PubMed

J Proteome Res. 2024 Nov 26. doi: 10.1021/acs.jproteome.4c00173. Online ahead of print.ABSTRACTPsoriasis, an immune-mediated chronic inflammatory skin disease, is primarily diagnosed through clinical assessment. Currently, specific markers for the accurate diagnosis and prediction of psoriatic disease are lacking. Here, we employed a three-step designed study to perform untargeted metabolomics, with the aim of identifying candidate biomarkers for psoriasis. Through comprehensive multivariate and univariate statistical analyses, we screened eight potential biomarkers specific to psoriasis, with five structurally identified. Two dipeptide biomarkers, γ-GluSer and ThrGly, along with a lysine glycation metabolite, Nα-fructosyl-lysine (Fruc-Lys), were found to be psoriasis biomarkers for the first time. Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) values of these eight metabolites/features ranged from 0.68 to 0.94. A biomarker panel comprising ThrGly and feature m/z 120.0656 (C4H9NO3) demonstrated high diagnostic accuracy (AUC = 0.97) in distinguishing psoriasis patients from healthy controls. Overall, our study identified and validated a panel of plasma metabolites/features that could serve as potential biomarkers for the diagnosis of psoriasis, providing new insights into the diagnosis and pathogenesis of this disease.PMID:39591524 | DOI:10.1021/acs.jproteome.4c00173

J Proteome Res. 2024 Nov 26. doi: 10.1021/acs.jproteome.4c00926. Online ahead of print.ABSTRACTCrossbreeding of zebu cattle (Bos indicus) with European breeds (Bos taurus) producing crossbred cattle was performed to overcome the low growth rates and milk production of indigenous tropical cattle breeds. However, zebu cattle fertility is higher than those of crossbred cattle and European breeds under warm conditions. Combination study of proteomics and metabolomics toward Malaysian indigenous breed Kedah × Kelantan-KK (B. indicus) and crossbreed Mafriwal-M (B. taurus × B. indicus) to understand physiological reasons for higher thermotolerance and fertility in Zebu cattle sperm. 161 regulated metabolites and 96 regulated proteins in KK and M (p < 0.05) showed more efficient carbohydrate and energy metabolism, higher integrity of the DNA and plasma membrane, a lower level of reactive oxygen species, and higher levels of phospholipids, which confirmed higher sperm plasma membrane integrity in KK. A stronger antioxidant system and lower polyunsaturated fatty acids help KK sperm cope with oxidative stress under warm conditions. The higher abundance of flagella structural proteins in KK provides a stronger structure that supports sperm motility. Abnormality of flagella, plasma membrane disruption, and DNA fragmentation were higher in M. These findings provide selective molecular markers for developing high-producing and more thermotolerant cattle breeds in tropical areas (197 words).PMID:39591502 | DOI:10.1021/acs.jproteome.4c00926

PLoS One. 2024 Nov 26;19(11):e0314053. doi: 10.1371/journal.pone.0314053. eCollection 2024.ABSTRACTPreeclampsia, a pregnancy-specific syndrome, poses substantial risks to maternal and neonatal health, particularly in cases with severe features. Our study focuses on evaluating the impact of low molecular weight metabolites on the intricate mechanisms and pathways involved in the pathophysiology of preeclampsia when severe features are present. We aim to pinpoint the distinct metabolomic profile in maternal plasma during pregnancies affected by hypertensive disorders and to correlate the metabolite levels with the clinical characteristics of the study cohort. A total of 173 plasma samples were collected, comprising 36 healthy pregnant women (HP), 52 patients with gestational hypertension (GH), 43 with preeclampsia without (PE-), and 42 with severe features (PE+). Nuclear magnetic resonance spectroscopy and metabolite identification were conducted to establish the metabolomic profiles. Univariate and chemometric analyses were conducted using MetaboAnalyst, and correlations were performed using GraphPad Prism. Our study unveils distinct metabolomic profiles differentiating HP women, patients featuring GH, and patients with PE-and PE+. Our analysis highlights an increase in acetate, N,N-dimethylglycine, glutamine, alanine, valine, and creatine levels in the PE+ group compared to the HP and GH groups. The PE+ group exhibited higher concentrations of N,N-dimethylglycine, glutamine, alanine, and valine compared to the PE-group. Moreover, elevated levels of specific metabolites, including N,N-dimethylglycine, alanine, and valine, were associated with increased blood pressure, worse obstetric outcomes, and poorer end-organ function, particularly renal and hepatic damage. Metabolomic analysis of PE+ individuals indicates heightened disturbances in nitrogen metabolism, methionine, and urea cycles. Additionally, the exacerbated metabolic disturbance may have disclosed renal impairment and hepatic dysfunction, evidenced by elevated levels of creatine and alanine. These findings not only contribute novel insights but also provide a more comprehensive understanding of the pathophysiological mechanisms at play in cases of PE+.PMID:39591465 | DOI:10.1371/journal.pone.0314053

Toxins (Basel). 2024 Nov 13;16(11):490. doi: 10.3390/toxins16110490.ABSTRACTTo protect ruminants from the harmful effects of mycotoxins, anti-mycotoxin agents can be added to the dietary ration, thus guaranteeing animal health and production. Therefore, the objective of this study was to evaluate the in vitro ruminal initial sequestration (weak binding) and subsequent desorption (strong binding) of an anti-mycotoxin agent based on a mixture of adsorbing material, turmeric and milk thistle extracts and yeast-based components to adsorb or bio-convert aflatoxins (AF), fumonisins B1 and B2 (FB), trichothecene deoxynivalenol (DON), T-2 and HT-2 toxins, and zearalenone (ZEN). Two doses were tested: Dose 1 simulated 30 mg/cow/d, while Dose 2 simulated 90 mg/cow/d of the anti-mycotoxin agent. Each treatment involved three analytical replicates at each of three incubation times (1, 4, and 24 h post-incubation), with two independent experimental runs providing experimental replicates. Analytical methods, including UHPLC-HRMS and multivariate analyses, were used to both quantify mycotoxin concentrations and reveal dose-dependent reductions, with statistical validations indicating significant changes in mycotoxin levels across both dose and time. The results indicated that the anti-mycotoxin agent was able to highly bind AFB1, T2, and HT-2 toxins since its concentration was always under the limit of detection (<1 ppb). Regarding ZEN (weak binding mean: 94.6%; strong binding mean: 62.4%) and FBs (weak binding mean: 58.7%; strong binding mean: 32.3%), orthogonal contrasts indicated that the anti-mycotoxin agent was able to effectively bind these toxins using Dose 1 (p < 0.05). This finding suggests that Dose 1 may be sufficient to achieve the targeted effect and that a further increase does not significantly improve the outcome. Regarding DON, a strong linear relationship was observed between dose and adsorption. However, the complex interactions between the mycotoxin, the ruminal environment, and the anti-mycotoxin agent made it difficult to establish a clear dose-effect relationship (p > 0.10). UHPLC-HRMS analysis identified over 1500 mass features in rumen samples, which were further analyzed to assess the effects of the anti-mycotoxin agent. Hierarchical clustering analysis (HCA) revealed significant changes in the untargeted metabolomic profiles of samples treated with mycotoxins compared to control samples, particularly after 24 h with the anti-mycotoxin treatments. Clear differences were noted between strong binding and weak binding samples. Further analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted distinct metabolomic profiles, with stronger predictive ability in the strong binding group (Q2 cumulative value of 0.57) compared to the weak binding group (0.30). The analysis identified 44 discriminant compounds in the strong binding model and 16 in the weak binding model. Seven compounds were common to both groups, while silibinin, known for its antioxidant and anti-inflammatory properties, was found among the unique compounds in the weak binding group. Overall, the findings suggest that both doses of the anti-mycotoxin agent significantly influenced the chemical profiles in the rumen, particularly enhancing the binding of mycotoxins, thereby supporting the role of phytogenic extracts in mitigating mycotoxin effects.PMID:39591245 | DOI:10.3390/toxins16110490

Toxics. 2024 Nov 16;12(11):822. doi: 10.3390/toxics12110822.ABSTRACTIt is imperative to comprehend the mechanisms that underlie drug toxicity in order to enhance the efficacy and safety of novel therapeutic agents. The capacity to identify molecular pathways that contribute to drug-induced toxicity has been significantly enhanced by recent developments in omics technologies, such as transcriptomics, proteomics, and metabolomics. This has enabled the early identification of potential adverse effects. These insights are further enhanced by computational tools, including quantitative structure-activity relationship (QSAR) analyses and machine learning models, which accurately predict toxicity endpoints. Additionally, technologies such as physiologically based pharmacokinetic (PBPK) modeling and micro-physiological systems (MPS) provide more precise preclinical-to-clinical translation, thereby improving drug safety assessments. This review emphasizes the synergy between sophisticated screening technologies, in silico modeling, and omics data, emphasizing their roles in reducing late-stage drug development failures. Challenges persist in the integration of a variety of data types and the interpretation of intricate biological interactions, despite the progress that has been made. The development of standardized methodologies that further enhance predictive toxicology is contingent upon the ongoing collaboration between researchers, clinicians, and regulatory bodies. This collaboration ensures the development of therapeutic pharmaceuticals that are more effective and safer.PMID:39591001 | DOI:10.3390/toxics12110822

Metabolites. 2024 Nov 20;14(11):645. doi: 10.3390/metabo14110645.ABSTRACTBackground/Objectives: Leflunomide, an isoxazole immunosuppressant, is widely used in the treatment of diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as lupus nephritis (LN). In recent years, clinical data have shown that some patients have obvious weight loss, liver injury, and other serious adverse reactions after taking leflunomide. However, the causes and mechanisms by which leflunomide reduces weight are unclear. Methods: Therefore, we used a mouse animal model to administer leflunomide, and we observed that the weight of mice in the leflunomide experimental group was significantly reduced (p < 0.01). In this animal experiment, a metabolomic method was used to analyze the livers of the mice in the experimental group and found that the main difference in terms of metabolic pathways was in the metabolism of aromatic amino acids, and it was confirmed that leflunomide can inhibit the limitations of phenylalanine, tyrosine, and tryptophan biosynthesis. Results: Our study revealed that leflunomide inhibited the activity of DAHPS in the gut microbiota, disrupting the metabolism of phenylalanine, tyrosine, and tryptophan, as well as the metabolism of carbohydrates and lipids. Leflunomide also increased endoplasmic reticulum stress by activating the PERK pathway, thereby promoting CHOP expression and increasing apoptosis-induced liver damage. Conclusions: These effects may be related to the observed weight loss induced by leflunomide.PMID:39590880 | DOI:10.3390/metabo14110645

Metabolites. 2024 Nov 20;14(11):641. doi: 10.3390/metabo14110641.ABSTRACTBackground: Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. Methods: This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Results: Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including FSHR and BMP7. Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as ANXA3 and IGFBP2 are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. Conclusions: These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms.PMID:39590877 | DOI:10.3390/metabo14110641

Metabolites. 2024 Nov 19;14(11):638. doi: 10.3390/metabo14110638.ABSTRACTAlterations in metabolism caused by SARS-CoV-2 infection have been highlighted in various investigations and have been used to search for biomarkers in different biological matrices. However, the selected biomarkers vary greatly across studies. Our objective is to provide a robust selection of biomarkers, including results from different sample treatments in the analysis of volatile organic compounds (VOCs) present in urine samples from patients with COVID-19. Between September 2021 and May 2022, urine samples were collected from 35 hospitalized COVID-19 patients and 32 healthy controls. The samples were analyzed by headspace (HS) solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). Analyses were conducted on untreated urine samples and on samples that underwent specific pretreatments: lyophilization and treatment with sulfuric acid. Partial Least Squares Linear Discriminant Analysis (PLS-LDA) and Subwindow Permutation Analysis (SPA) models were established to distinguish patterns between COVID-19 patients and healthy controls. The results identify compounds that are present in different proportions in urine samples from COVID-19 patients compared to those from healthy individuals. Analysis of urine samples using HS-SPME-GC-MS reveals differences between COVID-19 patients and healthy individuals. These differences are more pronounced when methods that enhance VOC formation are used. However, these pretreatments can cause reactions between sample components, creating additional products or removing compounds, so biomarker selection could be altered. Therefore, using a combination of methods may be more informative when evaluating metabolic alterations caused by viral infections and would allow for a better selection of biomarkers.PMID:39590874 | DOI:10.3390/metabo14110638

Metabolites. 2024 Nov 18;14(11):637. doi: 10.3390/metabo14110637.ABSTRACTBACKGROUND/OBJECTIVES: Dynamic changes in components from colostrum to mature milk occur in any mammal. However, the time it takes to reach the mature milk stage differs between taxa and species, as do the final concentrations of all the components. The white rhinoceros belongs to the family Perissodactyla, of which the milk and milk metabolome of the domesticated Equidae have been studied to some detail. Metabolomic information on the colostrum and milk of the Rhinocerotidae is lacking.METHODS: Colostrum and milk were obtained from seven white rhinoceroses. Of note is that it was their first parturition and all followed the same diet, two factors known to affect colostrum composition and its changes during early lactation in domesticated mammals. Milk serum was prepared by the ultrafiltration of the milk samples. Untargeted 1N NMR spectra were processed with Topspin 3.2, calibration was carried out according to the alanine signal and the identification of signals was carried out with Chenomx and assignments in the literature. Statistical analysis of the data was carried out using MetaboAnalyst 6.0.RESULTS: The changes in the metabolites were followed during the first 7 days of lactation as well as on day 20. The amounts of amino acids and their derivatives, organic acids and lipid metabolites decreased over lactation, while carbohydrates and their derivatives increased. The colostrum phase ended on day 2, while the transition to mature milk seemed to be complete by day 7. From day 3 to 7, galactose metabolism and tyrosine metabolism were uprated. Of interest is the presence of the oligosaccharide 3'-sialyllactose on days 3 and 4 of lactation.CONCLUSIONS: Mainly the content of carbohydrates increased over lactation, specifically lactose. The 3'-sialyllactose content peaked on days 3 and 4 of lactation. The colostrum phase ended on day 2. The mature milk stage was reached by day 7. The galactose metabolism and tyrosine metabolism were uprated after day 3 of lactation.PMID:39590873 | DOI:10.3390/metabo14110637

Metabolites. 2024 Nov 15;14(11):628. doi: 10.3390/metabo14110628.ABSTRACTBackground/Objectives: Sorghum bicolor is a source of many bioactive components, such as polyphenols. Those components are present mainly in its bran, often removed in industrial processes through decortication. In that sense, this work aimed to analyze the polyphenol content, especially free flavonoids, from the bran of a newly developed variety compared to other commercially available varieties. Methods: The samples were white sorghum TDN® Sorgho, red sorghum Mini Sorgho, and the newly developed red sorghum RILN-156. First, decortication was conducted to obtain the bran samples, which were triturated and then sieved. The use of colorimetric methods allowed the general quantification of the polyphenolic components. First, the polyphenol content was extracted using 70% methanol. Then, the samples' total phenolic content, total flavonoid content, total tannin content, total anthocyanin content, and antioxidant potential were determined. To analyze the different components and identify the free flavonoids, an untargeted metabolomics analysis (with liquid chromatography coupled with mass spectrometer (LC/MS) and capillary electrophoresis coupled with a mass spectrometer (CE/MS)) was performed. Results: The results have shown that apart from anthocyanin and tannin, the newly developed variety, RILN-156, presented the highest concentration of polyphenolic content, including a higher antioxidant capacity. The exploratory analysis identified 19 flavonoids within the samples, with galangin and daidzein being the most abundant ones. Conclusions: These results show a promising finding for using this newly developed sorghum variety (RILN-156) industrially and further investigating its health benefits. They also elucidate the differences between colored sorghum within themselves and with white sorghum varieties.PMID:39590864 | DOI:10.3390/metabo14110628

Metabolites. 2024 Nov 14;14(11):624. doi: 10.3390/metabo14110624.ABSTRACTOBJECTIVES: This study investigated metabolic changes associated with bovine leukemia virus (BLV) infection in dairy cows, focusing on pre-parturition alterations.METHODS: Metabolite identification in serum and urine samples was performed using a targeted metabolomics method, employing the TMIC Prime kit in combination with flow injection analysis and liquid chromatography-tandem mass spectrometry.RESULTS: Of 145 cows examined, 42 (28.9%) were BLV-seropositive. Around 38% of infected cows showed high somatic cell counts indicative of subclinical mastitis, with 15 experiencing additional health issues such as ketosis, milk fever, and lameness. Despite these conditions, no significant differences in milk yield or composition were observed between the infected and control groups. Metabolomic analysis conducted at -8 and -4 weeks prepartum revealed significant metabolic differences between BLV-infected and healthy cows. At -8 weeks, 30 serum metabolites were altered, including sphingomyelins, lysophosphatidylcholines, amino acids, and acylcarnitines, suggesting disruptions in membrane integrity, energy metabolism, and immune function indicative of early neoplastic transformations. By -4 weeks, the number of altered metabolites decreased to 17, continuing to reflect metabolic disruptions in cows with leukemia. Multivariate analysis highlighted distinct metabolic profiles between infected and control cows, identifying key discriminating metabolites such as choline, aspartic acid, phenylalanine, and arginine. Urine metabolomics revealed significant prepartum shifts in metabolites related to glucose, asymmetric dimethylarginine, and pyruvic acid, among others.CONCLUSIONS: The research confirmed metabolomics' efficacy in defining a BLV infection metabolic profile, elucidating leukosis-associated metabolic disruptions. This approach facilitates the identification of BLV-infected cows and enhances understanding of infection pathophysiology, providing a foundation for advanced management and intervention strategies in dairy herds. The study underscores the profound impact of leukosis on metabolic processes and highlights urine metabolomics' utility in non-invasively detecting BLV infection, offering the potential for improved herd health management.PMID:39590860 | DOI:10.3390/metabo14110624

Metabolites. 2024 Nov 14;14(11):623. doi: 10.3390/metabo14110623.ABSTRACTBackground: Plants constantly produce primary and secondary metabolites, and a significant fraction of these are volatile organic compounds (VOCs). Factors including the life stage of the plant, temperature, environment, and stress influence the abundance and types of VOCs emitted. The analysis of VOCs released by plants during different stages or with different conditions provides insight into plant metabolism and stress responses. Collecting the VOC profiles of plants in vivo makes it possible to obtain a representative sample of the entire plant volatilome under controlled conditions with minimal invasiveness. In addition, in vivo sampling can also be used to compare the impacts of different environmental conditions or stressors on plants, i.e., the presence/absence of a pest or amount of nitrogen in soil. Methods: In this study, an in vivo plant sampling technique is introduced and validated using active sampling and thermal desorption (TD) tubes with comprehensive two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer (TD-GC×GC-TOFMS). The purpose of this work is to highlight a novel technique to analyze headspace secondary plant metabolites with a minimal invasiveness. Results: It was concluded that in vivo active sampling onto TD tubes provides a wider global coverage of compounds and larger peak areas when compared to extraction by solid-phase microextraction (SPME). Additionally, the Horwitz ratio of active sampling onto TD tubes was 0.893, demonstrating this technique to be a reliable and reproducible method. Lastly, a variety of plants were sampled to assess the versatility of this technique across various plant species with different sizes and volatile profiles. Hundreds of compounds were measured with this analysis, including terpenes, aldehydes, ketones, terpenoids, and alcohols. Conclusions: This novel in vivo active sampling method provides an additional technique for extracting and analyzing volatile secondary plant metabolites.PMID:39590859 | DOI:10.3390/metabo14110623

Metabolites. 2024 Nov 14;14(11):622. doi: 10.3390/metabo14110622.ABSTRACTBackground/Objectives: Targeted metabolomics is often criticized for the limited metabolite coverage that it offers. Indeed, most targeted assays developed or used by researchers measure fewer than 200 metabolites. In an effort to both expand the coverage and improve the accuracy of metabolite quantification in targeted metabolomics, we decided to develop a comprehensive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay that could quantitatively measure more than 700 metabolites in serum or plasma. Methods: The developed assay makes use of chemical derivatization followed by reverse phase LC-MS/MS and/or direct flow injection MS (DFI-MS) in both positive and negative ionization modes to separate metabolites. Multiple reaction monitoring (MRM), in combination with isotopic standards and multi-point calibration curves, is used to detect and absolutely quantify the targeted metabolites. The assay has been adapted to a 96-well plate format to enable automated, high-throughput sample analysis. Results: The assay (called MEGA) is able to detect and quantify 721 metabolites in serum/plasma, covering 20 metabolite classes and many commonly used clinical biomarkers. The limits of detection were determined to range from 1.4 nM to 10 mM, recovery rates were from 80% to 120%, and quantitative precision was within 20%. LC-MS/MS metabolite concentrations of the NIST® SRM®1950 plasma standard were found to be within 15% of NMR quantified levels. The MEGA assay was further validated in a large dietary intervention study. Conclusions: The MEGA assay should make comprehensive quantitative metabolomics much more affordable, accessible, automatable, and applicable to large-scale clinical studies.PMID:39590858 | DOI:10.3390/metabo14110622

Metabolites. 2024 Nov 14;14(11):621. doi: 10.3390/metabo14110621.ABSTRACTChronobiology is the field of study focused on understanding the temporal patterns of biological functions, specifically examining the regular cycles or oscillations in these processes [...].PMID:39590857 | DOI:10.3390/metabo14110621

Metabolites. 2024 Nov 12;14(11):619. doi: 10.3390/metabo14110619.ABSTRACTBackground: Strains XG04 and XGT2 of Lentinus edodes (Berk.) Singer demonstrate a high degree of genomic similarity, with XGT2 representing a systematic selection of XG04 and exhibiting enhanced phenotypic traits. Methods: An investigation into the differences between these strains was conducted using untargeted metabolomics to identify potential causal factors. Five exogenous inducers were assessed for their relationship with the observed phenotypes, and their impacts on fruiting body characteristics were analyzed. Results: Notably, the exogenous inducer rolipram, at a concentration of 0.4%, was found to increase cAMP expression levels in L. edodes primordia, which subsequently affected gill development, leading to the formation of gill-free fruiting bodies. Morphological differences between the two strains were evident; XG04 exhibited a spherical morphology with absent gills, rendering it commercially unviable, whereas XGT2 displayed a thicker cap and a more robust stipe, maintaining its characteristic umbrella shape. Conclusions: As the concentration of rolipram increased, both cap retraction and gill reduction in XGT2 occurred in a dose-dependent manner. The endogenous cAMP levels in the fruiting bodies were measured before and after rolipram treatment, revealing that the cap retraction and gill reduction in XGT2 progressed in a dose-dependent manner alongside increasing cAMP expression levels. Furthermore, a positive correlation was observed between cAMP levels and rolipram concentration. This study provides a foundation for improving the quality and productivity of mushroom cultivation by manipulating fruiting body characteristics through external stimuli.PMID:39590855 | DOI:10.3390/metabo14110619

Metabolites. 2024 Nov 12;14(11):617. doi: 10.3390/metabo14110617.ABSTRACTBACKGROUND: In 2019, SARS-CoV-2, the novel coronavirus, entered the world scene, presenting a global health crisis with a broad spectrum of clinical manifestations. Recognizing the significance of metabolomics as the omics closest to symptomatology, it has become a useful tool for predicting clinical outcomes. Several metabolomic studies have indicated variations in the metabolome corresponding to different disease severities, highlighting the potential of metabolomics to unravel crucial insights into the pathophysiology of SARS-CoV-2 infection.METHODS: The PRISMA guidelines were followed for this scoping review. Three major scientific databases were searched: PubMed, the Directory of Open Access Journals (DOAJ), and BioMed Central, from 2020 to 2024. Initially, 2938 articles were identified and vetted with specific inclusion and exclusion criteria. Of these, 42 articles were retrieved for analysis and summary.RESULTS: Metabolites were identified that were repeatedly noted to change with COVID-19 and its severity. Phenylalanine, glucose, and glutamic acid increased with severity, while tryptophan, proline, and glutamine decreased, highlighting their association with COVID-19 severity. Additionally, pathway analysis revealed that phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis were the most significantly impacted pathways in COVID-19 severity.CONCLUSIONS: COVID-19 severity is intricately linked to significant metabolic alterations that span amino acid metabolism, energy production, immune response modulation, and redox balance.PMID:39590853 | DOI:10.3390/metabo14110617

Metabolites. 2024 Nov 12;14(11):616. doi: 10.3390/metabo14110616.ABSTRACTBackground/Objectives: To investigate the crisping mechanism of broad bean-based crisping diets on Nile Tilapia. Methods: Four crisping diets were designed to feed 360 fish for 90 days, and multiomics analyses were employed. Results: Our results indicated that the designed crisping diets for Nile tilapia can effectively make tilapia muscle crispy. The ingestion of broad bean-based diets induced metabolic reprogramming dominated by glycolytic metabolism inhibition in fish, and metabolic reprogramming is the initiator of muscle structural remodeling. Among these, glucose is the main DAMP to be recognized by cellular PRRs, activating further immune response and oxidative stress and finally resulting in muscle change. Conclusions: Based on our results of multiomics, pck2, and ldh played main roles in crisping molecular mechanisms in driving the initial metabolic reprogram. Moreover, the addition of the crisping package further activated the ErbB signaling pathway and downstream MAPK signaling pathway to strengthen immune response, promoting muscle fiber development and growth. Our study delved into the effects of crisping formula diet on the liver of Nile tilapia at the molecular level, providing theoretical guidance for the nutritional regulation of crispy Nile tilapia.PMID:39590852 | DOI:10.3390/metabo14110616

Metabolites. 2024 Nov 11;14(11):614. doi: 10.3390/metabo14110614.ABSTRACTBackground: Diabetes is a devastating disease that causes millions of deaths. Fermented rice bran (FRB), made by fermenting rice bran with Aspergillus kawachii and a mixture of lactic acid bacteria, was hypothesized to b able to improve diabetes-related symptoms. This study aimed to investigate the effects of FRB supplementation in mitigating type 2 diabetes symptoms and identifying FRB bioactive compounds. Methods: In this study, KK-Ay mice (4 w.o. male) were used as a model for type 2 diabetes. Mice were divided into three different groups. The first group received a control diet, the second received a 12.5% non-fermented rice bran (RB) supplemented diet, and the last group was fed a 12.5% FRB-supplemented diet. Supplementation was done for 4 weeks. Results: FRB supplementation lowered the blood glucose level, OGTT, HOMA-IR, total cholesterol, liver RAGE protein, and glucokinase in KK-Ay mice. Metabolome analysis of RB and FRB showed that fermentation increased bioactive compounds in rice bran, such as GABA, L-theanine, and carnitine. It also increased the levels of various free amino acids while converting some amino acids such as arginine, tyrosine, and tryptophan into other metabolites. Conclusions: This research showed the potency of FRB supplementation as a preventive agent against type 2 diabetes.PMID:39590850 | DOI:10.3390/metabo14110614

Metabolites. 2024 Nov 11;14(11):612. doi: 10.3390/metabo14110612.ABSTRACTCONTEXT: Schinus terebinthifolia Raddi is used in Brazilian folk medicine due to the wound healing and antiseptic properties of its bark, and its fruit are used as a condiment. However, the aerial parts of this plant have been studied and present some bioactive compounds as well.OBJECTIVES: The aim of this study was to investigate the variation in volatile and non-volatile composition of S. terebinthifolia leaves using untargeted metabolomics.MATERIAL AND METHODS: The leaves of four trees were collected over one year; ethanolic extracts were analyzed by UHPLC-MS and fresh leaves were analyzed by GC-MS using HS-SPME. The data were processed using online software.RESULTS: The results suggest seasonality interfered little with the chemical composition of leaves. On the other hand, the sex of the plant clearly determined the chemical composition of both volatile and non-volatile compounds.DISCUSSION AND CONCLUSIONS: Chemical variability between plants with male and female flowers is fundamental information for the standardized use of its leaves. Compounds with important biological activities were putatively identified, confirming the potential use of S. terebinthifolia leaves as a source of bioactive compounds, reducing waste and increasing economic gains for local farmers throughout the year.PMID:39590848 | DOI:10.3390/metabo14110612

Metabolites. 2024 Nov 10;14(11):609. doi: 10.3390/metabo14110609.ABSTRACTBackground/Objectives: Metabolic profiling of tissue samples via liquid-state nuclear magnetic resonance (NMR) requires the extraction of polar metabolites in a suitable deuterated solvent. Such methods often prioritise metabolite recovery over protein removal due to the relatively low sensitivity of NMR metabolomics and the routine use of methods able to supress residual protein signals. However, residual protein may impact metabolite integrity and the metabolite stability after NMR sample preparation is often overlooked. This study aimed to investigate the effect of residual protein contamination in rodent brain extracts and identify a reproducible extraction method that optimises metabolite recovery while ensuring sample stability. Methods: The performance of acetonitrile/water (50-100% MeCN), methanol/water (50-100% MeOH), and methanol/water/chloroform (MeOH/H2O/CHCl3) were assessed for extraction efficiency, reproducibility, residual protein contamination, and metabolite stability up to eight hours post NMR sample preparation. Results: Aspartate and glutamate deuteration were observed in 50% MeCN, 50% MeOH, and 67% MeOH extractions along with the conversion of N-acetyl aspartate to aspartate and acetate in 50% MeCN and 50% MeOH extractions. Both observations correlated with residual protein contamination and, thus, are a result of inadequate protein precipitation, as confirmed by ultrafiltration. MeOH/H2O/CHCl3 extraction preserved the stability of these metabolites while maintaining good extraction efficiency and reproducibility. Conclusions: Thus, we recommend MeOH/H2O/CHCl3 extraction for untargeted brain NMR metabolic profiling due to its effective protein precipitation and reliable performance. Nonetheless, the performance of detecting metabolites prone to oxidation such as ascorbate and glutathione is not improved by this method.PMID:39590845 | DOI:10.3390/metabo14110609