PubMed

Int J Mol Sci. 2023 Nov 13;24(22):16242. doi: 10.3390/ijms242216242.ABSTRACTThe vesicular transport system is important for substance transport in plants. In recent years, the regulatory relationship between the vesicular transport system and plant disease resistance has received widespread attention; however, the underlying mechanism remains unclear. MdSYP121 is a key protein in the vesicular transport system. The overexpression of MdSYP121 decreased the B. dothidea resistance of apple, while silencing MdSYP121 resulted in the opposite phenotype. A metabolome and transcriptome dataset analysis showed that MdSYP121 regulated apple disease resistance by significantly affecting sugar metabolism. HPLC results showed that the levels of many soluble sugars were significantly higher in the MdSYP121-OE calli. Furthermore, the expression levels of genes related to sugar transport were significantly higher in the MdSYP121-OE calli after B. dothidea inoculation. In addition, the relationships between the MdSYP121 expression level, the soluble sugar content, and apple resistance to B. dothidea were verified in an F1 population derived from a cross between 'Golden Delicious' and 'Fuji Nagafu No. 2'. In conclusion, these results suggested that MdSYP121 negatively regulated apple resistance to B. dothidea by influencing the soluble sugar content. These technologies and methods allow us to investigate the molecular mechanism of the vesicular transport system regulating apple resistance to B. dothidea.PMID:38003432 | DOI:10.3390/ijms242216242

Int J Mol Sci. 2023 Nov 12;24(22):16222. doi: 10.3390/ijms242216222.ABSTRACTOxygen deficiency is an environmental challenge which affects plant growth, the development and distribution in land and aquatic ecosystems, as well as crop yield losses worldwide. The capacity to exist in the conditions of deficiency or the complete lack of oxygen depends on a number of anatomic, developmental and molecular adaptations. The lack of molecular oxygen leads to an inhibition of aerobic respiration, which causes energy starvation and the acceleration of glycolysis passing into fermentations. We focus on systemic metabolic alterations revealed with the different approaches of metabolomics. Oxygen deprivation stimulates the accumulation of glucose, pyruvate and lactate, indicating the acceleration of the sugar metabolism, glycolysis and lactic fermentation, respectively. Among the Krebs-cycle metabolites, only the succinate level increases. Amino acids related to glycolysis, including the phosphoglycerate family (Ser and Gly), shikimate family (Phe, Tyr and Trp) and pyruvate family (Ala, Leu and Val), are greatly elevated. Members of the Asp family (Asn, Lys, Met, Thr and Ile), as well as the Glu family (Glu, Pro, Arg and GABA), accumulate as well. These metabolites are important members of the metabolic signature of oxygen deficiency in plants, linking glycolysis with an altered Krebs cycle and allowing alternative pathways of NAD(P)H reoxidation to avoid the excessive accumulation of toxic fermentation products (lactate, acetaldehyde, ethanol). Reoxygenation induces the downregulation of the levels of major anaerobically induced metabolites, including lactate, succinate and amino acids, especially members of the pyruvate family (Ala, Leu and Val), Tyr and Glu family (GABA and Glu) and Asp family (Asn, Met, Thr and Ile). The metabolic profiles during native and environmental hypoxia are rather similar, consisting in the accumulation of fermentation products, succinate, fumarate and amino acids, particularly Ala, Gly and GABA. The most intriguing fact is that metabolic alterations during oxidative stress are very much similar, with plant response to oxygen deprivation but not to reoxygenation.PMID:38003412 | DOI:10.3390/ijms242216222

Int J Mol Sci. 2023 Nov 10;24(22):16173. doi: 10.3390/ijms242216173.ABSTRACTMore than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some cardiovascular and metabolic diseases. Despite this evidence, it is not possible to prevent the onset of stroke. The use of innovative methods for metabolite analysis has been explored in the last years to detect new stroke biomarkers. We use NMR spectroscopy to identify small molecule variations between different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCF) to calculate the probability of suffering a stroke. Using this parameter, three study groups were formed: low stroke risk (LSR, control), moderate stroke risk (MSR) and high stroke risk (HSR). Univariate statistical analysis showed seven metabolites with increasing plasma levels across different stroke risk groups, from LSR to HSR: isoleucine, asparagine, formate, creatinine, dimethylsulfone and two unidentified molecules, which we termed "unknown-1" and "unknown-3". These metabolic markers can be used for early detection and to detect increasing stages of stroke risk more efficiently.PMID:38003362 | DOI:10.3390/ijms242216173

Int J Mol Sci. 2023 Nov 9;24(22):16145. doi: 10.3390/ijms242216145.ABSTRACTBrucella, a zoonotic facultative intracellular pathogenic bacterium, poses a significant threat both to human health and to the development of the livestock industry. Alanine racemase (Alr), the enzyme responsible for alanine racemization, plays a pivotal role in regulating virulence in this bacterium. Moreover, Brucella mutants with alr gene deletions (Δalr) exhibit potential as vaccine candidates. However, the mechanisms that underlie the detrimental effects of alr knockouts on Brucella pathogenicity remain elusive. Here, initially, we conducted a bioinformatics analysis of Alr, which demonstrated a high degree of conservation of the protein within Brucella spp. Subsequent metabolomics studies unveiled alterations in amino acid pathways following deletion of the alr gene. Furthermore, alr deletion in Brucella suis S2 induced decreased resistance to stress, antibiotics, and other factors. Transmission electron microscopy of simulated macrophage intracellular infection revealed damage to the cell wall in the Δalr strain, whereas propidium iodide staining and alkaline phosphatase and lactate dehydrogenase assays demonstrated alterations in cell membrane permeability. Changes in cell wall properties were revealed by measurements of cell surface hydrophobicity and zeta potential. Finally, the diminished adhesion capacity of the Δalr strain was shown by immunofluorescence and bacterial enumeration assays. In summary, our findings indicate that the alr gene that regulates amino acid metabolism in Brucella influences the properties of the cell wall, which modulates bacterial adherence capability. This study is the first demonstration that Alr impacts virulence by modulating bacterial metabolism, thereby providing novel insights into the pathogenic mechanisms of Brucella spp.PMID:38003334 | DOI:10.3390/ijms242216145

Int J Mol Sci. 2023 Nov 8;24(22):16086. doi: 10.3390/ijms242216086.ABSTRACTLiver fibrosis (LF) is a late-stage process observed in various chronic liver diseases with bile and retinol metabolism closely associated with it. Adipose-derived mesenchymal stem cells (ADMSCs) have shown significant therapeutic potential in treating LF. In this study, the transplantation of ADMSCs was applied to a CCl4-induced LF model to investigate its molecular mechanism through a multi-omics joint analysis. The findings reveal that ADMSCs effectively reduced levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), gamma-glutamyltransferase (GGT), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and α-Smooth muscle actin (α-SMA), thereby mitigating liver lesions, preventing liver parenchymal necrosis, and improving liver collagen deposition. Furthermore, 4751 differentially expressed genes (DEGs) and 270 differentially expressed metabolites (DMs) were detected via transcriptome and metabolomics analysis. Conjoint analysis showed that ADMSCs up-regulated the expression of Cyp7a1, Baat, Cyp27a1, Adh7, Slco1a4, Aldh1a1, and Adh7 genes to promote primary bile acids (TCDCA: Taurochenodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; GCA: glycocholic acid, TCA: Taurocholic acid) synthesis, secretion and retinol metabolism. This suggests that ADMSCs play a therapeutic role in maintaining bile acid (BA) homeostasis and correcting disturbances in retinol metabolism.PMID:38003277 | DOI:10.3390/ijms242216086

Int J Mol Sci. 2023 Nov 7;24(22):16057. doi: 10.3390/ijms242216057.ABSTRACTEndometrial cancer (EC) is the most frequent gynecologic cancer in postmenopausal women. Pathogenetic mechanisms that are related to the onset and progression of the disease are largely still unknown. A multi-omics strategy can help identify altered pathways that could be targeted for improving therapeutical approaches. In this study we used a multi-omics approach on four EC cell lines for the identification of common dysregulated pathways in type 1 and 2 ECs. We analyzed proteomics and metabolomics of AN3CA, HEC1A, KLE and ISHIKAWA cell lines by mass spectrometry. The bioinformatic analysis identified 22 common pathways that are in common with both types of EC. In addition, we identified five proteins and 13 metabolites common to both types of EC. Western blotting analysis on 10 patients with type 1 and type 2 EC and 10 endometria samples confirmed the altered abundance of NPEPPS. Our multi-omics analysis identified dysregulated proteins and metabolites involved in EC tumor growth. Further studies are needed to understand the role of these molecules in EC. Our data can shed light on common pathways to better understand the mechanisms involved in the development and growth of EC, especially for the development of new therapies.PMID:38003247 | DOI:10.3390/ijms242216057

Int J Mol Sci. 2023 Nov 7;24(22):16045. doi: 10.3390/ijms242216045.ABSTRACTThe phytohormone gibberellic acids (GAs) play a crucial role in the processes of growth, organ development, and secondary metabolism. However, the mechanism of exogenous GA3 regulating the growth and flavonoid synthesis in Phellodendron chinense Schneid (P. chinense Schneid) seedlings remains unclear. In this study, the physicochemical properties, gene expression level, and secondary metabolite of P. chinense Schneid seedlings under GA3 treatment were investigated. The results showed that GA3 significantly improved the plant height, ground diameter, fresh weight, chlorophyll content, soluble substance content, superoxide dismutase, and peroxidase activities. This was accompanied by elevated relative expression levels of Pc(S)-GA2ox, Pc(S)-DELLA, Pc(S)-SAUR50, Pc(S)-PsaD, Pc(S)-Psb 27, Pc(S)-PGK, Pc(S)-CER3, and Pc(S)-FBA unigenes. Conversely, a notable reduction was observed in the carotenoid content, catalase activity and the relative expression abundances of Pc(S)-KAO, Pc(S)-GID1/2, and Pc(S)-GH 3.6 unigenes in leaves of P. chinense Schneid seedlings (p < 0.05). Furthermore, GA3 evidently decreased the contents of pinocembrin, pinobanksin, isosakuranetin, naringin, naringenin, (-)-epicatechin, tricetin, luteolin, and vitexin belonged to flavonoid in stem bark of P. chinense Schneid seedlings (p < 0.05). These results indicated that exogenous GA3 promoted growth through improving chlorophyll content and gene expression in photosynthesis and phytohormone signal pathway and inhibited flavonoid synthesis in P. chinense Schneid seedlings.PMID:38003235 | DOI:10.3390/ijms242216045

Animals (Basel). 2023 Nov 18;13(22):3569. doi: 10.3390/ani13223569.ABSTRACTThe Tibetan antelope is an endangered species suffering from poaching and habitat fragmentation. The intestinal flora and metabolites play a crucial role in the physiological homeostasis of hosts, which are influenced by various environmental factors like seasonal variation. In this particular research, our main goal was to explore the alterations in the metabolism and gut microbiota of Tibetan antelopes between the cold season (XB) and warm season (DA), using untargeted metabolomics and 16S rRNA gene-sequencing analyses. The findings indicated that Tibetan antelopes had a higher alpha-diversity of intestinal microbes during the cold season than during the warm season. Principal co-ordinate analysis revealed notable seasonal discrepancies in the function and structure of intestinal microbes in Tibetan antelopes. The relative abundance of Firmicutes was significantly increased during the cold season compared to during the warm season. Furthermore, the Tibetan antelope's primary metabolic functions of the intestinal micro-organisms were significantly higher during the cold season. The untargeted metabolomics analysis results showed a total of 532 metabolites that were significantly different between the cold season and warm season groups. These metabolites were found to be enriched in a total of 62 metabolic pathways. Among the most significant pathways of enrichment were the purine metabolism and pyrimidine metabolism. The levels of related metabolites in those pathways were remarkably higher in the warm season compared to the cold season. The comprehensive analysis of 16S rRNA and the metabolome reveals there is a significant correlation between differential microbiota and differential metabolites. Therefore, the gut microbiota changes caused by seasonal changes influenced the metabolites as well. This research reveals the function of seasonal changes in the intestinal flora and metabolites in the adaptation of Tibetan antelopes to environmental fluctuations and supplies a theoretical basis for instructing the protection management of Tibetan antelopes.PMID:38003186 | DOI:10.3390/ani13223569

Animals (Basel). 2023 Nov 9;13(22):3461. doi: 10.3390/ani13223461.ABSTRACTMentha haplocalyx Briq (MHB) and its components have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of MHB addition on growth performance, rumen and fecal microbiota, rumen fluid, serum and urine metabolism, and transcriptomics of rumen epithelial cells in meat sheep. Twelve Hu sheep were selected for the experiment and fed with basic diet (CON) and a basal diet supplemented with 80 g/kg DM of Mentha haplocalyx Briq (MHB). The experimental period was 10 weeks with the first 2 weeks as the pre-trial period. The results showed that compared with the CON group, the average daily weight gain of meat sheep in the MHB group increased by 20.1%; the total volatile fatty acid (VFA) concentration significantly increased (p < 0.05); The thickness of the cecal mucosal layer was significantly reduced (p < 0.01), while the thickness of the colonic mucosal layer was significantly increased (p < 0.05), the length of ileal villi significantly increased (p < 0.01), the thickness of colonic mucosal layer and rectal mucosal muscle layer significantly increased (p < 0.05), and the thickness of cecal mucosal layer significantly decreased (p < 0.05); The serum antioxidant capacity has increased. At the genus level, the addition of MHB changed the composition of rumen and fecal microbiota, increased the relative abundance of Paraprevotella, Alloprevotella, Marinilabilia, Saccharibacteria_genera_incertae_sedis, Subdivision5_genera_incertae_sedis and Ornatilinea in rumen microbiota, and decreased the relative abundance of Blautia (p < 0.05). The relative abundance of Prevotella, Clostridium XlVb and Parasutterella increased in fecal microbiota, while the relative abundance of Blautia and Coprococcus decreased (p < 0.05). There were significant differences in the concentrations of 105, 163, and 54 metabolites in the rumen, serum, and urine between the MHB group and the CON group (p < 0.05). The main metabolic pathways of the differences were pyrimidine metabolism, taurine and taurine metabolism, glyceride metabolism, and pentose phosphate pathway (p < 0.05), which had a significant impact on protein synthesis and energy metabolism. The transcriptome sequencing results showed that differentially expressed genes were mainly enriched in immune regulation, energy metabolism, and protein modification. Therefore, adding MHB improved the growth performance of lambs by altering rumen and intestinal microbiota, rumen, serum and urine metabolomics, and transcriptome.PMID:38003078 | DOI:10.3390/ani13223461

Animals (Basel). 2023 Nov 7;13(22):3437. doi: 10.3390/ani13223437.ABSTRACTFermented distillers' grains (FDG) are commonly used to enhance the health and metabolic processes of livestock and poultry by regulating the composition and activity of the intestinal microbiota. Nevertheless, there is a scarcity of research on the effects of the FDG diet on the gastrointestinal microbiota and its metabolites in cattle. This study examines the impact of FDG dietary supplements on the gastrointestinal flora and metabolic profile of Guanling cattle. Eighteen cattle were randomly assigned to three treatment groups with six replicates per group. The treatments included a basal diet (BD), a 15% concentrate replaced by FDG (15% FDG) in the basal diet, and a 30% concentrate replaced by FDG (30% FDG) in the basal diet. Each group was fed for a duration of 60 days. At the conclusion of the experimental period, three cattle were randomly chosen from each group for slaughter and the microbial community structure and metabolic mapping of their abomasal and cecal contents were analyzed, utilizing 16S rDNA sequencing and LC-MS technology, respectively. At the phylum level, there was a significant increase in Bacteroidetes in both the abomasum and cecum for the 30%FDG group (p < 0.05). Additionally, there was a significant reduction in potential pathogenic bacteria such as Spirochetes and Proteobacteria for both the 15%FDG and 30%FDG groups (p < 0.05). At the genus level, there was a significant increase (p < 0.05) in Ruminococcaceae_UCG-010, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 fiber degradation bacteria. Non-target metabolomics analysis indicated that the FDG diet significantly impacted primary bile acid biosynthesis, bile secretion, choline metabolism in cancer, and other metabolic pathways (p < 0.05). There is a noteworthy correlation between the diverse bacterial genera and metabolites found in the abomasal and cecal contents of Guanling cattle, as demonstrated by correlation analysis. In conclusion, our findings suggest that partially substituting FDG for conventional feed leads to beneficial effects on both the structure of the gastrointestinal microbial community and the metabolism of its contents in Guanling cattle. These findings offer a scientific point of reference for the further use of FDG as a cattle feed resource.PMID:38003055 | DOI:10.3390/ani13223437

Foods. 2023 Nov 15;12(22):4140. doi: 10.3390/foods12224140.ABSTRACTActive functional microbiota for producing volatile flavors is critical to Chinese baijiu fermentation. Microbial communities correlated with the volatile metabolites are generally explored using DNA-based sequencing and metabolic analysis. However, the active functional microbiota related to the volatile flavor compounds is poorly understood. In this study, an integrated metatranscriptomic and metabolomics analysis was employed to unravel the metabolite profiles comprehensively and the contributing active functional microbiota for flavor generation during Niulanshan baijiu fermentation. A total of 395, 83, and 181 compounds were annotated using untargeted metabolomics, including LC-MS, GC-MS, and HS-SPME-GC-MS, respectively. Significant variances were displayed in the composition of compounds among different time-point samples according to the heatmaps and orthogonal partial least-square discriminant analysis. The correlation between the active microbiota and the volatile flavors was analyzed based on the bidirectional orthogonal partial least squares discriminant analysis (O2PLS-DA) model. Six bacterial genera, including Streptococcus, Lactobacillus, Pediococcus, Campylobacter, Yersinia, and Weissella, and five fungal genera of Talaromyces, Aspergillus, Mixia, Rhizophagus, and Gloeophyllum were identified as the active functional microbiota for producing the volatile flavors. In summary, this study revealed the active functional microbial basis of unique flavor formation and provided novel insights into the optimization of Niulanshan baijiu fermentation.PMID:38002197 | DOI:10.3390/foods12224140

Foods. 2023 Nov 13;12(22):4114. doi: 10.3390/foods12224114.ABSTRACTIn this paper, a combination of non-targeted metabolomics and multi-element analysis was used to investigate the impact of five different cultivars on the sensory quality of QTMJ tea and identify candidate markers for varietal authenticity assessment. With chemometric analysis, a total of 54 differential metabolites were screened, with the abundances significantly varied in the tea cultivars. By contrast, the QTMJ tea from the Yaoshan Xiulv (XL) monovariety presents a much better sensory quality as result of the relatively more abundant anthocyanin glycosides and the lower levels of 2'-o-methyladenosine, denudatine, kynurenic acid and L-pipecolic acid. In addition, multi-elemental analysis found 14 significantly differential elements among the cultivars (VIP > 1 and p < 0.05). The differences and correlations of metabolites and elemental signatures of QTMJ tea between five cultivars were discussed using a Pearson correlation analysis. Element characteristics can be used as the best discriminant index for different cultivars of QTMJT, with a predictive accuracy of 100%.PMID:38002172 | DOI:10.3390/foods12224114

Foods. 2023 Nov 9;12(22):4069. doi: 10.3390/foods12224069.ABSTRACTSheep and goat meats are increasingly popular worldwide due to their superior nutritional properties and distinctive flavor profiles. In recent decades, substantial progress in meat science has facilitated in-depth examinations of ovine and caprine muscle development during the antemortem phase, as well as post-mortem changes influencing meat attributes. To elucidate the intrinsic molecular mechanisms and identify potential biomarkers associated with meat quality, the methodologies employed have evolved from traditional physicochemical parameters (such as color, tenderness, water holding capacity, flavor, and pH) to some cutting-edge omics technologies, including transcriptomics, proteomics, and metabolomics approaches. This review provides a comprehensive analysis of multi-omics techniques and their applications in unraveling sheep and goat meat quality attributes. In addition, the challenges and future perspectives associated with implementing multi-omics technologies in this area of study are discussed. Multi-omics tools can contribute to deciphering the molecular mechanism responsible for the altered the meat quality of sheep and goats across transcriptomic, proteomic, and metabolomic dimensions. The application of multi-omics technologies holds great potential in exploring and identifying biomarkers for meat quality and quality control, thereby promoting the optimization of production processes in the sheep and goat meat industry.PMID:38002128 | DOI:10.3390/foods12224069

Biomedicines. 2023 Nov 1;11(11):2948. doi: 10.3390/biomedicines11112948.ABSTRACTBACKGROUND: Hypoxia and anaerobic glycolysis are cancer hallmarks and sources of the metabolite lactate. Intriguingly, lactate-induced protein lactylation is considered a novel epigenetic mechanism that predisposes cells toward a malignant state. However, the significance of comprehensive hypoxia-glycolysis-lactylation-related genes (HGLRGs) in cancer is unclear. We aimed to construct a model centered around HGLRGs for predicting survival, metabolic features, drug responsiveness, and immune response in gastric cancer.METHODS: The integration of bulk and single-cell RNA-Seq data was achieved using data obtained from the TCGA and GEO databases to analyze HGLRG expression patterns. A HGLRG risk-score model was developed based on univariate Cox regression and a LASSO-Cox regression model and subsequently validated. Additionally, the relationships between the identified HGLRG signature and multiple metabolites, drug sensitivity and various cell clusters were explored.RESULTS: Thirteen genes were identified as constituting the HGLRG signature. Using this signature, we established predictive models, including HGLRG risk scores and nomogram and Cox regression models. The stratification of patients into high- and low-risk groups based on HGLRG risk scores showed a better prognosis in the latter. The high-risk group displayed increased sensitivity to cytotoxic drugs and targeted inhibitors. The expression of the HGLRG BGN displayed a strong correlation with amino acids and lipid metabolites. Notably, a significant difference in immune infiltration, such as that of M1 macrophages and CD8 T cells, was correlated with the HGLRG signature. The abundant DUSP1 within the mesenchymal components was highlighted by single-cell transcriptomics.CONCLUSION: The innovative HGLRG signature demonstrates efficacy in predicting survival and providing a practical clinical model for gastric cancer. The HGLRG signature reflects the internal metabolism, drug responsiveness, and immune microenvironment components of gastric cancer and is expected to boost patients' response to targeted therapy and immunotherapy.PMID:38001949 | DOI:10.3390/biomedicines11112948

Antioxidants (Basel). 2023 Nov 16;12(11):2009. doi: 10.3390/antiox12112009.ABSTRACTCOVID-19, caused by the SARS-CoV-2 coronavirus, emerged as a global pandemic in late 2019, resulting in significant global public health challenges. The emerging evidence suggests that diminished high-density lipoprotein (HDL) cholesterol levels are associated with the severity of COVID-19, beyond inflammation and oxidative stress. Here, we used nuclear magnetic resonance spectroscopy to compare the lipoprotein and metabolic profiles of COVID-19-infected patients with non-COVID-19 pneumonia. We compared the control group and the COVID-19 group using inflammatory markers to ensure that the differences in lipoprotein levels were due to COVID-19 infection. Our analyses revealed supramolecular phospholipid composite (SPC), phenylalanine, and HDL-related parameters as key discriminators between COVID-19-positive and non-COVID-19 pneumonia patients. More specifically, the levels of HDL parameters, including apolipoprotein A-I (ApoA-I), ApoA-II, HDL cholesterol, and HDL phospholipids, were significantly different. These findings underscore the potential impact of HDL-related factors in patients with COVID-19. Significantly, among the HDL-related metrics, the cholesterol efflux capacity (CEC) displayed the strongest negative association with COVID-19 mortality. CEC is a measure of how well HDL removes cholesterol from cells, which may affect the way SARS-CoV-2 enters cells. In summary, this study validates previously established markers of COVID-19 infection and further highlights the potential significance of HDL functionality in the context of COVID-19 mortality.PMID:38001862 | DOI:10.3390/antiox12112009

Antioxidants (Basel). 2023 Nov 12;12(11):1995. doi: 10.3390/antiox12111995.ABSTRACTThe traditional processing of Dendrobium officinale (DO) is performed in five necessary processing steps: processing fresh strips, drying at 85 °C, curling, molding, and drying at 35 °C (Fengdou). The antioxidant activity of DO is increased after it is processed into Fengdou. To comprehensively analyze the changes in the functional components, a plant-wide target metabolomics approach was employed. In total, 739 differential chemical components were identified in five processing treatments, mainly highlighting differences in the levels of phenolic acids, flavonoids, lipids, and amino acids and their derivatives, and the glycosylation of aglycone resulted in the upregulation of flavonoid glycoside levels. Temperature is a key factor in DO processing during production. In addition, the enrichment of specific differential chemical components was found mainly in five different metabolic pathways: glucosinolate biosynthesis, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, and ubiquinone and other terpene quinone biosynthesis. A correlation analysis clarified that total phenols and flavonoids show a significant positive correlation with antioxidant capacity. This study provides new insights into the influence of the processing processes on DO quality, which may provide guidance for the high-quality production of DO.PMID:38001848 | DOI:10.3390/antiox12111995

Antioxidants (Basel). 2023 Nov 3;12(11):1964. doi: 10.3390/antiox12111964.ABSTRACTIndividuals with psychosocial stress often experience an exaggerated response to air pollutants. Ozone (O3) exposure has been associated with the activation of the neuroendocrine stress-response system. We hypothesized that preexistent mild chronic stress plus social isolation (CS), or social isolation (SI) alone, would exacerbate the acute effects of O3 exposure on the circulating adrenal-derived stress hormones, and the expression of the genes regulating glucocorticoid stress signaling via an altered stress adaptation in a brain-region-specific manner. Male Wistar-Kyoto rats (5 weeks old) were socially isolated, plus were subjected to either CS (noise, confinement, fear, uncomfortable living, hectic activity, and single housing), SI (single housing only, restricted handling and no enrichment) or no stress (NS; double housing, frequent handling and enrichment provided) for 8 weeks. The rats were then exposed to either air or O3 (0.8 ppm for 4 h), and the samples were collected immediately after. The indicators of sympathetic and hypothalamic-pituitary axis (HPA) activation (i.e., epinephrine, corticosterone, and lymphopenia) increased with O3 exposure, but there were no effects from CS or SI, except for the depletion of serum BDNF. CS and SI revealed small changes in brain-region-specific glucocorticoid-signaling-associated markers of gene expression in the air-exposed rats (hypothalamic Nr3c1, Nr3c2 Hsp90aa1, Hspa4 and Cnr1 inhibition in SI; hippocampal HSP90aa1 increase in SI; and inhibition of the bed nucleus of the stria terminalis (BNST) Cnr1 in CS). Gene expression across all brain regions was altered by O3, reflective of glucocorticoid signaling effects, such as Fkbp5 in NS, CS and SI. The SI effects on Fkbp5 were greatest for SI in BNST. O3 increased Cnr2 expression in the hypothalamus and olfactory bulbs of the NS and SI groups. O3, in all stress conditions, generally inhibited the expression of Nr3c1 in all brain regions, Nr3c2 in the hippocampus and hypothalamus and Bdnf in the hippocampus. SI, in general, showed slightly greater O3-induced changes when compared to NS and CS. Serum metabolomics revealed increased sphingomyelins in the air-exposed SI and O3-exposed NS, with underlying SI dampening some of the O3-induced changes. These results suggest a potential link between preexistent SI and acute O3-induced increases in the circulating adrenal-derived stress hormones and brain-region-specific gene expression changes in glucocorticoid signaling, which may partly underlie the stress dynamic in those with long-term SI.PMID:38001817 | DOI:10.3390/antiox12111964

Antioxidants (Basel). 2023 Nov 1;12(11):1953. doi: 10.3390/antiox12111953.ABSTRACTGlutathione (GSH) is a ubiquitous tripeptide that is biosynthesized in situ at high concentrations (1-5 mM) and involved in the regulation of cellular homeostasis via multiple mechanisms. The main known action of GSH is its antioxidant capacity, which aids in maintaining the redox cycle of cells. To this end, GSH peroxidases contribute to the scavenging of various forms of ROS and RNS. A generally underestimated mechanism of action of GSH is its direct nucleophilic interaction with electrophilic compounds yielding thioether GSH S-conjugates. Many compounds, including xenobiotics (such as NAPQI, simvastatin, cisplatin, and barbital) and intrinsic compounds (such as menadione, leukotrienes, prostaglandins, and dopamine), form covalent adducts with GSH leading mainly to their detoxification. In the present article, we wish to present the key role and significance of GSH in cellular redox biology. This includes an update on the formation of GSH-S conjugates or GSH adducts with emphasis given to the mechanism of reaction, the dependence on GST (GSH S-transferase), where this conjugation occurs in tissues, and its significance. The uncovering of the GSH adducts' formation enhances our knowledge of the human metabolome. GSH-hematin adducts were recently shown to have been formed spontaneously in multiples isomers at hemolysates, leading to structural destabilization of the endogenous toxin, hematin (free heme), which is derived from the released hemoglobin. Moreover, hemin (the form of oxidized heme) has been found to act through the Kelch-like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway as an epigenetic modulator of GSH metabolism. Last but not least, the implications of the genetic defects in GSH metabolism, recorded in hemolytic syndromes, cancer and other pathologies, are presented and discussed under the framework of conceptualizing that GSH S-conjugates could be regarded as signatures of the cellular metabolism in the diseased state.PMID:38001806 | DOI:10.3390/antiox12111953

Antioxidants (Basel). 2023 Oct 26;12(11):1915. doi: 10.3390/antiox12111915.ABSTRACTRapeseed seeding dates are largely delayed under the rice-rape rotation system, but how rapeseeds adapt to the delayed environment remains unclear. Here, five seeding dates (20 October, 30 October, 10 November, 20 November and 30 November, T1 to T5) were set and the dynamic differences between two late-seeding-tolerant (LST) and two late-seeding-sensitive (LSS) rapeseed cultivars were investigated in a field experiment. The growth was significantly repressed and the foldchange (LST/LSS) of yield increased from 1.50-T1 to 2.64-T5 with the delay in seeding. Both LST cultivars showed higher plant coverage than the LSS cultivars according to visible/hyperspectral imaging and the vegetation index acquired from an unmanned aerial vehicle. Fluorescence imaging, DAB and NBT staining showed that the LSS cultivars suffered more stress damage than the LST cultivars. Antioxidant enzymes (SOD, POD, CAT, APX) and osmoregulation substances (proline, soluble sugar, soluble protein) were decreased with the delay in seeding, while the LST cultivar levels were higher than those of the LSS cultivars. A comparative analysis of transcriptomes and metabolomes showed that 55 pathways involving 123 differentially expressed genes (DEGs) and 107 differentially accumulated metabolites (DAMs) participated in late seeding tolerance regulation, while 39 pathways involving 60 DEGs and 68 DAMs were related to sensitivity. Levanbiose, α-isopropylmalate, s-ribosyl-L-homocysteine, lauroyl-CoA and argino-succinate were differentially accumulated in both cultivars, while genes including isocitrate dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase and newgene_7532 were also largely regulated. This study revealed the dynamic regulation mechanisms of rapeseeds on late seeding conditions, which showed considerable potential for the genetic improvement of rapeseed.PMID:38001769 | DOI:10.3390/antiox12111915

Cancers (Basel). 2023 Nov 18;15(22):5465. doi: 10.3390/cancers15225465.ABSTRACTProstate cancer is a significant global health concern, and its prevalence is increasing worldwide. Despite extensive research efforts, the complexity of the disease remains challenging with respect to fully understanding it. Metabolomics has emerged as a powerful approach to understanding prostate cancer by assessing comprehensive metabolite profiles in biological samples. In this study, metabolic profiles of patients with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met) were characterized using an untargeted approach that included metabolomics and lipidomics via liquid chromatography and gas chromatography coupled with high-resolution mass spectrometry. Comparative analysis among these groups revealed distinct metabolic profiles, primarily associated with lipid biosynthetic pathways, such as biosynthesis of unsaturated fatty acids, fatty acid degradation and elongation, and sphingolipid and linoleic acid metabolism. PCa patients showed lower levels of amino acids, glycerolipids, glycerophospholipids, sphingolipids, and carnitines compared to BPH patients. Compared to Met patients, PCa patients had reduced metabolites in the glycerolipid, glycerophospholipid, and sphingolipid groups, along with increased amino acids and carbohydrates. These altered metabolic profiles provide insights into the underlying pathways of prostate cancer's progression, potentially aiding the development of new diagnostic, and therapeutic strategies.PMID:38001725 | DOI:10.3390/cancers15225465