PubMed

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

Molecules. 2023 Jul 9;28(14):5298. doi: 10.3390/molecules28145298.ABSTRACTOrganic selenium has been widely studied as a nutritional supplement for animal feed. However, there are few studies on the effect of organic selenium on flesh quality. In this study, the effects of organic selenium (yeast selenium (YS), Se 0.002 mg/L) on the metabolism and protein expression in Micropterus salmoides muscle under temporary fasting condition (6 weeks) were investigated. The muscle structure was observed through a microscope, and regulatory pathways were analyzed using proteomics and metabolomics methods. Electron microscopy showed that YS made the muscle fibers of M. salmoides more closely aligned. Differential analysis identified 523 lipid molecules and 268 proteins. The numbers of upregulated and downregulated proteins were 178 and 90, respectively, including metabolism (46.15%), cytoskeleton (11.24%) and immune oxidative stress (9.47%), etc. Integrated analyses revealed that YS enhanced muscle glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation metabolism. In the YS group, the content of eicosapentaenoic acid was increased, and that of docosahexaenoic acid was decreased. YS slowed down protein degradation by downregulating ubiquitin and ubiquitin ligase expression. These results suggest that organic selenium can improve M. salmoides muscle quality through the aforementioned pathways, which provides potential insights into the improvement of the quality of aquatic products, especially fish.PMID:37513172 | DOI:10.3390/molecules28145298

Microorganisms. 2023 Jul 21;11(7):1847. doi: 10.3390/microorganisms11071847.ABSTRACTThe use of biological inputs is an interesting approach to optimize crop production and reduce the use of chemical inputs. Understanding the chemical communication between bacteria and plants is critical to optimizing this approach. Recently, we have shown that Sphingomonas (S.) sediminicola can improve both nitrogen supply and yield in pea. Here, we used biochemical methods and untargeted metabolomics to investigate the chemical dialog between S. sediminicola and pea. We also evaluated the metabolic capacities of S. sediminicola by metabolic profiling. Our results showed that peas release a wide range of hexoses, organic acids, and amino acids during their development, which can generally recruit and select fast-growing organisms. In the presence of S. sediminicola, a more specific pattern of these molecules took place, gradually adapting to the metabolic capabilities of the bacterium, especially for pentoses and flavonoids. In turn, S. sediminicola is able to produce several compounds involved in cell differentiation, biofilm formation, and quorum sensing to shape its environment, as well as several molecules that stimulate pea growth and plant defense mechanisms.PMID:37513019 | DOI:10.3390/microorganisms11071847

Microorganisms. 2023 Jun 27;11(7):1669. doi: 10.3390/microorganisms11071669.ABSTRACTCandida albicans is a commensal fungus in healthy humans that causes infection in immunocompromised individuals through the secretion of several virulence factors. The successful establishment of infection is owing to elaborate strategies to cope with defensive molecules secreted by the host, including responses toward oxidative stress. Extracellular vesicle (EV) release is considered an alternative to the biomolecule secretory mechanism that favors fungal interactions with the host cells. During candidiasis establishment, the host environment becomes oxidative, and it impacts EV release and cargo. To simulate the host oxidative environment, we added menadione (an oxidative stress inducer) to the culture medium, and we explored C. albicans EV metabolites by metabolomics analysis. This study characterized lipidic molecules transported to an extracellular milieu by C. albicans after menadione exposure. Through Liquid Chromatography coupled with Mass Spectrometry (LC-MS) analyses, we identified biomolecules transported by EVs and supernatant. The identified molecules are related to several biological processes, such as glycerophospholipid and sphingolipid pathways, which may act at different levels by tuning compound production in accordance with cell requirements that favor a myriad of adaptive responses. Taken together, our results provide new insights into the role of EVs in fungal biology and host-pathogen interactions.PMID:37512842 | DOI:10.3390/microorganisms11071669

Microorganisms. 2023 Jun 22;11(7):1630. doi: 10.3390/microorganisms11071630.ABSTRACTHigher alcohols produced by yeast during the fermentation of sparkling wine must have the greatest impact on the smell and taste of wine. At present, the metabolic response to methanol and higher alcohols formation of Saccharomyces cerevisiae under endogenous CO2 overpressure has not been fully elucidated. In this work, a proteomics and metabolomics approach using a OFFGEL fractionator and the LTQ Orbitrap for the protein identification, followed by a metabolomic study for the detection and quantification of both higher alcohols (GC-FID and SBSE-TD-GC-MS) and amino acids (HPLC), was carried out to investigate the proteomic and metabolomic changes of S. cerevisiae in relation to higher alcohols formation under a CO2 overpressure condition in a closed bottle. The control condition was without CO2 overpressure in an open bottle. Methanol and six higher alcohols were detected in both conditions, and we have been able to relate to a total of 22 proteins: 15 proteins in the CO2 overpressure condition and 22 proteins in the control condition. As for the precursors of higher alcohols, 18 amino acids were identified in both conditions. The metabolic and proteomic profiles obtained in both conditions were different, so CO2 overpressure could be affecting the metabolism of higher alcohols. Furthermore, it was not possible to establish direct correlations in the condition under CO2 overpressure; however, in the condition without pressure it was possible to establish relationships. The data presented here can be considered as a platform that serves as a basis for the S. cerevisiae metabolome-proteome with the aim of understanding the behavior of yeast under conditions of second fermentation in the production of sparkling wines.PMID:37512803 | DOI:10.3390/microorganisms11071630

Metabolites. 2023 Jul 24;13(7):879. doi: 10.3390/metabo13070879.ABSTRACTBrazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.PMID:37512587 | DOI:10.3390/metabo13070879

Metabolites. 2023 Jul 24;13(7):877. doi: 10.3390/metabo13070877.ABSTRACTSeasonal variation in fatty acids and minerals concentrations was investigated through the analysis of Pecorino Romano cheese samples collected in January, April, and June. A fraction of samples contained missing values in their fatty acid profiles. Probabilistic principal component analysis, coupled with Linear Discriminant Analysis, was employed to classify cheese samples on a production season basis while accounting for missing data and quantifying the missing fatty acid concentrations for the samples in which they were absent. The levels of rumenic acid, vaccenic acid, and omega-3 compounds were positively correlated with the spring season, while the length of the saturated fatty acids increased throughout the production seasons. Concerning the classification performances, the optimal number of principal components (i.e., 5) achieved an accuracy in cross-validation equal to 98%. Then, when the model was tasked with imputing the lacking fatty acid concentration values, the optimal number of principal components resulted in an R2 value in cross-validation of 99.53%.PMID:37512584 | DOI:10.3390/metabo13070877

Metabolites. 2023 Jul 23;13(7):875. doi: 10.3390/metabo13070875.ABSTRACTThe poor availability of oxygen and nutrients in malignant tumors drives the activation of various molecular responses and metabolic reprogramming in cancer cells. Hypoxic tumor regions often exhibit resistance to chemotherapy and radiotherapy. One approach to enhance cancer therapy is to indirectly increase tumor oxygen availability through targeted metabolic reprogramming. Thus, understanding the underlying metabolic changes occurring during hypoxia and reoxygenation is crucial for improving therapy efficacy. In this study, we utilized the HT29 colorectal adenocarcinoma cell line as a hypoxia-reoxygenation model to investigate central carbon and lipid metabolism. Through quantitative NMR spectroscopy and flow injection analysis - differential mobility spectroscopy-tandem mass spectrometry (FIA-DMS-MS/MS) analysis, we observed alterations in components of mitochondrial metabolism, redox status, specific lipid classes, and structural characteristics of lipids during hypoxia and up to 24 h of reoxygenation. These findings contribute to our understanding of the metabolic changes occurring during reoxygenation and provide the basis for functional studies aimed at metabolic pathways in cancer cells.PMID:37512582 | DOI:10.3390/metabo13070875

Metabolites. 2023 Jul 23;13(7):874. doi: 10.3390/metabo13070874.ABSTRACTMass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy techniques have been used extensively for metabolite profiling. Although combining these two analytical modalities has the potential of enhancing metabolite coverage, such studies are sparse. In this study we test the hypothesis that combining the metabolic information obtained using liquid chromatography (LC) MS and 1H NMR spectroscopy improves the discrimination of metabolic disease development. We induced metabolic syndrome in male mice using a high-fat diet (HFD) exposure and performed LC-MS and NMR spectroscopy on plasma samples collected after 1 and 8 weeks of dietary intervention. In an orthogonal projection to latent structures (OPLS) analysis, we observed that combining MS and NMR was stronger than each analytical method alone at determining effects of both HFD feeding and time-on-diet. We then tested our metabolomics approach on plasma from 56 individuals from the Malmö Diet and Cancer Study (MDCS) cohort. All metabolic pathways impacted by HFD feeding in mice were confirmed to be affected by diabetes in the MDCS cohort, and most prominent HFD-induced metabolite concentration changes in mice were also associated with metabolic syndrome parameters in humans. The main drivers of metabolic disease discrimination emanating from the present study included plasma levels of xanthine, hippurate, 2-hydroxyisovalerate, S-adenosylhomocysteine and dimethylguanidino valeric acid. In conclusion, our combined NMR-MS approach provided a snapshot of metabolic imbalances in humans and a mouse model, which was improved over employment of each analytical method alone.PMID:37512581 | DOI:10.3390/metabo13070874

Metabolites. 2023 Jul 23;13(7):873. doi: 10.3390/metabo13070873.ABSTRACTInflammatory bowel diseases (IBD) involve complex interactions among genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The goals of this study were twofold: to test the hypothesis that gut microbial dysbiosis from chronic intestinal inflammation leads to mucosal metabolic alterations suitable for therapeutic targeting, and to address gaps in metabolomic studies of intestinal inflammation that have overlooked the mucosal metabolome. The chronic DSS colitis was induced for five weeks in 7-9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. The novel findings demonstrated increases in several host- and microbe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed that microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.PMID:37512580 | DOI:10.3390/metabo13070873

Metabolites. 2023 Jul 22;13(7):872. doi: 10.3390/metabo13070872.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms "Biomarkers, Tumor", "Pancreatic Neoplasms", "Early Diagnosis", "Metabolomics" and "Lipidome" (January 2018-March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.PMID:37512579 | DOI:10.3390/metabo13070872

Metabolites. 2023 Jul 21;13(7):871. doi: 10.3390/metabo13070871.ABSTRACTWhite, green, and oolong teas are produced from the tea plant (Camellia sinensis (L.) Kuntze) and are reported to have anti-obesity and hypolipidemic effects. The current study aims to investigate the anti-obesity effects of a tea mixture nano-formulation by targeting the AMPK/Sirt-1/GLUT-4 axis in rats. In vitro lipase and α-amylase inhibition assays were used to determine the active sample, which was then incorporated into a nanoparticle formulation subjected to in vivo anti-obesity testing in rats by measuring the expression level of different genes implicated in adipogenesis and inflammation using qRT-PCR. Moreover, metabolomic analysis was performed for each tea extract using LC/ESI MS/MS coupled to chemometrics in an attempt to find a correlation between the constituents of the extracts and their biological activity. The in vitro pancreatic lipase and α-amylase inhibition assays demonstrated more effective activity in the tea mixture than the standards, orlistat and acarbose, respectively, and each tea alone. Thus, the herbal tea mixture and its nanoparticle formulation were evaluated for their in vivo anti-obesity activity. Intriguingly, the tea mixture significantly decreased the serum levels of glucose and triglycerides and increased the mRNA expression of GLUT-4, P-AMPK, Sirt-1, and PPAR-γ, which induce lipolysis while also decreasing the mRNA expression of TNF-α and ADD1/SREBP-1c, thereby inhibiting the inflammation associated with obesity. Our study suggests that the tea mixture nano-formulation is a promising therapeutic agent in the treatment of obesity and may also be beneficial in other metabolic disorders by targeting the AMPK/Sirt-1/Glut-4 pathway.PMID:37512578 | DOI:10.3390/metabo13070871

Metabolites. 2023 Jul 20;13(7):869. doi: 10.3390/metabo13070869.ABSTRACTCathodic protection is widely used to protect metal structures from corrosion in marine environments using sacrificial galvanic anodes. These anodes, either in Zinc, or preferentially nowadays in Al-Zn-In alloys, are expected to corrode instead of the metal structures. This leads to the release of dissolved species, Zn2+, Al3+, and In3+, and solid phases such as Al(OH)3. Few studies have been conducted on their effects on marine organisms, and they concluded that further investigations are needed. We therefore evaluated the effects of Zn and Al-Zn-In anodes on oysters stabulated in tanks, under controlled conditions defined through a comparison with those prevailing in a given commercial seaport used as reference. We analyzed the entire metabolome of gills with a non-targeted metabolomic approach HRMS. A modelling study of the chemical species, corresponding to the degradation products of the anodes, likely to be present near the exposed oysters, was also included. We identified 16 and two metabolites modulated by Zn- and Al-Zn-In-anodes, respectively, that were involved in energy metabolism, osmoregulation, oxidative stress, lipid, nucleotide nucleoside and amino acid metabolisms, defense and signaling pathways. The combination of chemical modelling and metabolomic approach, used here for the first time, enlightened the influence of Zn present in the Al-Zn-In anodes.PMID:37512576 | DOI:10.3390/metabo13070869

Metabolites. 2023 Jul 20;13(7):868. doi: 10.3390/metabo13070868.ABSTRACTFormed by L-phenylalanine (L-phe) ammonia under the action of aromatic amino acid aminotransferases (AAATs), volatile benzenoids (VBs) and volatile phenylpropanoids (VPs) are essential aromatic components in oolong tea (Camellia sinensis). However, the key VB/VP components responsible for the aromatic quality of oolong tea need to be revealed, and the formation mechanism of VBs/VPs based on AAAT branches during the post-harvest process of oolong tea remains unclear. Therefore, in this study, raw oolong tea and manufacturing samples were used as the test materials, and targeted metabolomics combined with transcriptome analysis was also conducted. The results showed that thirteen types of VBs/VPs were identified, including nine types of VPs and four types of VBs. Based on the OAV calculation, in raw oolong tea, 2-hydroxy benzoic acid methyl ester and phenylethyl alcohol were identified as key components of the aromatic quality of oolong tea. As for the results from the selection of related genes, firstly, a total of sixteen candidate CsAAAT genes were selected and divided into two sub-families (CsAAAT1 and CsAAAT2); then, six key CsAAAT genes closely related to VB/VP formation were screened. The upregulation of the expression level of CsAAAT2-type genes may respond to light stress during solar-withering as well as the mechanical force of turnover. This study can help to understand the formation mechanism of aromatic compounds during oolong tea processing and provide a theoretical reference for future research on the formation of naturally floral and fruity aromas in oolong tea.PMID:37512575 | DOI:10.3390/metabo13070868

Metabolites. 2023 Jul 20;13(7):865. doi: 10.3390/metabo13070865.ABSTRACTThis study aimed to investigate metabolic changes following the acquisition of resistance to doxorubicin in the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Two drug-resistant cell lines, DOX-RES-50 and DOX-RES-100, were generated by treating MDA-MB-231 cells with doxorubicin for 24 h and allowing them to recover for six weeks. Both drug-resistant cell lines demonstrated an increase in doxorubicin IC50 values, indicating acquired drug resistance. Metabolomics analysis showed clear separation between the parental MDA-MB-231 cell line and the drug-resistant cell lines. Pathway analysis revealed that arginine and proline metabolism, glutathione metabolism, and beta-alanine metabolism were significantly perturbed in the drug-resistant cell lines compared to the parental cell line. After matching signals to an in-house library of reference standards, significant decreases in short- and medium-chain acylcarnitines and significant increases in long-chain acylcarnitines, 5-oxoproline, and 7-ketodeoxycholic acid were observed in the resistant cell lines as compared to the parental MDA-MB-231 cell line. In addition to baseline metabolic differences, we also investigated differences in metabolic responses in resistant cell lines upon a second exposure at multiple concentrations. Results indicate that whereas the parental MDA-MB-231 cell line had many metabolites that responded to doxorubicin in a dose-dependent manner, the two resistant cell lines lost a dose-dependent response for the majority of these metabolites. The study's findings provide insight into how metabolism is altered during the acquisition of resistance in TNBC cells and how the metabolic response to doxorubicin changes upon repeated treatment. This information can potentially identify novel targets to prevent or reverse multi-drug resistance in TNBC, and also demonstrate the usefulness of metabolomics technology in identifying new mechanisms of drug resistance in cancer and potential drug targets.PMID:37512572 | DOI:10.3390/metabo13070865

Metabolites. 2023 Jul 20;13(7):864. doi: 10.3390/metabo13070864.ABSTRACTTea's biochemical compounds and flavor quality vary depending on its grade ranking. Dianhong Congou black tea (DCT) is a unique tea category produced using the large-leaf tea varieties from Yunnan, China. To date, the flavor characteristics and critical components of two grades of high-quality DCT, single-bud-grade DCT (BDCT), and special-grade DCT (SDCT) manufactured mainly with single buds and buds with one leaf, respectively, are far from clear. Herein, comparisons of two grades were performed by the integration of human sensory evaluation, an electronic tongue, chromatic differences, the quantification of major components, and metabolomics. The BDCT possessed a brisk, umami taste and a brighter infusion color, while the SDCT presented a comprehensive taste and redder liquor color. Quantification analysis showed that the levels of total polyphenols, catechins, and theaflavins (TFs) were significantly higher in the BDCT. Fifty-six different key compounds were screened by metabolomics, including catechins, flavone/flavonol glycosides, amino acids, phenolic acids, etc. Correlation analysis revealed that the sensory features of the BDCT and SDCT were attributed to their higher contents of catechins, TFs, theogallin, digalloylglucose, and accumulations of thearubigins (TRs), flavone/flavonol glycosides, and soluble sugars, respectively. This report is the first to focus on the comprehensive evaluation of the biochemical compositions and sensory characteristics of two grades of high-quality DCT, advancing the understanding of DCT from a multi-dimensional perspective.PMID:37512571 | DOI:10.3390/metabo13070864

Metabolites. 2023 Jul 18;13(7):856. doi: 10.3390/metabo13070856.ABSTRACTRemote ischemic preconditioning (RIPC) has demonstrated protective effects in patients with lower extremity arterial disease (LEAD) undergoing digital subtraction angiography (DSA) and/or percutaneous transluminal angioplasty (PTA). This study aimed to investigate the impact of RIPC on the metabolomical profile of LEAD patients undergoing these procedures and to elucidate its potential underlying mechanisms. A total of 100 LEAD patients were enrolled and randomly assigned to either the RIPC group (n = 46) or the sham group (n = 54). Blood samples were drawn before and 24 h after intervention. Targeted metabolomics analysis was performed using the AbsoluteIDQ p180 Kit, and changes in metabolite concentrations were compared between the groups. The RIPC group demonstrated significantly different dynamics in nine metabolites compared to the sham group, which generally showed a decrease in metabolite concentrations. The impacted metabolites included glutamate, taurine, the arginine-dimethyl-amide-to-arginine ratio, lysoPC a C24:0, lysoPC a C28:0, lysoPC a C26:1, PC aa C38:1, PC ae C30:2, and PC ae C44:3. RIPC exhibited a 'stabilization' effect, maintaining metabolite levels amidst ischemia-reperfusion injuries, suggesting its role in enhancing metabolic control. This may improve outcomes for LEAD patients. However, additional studies are needed to definitively establish causal relationships among these metabolic changes.PMID:37512563 | DOI:10.3390/metabo13070856

Metabolites. 2023 Jul 17;13(7):853. doi: 10.3390/metabo13070853.ABSTRACTCaloric restriction and aerobic and resistance exercise are safe and effective lifestyle interventions for achieving weight loss in the obese older population (>65 years) and may improve physical function and quality of life. However, individual responses are heterogeneous. Our goal was to explore the use of untargeted metabolomics to identify metabolic phenotypes associated with achieving weight loss after a multi-component weight loss intervention. Forty-two older adults with obesity (body mass index, BMI, ≥30 kg/m2) participated in a six-month telehealth-based weight loss intervention. Each received weekly dietitian visits and twice-weekly physical therapist-led group strength training classes with a prescription for aerobic exercise. We categorized responders' weight loss using a 5% loss of initial body weight as a cutoff. Baseline serum samples were analyzed to determine the variable importance to the projection (VIP) of signals that differentiated the responder status of metabolic profiles. Pathway enrichment analysis was conducted in Metaboanalyst. Baseline data did not differ significantly. Weight loss was 7.2 ± 2.5 kg for the 22 responders, and 2.0 ± 2.0 kg for the 20 non-responders. Mummichog pathway enrichment analysis revealed that perturbations were most significant for caffeine and caffeine-related metabolism (p = 0.00028). Caffeine and related metabolites, which were all increased in responders, included 1,3,7-trimethylxanthine (VIP = 2.0, p = 0.033, fold change (FC) = 1.9), theophylline (VIP = 2.0, p = 0.024, FC = 1.8), paraxanthine (VIP = 2.0, p = 0.028, FC = 1.8), 1-methylxanthine (VIP = 1.9, p = 0.023, FC = 2.2), 5-acetylamino-6-amino-3-methyluracil (VIP = 2.2, p = 0.025, FC = 2.2), 1,3-dimethyl uric acid (VIP = 2.1, p = 0.023, FC = 2.3), and 1,7-dimethyl uric acid (VIP = 2.0, p = 0.035, FC = 2.2). Increased levels of phytochemicals and microbiome-related metabolites were also found in responders compared to non-responders. In this pilot weight loss intervention, older adults with obesity and evidence of significant enrichment for caffeine metabolism were more likely to achieve ≥5% weight loss. Further studies are needed to examine these associations in prospective cohorts and larger randomized trials.PMID:37512560 | DOI:10.3390/metabo13070853