PubMed

Metabolites. 2024 Apr 12;14(4):216. doi: 10.3390/metabo14040216.ABSTRACTRhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.PMID:38668344 | DOI:10.3390/metabo14040216

Metabolites. 2024 Apr 11;14(4):215. doi: 10.3390/metabo14040215.ABSTRACTMycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of bovine paratuberculosis, a chronic granulomatous enteritis leading to economic losses and posing a risk to human health due to its zoonotic potential. The pathogen cannot reliably be detected by standard methods, and immunological procedures during the infection are not well understood. Therefore, the aim of our study was to explore host-pathogen interactions in MAP-infected dairy cows and to improve diagnostic tests. Serum proteomics analysis using quantitative label-free LC-MS/MS revealed 60 differentially abundant proteins in MAP-infected dairy cows compared to healthy controls from the same infected herd and 90 differentially abundant proteins in comparison to another control group from an uninfected herd. Pathway enrichment analysis provided new insights into the immune response to MAP and susceptibility to the infection. Furthermore, we found a higher abundance of Cathepsin S (CTSS) in the serum of MAP-infected dairy cows, which is involved in multiple enriched pathways associated with the immune system. Confirmed with Western blotting, we identified CTSS as a potential biomarker for bovine paratuberculosis. This study enabled a better understanding of procedures in the host-pathogen response to MAP and improved detection of paratuberculosis-diseased cattle.PMID:38668343 | DOI:10.3390/metabo14040215

Metabolites. 2024 Apr 11;14(4):214. doi: 10.3390/metabo14040214.ABSTRACTRheumatoid arthritis (RA) is a metabolic joint disorder influenced by hormonal regulation, notably estrogen, which plays a cytoprotective role against inflammation. While estrogen's impact on RA pathogenesis has been studied, the altered metabolite expression under estrogen's influence remains unexplored. This study investigated the changes in the metabolome of synovial fibroblasts isolated from RA patients under 17β-estradiol (E2) using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach followed by multivariate and biological pathway analysis along with in vitro validation. Results identified 3624 m/z, among which eight metabolites were significant (p < 0.05). Nicotinate and nicotinamide metabolism was found to be highly correlated with the treatment of E2, with metabolites NAD+ and 1-methynicotinamide (1-MNA) upregulated by E2 induction in RA-FLS. PharmMapper analysis identified potential gene targets of 1-MNA, which were further matched with RA gene targets, and thus, STAT1, MAPK14, MMP3, and MMP9 were concluded to be the common targets. E2 treatment affected the expression of these gene targets and ameliorated the development of oxidative stress associated with RA inflammation, which can be attributed to increased concentration of 1-MNA. Thus, an LC-MS/MS-based metabolomics study revealed the prominent role of estrogen in preventing inflammatory progression in RA by altering metabolite concentration, which can support its therapeutic capacity in remitting RA.PMID:38668342 | DOI:10.3390/metabo14040214

Metabolites. 2024 Apr 5;14(4):206. doi: 10.3390/metabo14040206.ABSTRACTPhytophthora parasitica is an oomycete pathogen that infects a broad range of crops of worldwide economic interest; among them are citrus species. In general, some Citrus and the rootstocks of related genera offer considerable resistance against P. parasitica; therefore, understanding the mechanisms involved in the virulence of this pathogen is crucial. In this work, P. parasitica secondary metabolite production was studied using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-Q-TOF-MS) combined with chemometric tools, and its metabolic profile was evaluated under the influence of Citrus sunki (a highly susceptible host) and Poncirus trifoliata (a resistant genotype) extracts. The root extracts of Citrus sunki had an influence on the growth and hyphae morphology, and the root extracts of P. trifoliata had an influence on the zoospore behavior. In parallel, the spatial distribution of several metabolites was revealed in P. parasitica colonies using MALDI-MSI, and the metabolite ion of m/z 246 was identified as the protonated molecule of Arg-Ala. The MALDI-MSI showed variations in the surface metabolite profile of P. parasitica under the influence of the P. trifoliata extract. The P. parasitica metabolome analysis using UHPLC-ESI-Q-TOF-MS resulted in the detection of Arg-Gln (m/z 303.1775), as well as L-arginine (m/z 175.1191) and other unidentified metabolites. Significant variations in this metabolome were detected under the influence of the plant extracts when evaluated using UHPLC-ESI-Q-TOF-MS. Both techniques proved to be complementary, offering valuable insights at the molecular level when used to assess the impact of the plant extracts on microbial physiology in vitro. The metabolites identified in this study may play significant roles in the interaction or virulence of P. parasitica, but their functional characterization remains to be analyzed. Overall, these data confirm our initial hypotheses, demonstrating that P. parasitica has the capabilities of (i) recognizing host signals and altering its reproductive programing and (ii) distinguishing between hosts with varying responses in terms of reproduction and the production of secondary metabolites.PMID:38668334 | DOI:10.3390/metabo14040206

Metabolites. 2024 Apr 4;14(4):205. doi: 10.3390/metabo14040205.ABSTRACTMastitis is a significant infectious disease in dairy cows, resulting in milk yield loss and culling. Early detection of mastitis-prone cows is crucial for implementing effective preventive measures before disease onset. Current diagnosis of subclinical mastitis (SCM) relies on somatic cell count assessment post-calving, lacking predictive capabilities. This study aimed to identify metabolic changes in pre-SCM cows through targeted metabolomic analysis of urine samples collected 8 wks and 4 wks before calving, using mass spectrometry. A nested case-control design was employed, involving a total of 145 multiparous dairy cows, with disease occurrence monitored pre- and postpartum. Among them, 15 disease-free cows served as healthy controls (CON), while 10 cows exclusively had SCM, excluding those with additional diseases. Urinary metabolite profiling revealed multiple alterations in acylcarnitines, amino acids, and organic acids in pre-SCM cows. Metabotyping identified 27 metabolites that distinguished pre-SCM cows from healthy CON cows at both 8 and 4 wks before parturition. However, only four metabolites per week showed significant alterations (p < 0.005). Notably, a panel of four serum metabolites (asymmetric dimethylarginine, proline, leucine, and homovanillate) at 8 wks prepartum, and another panel (asymmetric dimethylarginine, methylmalonate, citrate, and spermidine) at 4 wks prepartum, demonstrated predictive ability as urinary biomarkers for SCM risk (AUC = 0.88; p = 0.02 and AUC = 0.88; p = 0.03, respectively). In conclusion, our findings indicate that metabolite testing can identify cows at risk of SCM as early as 8 and 4 wks before parturition. Validation of the two identified metabolite panels is warranted to implement these predictive biomarkers, facilitate early intervention strategies, and improve dairy cow management to mitigate the impact of SCM. Further research is needed to confirm the efficacy and applicability of these biomarkers in practical farm settings.PMID:38668333 | DOI:10.3390/metabo14040205

Metabolites. 2024 Apr 4;14(4):204. doi: 10.3390/metabo14040204.ABSTRACTCasper, a type of transparent mutant-line zebrafish, was generated to overcome the opaque trunk of an adult zebrafish for tumor modeling to realize real-time visualization of transplanted cells in vivo. However, the molecular information at the metabolic level has not received much attention. Herein, a spatially resolved metabolomics method based on an airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) system for whole-body zebrafish was used to investigate small molecules and the distribution of adult casper (Mitfaw2/w2, roya9/a9) and the differences from wild-type zebrafish. Finally, the spatial distribution information of more than 1500 endogenous ions was obtained in positive and negative detection modes, and 186 metabolites belonging to a variety of structural categories were identified or annotated. Compared with wild-type samples, 85 variables, including 37 known metabolites, were screened out. In addition, the disordered metabolic pathways caused by the genetic mutation were excavated, involving downregulation of purine metabolism and arachidonic acid metabolism, upregulation of glycerophospholipid metabolism, and biosynthesis of unsaturated fatty acids. All these results were observed in the most intuitive way through MSI. This study revealed important metabolic characteristics of and perturbation in adult casper zebrafish, and provides indispensable fundamental knowledge for tumor research based on it.PMID:38668332 | DOI:10.3390/metabo14040204

Metabolites. 2024 Apr 3;14(4):201. doi: 10.3390/metabo14040201.ABSTRACTBetaine structural analogs are compounds characterized by the presence of positive and negative charges in a single molecule and have been reported to have physiological properties, such as anti-inflammatory activities. In this study, we performed a metabolomic analysis of metabolite composition changes during the fermentation of Neopyropia yezoensis, an edible red alga, with Aspergillus oryzae for 72 h. The results indicated that three specific betaine structural analogs (betaine, stachydrine, and carnitine) exhibited significant changes in production by the end of the 72 h fermentation period. Time-course analysis suggested that betaine was generated from the precursor choline at 12-24 h during the late stage of fungal growth, while stachydrine was generated from the precursor-related compound glutamic acid at 48-72 h during the sporulation stage. However, the contribution of the precursor lysine to the increased production of carnitine during the 12-72 h period was unclear. This study provides useful information on the efficient production of betaine structural analogs by the fungal fermentation of seaweed as well as various other food materials.PMID:38668329 | DOI:10.3390/metabo14040201

Metabolites. 2024 Apr 3;14(4):200. doi: 10.3390/metabo14040200.ABSTRACTAs end-products of the intersection between the genome and environmental influences, metabolites represent a promising approach to the discovery of novel biomarkers for diseases. However, many potential biomarker candidates identified by metabolomics studies fail to progress beyond analytical validation for routine implementation in clinics. Awareness of the challenges present can facilitate the development and advancement of innovative strategies that allow improved and more efficient applications of metabolite-based markers in clinical settings. This minireview provides a comprehensive summary of the pre-analytical factors, required analytical validation studies, and kit development challenges that must be resolved before the successful translation of novel metabolite biomarkers originating from research. We discuss the necessity for strict protocols for sample collection, storage, and the regulatory requirements to be fulfilled for a bioanalytical method to be considered as analytically validated. We focus especially on the blood as a biological matrix and liquid chromatography coupled with tandem mass spectrometry as the analytical platform for biomarker validation. Furthermore, we examine the challenges of developing a commercially viable metabolomics kit for distribution. To bridge the gap between the research lab and clinical implementation and utility of relevant metabolites, the understanding of the translational challenges for a biomarker panel is crucial for more efficient development of metabolomics-based precision medicine.PMID:38668328 | DOI:10.3390/metabo14040200

Metabolites. 2024 Mar 30;14(4):196. doi: 10.3390/metabo14040196.ABSTRACTRespiratory distress syndrome (RDS) is a major morbidity of prematurity. In this case-control study, we prospectively evaluated whether untargeted metabolomic analysis (gas chromatography-mass spectrometry) of the gastric fluid could predict the need for surfactant in very preterm neonates. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants who were not treated with surfactant (controls). Perinatal-neonatal characteristics were recorded. Significant differences in gastric fluid metabolites (L-proline, L-glycine, L-threonine, acetyl-L-serine) were observed between groups, but none could solely predict surfactant administration with high accuracy. Univariate analysis revealed significant predictors of surfactant administration involving gastric fluid metabolites (L-glycine, acetyl-L-serine) and clinical parameters (gestational age, Apgar scores, intubation in the delivery room). Multivariable models were constructed for significant clinical variables as well as for the combination of clinical variables and gastric fluid metabolites. The AUC value of the first model was 0.69 (95% CI 0.57-0.81) and of the second, 0.76 (95% CI 0.64-0.86), in which acetyl-L-serine and intubation in the delivery room were found to be significant predictors of surfactant therapy. This investigation adds to the current knowledge of biomarkers in preterm neonates with RDS, but further research is required to assess the predictive value of gastric fluid metabolomics in this field.PMID:38668324 | DOI:10.3390/metabo14040196

Metabolites. 2024 Mar 30;14(4):195. doi: 10.3390/metabo14040195.ABSTRACTThe COVID-19 pandemic has brought about diverse impacts on the global population. Individuals with comorbidities were more susceptible to the severe symptoms caused by the virus. Within the crisis scenario, metabolomics represents a potential area of science capable of providing relevant information for understanding the metabolic pathways associated with the intricate interaction between the viral disease and previous comorbidities. This work aims to provide a comprehensive description of the scientific production pertaining to metabolomics within the specific context of COVID-19 and comorbidities, while highlighting promising areas for exploration by those interested in the subject. In this review, we highlighted the studies of metabolomics that indicated a variety of metabolites associated with comorbidities and COVID-19. Furthermore, we observed that the understanding of the metabolic processes involved between comorbidities and COVID-19 is limited due to the urgent need to report disease outcomes in individuals with comorbidities. The overlap of two or more comorbidities associated with the severity of COVID-19 hinders the comprehension of the significance of each condition. Most identified studies are observational, with a restricted number of patients, due to challenges in sample collection amidst the emergent situation.PMID:38668323 | DOI:10.3390/metabo14040195

Metabolites. 2024 Mar 28;14(4):191. doi: 10.3390/metabo14040191.ABSTRACTLittle is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.PMID:38668319 | DOI:10.3390/metabo14040191

Metabolites. 2024 Mar 27;14(4):189. doi: 10.3390/metabo14040189.ABSTRACTThe wide spread of microplastics has fueled growing public health concern globally. Due to their porous structure and large surface area, microplastics can serve as carriers for other environmental pollutants, including heavy metals. Although the toxic effects of microplastics or heavy metals have been reported previously, investigations into the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In the present study, the effects of polystyrene microplastics and lead(II) co-exposure on the gut microbiome, intestinal permeability, and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead(II) increased intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. In particular, Shannon and Simpson indices of gut bacteria were reduced by the co-exposure only in female mice. A total of 34 and 13 fecal metabolites were altered in the co-exposure group in female and male mice, respectively, among which only three metabolites were shared by both sexes. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.PMID:38668317 | DOI:10.3390/metabo14040189

Metabolites. 2024 Mar 25;14(4):184. doi: 10.3390/metabo14040184.ABSTRACTOrbitrap mass spectrometry in full scan mode enables the simultaneous detection of hundreds of metabolites and their isotope-labeled forms. Yet, sensitivity remains limiting for many metabolites, including low-concentration species, poor ionizers, and low-fractional-abundance isotope-labeled forms in isotope-tracing studies. Here, we explore selected ion monitoring (SIM) as a means of sensitivity enhancement. The analytes of interest are enriched in the orbitrap analyzer by using the quadrupole as a mass filter to select particular ions. In tissue extracts, SIM significantly enhances the detection of ions of low intensity, as indicated by improved signal-to-noise (S/N) ratios and measurement precision. In addition, SIM improves the accuracy of isotope-ratio measurements. SIM, however, must be deployed with care, as excessive accumulation in the orbitrap of similar m/z ions can lead, via space-charge effects, to decreased performance (signal loss, mass shift, and ion coalescence). Ion accumulation can be controlled by adjusting settings including injection time and target ion quantity. Overall, we suggest using a full scan to ensure broad metabolic coverage, in tandem with SIM, for the accurate quantitation of targeted low-intensity ions, and provide methods deploying this approach to enhance metabolome coverage.PMID:38668312 | DOI:10.3390/metabo14040184

Metabolites. 2024 Mar 25;14(4):183. doi: 10.3390/metabo14040183.ABSTRACTOsteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, metabolite extracts from healthy (n = 11) and end-stage osteoarthritic cartilage (n = 35) were analyzed using liquid chromatography-mass spectrometry metabolomic profiling. Specific metabolites and metabolic pathways, including lipid and amino acid pathways, were differentially regulated in osteoarthritis-derived and healthy cartilage. The detected alterations in amino acids and lipids highlighted key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in OA-derived cartilage compared to healthy cartilage. Moreover, the metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes, highlighting the heterogenous nature of OA metabolism and the diverse landscape within the joint in patients. The results of this study demonstrate that human cartilage has distinct metabolomic profiles in healthy and end-stage OA patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.PMID:38668311 | DOI:10.3390/metabo14040183

Metabolites. 2024 Mar 23;14(4):180. doi: 10.3390/metabo14040180.ABSTRACTFlavonoids and alkaloids are the major active ingredients in mulberry leaves that have outstanding medicinal value. Bacillus subtilis can effectively activate the plants defense response and regulate the plant secondary metabolism. In this study, we explored the effects of soil application of B. subtilis on the content of flavonoids and the most important alkaloids (1-deoxynojirimycin, DNJ) in mulberry leaves. Significant decreases in flavonoid content were observed in tender leaves and mature leaves after treatment with B. subtilis; at the same time, significant increases in DNJ content were observed in tender leaves. Based on widely targeted LC-MS/MS and high-throughput approaches, we screened out 904 differentially synthesized metabolites (DSMs) and 9715 differentially expressed genes (DEGs). KEGG analyses showed that these DSMs and DEGs were both significantly enriched in the biosynthesis of secondary metabolites, flavonoid synthesis and plant hormone signal transduction. Further correlation analysis of DEMs and DEGs showed that 40 key genes were involved in flavonoid biosynthesis, with 6 key genes involved in DNJ biosynthesis. The expression of CHS, CHI, F3H, F3'H, FLS, UGT and AOC significantly responded to B. subtilis soil application. This study broadens our understanding of the molecular mechanisms underlying the accumulation of flavonoids and alkaloids in mulberry leaves.PMID:38668308 | DOI:10.3390/metabo14040180

Metabolites. 2024 Mar 22;14(4):177. doi: 10.3390/metabo14040177.ABSTRACTIn the context of dietary transition toward plant proteins, it is necessary to ensure protein security in populations. It would thus be of interest to identify biomarkers of altered protein digestibility in populations. We examined the association between urinary metabolites and the acute intake of low- or highly digestible protein in healthy volunteers. The urine samples were collected before and 9 h after the ingestion of a meal containing either no protein, zein (low-digestible) or whey protein isolate (highly digestible). The liquid chromatography-high resolution mass spectrometry metabolomics approach was used for the profiling of the urinary metabolites. For the standardization of metabolomics data sets, osmolality-based, standard normal variates (SNV) and probabilistic quotient normalization (PQN) techniques were used. The ANOVA-based factorial method, AComDim_ICA, was used for chemometrics analysis. The osmolality adjustment has a beneficial effect and the subsequent mathematical normalization improves the chemometric analysis further. Some changes in the urinary metabolomes were observed 9 h after the meal in the three groups. However, there was no difference in the urine metabolome between groups. No biomarker of protein digestibility can be identified after the ingestion of a single meal, even when marked differences in the digestion efficiency of protein have been observed.PMID:38668305 | DOI:10.3390/metabo14040177

Metabolites. 2024 Mar 22;14(4):176. doi: 10.3390/metabo14040176.ABSTRACTThe quality of crops is closely associated with their geographical location and yield, which is reflected in the composition of their metabolites. Hence, we employed GC-MS pseudotargeted metabolomics to investigate the metabolic characteristics of high-, medium-, and low-yield Nicotiana tabacum (tobacco) leaves from the Bozhou (sweet honey flavour) and Shuicheng (light flavour) regions of Guizhou Province. A total of 124 metabolites were identified and classified into 22 chemical categories. Principal component analysis revealed that the geographical location exerted a greater influence on the metabolic profiling than the yield. Light-flavoured tobacco exhibited increased levels of sugar metabolism- and glycolysis-related intermediate products (trehalose, glucose-6-phosphate, and fructose-6-phosphate) and a few amino acids (proline and leucine), while sweet honey-flavoured tobacco exhibited increases in the tricarboxylic acid cycle (TCA cycle) and the phenylpropane metabolic pathway (p-hydroxybenzoic acid, caffeic acid, and maleic acid). Additionally, metabolite pathway enrichment analysis conducted at different yields and showed that both Shuicheng and Bozhou exhibited changes in six pathways and four of them were the same, mainly C/N metabolism. Metabolic pathway analysis revealed higher levels of intermediates related to glycolysis and sugar, amino acid, and alkaloid metabolism in the high-yield samples, while higher levels of phenylpropane in the low-yield samples. This study demonstrated that GC-MS pseudotargeted metabolomics-based metabolic profiling can be used to effectively discriminate tobacco leaves from different geographical locations and yields, thus facilitating a better understanding of the relationship between metabolites, yield, and geographical location. Consequently, metabolic profiles can serve as valuable indicators for characterizing tobacco yield and geographical location.PMID:38668304 | DOI:10.3390/metabo14040176

J Fungi (Basel). 2024 Mar 27;10(4):254. doi: 10.3390/jof10040254.ABSTRACTFlavonoids are a diverse family of natural compounds that are widely distributed in plants and play a critical role in plant growth, development, and stress adaptation. In recent years, the biosynthesis of flavonoids in plants has been well-researched, with the successive discovery of key genes driving this process. However, the regulation of flavonoid biosynthesis in fungi remains unclear. Stropharia rugosoannulata is an edible mushroom known for its high nutritional and pharmacological value, with flavonoids being one of its main active components. To investigate the flavonoid content of S. rugosoannulata, a study was conducted to extract and determine the total flavonoids at four stages: young mushroom (Ym), gill (Gi), maturation (Ma), and parachute-opening (Po). The findings revealed a gradual increase in total flavonoid concentration as the fruiting body developed, with significant variations observed between the Ym, Gi, and Ma stages. Subsequently, we used UPLC-MS/MS and transcriptome sequencing (RNA-seq) to quantify the flavonoids and identify regulatory genes of Ym, Gi, and Ma. In total, 53 flavonoid-related metabolites and 6726 differentially expressed genes (DEGs) were identified. Through KEGG pathway enrichment analysis, we identified 59 structural genes encoding flavonoid biosynthesis-related enzymes, most of which were up-regulated during the development of the fruiting body, consistent with the accumulation of flavonoids. This research led to the establishment of a comprehensive transcriptional metabolic regulatory network encompassing flavonoids, flavonoid synthases, and transcription factors (TFs). This represents the first systematic exploration of the molecular mechanism of flavonoids in the fruiting of fungi, offering a foundation for further research on flavonoid mechanisms and the breeding of high-quality S. rugosoannulata.PMID:38667925 | DOI:10.3390/jof10040254

Mar Drugs. 2024 Apr 20;22(4):187. doi: 10.3390/md22040187.ABSTRACTHigh blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells' metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids' metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract's compounds on intestinal cells.PMID:38667804 | DOI:10.3390/md22040187

Insects. 2024 Apr 21;15(4):294. doi: 10.3390/insects15040294.ABSTRACTIn this study, the changes in the conventional nutrient and mineral compositions as well as the metabolomics characteristics of the red palm weevil (RPW) Rhynchophus ferrugineus Olivier (Curculionidae: Coleoptera) larvae at early (EL), middle (ML) and old (OL) developmental stages were investigated. Results showed that the EL and ML had the highest content of protein (53.87 g/100 g dw) and fat (67.95 g/100 g), respectively, and three kinds of RPW larvae were all found to be rich in unsaturated fatty acids (52.17-53.12%), potassium (5707.12-15,865.04 mg/kg) and phosphorus (2123.87-7728.31 mg/kg). In addition, their protein contained 17 amino acids with the largest proportion of glutamate. A total of 424 metabolites mainly including lipids and lipid-like molecules, organic acids and their derivatives, organic heterocycle compounds, alkaloids and their derivatives, etc. were identified in the RPW larvae. There was a significant enrichment in the ABC transport, citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, and mTOR signaling pathways as the larvae grow according to the analysis results of the metabolic pathways of differential metabolites. The water extract of EL exhibited relatively higher hydroxyl, 2,2-diphenyl-1-pyrroline hydrochloride (DPPH) and 2,2'-azobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging ability with the EC50 values of 1.12 mg/mL, 11.23 mg/mL, and 2.52 mg/mL, respectively. These results contribute to a better understanding of the compositional changes of the RPW larvae during its life cycle and provide a theoretical grounding for its deep processing and high-value utilization.PMID:38667424 | DOI:10.3390/insects15040294