PubMed

PLoS One. 2025 Mar 4;20(3):e0318557. doi: 10.1371/journal.pone.0318557. eCollection 2025.ABSTRACTMetabolic Dysfunction-Associated Steatohepatitis (MASH) represents the severe condition of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Currently, there is a need to identify non-invasive biomarkers for an accurate diagnosis of MASH. Previously, omics studies identified alterations in lipid metabolites involved in MASLD. However, these studies require validation in other cohorts. In this sense, our aim was to perform lipidomics to identify the circulating lipid metabolite profile of MASH. We assessed a liquid chromatography coupled to a mass spectrometer-based untargeted lipidomic assay in serum samples of 216 women with morbid obesity that were stratified according to their hepatic diagnosis into Normal Liver (NL, n = 44), Simple Steatosis (SS, n = 66) and MASH (n = 106). First, we identified a profile of lipid metabolites that are increased in MASLD, composed of ceramides, triacylglycerols (TAG) and some phospholipids. Then, we identified that patients with SS have a characteristic profile of increased levels of ceramides, diacylglycerols DG (36:2) and DG (36:4), some TAG and a few phospholipids such as PC (32:1), PE (38:3), PE (40:6), PI (32:0) and PI (32:1). Later, in MASH patients, we found increased levels of ceramides, deoxycholic acid, a set of TAG, and some phospholipids such as PC, PE, PI and LPI; while we found decreased levels of the DG (36:0). Finally, we have reported a panel of lipid metabolites that might be used to differentiate patients with MASH from SS patients, made up of increased levels of 9-HODE some PC and PE, the LPI (16:0) and decreased levels of DG (36:0). To conclude, our investigation has suggested a lipid metabolite profile associated with MASLD and MASH. Specifically, a set of lipid metabolites seems to be discriminatory in MASH subjects compared to SS individuals. Thus, this panel of lipid metabolites could be used as a non-invasive diagnostic tool.PMID:40036208 | DOI:10.1371/journal.pone.0318557

J Proteome Res. 2025 Mar 4. doi: 10.1021/acs.jproteome.4c00715. Online ahead of print.ABSTRACTCoal worker's pneumoconiosis (CWP) is characterized by chronic inflammation and pulmonary fibrosis. The key factor contributing to the incurability of CWP is the unclear pathogenesis. This study explored the characteristic changes in proteomics and metabolomics of early and advanced CWP patients through proteomics and metabolomics techniques. Proteomics identified proteins that change with the progression of CWP, with significant enrichment in the TGF-β signaling pathway and autoimmune disease pathways. Metabolomics revealed the metabolic characteristics of CWP at different stages. These metabolites mainly include changes in amino acid metabolism, unsaturated fatty acid synthesis, and related metabolites. Integrated analysis found that ABC transporters are a shared pathway among the three groups, and ABCD2 is involved in the ABC transporter pathway. In the subsequent independent sample verification analysis, consistent with proteomics experiments, compared to the CM group, FMOD expression level was upregulated in the NIC group. TFR expression level was consistently downregulated in both the IC and NIC groups. Additionally, ABCD2 increased in the IC group but decreased in the NIC group. In summary, this study revealed the metabolic characteristics of CWP at different stages. These findings may provide valuable insights for the early prediction, diagnosis, and treatment of CWP.PMID:40036136 | DOI:10.1021/acs.jproteome.4c00715

Eur J Nutr. 2025 Mar 4;64(3):106. doi: 10.1007/s00394-025-03627-8.ABSTRACTPURPOSE: Assessing the health impacts of nutritional interventions in metabolically compromised but otherwise healthy individuals is challenging, necessitating sensitive tools. Phenotypic flexibility offers an innovative way to measure homeostatic capacity during challenge tests. A composite biomarker of inflammatory resilience has proven useful in evaluating the health benefits of whole-grain wheat interventions in overweight and obese individuals. Expanding this method to other dietary interventions to combat low-grade inflammation is essential.METHODS: This study investigated the feasibility of a composite biomarker of inflammatory resilience through secondary analysis of samples from two independent energy restriction (ER) trials, Bellyfat (NCT02194504) and Nutritech (NCT01684917). In these trials, fasting and postprandial inflammation was analysed using a variety of markers. Four composite biomarker models were developed on the basis of postprandial inflammatory marker responses via the 'health space' model method. These models were statistically evaluated for their sensitivity in detecting the effects of 12 weeks of ER.RESULTS: The minimal composite biomarkers, consisting of IL-6, IL-8, IL-10, and TNF-α, lacked the ability to detect postprandial intervention effects in both ER trials. However, in the Nutritech study, the extended, endothelial, and optimized composite biomarkers of inflammatory resilience displayed significant responses to the ER (all P < 0.005). In the latter 3 models, a reduction in the inflammatory score was correlated with a reduction in BMI and body fat percentage.CONCLUSION: This study underscores the feasibility of employing a composite biomarker of inflammatory resilience to evaluate ER interventions. Further validation in additional nutritional intervention studies is necessary. Once validated, this composite biomarker could offer a novel approach for assessing low-grade inflammation and phenotypic flexibility.PMID:40035864 | DOI:10.1007/s00394-025-03627-8

Cell Mol Life Sci. 2025 Mar 4;82(1):101. doi: 10.1007/s00018-025-05629-5.ABSTRACTAdult neurogenesis in the hippocampus, involving the generation and integration of new neurons, is essential for behavioral pattern separation, which supports accurate memory recall and cognitive plasticity. Here, we explore the role of the DNA repair protein NEIL3 in adult hippocampal neurogenesis and behavioral pattern separation. NEIL3 is required for efficient proliferation and neuronal differentiation of neonatal NSPCs and adult-born NPCs in the hippocampus following a behavioral pattern separation task. NEIL3-depleted mice exhibited a reduced preference for the novel object location, indicating a deficit in pattern separation. NEIL3-deficient adult-born neurons exhibited a significant reduction in mature-like membrane properties, indicating impaired functional maturation. Interestingly, these impairments were not associated with the decreased genomic integrity but with the altered transcriptional regulation of the Wnt signaling pathway. Given the importance of adult neurogenesis in cognitive function, targeting NEIL3 could offer therapeutic potential for addressing age-related hippocampal dysfunction and cognitive decline.PMID:40035863 | DOI:10.1007/s00018-025-05629-5

Int J Colorectal Dis. 2025 Mar 4;40(1):57. doi: 10.1007/s00384-025-04843-8.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) encompasses chronic inflammation of the colon and rectum, posing significant health challenges. Previous studies have shown potential therapeutic effects of natural compounds on IBD. Chrysin, a naturally occurring flavonoid, has been suggested to modulate inflammatory pathways and gut microbiota, but its comprehensive impact on ulcerative colitis remains inadequately explored.METHODS: This study employed a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice to investigate the effects of Chrysin. Using network pharmacology, we identified key signaling pathways potentially influenced by Chrysin. Experimental approaches included measuring disease activity index scores, serum levels of TNF-α, and assessing colon damage histologically. Transcriptomic and microbiome analyses were conducted to examine changes in gene expression and gut bacterial populations, respectively. Additionally, metabolomic profiling was used to identify alterations in colon metabolites.RESULTS: Chrysin treatment significantly mitigated weight loss and reduced disease activity index scores in DSS-induced mice. There was a notable decrease in serum TNF-α levels and less histological damage in the colon. Transcriptomic analysis revealed significant alterations in gene expression within the NF-κB and IL-17 signaling pathways. Microbiome analysis showed significant shifts in the populations of Bacteroidetes and Firmicutes. Metabolomics analysis identified changes in 298 colon metabolites, implicating several essential metabolic pathways.CONCLUSIONS: The findings suggest that Chrysin exerts a dual-action therapeutic effect on ulcerative colitis by reducing inflammation and modulating the gut microbiota. These multifaceted impacts highlight Chrysin's potential utility as a novel therapeutic agent in the clinical management of IBD, offering valuable insights into its mechanisms of action and paving the way for future clinical trials.PMID:40035853 | DOI:10.1007/s00384-025-04843-8

JPEN J Parenter Enteral Nutr. 2025 Mar 4. doi: 10.1002/jpen.2742. Online ahead of print.ABSTRACTBACKGROUND: Intestinal failure (IF) is a life-limiting condition that includes a variety of intestinal pathologies. Currently, there are few clinical biomarkers that reflect intestinal function or a patient's potential to wean off parenteral nutrition (PN), making it difficult to predict the clinical trajectory. By associating gut microbiome taxonomic and functional features and blood analytes with the proportion of daily energy delivered via PN-a proxy for intestinal function-our study aimed to discover potential predictors of intestinal function and PN weaning potential.METHODS: In this longitudinal multiomics cohort study, we followed 18 pediatric patients with IF and PN support for ≤1.5 years. Fecal and stoma samples were analyzed using metagenomic shotgun sequencing to assess bacterial taxonomy and function and internal transcribed spacer 2 ribosomal RNA sequencing to characterize the fungal community. Targeted metabolomics was used to quantify 257 blood analytes. Linear mixed models were used to analyze the associations of PN dependence with microbiome features and blood analytes.RESULTS: The bacterial and fungal taxonomic composition exhibited substantial interpatient and intrapatient variability, with no link to PN dependence. In contrast, bacterial functional analysis revealed 63 MetaCyc pathways significantly associated with PN dependence. Additionally, 32 blood analytes were associated with PN dependence.CONCLUSION: In this exploratory study, we found that functional microbiome features and blood metabolomic profiles-particularly urea cycle metabolites, creatinine, asparagine, and tryptophan-derived metabolites-show promise for predicting intestinal function. Furthermore, they may have therapeutic implications for promoting intestinal adaptation. Confirmatory trials with larger sample sizes are needed to validate these findings.PMID:40035787 | DOI:10.1002/jpen.2742

Microbiol Spectr. 2025 Mar 4:e0119124. doi: 10.1128/spectrum.01191-24. Online ahead of print.ABSTRACTA temporary loop ileostomy is a routine procedure for protecting the anastomosis in patients undergoing radical resection of rectal cancer. Fecal diversion by a diverting ileostomy may induce microbiota dysbiosis in the defunctioned colon; however, data on temporal and spatial microbiome and metabolome changes in these patients are sparse. Thirty patients who underwent ileostomy closure were enrolled. Fecal and plasma samples were collected successively before ileostomy closure, at the first postoperative defecation, and 1 month postoperatively. The 16S rRNA gene sequencing was used to assess changes in gut microbes, and metabolic components in the plasma were analyzed using global untargeted metabolomics. Advanced data analysis methods were used to examine the differences and correlations between flora and metabolites. The gut microbiota in the ileostomy effluent and defunctioned colon had lesser species diversity and richness, with an abundance of aerobic, gram-negative, and potentially pathogenic bacteria. After the intestinal continuity was restored with routine meal feeding, the gut microbes recovered to a standard composition within 1 month. Moreover, xanthine, traumatic acid, L-glutamine, and norepinephrine levels increased markedly in patients with ileostoma. The ileostomy closure reversed the ileostomy-associated metabolic alterations, including an increased abundance of L-leucine, creatine, and 2-ketobutyric acid. Furthermore, Agathobacter and Peptostreptococcus were most closely associated with the reconstruction of postoperative gut microbes. We described a spatiotemporal map of the intestinal microbial ecological reconstruction and metabolic recovery before and after ileostomy reversal for perioperative intervention in patients with ileostomy closure surgery.IMPORTANCE: In this paper, the changes in the intestinal microbiome and plasma metabolome before and after temporary ileostomy were reported for the first time, and the dynamic changes in intestinal contents were described. At the same time, the key bacterial genera involved in the reestablishment of microflora after the restoration of intestinal continuity were found, and the key relationship between them and plasma metabolites was also found. More importantly, we found that patients with ileal fistula may be at risk of metabolic imbalance and that this particular metabolic state may potentially affect the course of tumor treatment. Finally, the samples in this study were obtained in their natural state and can be easily applied to the clinic to avoid unnecessary invasive examinations.PMID:40035564 | DOI:10.1128/spectrum.01191-24

Crit Rev Anal Chem. 2025 Mar 4:1-21. doi: 10.1080/10408347.2025.2468926. Online ahead of print.ABSTRACTMetabolomics is an emerging interdisciplinary field focused on the comprehensive analysis of all metabolites within biological samples, making it valuable for areas such as drug development, and environmental analysis. Many compounds, including pharmaceuticals and agrochemicals that have been extensively studied by metabolomics are chiral. The intrinsic chirality of biological targets can lead to a selective recognition of enantiomers resulting in distinct pharmacokinetic, pharmacodynamic and/or toxicological profiles (enantioselectivity). Given that metabolomics captures an instant snapshot of an organism's metabolic state, it serves as a powerful tool to investigate chiral compounds and understand enantioselective effects. Herein, a systematic compilation of scientific literature was performed and 48 enantioselectivity studies using metabolomics were selected. These studies revealed an increasing focus on chiral pesticides (77%), the use of animal models (59%), reliance on LC-MS techniques (52%), and predominantly untargeted approaches (83%). Enantioselective effects were described in most studies. This review describes significant advances in this emerging field and highlights the use of metabolomics to unravel the role of stereochemistry in cellular metabolism by the examination of enantiomer-specific metabolic effects. Furthermore, it elucidates enantioselectivity mechanism that can be further applied to other groups of chiral compounds.PMID:40035488 | DOI:10.1080/10408347.2025.2468926

CNS Neurosci Ther. 2025 Mar;31(3):e70297. doi: 10.1111/cns.70297.ABSTRACTBACKGROUND: Post-cardiopulmonary resuscitation brain injury (PBI) is essentially the cerebral ischemia reperfusion (CIR) injury, which is the main cause of death and long-term disability in patients with cardiac arrest. So far, there is no treatment for PBI; thus, it is urgent to develop new drugs or therapies for the prevention and treatment of brain injury after cardiopulmonary resuscitation. Although multiple constituent herbs or active ingredients of Xinbao Pill (XBP) have shown neuroprotective effects, whether XBP could play a therapeutic role on PBI is still unknown. This study aimed to illustrate the neuroprotective effect of XBP on PBI and probe the underlying mechanisms.METHOD: We first performed the cell and animal experiments to validate the protective effect of XBP on neurological function. We next identified the potential differential metabolites via metabolomics analysis. We further conducted a comprehensive network pharmacology analysis including overlap gene analysis, protein-protein interaction network, and gene-biological process-module function network to preliminarily investigate the specific mechanism of action (MOA) of XBP against PBI. Finally, PCR, MTT, ELISA assay, as well as Western blotting experiments were made to validate our proposed molecular mechanisms.RESULT: The in vitro experiment showed that XBP could increase cell viability and ameliorate cell morphological damage in PC12 cells exposed to oxygen-glucose deprivation and reoxygenation (OGD/RO) conditions. The in vivo experiment demonstrated that XBP improved the Neurologic Deficit Score (NDS), lowered the Neuron-Specific Enolase (NSE) level as well as reversed the typical neuropathological changes in PBI rats, indicating its neuroprotective effect on PBI. Further metabolomics analysis identified 94 differential metabolites after XBP treatment, and multiple metabolites were highly related to CIR. Moreover, network pharmacology results revealed that the therapeutic effect of XBP on PBI may be relevant to mitochondrial quality control (MQC). Mechanistically, XBP could not only promote the expressions of marker proteins including PGC1α, NRF1, TFAM, OPA1, MFN1 as well as MFN2 in mitochondrial biogenesis and mitochondrial fusion but also inhibit those proteins containing DRP1, MFF, FIS1, p62, PINK1, Parkin as well as LC3 in mitochondrial fission and mitophagy. Finally, AMP-activated protein kinase (AMPK) inhibitor was demonstrated to play a crucial role in regulating MQC.CONCLUSIONS: Our study first determined that XBP might be an underlying anti-PBI formula, which also deciphered the potential MOAs of XBP against PBI by a network pharmacology approach combined with in vivo and in vitro experimental validation.PMID:40035287 | DOI:10.1111/cns.70297

Plant Cell Environ. 2025 Mar 4. doi: 10.1111/pce.15454. Online ahead of print.ABSTRACTPrior exposure of plants to a triggering factor can enhance their tolerance to more severe stressful events. Transcriptome reprogramming of metabolism and hormonal modulation processes in the resurrection plant Boea hygrometrica was observed during drought acclimation. However, the metabolic dynamics and underlying regulatory networks that modulate drought acclimation-induced rapid desiccation tolerance (RDT) remain unexplored. Here, we performed an integrated transcriptome and metabolome analysis to investigate the phytohormone profiles and metabolic landscapes of B. hygrometrica during drought acclimation and dehydration stress. We identified a set of RDT acquisition-associated biomarkers, including trans-zeatin and some disaccharides (lactose, trehalose, sucrose, and isomaltulose). Exogenous application of lactose effectively enhanced the RDT of B. hygrometrica seedlings and improved drought tolerance in Arabidopsis, tobacco, maize, and wheat. In addition, transient overexpression of lactose-associated transcription factors MYB330 and APETALA2 in B. hygrometrica can promote the RDT and transcription of drought acclimation-inducible genes involved in calcium and ABA signalling and autophagy. In summary, our findings demonstrate that drought acclimation-induced lactose accumulation facilitates the establishment of an "acclimated state", leading to transcriptome reprogramming in response to rapid desiccation. These results will also pave the way for using RDT biomarkers to improve crop drought tolerance in an environmentally sustainable manner.PMID:40035125 | DOI:10.1111/pce.15454

Food Chem X. 2025 Feb 8;26:102269. doi: 10.1016/j.fochx.2025.102269. eCollection 2025 Feb.ABSTRACTVanilla planifolia Jacks. ex Andrews, is cultivated for its aromatic pods, obtaining the primary source of vanillin, a molecule valued for its flavor and bioactivity. Mexico ranks among the top five global producers, and Papantla, Veracruz, contributes 70 % of national production. Developing vanilla's characteristic aroma involves a curing process composed of killing, sweating, drying, and conditioning, which enzymatic reactions and microbial activity play essential roles. This study assessed the impact of four killing treatments: microwave, hot water immersion, sonication, and freezing on the phenolic composition and bacterial communities in vanilla curing through metabolomic and 16S sequencing approaches. Freezing treatment resulted in the most substantial changes in phenolic profiles, including higher vanillin concentrations. Bacillus was the dominant bacterial genus, with hot water immersion and sonication showing the greatest α-diversity. These findings underscore the value of omic sciences in refining curing processes, enabling producers to achieve higher-quality vanilla through more efficient and technical methods.PMID:40034982 | PMC:PMC11872573 | DOI:10.1016/j.fochx.2025.102269

Eco Environ Health. 2025 Jan 17;4(1):100133. doi: 10.1016/j.eehl.2024.12.002. eCollection 2025 Mar.ABSTRACTThiamethoxam (THM) is one of the most widely used insecticides globally, which was designed to selectively target nicotinic acetylcholine receptors (nAChRs) in the insect nervous system and is generally considered safe for non-targeted organisms. However, increasing evidence has demonstrated its neurotoxicity in aquatic organisms, though the underlying mechanisms, especially at environmentally relevant concentrations, remain largely unclear. In this study, the swimming distance of zebrafish was significantly shortened by 14.06%-21.64% after exposure to THM at 10-1000 ng/L. This behavioral impairment may result from the damage to nervous and visual systems, as confirmed by notable apoptosis, histological analysis of the eyes, and differential expression of numerous genes. Molecular docking and biomarkers assays found that THM can bind with nAChR and multiple hormone receptors, with binding energies varying from -3.75 to -6.74 kcal/mol. Consequently, the concentrations of a neurotransmitter (acetylcholine) and related hormones (cortisol, triiodothyronine, thyroxine, and thyroid-stimulating hormone) were significantly affected. Further investigations using a weighted gene correlation network and metabolomics suggest that THM may enter the cell via endocytosis and bind with multiple hormone receptors, potentially activating the MAPK signaling pathway. This activation may disrupt purine and pyrimidine metabolism in the cell nucleus, ultimately leading to cell apoptosis and neurotoxicity. This study reveals that THM, even at environmentally relevant concentrations, poses neurological risks to zebrafish and underscore the need for urgent attention to the ecological impacts of THM in aquatic environments.PMID:40034871 | PMC:PMC11872479 | DOI:10.1016/j.eehl.2024.12.002

medRxiv [Preprint]. 2025 Feb 21:2025.02.20.25322611. doi: 10.1101/2025.02.20.25322611.ABSTRACTOBJECTIVE: Identify microbial and microbiota-associated metabolites in monozygotic (MZ) and dizygotic (DZ) twins discordant for type 1 diabetes (T1D) to gain insight into potential environmental factors that may influence T1D.RESEARCH DESIGN AND METHODS: Serum samples from 39 twins discordant for T1D were analyzed using a semi-targeted metabolomics approach via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS). Statistical analyses identified significant metabolites (p < 0.1) within three groups: All twins (combined group), MZ twins, and DZ twins.RESULTS: Thirteen metabolites were identified as significant. 3-indoxyl sulfate and 5-hydroxyindole were significantly reduced in T1D individuals across all groups. Carnitine was reduced, and threonine, muramic acid, and 2-oxobutyric acid were significantly elevated in both All and MZ groups. Allantoin was significantly reduced and 3-methylhistidine was significantly elevated in All and DZ groups.CONCLUSIONS: Metabolite dysregulation associated with gut dysbiosis was observed. However, further validation of our findings in a larger cohort is needed.ARTICLE HIGHLIGHTS: Why did we undertake this study? We believed this cohort of twins discordant for type 1 diabetes (T1D) would allow for control over genetic variability to examine environmental factors.What is the specific question(s) we wanted to answer? We aimed to identify differences in microbial and microbiota-associated metabolites in twins discordant for T1D to examine the effect of the gut microbiome on T1D.What did we find? Thirteen metabolites were identified as significantly different.What are the implications of our findings? Our results show the dysregulation of several microbial metabolites in twin pairs, suggesting that the gut microbiome plays a role in the pathogenesis of T1D.PMID:40034756 | PMC:PMC11875319 | DOI:10.1101/2025.02.20.25322611

Front Immunol. 2025 Feb 17;16:1534009. doi: 10.3389/fimmu.2025.1534009. eCollection 2025.ABSTRACTINTRODUCTION: Macrophages, which tend to aggregate in the hypoxic regions of tissues, have a significant impact on disease progression and outcome because of their plastic responsiveness to hypoxia, particularly in the early stages. Understanding macrophages'participation in hypoxia-related disorders requires demonstrating the impact of acute hypoxia on their survival, phenotype, and function.METHODS: Here we conducted a systematic evaluation of macrophage responses to hypoxia over 24 and 48 h including cell growth and activity, inflamatory response, macrophage polarization and transcriptional and metabolic changes.RESULTS: We found that acute hypoxia suppresses macrophage proliferation and phagocytosis function with a parallel change of transcriptome re-programming and metabolic re-modeling. Although macrophages accumulate transcriptome heterogeneity based on oxygen concentration and culture period, genes involved in hypoxia response, chemotaxis, and glycolytic process were commonly altered during acute hypoxia. Furthermore, the pro-inflammatory response of macrophages was activated during acute hypoxia concomitantly with an enhanced anti-inflammatory regulatory mechanism characterized by increased M2 macrophage population and anti-inflammatory metabolite itaconic acid. Aside from increased glycolysis, the key intermediates in the pentose phosphate pathway significantly increased, such as fructose 1,6-bisphosphate (fold change: 7.8), 6-phosphogluconate (fold change: 6.1), and ribose 5-phosphate (fold change: 3.9), which indicated that the pentose phosphate pathway was an important compensatory metabolic regulation that rules for the response of macrophages to acute hypoxia.DISCUSSION: These findings highlight that acute hypoxia suppresses macrophage viability and phagocytosis, while acute hypoxia modifies the transcriptome and metabolome in specific inflammatory responses and metabolic pathways to facilitate the adaptation of macrophage in hypoxic conditions.PMID:40034701 | PMC:PMC11872928 | DOI:10.3389/fimmu.2025.1534009

Anim Nutr. 2024 Dec 3;20:376-386. doi: 10.1016/j.aninu.2024.11.009. eCollection 2025 Mar.ABSTRACTThe objectives of the experiment were to compare the effects of rumen-protected taurine (RPT) and rumen-protected methionine (RPM) on the nitrogen (N) metabolism, plasma biochemical parameters, and metabolomics in beef steers and to clarify whether taurine plays similar roles as methionine (Met) in the regulation of N metabolism in beef steers. Six Simmental steers aged 12 months (liveweight 325 ± 7 kg) were used as experimental animals. The experimental treatments included a basal diet, the basal diet + 70.0 g/d RPT and the basal diet + 74.2 g/d RPM. The treatments were assigned in a replicated 3 × 3 Latin square design. Each experimental period included 15 d for adaptation and 5 d for sampling. The results showed that supplementing the diet with RPT or RPM did not affect the apparent nutrient digestibility (P > 0.05). Supplementing the diet with RPT or RPM increased the N retention (P < 0.05) and the N utilization efficiency (NUE) (P < 0.05) and decreased the urinary excretion of 3-methylhistidine (P < 0.05) and the estimated skeletal protein degradation rate (P < 0.05). Supplementing the diet with RPT increased the plasma concentrations of taurine (P < 0.001), cysteine (P = 0.010), valine (P = 0.013) and total non-essential amino acids (NEAA) (P = 0.047) and tended to increase the plasma concentrations of essential amino acids (EAA) + NEAA (P = 0.087), but it did not affect the plasma concentrations of total EAA (P > 0.05). Supplementing the diet with RPM increased the plasma concentrations of methionine (P = 0.033), lysine (P = 0.047), cysteine (P = 0.007), leucine (P = 0.046), isoleucine (P = 0.046), valine (P = 0.034), total EAA (P = 0.028), total NEAA (P = 0.004) and EAA + NEAA (P = 0.004). The plasma metabolomics profiling revealed that supplementing the diet with RPT upregulated the plasma concentrations of taurine (P < 0.001), L-cysteine (P = 0.004) and some amino acid (AA) analogues (P < 0.05) and RPM upregulated the plasma concentrations of Met (P = 0.021), L-isoleucine (P = 0.036), L-tryptophan (P = 0.006) and some AA analogues (P < 0.05). In conclusion, taurine has similar impacts to Met in improving the N retention and the NUE in beef steers. Taurine deficiency negatively affects the NUE of beef steers. Supplementation of the diet with taurine is beneficial to the N utilization in beef steers.PMID:40034455 | PMC:PMC11872661 | DOI:10.1016/j.aninu.2024.11.009

J Alzheimers Dis Rep. 2024 Dec 4;8(1):1611-1638. doi: 10.1177/25424823241296740. eCollection 2024.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is a growing public health problem in the aging population, with limited treatment options. We previously reported that Centella asiatica herb water extract (CAW) attenuates cognitive decline in murine models of AD and aging.OBJECTIVE: To explore changes in the hippocampal metabolome associated with CAW's modulation of cognitive function and amyloid-β (Aβ) plaque load in aged Tg2576 and wild-type (WT) mice.METHODS: We compared cognitive function, hippocampal Aβ plaque burden, and hippocampal metabolite profile in 20-month-old Tg2576 female mice and their WT littermates following 3-5 weeks treatment with CAW (0, 200, or 1000 mg/kg/d p.o.). Cognitive testing included contextual fear response (CFR) and novel object recognition task (NORT). Aβ plaque burden was measured via immunohistochemistry. Metabolomic profiles of mouse hippocampi were obtained using liquid chromatography coupled with high resolution tandem mass spectrometry.RESULTS: CAW treatment resulted in dose-related improvements in CFR and NORT performance of Tg2576 and WT mice. However, while CFR correlated with neurosignaling and glycosylated ceramide levels, NORT performance correlated with lysophosphatidylcholines and oxidized metabolites, and Aβ accumulation was linked to elevated excitatory and suppressed inhibitory neurotransmission. Only a subset of the metabolite changes induced by CAW in Tg2576 mice represented a reversal of metabolite differences between Tg2576 and WT mice, suggesting the involvement of other pathways in CAW's cognitive effects.CONCLUSIONS: Mechanisms underlying CAW's cognitive effects extend beyond reversing metabolic effects of Aβ accumulation. The data support the potential use of CAW to manage memory challenges in aged individuals with or without AD.PMID:40034352 | PMC:PMC11863750 | DOI:10.1177/25424823241296740

Heliyon. 2025 Feb 8;11(4):e42565. doi: 10.1016/j.heliyon.2025.e42565. eCollection 2025 Feb 28.ABSTRACTMaize (Zea mays) is one of the most important cereal crops worldwide. Insect control through host plant resistance plays an important part in improving both yield and quality of maize. Spodoptera exigua is a common insect pest causing destructive damages to maize. To comprehensively understand molecular mechanism of maize defense against S. exigua, integrated transcriptomics and metabolomics analyses were conducted in the insect-resistant maize inbred line CML139 infested with S. exigua for 24 h. 9845 differentially expressed genes and 34 significantly changed metabolites were identified in infested leaves. Maize transcriptional response to S. exigua infestation involved in genes encoding enzymes in biosynthetic process (ribosome, glycerolipid, glycerophospholipid metabolism), genes in valine, leucine and isoleucine degradation, phenylpropanoid pathway and transcription factors. By metabolism analysis, accumulations of amino acids, organic acids, phenylpropanoids and benzoxazinoids (Bxs) were significantly enhanced, with the exception of salicylic acid (SA) and jasmonic acid (JA). The integrated analysis of transcriptomic and metabolic data demonstrated that both transcripts and metabolites involved in phenylpropanoid and Bxs biosynthesis were differentially modulated in S. exigua infested leaves. This study is valuable in understanding the complex mechanism of interaction between plants and insect herbivores and provide a potential strategy to maize pest control.PMID:40034323 | PMC:PMC11872508 | DOI:10.1016/j.heliyon.2025.e42565

Food Sci Nutr. 2025 Mar 2;13(3):e70027. doi: 10.1002/fsn3.70027. eCollection 2025 Mar.ABSTRACTA low-temperature condition in a root zone is a major abiotic stress that threatens cucumber (Cucumis sativus L.) growth and development, yet the molecular mechanism by which the leaf reacts to root zone chilling stress remains largely unknown. In this study, we applied three temperature treatments, including room temperature (20°C-22°C), suboptimal temperature (13°C-15°C), and low temperature (8°C-10°C), to investigate how root zone chilling affects hormone dynamics, metabolomics, and transcriptomics in the leaves of the cucumber variety "Jinyou 35", the main cultivar in northwest and southwest China. Through integrative physiological and biochemical analysis, auxin emerges as the most significant accumulated hormone, accounting for 88% in room temperature-treated leaves (RL), 99% in suboptimal temperature-treated leaves (SL), and 94% in low-temperature-treated leaves (LL). Under chilling stress, flavanones were the most abundant metabolite in cucumber leaves, constituting over 50% of total metabolites, while phenolic acids showed a marked decrease. Several differentially expressed transcription factors (DETFs), such as LOB (CsaV3_3G020650), MYB (CsaV3_3G043510), and bHLH (CsaV3_2G005070 and CsaV3_4G029740), were upregulated in SL and LL, potentially enhancing cucumber's defense against chilling injury. Additionally, terminal flower formation was observed under suboptimal and low-temperature conditions, with CsFT expression in SL and LL lower than in RL, and a significant negative correlation observed between CsFT and CsNAC6. These findings deepen our understanding of cucumber's resilience mechanisms to root zone chilling stress, shedding light on its cold tolerance strategies.PMID:40034224 | PMC:PMC11873373 | DOI:10.1002/fsn3.70027

Synth Syst Biotechnol. 2025 Feb 8;10(2):511-522. doi: 10.1016/j.synbio.2025.02.002. eCollection 2025 Jun.ABSTRACTCorynebacterium glutamicum is a versatile industrial microorganism for producing various amino acids. However, there have been no reports of well-defined C. glutamicum strains capable of hyperproducing l-tryptophan. This study presents a comprehensive metabolic engineering approach to establish robust C. glutamicum strains for l-tryptophan biosynthesis, including: (1) identification of potential targets by enzyme-constrained genome-scale modeling; (2) enhancement of the l-tryptophan biosynthetic pathway; (3) reconfiguration of central metabolic pathways; (4) identification of metabolic bottlenecks through comparative metabolome analysis; (5) engineering of the transport system, shikimate pathway, and precursor supply; and (6) repression of competing pathways and iterative optimization of key targets. The resulting C. glutamicum strain achieved a remarkable l-tryptophan titer of 50.5 g/L in 48h with a yield of 0.17 g/g glucose in fed-batch fermentation. This study highlights the efficacy of integrating computational modeling with systems metabolic engineering for significantly enhancing the production capabilities of industrial microorganisms.PMID:40034180 | PMC:PMC11872490 | DOI:10.1016/j.synbio.2025.02.002

Front Plant Sci. 2025 Feb 17;16:1510184. doi: 10.3389/fpls.2025.1510184. eCollection 2025.ABSTRACTPogostemon cablin (patchouli) is a well-known perennial herbaceous plant for traditional Chinese medicine, and its primary bioactive compounds are patchoulol and pogostone. The biosynthesis pathway of patchouli has been well resolved early, while the biosynthesis pathway of pogostone is still not fully resolved due to the lack of terminal enzyme directly synthesizing pogostone. Here, the present study aims to predict the terminal enzyme of pogostone biosynthesis and reconstruct its most possible complete biosynthesis, through the integrated transcriptomic and metabolomic analysis. The metabolomic and transcriptomic profiles of patchouli leaf were largely different to those of root and stem. Patchoulol analogs like patchoulene and germacrene mainly accumulated in leaf, while pogostone content was much higher in root. Based on the integrated analysis of differentially expressed genes and metabolites, we reconstructed the biosynthesis pathways of patchoulol, and predicted the most likely complete biosynthesis pathway of pogostone. Besides, we identified 29 highly-expressed genes involved in pogostone biosynthesis for the neo-octoploid genome of patchouli, and most of their expression levels were strongly correlated with pogostone content. In particular, patchouli BAHD-DCR acyltransferases (BAHD-DCRs) were phylogenetically distant from but structurally similar to the other known plant BAHD acyltransferases. Most of them possessed the conservative catalysis motif HXXXD, and the catalysis center could bind to the widely recognized substrate molecules of 4-hydroxy-6-methyl-2-pyrone and 4-methylvaleryl-CoA and product molecule of pogostone. Thus, the highly-expressed BAHD-DCRs in patchouli root were proposed to be terminal enzymes directly synthesizing pogostone. The findings here provide more supporting evidence for the medical use of patchouli whole plants, and make an important step forward fully resolving the pogostone biosynthesis pathway. The identified genes involved in pogostone biosynthesis, especially BAHD-DCRs, deserve further investigation and utilization in the synthetic production of pogostone.PMID:40034152 | PMC:PMC11872920 | DOI:10.3389/fpls.2025.1510184