PubMed

BMC Plant Biol. 2024 Dec 27;24(1):1263. doi: 10.1186/s12870-024-05991-9.ABSTRACTBACKGROUND: Lavandula angustifolia Mill., a valuable aromatic plant, often encounters low temperature stress during its growth in Northeast China. Understanding the mechanisms behind its resistance to low temperatures is essential for enhancing this trait. Flavonoids play a vital role as stress-resistant compounds, significantly contributing to plants' responses to low-temperature stress. However, the molecular mechanism governing flavonoid biosynthesis in L. angustifolia under low-temperature stress is remains inadequately understood.RESULTS: In this study, the physiological indexes, metabolome, and transcriptome of L. angustifolia were studied under temperatures of 30 °C, 20 °C, 10 °C, and 0 °C. The activities of peroxidase (POD) and superoxide dismutase (SOD) were notably the highest at 0 ℃, demonstrating optimal scavenging of reactive oxygen species (ROS). Among the 1150 metabolites analyzed, 52 flavonoid differential expression metabolites (DEMs) significantly increased at 10 °C and 0 °C. Furthermore, 55 differential expression genes (DEGs) involved in the flavonoid biosynthesis pathway showed significant up-regulation as the temperature dropped from 30 °C to 0 °C, indicating their role in positively regulating flavonoid biosynthesis under low temperatures. The flavonoid biosynthetic pathway was established based on key DEGs, including LaPAL-5, LaPAL-11, LaC4H-2, LaHCT, LaC3'H-4, LaCHS, LaF3PH-3, LaCCoAOMT-2, LaCCoAOMT-3, and LaDFR. Conserved domains predicted in 10 key proteins were identified as being responsible for catalytic functions that promote flavonoid biosynthesis under low temperatures. The synergistic enhancement between flavonoid DEMs and antioxidant enzymes was found to significantly contribute to the cold resistance of L.angustifolia.CONCLUSIONS: The findings of this study provide a valuable reference for understanding the molecular regulation of L. angustifolia in response to low temperatures, laying a crucial foundation for future molecular breeding efforts aimed at developing cold-resistant varieties.PMID:39731022 | DOI:10.1186/s12870-024-05991-9

Mol Med. 2024 Dec 27;30(1):279. doi: 10.1186/s10020-024-01019-y.ABSTRACTMetabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes. Insulin, a vital peptide hormone, regulates glucose metabolism throughout the body. When cells become resistant to insulin's effects, it disrupts various molecular pathways, leading to IR. This condition is linked to a range of disorders, including obesity, diabetes, fatty liver disease, cardiovascular disease, and polycystic ovary syndrome. Atherogenic dyslipidemia is characterized by three key factors: high levels of small, low-dense lipoprotein (LDL) particles and triglycerides, alongside low levels of high-density lipoprotein (HDL), the "good" cholesterol. Such a combination is a major player in MetS, where IR is a driving force. Atherogenic dyslipidemia contributes significantly to the development of atherosclerosis, which can lead to cardiovascular disease. On top of that, genetic alteration and lifestyle factors such as diet and exercise influence the complexity and progression of MetS. To enhance our understanding and consciousness, it is essential to understand the fundamental pathogenesis of MetS. This review highlights current advancements in MetS research including the involvement of gut microbiome, epigenetic regulation, and metabolomic profiling for early detection of Mets. In addition, this review emphasized the epidemiology and fundamental pathogenesis of MetS, various risk factors, and their preventive measures. The goal of this effort is to deepen understanding of MetS and encourage further research to develop effective strategies for preventing and managing complex metabolic diseases.PMID:39731011 | DOI:10.1186/s10020-024-01019-y

Sci Rep. 2024 Dec 28;14(1):30978. doi: 10.1038/s41598-024-82047-w.ABSTRACTHigh-altitude pulmonary edema (HAPE) is a life-threatening altitude sickness afflicting certain individuals after rapid ascent to high altitude above 2500 m. In the setting of HAPE, an early diagnosis is critical and currently based on clinical evaluation. The aim of this study was to utilize the metabolomics to identify the altered metabolic patterns and potential biomarkers for HAPE. Serum samples from HAPE patients (n = 24) and healthy controls (n = 21) were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to profile differential metabolites and explore dysregulated metabolic pathways. The correlation analysis and receiver operating characteristic (ROC) curve analysis were further performed to screen biomarkers for HAPE. A total of 119 differential metabolites between the control and HAPE groups were identified. Top dysregulated pathways included pyrimidine metabolism, citrate cycle, sulfur metabolism, phenylalanine metabolism and purine metabolism. After correlation analysis with clinical indices, 39 differential metabolites were obtained as potential biomarkers related to HAPE. Finally, 7 biomarkers, specifically S-nitroso-N-acetylcysteine, aminocaproic acid, emodin, threo-hydroxyaspartic acid, 6-hydroxynicotinic acid, 3-acetylphenol sulfate and cis-aconitic acid, were screened out through ROC analysis, which displayed high diagnostic accuracy for HAPE. Taken together, the altered serum metabolic profile is associated with the occurrence of HAPE. Diagnostic tests based on the biomarkers from metabolomics may hold promise as a strategy for early detection of HAPE.PMID:39730680 | DOI:10.1038/s41598-024-82047-w

Sci Rep. 2024 Dec 28;14(1):31072. doi: 10.1038/s41598-024-82150-y.ABSTRACTPhysical exercise is beneficial to keep physical and mental health. The molecular mechanisms underlying exercise are still worth exploring. The healthy adult mice after six weeks of moderate-intensity exercise (experimental group) and sedentary mice (control group) were used to perform transcriptomic, proteomic, lactylation modification, and metabolomics analysis. In addition, gene sets related to hypoxia, glycolysis, and fatty acid metabolism were used to aid in the screening of hub genes. The mMCP-counter was employed to evaluate infiltration of immune cells in murine liver tissues. Transcriptomics analysis revealed 82 intersection genes related to hypoxia, glycolysis, and fatty acid metabolism. Proteomics and lactylation modification analysis identified 577 proteins and 141 differentially lactylation modification proteins. By overlapping 82 intersection genes with 577 differentially expressed proteins and 141 differentially lactylation modification proteins, three hub genes (Aldoa, Acsl1, and Hadhb) were obtained. The immune infiltration analysis revealed a decreased score for monocytes/macrophages and an increased score for endothelial cells in the experimental group. Then, 459 metabolites in positive mode and 181 metabolites in negative mode were identified. The "Metabolic pathways" (mmu01100) was a common pathway between intersection genes-enriched pathways and metabolites-enriched pathways. These findings highlight the pivotal roles of hub genes in the glycolysis and fatty acid metabolism under the context of chronic exercise.PMID:39730655 | DOI:10.1038/s41598-024-82150-y

Sci Rep. 2024 Dec 28;14(1):30964. doi: 10.1038/s41598-024-82041-2.ABSTRACTDried blood spot (DBS) sampling offers significant advantages over conventional blood collection methods, such as reduced sample volume, minimal invasiveness, suitability for home-based sampling, and ease of transport. However, understanding the effects of variable storage temperatures and times on metabolite stability is crucial due to varying intervals and delivery conditions between sample collection and metabolomics analysis. To minimize biological variances, all samples were collected from the same individual simultaneously and stored at three different temperatures (4 °C, 25 °C, and 40 °C) for diverse time points (3, 7, 14, and 21 days). Metabolic profiling was conducted an untargeted gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based multi-platform metabolomics. Principal component analysis (PCA) showed alterations in metabolite stability at different temperatures, with phosphatidylcholines (PCs) and triglycerides (TAGs) as the first principal component (PC1). Specifically, we identified 69 metabolites that remained stable across all three temperatures over the 21-day period, while 78 metabolites exhibited instability. Furthermore, linear correlations between metabolite intensity and storage time were observed. Overall, our study elucidated the influence of storage temperature and time on specific metabolite stability in DBS samples, providing valuable insights for study design, biomarker selection, and data improvement.PMID:39730629 | DOI:10.1038/s41598-024-82041-2

Sci Rep. 2024 Dec 28;14(1):30841. doi: 10.1038/s41598-024-81501-z.ABSTRACTCarbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be have some predictability based on structural factors. Additionally, the identified minor isoforms also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe therefore somewhat predictable based on specific structural properties and further investigation may lead to new strategies for mitigating antibiotic resistance.PMID:39730591 | DOI:10.1038/s41598-024-81501-z

J Am Chem Soc. 2024 Dec 27. doi: 10.1021/jacs.4c09727. Online ahead of print.ABSTRACTReactive carbonyl species (RCS) are important biomarkers of oxidative stress-related diseases because of their highly reactive electrophilic nature. Despite their potential as triggers for prodrug activation, selective labeling approaches for RCS remain limited. Here, we utilized triphenylphosphonium groups to chemoselectively capture RCS via an aqueous Wittig reaction, forming α,β-unsaturated carbonyls that enable further functionalization. We first designed native (light) and deuterated (heavy) probes to facilitate RCS metabolomic identification through distinct MS isotope patterns. This approach allowed us to capture and relatively quantify several endogenous RCS related to advanced lipoxidation/glycation end products (ALEs/AGEs). Second, we demonstrated that various endogenous RCS can trigger the in situ generation of acrylamide warheads of targeted covalent inhibitors (TCIs) with different substituents. These structural variations influence their protein binding profiles and consequently alter their cytotoxicity, which is beneficial for the development of inhibitor cocktails.PMID:39730301 | DOI:10.1021/jacs.4c09727

Microb Pathog. 2024 Dec 25:107262. doi: 10.1016/j.micpath.2024.107262. Online ahead of print.ABSTRACTAeromonas schubertii infections has caused severe economic losses in aquaculture in China. In this study, we first induced enrofloxacin (ENR) resistance in A. schubertii strains and then analyzed the mechanisms of drug resistance using transcriptomics and metabolomics. We found that the minimal inhibitory concentration (MIC) was 0.03125 μg/mL for the sensitive strain (WL23S) and 32 μg/mL for the resistant strain (WL23R), which is a 1,024-fold increase. After 40 serial passages, the WL23R strain maintained a MIC of 32 μg/mL, even in the absence of ENR-induced stress. Notably, it had also developed resistance to several other antibiotics, such as neomycin sulfate and flumequine. There was no significant difference in the growth rates of the two strains, highlighting the strong adaptability and growth characteristics of the WL23R strain. Comparison of the transcriptome data between the WL23R and WL23S strains identified 579 differentially expressed genes. Expression of the efflux pump-related genes (e.g., acrA, acrB, pstB, pstC, pstS) was significantly upregulated in the WL23R strain (P < 0.05). The highest enrichment of differential genes in the Gene Ontology analysis was in the catabolism of various amino acids, and that in the Kyoto Encyclopedia of Genes and Genomes pathway was in ATP-binding cassette (ABC) transport. Comparison of the metabolomics data between the WL23R and WL23S strains revealed 1, 059 differentially expressed metabolites. Metabolomics analysis revealed the impact of drug resistance on the levels of amino acids, the activity of amino acid biosynthesis/metabolism pathways, and the ABC transport protein pathway, which confirmed the transcriptomics results. The joint analysis results showed that ABC transporters were most prominent in the shared pathways between enriched differentially expressed genes and metabolites. To further validate the resistance mechanism of A. schubertii, we exposed the WL23R strain to the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone. The minimal inhibitory concentration of the induced resistant strain decreased by 4-fold after the addition of the inhibitor, indicating the overexpression of active efflux pumps in WL23R. Our results indicate that the efflux system and ABC transporters play crucial roles during the development of multidrug resistance in A. schubertii. This study will serve as an important reference for understanding bacterial resistance to quinolones and multidrug resistance in aquatic environments.PMID:39730098 | DOI:10.1016/j.micpath.2024.107262

Bone. 2024 Dec 25:117382. doi: 10.1016/j.bone.2024.117382. Online ahead of print.ABSTRACTMetabolic pathways exhibit fluctuating activities during bone and dental loss and defects, suggesting a regulated metabolic plasticity. Skeletal remodeling is an energy-demanding process related to altered metabolic activities. These metabolic changes are frequently associated with epigenetic modifications, including variations in the expression or activity of enzymes modified through epigenetic mechanisms, which directly or indirectly impact cellular metabolism. Metabolic reprogramming driven by bone and dental conditions alters the epigenetic landscape by modulating the activities of DNA and histone modification enzymes at the metabolite level. Epigenetic mechanisms modulate the expression of metabolic genes, consequently influencing the metabolome. The interplay between epigenetics and metabolomics is crucial in maintaining bone and dental homeostasis by preserving cell proliferation and pluripotency. This review, therefore, aimed to examine the effects of metabolic reprogramming in bone and dental-related cells on the regulation of epigenetic modifications, particularly acetylation, methylation, and lactylation. We also discuss the effects of chromatin-modifying enzymes on metabolism and the potential therapeutic benefits of dietary compounds as epigenetic modulators. In this review, we highlight the inconsistencies in current research findings and suggest potential approaches to translate fundamental insights into clinical treatments for bone and tooth diseases.PMID:39730093 | DOI:10.1016/j.bone.2024.117382

Int J Biol Macromol. 2024 Dec 25:139191. doi: 10.1016/j.ijbiomac.2024.139191. Online ahead of print.ABSTRACTDendrobium flexicaule (DF) is an endemic plant primarily found in the mountains of central China with important medicinal and edible values. In traditional Chinese medicine, DF has the effects of nourishing stomach and "Yin", and clearing heat. At present, no studies have explored the mechanisms by which Dendrobium flexicaule polysaccharides (DFP) exert pre-protect effects against alcohol-induced gastric mucosal injury. In this study, DFP (367.478 kDa) was extracted through water extraction and ethanol precipitation, and composed of mannose (79.89 %), glucose (19.05 %), xylose (0.42 %), arabinose (0.33 %), and galactose (0.31 %). A rat model of alcohol-induced gastric mucosal injury was established to evaluate the pre-protective effects of DFP. Histological analysis, using hematoxylin-eosin staining, revealed that DFP alleviated gastric mucosal congestion and redness. Furthermore, DFP downregulated the expression of IL-6, IL-1β, MPO and MDA, while upregulating the expression of PGE2, GSH and SOD. Immunofluorescence analysis demonstrated that DFP upregulated the expression of ZO-1 and Occludin, thereby improving gastric barrier function. Multi-omics analysis revealed its regulation of the complement and coagulation cascade signaling pathway, as well as the propanoate metabolism pathway. Immunohistochemical analysis further confirmed that DFP significantly down-regulated the expression of C3, VTN, F2, Serpind1, CPB2, FGA and VWF. Overall, this study offers novel insights into the pre-protective effects and mechanisms of DFP against alcohol-induced gastric mucosal injury, laying the groundwork for the development of DF based therapeutic resources.PMID:39730050 | DOI:10.1016/j.ijbiomac.2024.139191

Environ Pollut. 2024 Dec 25:125580. doi: 10.1016/j.envpol.2024.125580. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are widely distributed in paddy soils, and their multi-phase partitioning in soil fractions was proved to be strongly interact with soil microbial community composition and functions. Despite this, soil bacterial and fungal metabolic molecular effects on PFAS water-soil interface migration in waterlogged paddy fields still remain unclear. This study integrated soil untargeted metabolomics with microbial amplicon sequencing to elucidate soil metabolic modulations of 15 PFAS interface release. Inhibition of bacterial and fungal metabolic activity both significantly altered PFAS cross-media translocation (p < 0.05). Gemmatimonadota, Desulfobacterota, Acidobacteriota, Actinobacteriota, and Bacteroidota were vital bacterial taxa affecting PFAS transport, while Basidiobolomycota and Chytridiomycota were vital fungal taxa. Fungi regulated PFAS migration more (R2 = 0.379-0.526) than bacteria (R2 = 0.021-0.030) due to the higher metabolic stability of stochastic-dominated fungi than deterministic-dominated bacteria. At the water-soil interface, the amino acid-like dissolved organic matter (Tyrosine and Tryptophan) contributed most (48.5-58.6 %) to the PFAS multiphase distribution. Untargeted metabolomics further clarified that fungal amino acid-like metabolites, including Phosphoenolpyruvate and Methionine, were key triggers stimulating Tyrosine and Tryptophan biosynthesis (p < 0.001), which were vital in modulating PFAS interface translocation (p < 0.001). These results provide novel insights into soil microbial metabolites' participation in PFAS water-soil interface migration, benefiting PFAS pollution control and agricultural security risk assessment in waterlogged paddy ecosystems.PMID:39730035 | DOI:10.1016/j.envpol.2024.125580

Domest Anim Endocrinol. 2024 Dec 19;91:106909. doi: 10.1016/j.domaniend.2024.106909. Online ahead of print.ABSTRACTEnergy supply is crucial for testicular development. Nevertheless, the specific alterations in the energy metabolic pathways that affect testicular development have not been extensively investigated. This study aimed to investigate the variations in metabolites and alterations in energy metabolic pathways in the testes of Hu sheep with different developmental status at 6 months of age. Twelve rams with similar body weights but distinct testis developmental status were selected among 345 Hu sheep based on testis size and histomorphology results, and they were divided into the well-developed (L group, n = 6) and developmentally delayed group (S group, n = 6). A total of 660 metabolites were identified via widely targeted metabolic analysis. Among 148 differentially expressed metabolites, 78 were up-regulated and 70 were downregulated in the L group compared with the S group. Functional enrichment analysis indicated that a significant proportion of the identified differential metabolites was implicated in energy metabolism-related pathways. Moreover, the L group exhibited significantly higher expression levels of genes involved in glycolysis (GLTU8 and LDH), TCA (PDHA2, CS and IDH3G), gluconeogenesis (PCK1), pentose phosphate (G6PD), and fatty acid degradation (GK, ACSL1, FABP3, CPT1 and CTP2). The activity enzymes such as citrate synthase, pyruvate dehydrogenase, and lactate dehydrogenase also increased in the L group. In summary, this observation implied that the augmentation of energy metabolic pathways plays a crucial role in facilitating testicular development. The upregulation of energy metabolic pathways collectively facilitates the testicular development in Hu sheep.PMID:39729915 | DOI:10.1016/j.domaniend.2024.106909

Environ Int. 2024 Dec 25;195:109236. doi: 10.1016/j.envint.2024.109236. Online ahead of print.ABSTRACTMicroplastics (MPs) are pervasive environmental contaminants, resulting in unavoidable human exposure. This study identified MPs in follicular fluid and investigated the specific MPs and mechanisms that adversely affect oocytes. MPs in the follicular fluid of 44 infertile women undergoing assisted reproductive technology were measured using Raman microspectroscopy. Differential metabolites in follicular fluid were analyzed via untargeted metabolomics. Female mice were exposed to polyethylene (PE) to validate human findings. MPs, particularly PE, exhibited the highest detection rate (86.4 %) in human follicular fluid and showed a negative correlation with fertilization rates (r = -0.407, P = 0.007). Elevated PE levels altered metabolites primarily involved in metabolic pathways, ferroptosis, and ovarian steroidogenesis. In mice, PE exposure significantly reduced the number of retrieved oocytes (31.5 vs. 36.3, P < 0.05) and fertilization rate (70.8 % vs. 85.2 %, P < 0.001), while increasing the proportion of poor-quality oocytes (28.2 % vs. 16.5 %, P < 0.001) and reactive oxygen species (ROS) production compared to controls. RNA sequencing indicated significant upregulation of inflammation-related genes (Il10ra, Il1a, Il33, Tnfaip8l2, and Tnfrsf1b) in the PE-exposed group. In conclusion, PE exposure impairs oocyte quality possibly by disrupting follicular fluid metabolism, elevating inflammation-related gene expression, and increasing ROS production in oocytes.PMID:39729868 | DOI:10.1016/j.envint.2024.109236

Sci Total Environ. 2024 Dec 26;959:178181. doi: 10.1016/j.scitotenv.2024.178181. Online ahead of print.ABSTRACTCadmium (Cd) accumulation in rice poses significant risks to human health. The Cd accumulation levels vary widely among cultivars and are strongly associated with the rhizosphere microecosystem. However, the underlying mechanisms remain poorly understood. Here, we conducted a field experiment in Cd-contaminated areas with 24 popular regional cultivars. These cultivars were categorized into high Cd accumulation (HA) and low Cd accumulation (LA) groups based on their grain Cd content. Rhizosphere soil physicochemical properties were monitored, and key metabolites, microbiomes, and their interaction contributing to Cd accumulation were analyzed using omics-sequencing technologies and bioinformatics analysis. Metabolomic analysis identified distinct rhizosphere metabolite profiles between the HA and LA groups, with key metabolites showing strong correlations with Cd accumulation. Key metabolites in the LA group were linked to reduced Cd uptake and enhanced antioxidant defense mechanisms, while those in the HA group were associated with increased Cd mobility and uptake. Metagenomic analysis of the rhizosphere soil showed that the LA group harbored a more diverse and interconnected microbial community, with tax such as Syntrophaceae, Anaerolineae, Thermoflexales, and Syntrophales, along with metabolite such as disopyramide, playing central roles in Cd immobilization and detoxification. Additionally, the enhanced carbon, nitrogen, and phosphorus cycling in the LA group suggests a more robust nutrient assimilation process that supports plant growth and reduces Cd uptake. This study highlights the critical role of the rhizosphere microecosystem in regulating Cd accumulation and underscores the potential of selecting rice cultivars with favorable rhizosphere traits as a strategy for reducing Cd uptake.PMID:39729842 | DOI:10.1016/j.scitotenv.2024.178181

Poult Sci. 2024 Dec 22;104(2):104727. doi: 10.1016/j.psj.2024.104727. Online ahead of print.ABSTRACTThis study aimed to investigate the effects of soybean bioactive peptide (SBP) on the growth performance and intestinal health of yellow-feathered broilers and to further elucidate the regulatory mechanisms of intestinal health using multi-omics analysis. A total of 320 1-day-old yellow-feathered broilers were randomly divided into two groups, with 10 replicates per group and 16 birds per replicate. Broilers in the control group received the basal diet, and those in the experimental group (SBPG) received the basal diet with 0.2 % SBP replacing the same amount of soybean meal. The experiment lasted for 70 d. The results showed that, compared with those in the control group, the final body weight and average daily gain of SBPG broilers were significantly higher (P < 0.05), and the feed conversion ratio was significantly lower (P < 0.05). Notably, SBP significantly improved gut health in chickens, including increased intestinal villus height, decreased levels of proinflammatory factors, such as IL-1β and interferon-γ, and upregulated expression of tight junction proteins, such as ZO-1 and occludin. In addition, transcriptome sequencing results revealed that broilers in the SBP group exhibited significant enrichment in multiple metabolic pathways, including fatty acid metabolism, fatty acid degradation, and the biosynthesis of unsaturated fatty acids (P < 0.05). Cecal 16S rRNA sequencing showed that SBPG increased the abundance of the butyrate-producing beneficial bacteria Muribaculaceae. Subsequent cecal metabolome analysis also revealed that SBPG enhanced lipid-related metabolic pathways, such as alpha-linolenic acid metabolism and GPI-anchor biosynthesis. In conclusion, SBP is a potential feed additive that can improve intestinal morphology, enhance intestinal immunity and barrier function, optimize the structure of the intestinal microbiota, and enhance metabolic function.PMID:39729732 | DOI:10.1016/j.psj.2024.104727

Poult Sci. 2024 Dec 17;104(2):104686. doi: 10.1016/j.psj.2024.104686. Online ahead of print.ABSTRACTCD8 subunit alpha (CD8A) is an important gene in immunity and is involved in the functional regulation of T lymphocytes. However, the specific role and regulatory mechanism of CD8A in chicken T lymphocytes remain unknown. In this study, we overexpressed and interfered with CD8A in chicken T lymphocytes and found that interfering with CD8A expression inhibited the proliferation and induced the apoptosis of T lymphocytes and that the overexpression of CD8A promoted T lymphocyte activation. Additionally, transcriptomic and metabolomic analyses of chicken T lymphocytes with CD8A overexpression or interference were performed. The overexpression and interference of the CD8A gene caused widespread changes in gene and metabolite expression in chicken T cells. The results of the transcriptome analysis revealed that differentially expressed genes (DEGs) caused by altered expression of the CD8A gene were associated with multiple "neuroactive ligand-receptor interaction", "cell adhesion molecules", "calcium signaling pathway", etc. The metabolome analysis results revealed that different metabolites (DMs) caused by altered CD8A gene expression were associated with "Glutathione metabolism", "Arginine biosynthesis", "D-amino acid metabolism", etc. The combined transcriptional and metabolic analysis revealed one metabolically related pathway, "Glutathione metabolism". Our findings further revealed that interference and overexpression of CD8A plays a role in the metabolism of Glutathione. Thus, CD8A may be a critical regulator of "Glutathione metabolism" and may subsequently affect T-cell function in chickens. These results provide an important reference for further research on the effect of CD8A on the immune performance of chickens.PMID:39729724 | DOI:10.1016/j.psj.2024.104686

Food Chem. 2024 Dec 19;469:142128. doi: 10.1016/j.foodchem.2024.142128. Online ahead of print.ABSTRACTThe epidemiological assessment of wine consumption usually has been obtained using self-reporting questionnaires. In this study, two metabolomic approaches, targeted and untargeted, were applied to 24-h urine samples from a cohort of La Rioja (Spain) (aged 52-78), comparing moderate and daily wine consumers (20 males and 13 females) without diet intervention, versus non-consumers (8 males and 35 females). Results showed that the non-targeted metabolomics approach has allowed for the annotation of sixteen compounds in 24-h urine samples from regular wine-consumers that were not detected in the urine of non-wine consumers. Additionally, the targeted metabolomics approach showed a wide range of phenol metabolites, mainly hepatic phase-II conjugates, whose concentration was significantly higher in the urine of wine consumers. As a novelty, this study focuses on discovering the main urinary biomarkers of regular wine consumption involving free-living volunteers, without dietary intervention or restrictions that might alter their regular behaviors and lifestyles.PMID:39729665 | DOI:10.1016/j.foodchem.2024.142128

Food Chem. 2024 Dec 18;469:142573. doi: 10.1016/j.foodchem.2024.142573. Online ahead of print.ABSTRACTGrape pomace (GP), a by-product of the wine supply chain process, contains bioactive molecules with known healthy properties. This study examines the impact of different extraction techniques on three GPs of Aglianico cultivar [Cantine del Notaio, Barile, and Torrecuso]. Five eco-friendly extractive techniques [maceration (MAC), digestion (DIG), accelerated solvent extraction (ASE), microwaves (MW), and ultrasound (US)] were used with 50 % ethanol/water as solvent. Spectrophotometric assays showed that DIG and ASE extracts had the highest antioxidant activity and specialized metabolite content. Using the HRMS/MS-based molecular networking, DIG and ASE extract metabolome profiles were analyzed, identifying unknown compounds and known ones with validated antioxidant and chemopreventive effects. In vitro cell-based assay on HepG2 cells demonstrated that Barile GP DIG extract has the highest anti-proliferative activity. Hence, this work provides insight into the potential application of Barile GP DIG extract as a rich source of specialized metabolites with antioxidant and anti-proliferative activity.PMID:39729654 | DOI:10.1016/j.foodchem.2024.142573

Anal Chem. 2024 Dec 27. doi: 10.1021/acs.analchem.4c03513. Online ahead of print.ABSTRACTMass spectrometry (MS)-based metabolomics often rely on separation techniques when analyzing complex biological specimens to improve method resolution, metabolome coverage, quantitative performance, and/or unknown identification. However, low sample throughput and complicated data preprocessing procedures remain major barriers to affordable metabolomic studies that are scalable to large populations. Herein, we introduce PeakMeister as a new software tool in the R statistical environment to enable standardized processing of serum metabolomic data acquired by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), a high-throughput separation platform (<4 min/sample) which takes advantage of a serial injection format of 13 samples within a single analytical run. We performed a rigorous validation of PeakMeister by analyzing 47 cationic metabolites consistently measured in 5,000 serum and 420 quality control samples from the Brazilian National Survey on Child Nutrition (ENANI-2019) comprising a total of 224,983 metabolite peaks acquired in 40 days across three batches over an eight-month period. A migration time index using a panel of 11 internal standards was introduced to correct for large variations in migration times, which allowed for reliable peak annotation, peak integration, and sample position assignment for serum metabolites having two flanking internal standards or a single comigrating stable-isotope internal standard. PeakMeister accelerated data preprocessing times by 30-fold compared to manual processing of MSI-CE-MS data by an experienced analyst using vendor software, while also achieving excellent peak annotation fidelity (median accuracy >99.9%), acceptable intermediate precision (median CV = 16.0%), consistent metabolite peak integration (mean bias = -2.1%), and good mutual agreement when quantifying 16 plasma metabolites from NIST SRM-1950 (mean bias = -1.3%). Reference ranges are also reported for 40 serum metabolites in a national nutritional survey of Brazilian children under 5 years of age from the ENANI-2019 study. MSI-CE-MS in conjunction with PeakMeister allows for rapid and automated processing of large-scale metabolomic studies that tolerate nonlinear migration time shifts without complicated dynamic time warping or effective mobility scale transformations.PMID:39729551 | DOI:10.1021/acs.analchem.4c03513

Metabolomics. 2024 Dec 27;21(1):13. doi: 10.1007/s11306-024-02215-x.ABSTRACTINTRODUCTION: Tree bacterial diseases are a threat in forestry due to their increasing incidence and severity. Understanding tree defence mechanisms requires evaluating metabolic changes arising during infection. Metabolite extraction affects the chemical diversity of the samples and, therefore, the biological relevance of the data. Metabolite extraction has been standardized for several biological models. However, little information is available regarding how it influences wood extract's chemical diversity.OBJECTIVES: This study aimed to develop a methodological approach to obtain extracts from different tree species with the highest reproducibility and chemical diversity possible, to ensure proper coverage of the trees' metabolome.METHODS: A full factorial design was used to evaluate the effect of solvent type, extraction temperature and number of extraction cycles on the metabolic profile, chemical diversity and antibacterial activity of four tree species.RESULTS: Solvent, temperature and their interaction significantly affected the extracts' chemical diversity, while the number of extraction cycles positively correlated with yield and antibacterial activity. Although 60% of the features were recovered in all the tested conditions, differences in the presence and abundance of specific chemical classes per tree were observed, including organooxygen compounds, prenol lipids, carboxylic acids, and flavonoids.CONCLUSIONS: Each tree species has a unique metabolic profile, which means that no single protocol is universally effective. Extraction at 50 °C for three cycles using 80% methanol or chloroform/methanol/water showed the best results and is suggested for studying wood metabolome. These observations highlight the need to tailor extraction protocols to each tree species to ensure comprehensive metabolome coverage for metabolic profiling.PMID:39729149 | DOI:10.1007/s11306-024-02215-x