total of 1009 differential metabolites were differentially expressed based on untargeted metabolomics and high-resolution mass spectrometry detection techniques. According to Kyoto Encyclopedia of Genes and Genomes enrichment, SDC-1 knockout significantly altered fat digestion and absorption, GnRH signaling pathway, fructose and mannose metabolism, and some other amino-related metabolic pathways and significantly modulated positively regulated longevity regulatory pathways, longevity regulatory pathways-worm, nicotinamide and niacinamide metabolism, and vitamin digestion and absorption pathways after its shock. Our findings indicate that SDC-1 knockout may have potential therapeutic effects in hemorrhagic shock by increasing nicotinamide metabolism.PMID:37515659 | DOI:10.1007/s12033-023-00809-9

Plants (Basel). 2023 Jul 22;12(14):2729. doi: 10.3390/plants12142729.ABSTRACTPlants of the Phoradendron genus have been traditionally used for their lipid- and glucose-lowering effects. However, the compounds responsible for these effects and the overall chemical profile of these plants have not been thoroughly investigated. We aimed to characterize the metabolome of leaves, stems, and aerial parts of the Phoradendron brachystachyum plant. We used mass spectrometry and colorimetric screening techniques (with various solvents) to identify and characterize the metabolites present. We also evaluated the antioxidant (FRAP, ORAC, TEAC, and DPPH assays) and inhibitory effects on pancreatic lipase and α-glucosidase enzymes of hydrophilic extracts. Furthermore, we compared the molecular fingerprints between the identified metabolites and FDA-approved drugs to gain insights into the metabolites that might be responsible for the observed effects on enzymes. Our findings revealed the presence of 59 putative metabolites, primarily flavonoids. However, we also hint at the presence of peptide and carbohydrate derivatives. The leaf extracts demonstrated the most promising metrics across all assays, exhibiting strong antioxidant and enzyme inhibitory effects as well as high levels of phenolic compounds, flavonoids, and tannins. Fingerprint analysis suggested potential peptide and carbohydrate metabolites as pancreatic lipase and α-glucosidase inhibitors. Overall, our study provides evidence on specific metabolites in Phoradendron brachystachyum that could be responsible for the therapeutic effects noted in obese and type 2 diabetes subjects.PMID:37514343 | DOI:10.3390/plants12142729

Plants (Basel). 2023 Jul 20;12(14):2700. doi: 10.3390/plants12142700.ABSTRACTSeed germination is an important stage of growth and reproduction and plays an important role in the life cycle of spermatophyte. It is co-determined by both genetic and environmental factors, and plant hormone regulation may be a highly conservative mechanism. Coix lachryrma-jobi (coix) is a grain with balanced nutrition for medicine and food and has substantial production value. It is an important part of agricultural production, and the efficiency of seed germination after sowing is a key link. In this study, coix species "small white shell Xingren" was used as the experimental material, and changes in gene expression levels and metabolite enrichment in seeds were identified by transcriptome and metabonomic analysis before and after seed germination. A total of 599 metabolites, including those from amino acid metabolism, sugar metabolism, and fatty acid metabolism, were significantly increased in germinating coix. Simultaneously, 10,929 differentially expressed genes (DEGs) were identified, and functional clusters of genes were also significantly clustered in hormone-signaling and glucose and fatty acid metabolism. In addition, this study found that a considerable number of hormone-signaling genes were significantly up-regulated during seed germination, activating multiple metabolic processes. The results of our conjoint analysis of multi omics showed that glucose and fatty acid metabolism played an important role in seed germination under hormone regulation.PMID:37514314 | DOI:10.3390/plants12142700

Plants (Basel). 2023 Jul 19;12(14):2696. doi: 10.3390/plants12142696.ABSTRACTTaxus cell cultures are a reliable biotechnological source of the anticancer drug paclitaxel. However, the interplay between taxane production and other metabolic pathways during elicitation remains poorly understood. In this study, we combined untargeted metabolomics and elicited Taxus baccata cell cultures to investigate variations in taxane-associated metabolism under the influence of 1 µM coronatine (COR) and 150 µM salicylic acid (SA). Our results demonstrated pleiotropic effects induced by both COR and SA elicitors, leading to differential changes in cell growth, taxane content, and secondary metabolism. Metabolite annotation revealed significant effects on N-containing compounds, phenylpropanoids, and terpenoids. Multivariate analysis showed that the metabolomic profiles of control and COR-treated samples are closer to each other than to SA-elicited samples at different time points (8, 16, and 24 days). The highest level of paclitaxel content was detected on day 8 under SA elicitation, exhibiting a negative correlation with the biomarkers kauralexin A2 and taxusin. Our study provides valuable insights into the intricate metabolic changes associated with paclitaxel production, aiding its potential optimization through untargeted metabolomics and an evaluation of COR/SA elicitor effects.PMID:37514310 | DOI:10.3390/plants12142696

Plants (Basel). 2023 Jul 19;12(14):2695. doi: 10.3390/plants12142695.ABSTRACT"Bois noir" disease associated with 'Candidatus Phytoplasma solani' seriously compromises the production and survival of grapevines (Vitis vinifera L.) in Europe. Understanding the plant response to phytoplasmas should help to improve disease control strategies. Using a combined metabolomic and transcriptomic analysis, this work, therefore, investigated the phytoplasma-grapevine interaction in red cultivar Sangiovese in a vineyard over four seasonal growth stages (from late spring to late summer), comparing leaves from healthy and infected grapevines (symptomatic and symptomless). We found an accumulation of both conjugate and free salicylic acids (SAs) in the leaves of 'Ca. P. solani'-positive plants from early stages of infection, when plants are still asymptomatic. A strong accumulation of gentisic acid (GA) associated with symptoms progression was found for the first time. A detailed analysis of phenylpropanoids revealed a significant accumulation of hydroxycinnamic acids, flavonols, flavan 3-ols, and anthocyanin cyanidin 3-O-glucoside, which are extensively studied due to their involvement in the plant response to various pathogens. Metabolomic data corroborated by gene expression analysis indicated that phenylpropanoid biosynthetic and salicylic acid-responsive genes were upregulated in 'Ca. P. solani-positive plants compared to -negative ones during the observed period.PMID:37514309 | DOI:10.3390/plants12142695

Plants (Basel). 2023 Jul 18;12(14):2680. doi: 10.3390/plants12142680.ABSTRACTCitrus sinensis seedlings were supplied with a nutrient solution containing 15 (control) or 0 (nitrogen (N) deficiency) mM N for 10 weeks. Extensive metabolic and gene reprogramming occurred in 0 mM N-treated roots (RN0) to cope with N deficiency, including: (a) enhancing the ability to keep phosphate homeostasis by elevating the abundances of metabolites containing phosphorus and the compartmentation of phosphate in plastids, and/or downregulating low-phosphate-inducible genes; (b) improving the ability to keep N homeostasis by lowering the levels of metabolites containing N but not phosphorus, upregulating N compound degradation, the root/shoot ratio, and the expression of genes involved in N uptake, and resulting in transitions from N-rich alkaloids to carbon (C)-rich phenylpropanoids and phenolic compounds (excluding indole alkaloids) and from N-rich amino acids to C-rich carbohydrates and organic acids; (c) upregulating the ability to maintain energy homeostasis by increasing energy production (tricarboxylic acid cycle, glycolysis/gluconeogenesis, oxidative phosphorylation, and ATP biosynthetic process) and decreasing energy utilization for amino acid and protein biosynthesis and new root building; (d) elevating the transmembrane transport of metabolites, thus enhancing the remobilization and recycling of useful compounds; and (e) activating protein processing in the endoplasmic reticulum. RN0 had a higher ability to detoxify reactive oxygen species and aldehydes, thus protecting RN0 against oxidative injury and delaying root senescence.PMID:37514294 | DOI:10.3390/plants12142680

Plants (Basel). 2023 Jul 11;12(14):2612. doi: 10.3390/plants12142612.ABSTRACTThe agronomic potential of glutamate dehydrogenase 2 (GDH2) in maize kernel production was investigated by examining the impact of a mutation on the corresponding gene. Mu-insertion homozygous and heterozygous mutant lines lacking GDH2 activity were isolated and characterized at the biochemical, physiological and agronomic levels. In comparison to the wild type and to the homozygous ghd2 mutants, the heterozygous gdh2 mutant plants were characterized by a decrease in the root amino acid content, whereas in the leaves an increase of a number of phenolic compounds was observed. On average, a 30 to 40% increase in kernel yield was obtained only in the heterozygous gdh2 mutant lines when plants were grown in the field over two years. The importance of GDH2 in the control of plant productivity is discussed in relation to the physiological impact of the mutation on amino acid content, with primary carbon metabolism mostly occurring in the roots and secondary metabolism occurring in the leaves.PMID:37514227 | DOI:10.3390/plants12142612

Plants (Basel). 2023 Jul 8;12(14):2591. doi: 10.3390/plants12142591.ABSTRACTCamellia seed oil is a top-end quality of cooking oil in China. The oil quality and quantity are formed during seed maturation and desiccation. So far, it remains largely unresolved whether lipid degradation occurs and contributes to Camellia oil traits. In this study, three different Camellia germplasms, C. oleifera cv. Min 43 (M43), C. meiocarpa var. Qingguo (QG), and C. meiocarpa cv Hongguo (HG) were selected, their seed oil contents and compositions were quantified across different stages of seed desiccation. We found that at the late stage of desiccation, M43 and QG lost a significant portion of seed oil, while such an event was not observed in HG. To explore the molecular bases for the oil loss In M43, the transcriptomic profiling of M43 and HG was performed at the early and the late seed desiccation, respectively, and differentially expressed genes (DEGs) from the lipid metabolic pathway were identified and analyzed. Our data demonstrated that different Camellia species have diverse mechanisms to regulate seed oil accumulation and degradation, and that triacylglycerol-to-terpenoid conversion could account for the oil loss in M43 during late seed desiccation.PMID:37514206 | DOI:10.3390/plants12142591

Nutrients. 2023 Jul 24;15(14):3273. doi: 10.3390/nu15143273.ABSTRACTDietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1-V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism.PMID:37513690 | DOI:10.3390/nu15143273

Nutrients. 2023 Jul 19;15(14):3206. doi: 10.3390/nu15143206.ABSTRACTThe gestational period is an incredibly stressful time for a pregnant woman. Pregnant patients constantly seek effective and reliable compounds in order to achieve a healthy labor. Nowadays, increasing numbers of women use herbal preparations and supplements during pregnancy. One of the most popular and most frequently chosen herbs during pregnancy is the raspberry leaf (Rubus idaeus). Raspberry extracts are allegedly associated with a positive effect on childbirth through the induction of uterine contractions, acceleration of the cervical ripening, and shortening of childbirth. The history of the consumption of raspberry leaves throughout pregnancy is vast. This review shows the current status of the use of raspberry leaves in pregnancy, emphasizing the effect on the cervix, and the safety profile of this herb. The majority of women apply raspberry leaves during pregnancy to induce and ease labor. However, it has not been possible to determine the exact effect of using raspberry extracts on the course of childbirth and the perinatal period. Additionally, it is unclear whether this herb has only positive effects. The currently available data indicate a weak effect of raspberry leaf extracts on labor induction and, at the same time, their possible negative impact on cervical ripening.PMID:37513625 | DOI:10.3390/nu15143206

Nutrients. 2023 Jul 19;15(14):3200. doi: 10.3390/nu15143200.ABSTRACTObesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.PMID:37513618 | DOI:10.3390/nu15143200

Nutrients. 2023 Jul 18;15(14):3184. doi: 10.3390/nu15143184.ABSTRACTSenescence is a normal biological process that is accompanied with a series of deteriorations in physiological function. This study aimed to investigate the effects of bovine colostrum milk supplementation on metabolic changes and the expression of various biomarkers on inflammation, antioxidant and oxidative damage, nutrient metabolism, and genomic stability among older adults. Older adults (50-69 years old) who participated in the 12-week randomized, double-blinded, placebo-controlled trial were instructed to consume the IgCo bovine colostrum-enriched skim milk or regular skim milk (placebo) twice daily. Following 12 weeks of intervention, participants in the intervention group had lower expression levels in pro-inflammatory mediators (CRP, IL-6, and TNF-α), with significant (p < 0.05) interaction effects of the group and time observed. However, no significant interaction effect was observed in the vitamin D, telomerase, 8-OHdG, MDA, and SOD activities. UPLC-MS-based untargeted metabolomics analysis revealed that 22 metabolites were upregulated and 11 were downregulated in the intervention group compared to the placebo group. Glycerophospholipid metabolism, along with cysteine and methionine metabolism were identified as the potential metabolic pathways that are associated with bovine colostrum milk consumption. In conclusion, consuming bovine colostrum milk may induce metabolic changes and reduce the expression of various pro-inflammatory mediators, thus improving the immune function in older adults.PMID:37513601 | DOI:10.3390/nu15143184

Nutrients. 2023 Jul 14;15(14):3143. doi: 10.3390/nu15143143.ABSTRACT(1) Background: Many studies have attempted to explore potential biomarkers for the early detection of gout, but consistent and high levels of evidence are lacking. In this study, metabolomics was used to summarize the changes of metabolites in the literature and explore the potential value of metabolites in predicting the occurrence and development of gout. (2) Methods: We searched the databases including the EMBASE, the Cochrane Library, PubMed, Web of Science, VIP Date, Wanfang Data, and CNKI, and the screening was fulfilled on 30 July 2022. The records were screened according to the inclusion criteria and the risk of bias was assessed. Qualitative analysis was performed for all metabolites, and meta-analysis was performed for metabolite concentrations using random effects to calculate the Std mean difference and 95% confidence interval. (3) Results: A total of 2738 records were identified, 33 studies with 3422 participants were included, and 701 metabolites were identified. The qualitative analysis results showed that compared with the healthy control group, the concentration of 56 metabolites increased, and 22 metabolites decreased. The results of the meta-analysis indicated that 17 metabolites were statistically significant. (4) Conclusions: Metabolites are associated with gout. Some specific metabolites such as uric acid, hypoxanthine, xanthine, KYNA, guanosine, adenosine, creatinine, LB4, and DL-2-Aminoadipic acid have been highlighted in the development of gout.PMID:37513561 | DOI:10.3390/nu15143143

Molecules. 2023 Jul 19;28(14):5507. doi: 10.3390/molecules28145507.ABSTRACTThe differential metabolite profiles of four wild and ten cultivated soybeans genotypes were explored using an untargeted metabolomics approach. Ground soybean seed samples were extracted with methanol and water, and metabolic features were obtained using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) in both positive and negative ion modes. The UHPLC-HRMS analysis of the two different extracts resulted in the putative identification of 98 metabolites belonging to several classes of phytochemicals, including isoflavones, organic acids, lipids, sugars, amino acids, saponins, and other compounds. The metabolic profile was significantly impacted by the polarity of the extraction solvent. Multivariate analysis showed a clear difference between wild and cultivated soybean cultivars. Unsupervised and supervised learning algorithms were applied to mine the generated data and to pinpoint metabolites differentiating wild and cultivated soybeans. The key identified metabolites differentiating wild and cultivated soybeans were isoflavonoids, free amino acids, and fatty acids. Catechin analogs, cynaroside, hydroxylated unsaturated fatty acid derivatives, amino acid, and uridine diphosphate-N-acetylglucosamine were upregulated in the methanol extract of wild soybeans. In contrast, isoflavonoids and other minor compounds were downregulated in the same soybean extract. This metabolic information will benefit breeders and biotechnology professionals to develop value-added soybeans with improved quality traits.PMID:37513379 | DOI:10.3390/molecules28145507

Molecules. 2023 Jul 18;28(14):5494. doi: 10.3390/molecules28145494.ABSTRACTRecent years have seen an increase in research focusing on the amelioration of apple pomace waste for use in the food and nutraceutical industries. Much of this work has concentrated on the characterisation of the polyphenol composition of apple pomace materials to determine their role in conferring nutritional and health benefits. Although apples contain substantial quantities of polymeric procyanidins (condensed tannins), this class of compounds has received limited attention in apple research. This study quantified the polymeric procyanidins in apple pomace extracts using a rapid, methyl-cellulose precipitation (MCP) approach for the first time. In addition, a non-targeted metabolomics approach was applied to determine the most abundant phenolic classes present. Polymeric procyanidins were found to be the most abundant type of polyphenol in apple pomace extracts and were generally oligomeric in nature. Multivariate statistical analysis revealed that the ferric-reducing antioxidant power (FRAP) was most strongly correlated with the polymeric procyanidin concentration. Noting that polymeric procyanidins may not cross the cell layer to exert antioxidant activity in vivo, their presence in apple pomace extracts may therefore overestimate the FRAP. This work highlights the importance of polymeric procyanidins in the phenolic diversity of apple pomaces, and it is proposed that in future studies, rapid MCP assays may be used for their quantification.PMID:37513366 | DOI:10.3390/molecules28145494

Molecules. 2023 Jul 18;28(14):5488. doi: 10.3390/molecules28145488.ABSTRACTGraviera is a very popular yellow hard cheese produced in mainland Greece and the Aegean islands, and in three PDO (protected denomination of origin) locations. Apart from geographic location, type of milk and production practices are also factors that affect cheese composition, and make this dairy product unique in taste and aroma. In this work, 1H nuclear magnetic resonance (NMR) spectroscopy in combination with chemometrics has been used to determine the metabolite profile (40 compounds) of graviera cheese produced in different geographic locations, with emphasis on cheeses produced on the island of Crete. Organic acids and amino acids were the main components quantified in the polar cheese fraction, while the fatty acid (FA) composition of the lipid fraction was also obtained. Analysis of variance (Anova) of the dataset showed that γ-aminobutyric acid (GABA), conjugated linoleic acids (CLA) and linoleic acid differentiate gravieras produced in different areas of Crete, and that the total amino acid content was higher in cheeses produced in eastern Crete. Targeted discriminant analysis models classified gravieras produced in mainland Greece, Cyclades and Crete based on differences in 1,2-diglycerides, sterols, GABA and FA composition. Targeted and untargeted orthogonal partial least squares discriminant analysis (OPLS-DA) models were capable of differentiating gravieras produced in the island of Crete and hold promise as the basis for the authentication of PDO graviera products.PMID:37513360 | DOI:10.3390/molecules28145488

Molecules. 2023 Jul 17;28(14):5451. doi: 10.3390/molecules28145451.ABSTRACTThe growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2](NO3)2 (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), were studied as potential scaffolds for future anticancer drug development. Their cytotoxicity and cell migration inhibitory activity were analyzed, and an untargeted metabolomics approach was employed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2](NO3)2 was particularly cytotoxic against the HCT116 cell line. While [Co(κ3-TpmOH)2](NO3)2 significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] was associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2](NO3)2 was associated with dysregulation of cell adhesion and membrane structural pathways, suggesting that its antiproliferative and anti-migration properties could be due to changes in the overall cellular adhesion mechanisms.PMID:37513324 | DOI:10.3390/molecules28145451

Molecules. 2023 Jul 11;28(14):5345. doi: 10.3390/molecules28145345.ABSTRACTBACKGROUND: The perturbation of fatty acid metabolism in heart failure (HF) has been a critical issue. It is unclear whether the amounts of circulating carnitines will benefit primary etiology diagnosis and prognostic prediction in HF. This study was designed to assess the diagnostic and prognostic values of serum carnitine profiles between ischemic and non-ischemic derived heart failure.METHODS: HF patients (non-ischemic dilated cardiomyopathy: DCM-HF, n = 98; ischemic heart disease: IHD-HF, n = 63) and control individuals (n = 48) were enrolled consecutively. The serum carnitines were quantitatively measured using the UHPLC-MS/MS method. All patients underwent a median follow-up of 28.3 months. Multivariate Cox regression analysis was performed during the prognosis evaluation.RESULTS: Amongst 25 carnitines measured, all of them were increased in HF patients, and 20 acylcarnitines were associated with HF diagnosis independently. Seven acylcarnitines were confirmed to increase the probability of DCM diagnosis independently. The addition of isobutyryl-L-carnitine and stearoyl-L-carnitine to conventional clinical factors significantly improved the area under the receiver operating characteristic curve (ROC) from 0.771 to 0.832 (p = 0.023) for DCM-HF diagnosis (calibration test for the composite model: Hosmer-Lemeshow χ2 = 7.376, p = 0.497 > 0.05). Using a multivariate COX survival analysis adjusted with clinical factors simultaneously, oleoyl L-carnitine >300 nmol/L (HR = 2.364, 95% CI = 1.122-4.976, p = 0.024) and isovaleryl-L-carnitine <100 nmol/L (HR = 2.108, 95% CI = 1.091-4.074, p = 0.026) increased the prediction of all-cause mortality independently, while linoleoyl-L-carnitine >420 nmol/L, succinyl carnitine >60 nmol/L and isovaleryl-L-carnitine <100 nmol/L increased the risk of HF rehospitalization independently.CONCLUSIONS: Serum carnitines could not only serve as diagnostic and predictive biomarkers in HF but also benefit the identification of HF primary etiology and prognosis.PMID:37513217 | DOI:10.3390/molecules28145345