Search Results (13,633)

Salicylic acid (SA) is an important signaling molecule that regulates plant primary and secondary metabolites accumulation. Although SA has been shown to promote folate accumulation, the underlying mechanism remains unclear. In this study, the effect of SA on folate biosynthesis in spinach (Spinacia oleracea L.) and its regulatory mechanisms were investigated. Physiological and metabolomic analyses showed that foliar SA application increased the contents of folate, soluble protein, and soluble sugar and the abundance of 5-methyltetrahydrofolate, p-aminobenzoate (pABA), and Trp, while the abundance of Ser decreased. The expression of aminodeoxychorismate synthase (ADCS) and alkaline phosphatase (ALP) genes in the folate biosynthesis pathway was upregulated, while the expression of five genes in the folate interconversion pathway and two genes in the Phe/Tyr synthesis pathway was downregulated. Fifty-one transcription factors (TFs) showed expression patterns correlated with those of ADCS and ALP and were predicted to bind to their promoter regions. SA upregulated many hormone genes, and 12 of these correlated strongly with both ADCS and ALP. Moreover, transgenic Arabidopsis lines overexpressing SoADCS constitutively displayed higher folate content in leaves. Taken together, our results suggested that SA may promote folate accumulation by enhancing folate precursor supply, and several candidate TFs and hormone-related genes that may be involved in the regulation of this pathway warrant further study. Full article

Pancreatic cancer is among the most aggressive malignancies, and late diagnosis remains a key challenge. For a systematic review of pancreatic cancer diagnosis and prognosis, Scopus and Web of Science databases were used for the period from 2016 to 2026. The search query included the following keywords and their combinations: pancreatic cancer, diagnosis, early detection, prognosis, biomarkers, metabolomic profiling, CA19-9, microbiome, metagenomic changes, circulating tumor DNA, genomic analysis. Inclusion criteria included only articles published in English. Exclusion criteria included case reports and studies that did not examine pancreatic cancer. Our analysis demonstrates that integrating multi-omics data, particularly combining traditional CA19-9 with circulating tumor DNA (ctDNA) and metabolomic profiles (lipids, amino acids, carbohydrates), significantly improves diagnostic accuracy. Microbiome composition and genomic alterations further refine risk stratification and prognostic assessment. The synergistic use of these biomarkers may facilitate the development of screening, early diagnosis, risk stratification, and treatment optimization. However, the introduction of new diagnostic approaches into clinical practice requires additional verification, standardization and prospective clinical studies. Full article

Phenolic acids are known allelopathic compounds that may serve as the primary cause of continuous cropping obstacles in Coix lacryma-jobi L. (Coix). However, the concentrations, types, and specific stress responses of Coix to these phenolic acids still require further investigation. In this study, the cultivar ‘Wanyi 2′ was used to examine the effects of different phenolic acids and their concentrations on the growth of Coix. Four concentrations (0 mg/L, 10 mg/L, 100 mg/L, and 1000 mg/L) and four phenolic acid types (p-hydroxybenzoic acid, salicylic acid, cinnamic acid, and ferulic acid) were used to assess their influences on plant growth, leaf physiological parameters, and metabolic pathways under greenhouse conditions. In this greenhouse pot experiment, the effects of the four phenolic acids showed a similar tendency: a low concentration (10 mg/L) tended to promote the growth and root development of Coix seedlings, whereas high concentrations (100 and 1000 mg/L) generally showed inhibitory effects. Among these phenolic acids, ferulic acid exhibited the strongest inhibitory effect at the highest concentration (1000 mg/L), while salicylic acid showed the most pronounced growth-promoting effect at low concentrations (10 mg/L). In addition, high levels of phenolic acids markedly increased antioxidant enzyme activities and oxidative stress-related substances in Coix leaves, while reducing soluble sugar (SS) and soluble protein (SP) contents. Our data suggest that under phenolic acid stress, Coix leaves exhibited changes in the metabolism of phenolic acids (e.g., 4-methoxysalicylic acid, gallic acid) and amino acids (e.g., glutathione, proline), which may be associated with the adaptive response to allelochemical-induced stress. Overall, this study provides insights that may support strategies to optimize plant growth regulators and mitigate continuous cropping barriers in Coix. Full article

Background/Objectives: This study evaluated the effects of a compound probiotic fermented feed (CPFF) containing Lactobacillus plantarum, Bacillus subtilis, yeast, and Aspergillus niger on rumen in vitro fermentation, in situ feed degradation, and growth performance in beef cattle. Methods: We established a control group (CON) and experimental groups with 2%, 4%, and 8% CPFF supplementation for in vitro fermentation. Results: The results indicated that the NH₃-N concentration in the 4% CPFF group was significantly higher than in the other groups (p < 0.001). Similarly, microbial crude protein (MCP) production was significantly greater in the 4% CPFF group compared to the CON group (p = 0.016). The molar proportions of acetate, butyrate, isobutyrate, and valerate were significantly higher in the 2% and 4% CPFF groups than in the control group (p < 0.001), while propionate levels were significantly lower (p < 0.001). After 48 h, gas production was highest in the 4% CPFF group. Based on improvements in gas production, MCP synthesis, and fermentation intensity, the 4% inclusion level was determined to be optimal for further studies. We conducted an in situ degradation trial using 4% CPFF. Results showed that at 12 h, the neutral detergent fiber (NDF) degradation rate in the 4% CPFF group was significantly higher than in the CON group at 4, 8, 12, and 48 h (p < 0.05). At 48 h, the acid detergent fiber (ADF) degradation rate in the 4% CPFF group was also significantly higher than in the CON group (p < 0.001), and this group exhibited a significant increase in crude protein (CP) degradation (p = 0.030). We analyzed rumen fluid samples from both the CON and 4% CPFF groups after in vitro fermentation using 16S rRNA sequencing and untargeted metabolomics. Microbial community analysis revealed significantly increased abundances of functional bacterial groups such as Rikenellaceae_RC9_gut_group, Christensenellaceae_R-7_group, and UCG-002 in the 4% CPFF group (p < 0.05). Differential metabolites were primarily involved in pathways related to tryptophan metabolism, and tyrosine metabolism signaling. A feeding trial was conducted by adding 4% CPFF to the diet of Angus growing cattle. The results indicated that average daily gain (ADG) (p = 0.004) and average daily feed intake (ADFI) (p = 0.001) were significantly higher in the CPFF group than in the CON group. Conclusions: In conclusion, our results demonstrate that CPFF enhances rumen fermentation activity, optimizes the microbiota and metabolic profiles of rumen fluid, and improves the average daily gain of beef cattle. This research provides a valuable theoretical basis for applying CPFF in beef cattle breeding. Full article

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological interest. This narrative review integrates current evidence on the bioactive composition, mechanistic activities, and translational relevance of S. europaea and related Salicornia species. Their secondary metabolome includes flavonols, isorhamnetin glycosides, hydroxycinnamic acids, oleanane-type triterpene saponins, fermentable polysaccharides, carotenoids, and a mineral-rich ionic matrix. Reported activities span antioxidant, anti-inflammatory, vascular-protective, anti-adipogenic, glycaemic-modulating, antimicrobial, and microbiome-related effects, mediated through pathways involving NF-κB, PPAR-γ, endothelial nitric oxide signalling, and short-chain fatty acid production. Beyond its individual phytochemical components, the matrix as a whole may also support sodium-reduction strategies in food formulation, providing a complementary nutritional rationale for its incorporation as a functional ingredient. Despite a coherent body of mechanistic and preclinical findings, clinical evidence remains limited, particularly regarding long-term efficacy, dose standardisation, and bioavailability in humans. Future work should prioritise adequately powered intervention trials and standardised characterisation of marine halophyte bioactives to clarify their evidence-based role in functional food development and future precision nutrition applications. Full article

Good canine gastrointestinal health depends on the suppression of enteric pathogens and maintenance of epithelial barrier integrity. Limosilactobacillus reuteri ATCC PTA 6127 (Lr6127) is a dog-derived probiotic, but evidence supporting its functional properties remains limited. Here, we evaluated the antimicrobial and epithelial-supportive effects of Lr6127 using a canine epithelial cell model. Cell-free supernatant (CFS) from Lr6127 significantly inhibited the growth of canine-relevant pathogens, including Enterotoxigenic Escherichia coli (52.0 ± 1.3%), Clostridium perfringens (54.0 ± 2.7%), and Salmonella enterica subsp. enterica serovar Typhimurium (48.6 ± 1.2%), compared with the medium control (p < 0.0001). Pathogen inhibition increased in a dose-dependent manner with increasing CFS concentration. Untargeted metabolomic analysis revealed enrichment of multiple antimicrobial-associated metabolites, indicating a multi-component profile consistent with pathogen suppression, with genomic analysis supporting the aromatic amino acid-derived metabolite findings. In addition, viable Lr6127 significantly reduced the epithelial adhesion of all the tested pathogens (p < 0.01). Beyond direct antimicrobial effects, Lr6127 CFS promoted epithelial wound healing at later time points, accompanied by the coordinated modulation of proteins associated with cytoskeletal remodeling and barrier repair. Collectively, these findings support the idea that Lr6127 is associated with antimicrobial and epithelial-related effects, highlighting its potential to contribute to epithelial function under controlled in vitro conditions. Full article

Anti-nutritional factors (ANFs) in terrestrial plant feeds constrain efficient herbivore production, an issue intensified by rising feed costs and growing demand for animal products. Unlike previous reviews that focus on single ANFs or feed types, this review provides an integrated, cross-species framework linking ANF chemistry, rumen microbial interactions, and mitigation strategies. It examines major ANF classes—tannins, phytates, saponins, oxalates, protease inhibitors, lectins, glucosinolates, and gossypol—and their distribution and biochemical modes of action. Mechanistic pathways are grouped into digestive effects (reduced palatability and enzyme inhibition), microbial effects (altered rumen microbiota and fermentation), metabolic effects (impaired absorption), and mineral interactions (nutrient complexation and chelation). Species-specific responses are evaluated, emphasizing the partial detoxification capacity of the rumen microbiome and the dose-dependent nature of ANF effects. Mitigation strategies—physical, chemical, microbial, enzymatic, probiotic, and genetic—are critically assessed for efficacy, scalability, and sustainability. Emerging metabolomic and metagenomic evidence shows that certain ANFs confer functional benefits at controlled doses; for example, tannins improve nitrogen retention, saponins reduce methane, and phytic acid scavenges free radicals. This synthesis supports strategic management rather than complete elimination, informing safe and sustainable use of terrestrial feeds under evolving food-security and environmental challenges. Full article

The protective effects of Lactobacillus murinus on chemotherapy-related intestinal injury and immune imbalances were explored by establishing a cyclophosphamide (CTX)-induced mouse model of immunosuppression. CTX treatment led to intestinal barrier destruction, exacerbated local inflammation, and significantly reduced short-chain fatty acid levels (especially butyrate), accompanied by systemic immune suppression. Lactobacillus murinus intervention, especially at medium and high doses, dose-dependently repaired the intestinal barrier, inhibited inflammatory responses, restored levels of metabolites such as butyrate, and systematically regulated splenic immune cell proportions, restoring the CD4⁺/CD8⁺ balance. Metabolomic analysis further revealed that, at different doses, this regulation affected distinct metabolic pathways: low doses enhanced glutathione and purine metabolism, medium doses restored folate and steroid hormone metabolism, and high doses promoted fatty acid β-oxidation and galactose metabolism, forming a multi-level metabolic protective network. This suggests that L. murinus can alleviate chemotherapy-induced intestinal mucositis and mitigate systemic immune suppression through a dual local anti-inflammatory and systemic immune-regulatory effect, with potential mechanisms related to butyrate-mediated regulation of the “metabolism–immune axis,” providing evidence for probiotic-assisted chemotherapy. Full article

Influenza virus outbreaks remain a persistent public health concern, yet traditional metabolomics methods are inadequate for addressing key analytical challenges of “dark matter” in influenza research. By integrating quantitative MS¹ data, MS²-derived fragmentation trees and molecular fingerprints, structure-based comparative metabolomics enhances predictive capability for chemical structures, and enables the discovery of candidate metabolic markers without the need for database spectra. In this study, we established a C57BL/6J mouse model of H1N1 infection (with PBS as control) and performed structure-based comparative metabolomics on fecal samples using liquid chromatography–mass spectrometry (LC-MS). Quantitative analysis of MS¹ data identified 40 differential metabolites, while qualitative analysis of MS² data enabled their structural annotation. A candidate metabolite marker, LysoPE 15:0, along with other potential metabolic markers, was annotated and validated using Mirror plot, CFM-ID, and sim-Rank-Network. Our findings demonstrate that structure-based comparative metabolomics enables library spectra-free annotation of metabolomic “dark matter” and provides a methodological workflow for discovering candidate metabolite markers in other diseases. Full article

Background: Hugan tablets (HGP) are a commercially available traditional Chinese medicine preparation used for liver disorders, but the mechanisms underlying their effects on alcoholic liver injury (ALI) remain incompletely understood. This study investigated the hepatoprotective effects and potential mechanisms of HGP in ALI. Methods: An ALI mouse model was established using a Lieber–DeCarli ethanol liquid diet. The effects of HGP were evaluated using biochemical and histopathological assessments, followed by integrated liver and serum metabolomics, liver transcriptomics, and ELISA-based protein validation. Results: HGP alleviated alcohol-induced liver injury, hepatic lipid accumulation, oxidative stress, and inflammatory responses. Integrated multi-omics analyses indicated that HGP treatment was associated with changes in hepatic glutathione metabolism, PPAR signaling, and antioxidant-related processes. ELISA validation showed increased measured concentrations in liver homogenate supernatants of PPARγ, NRF2, GCL, and GPX4 following HGP treatment. These findings support the potential involvement of a PPARγ/NRF2/GPX4-related antioxidant network. Conclusions: HGP alleviated ALI in mice, and its effects may be associated with modulation of hepatic glutathione metabolism and a PPARγ/NRF2/GPX4-related antioxidant network. These findings provide experimental evidence for the potential use of HGP in alcohol-induced liver injury. Full article

The widespread environmental presence of microplastics has led to their increasing co-occurrence with pesticides in agricultural soils, which raises concerns about their potential combined effects on pollutant behavior and toxicity. In this study, we investigated the environmental fate of boscalid and its toxicity to earthworms under co-exposure with two types of microplastics. Both polyethylene microplastics (PE) and polylactic acid microplastics (PLA) significantly enhanced boscalid retention in soil and delayed its degradation. Co-exposure impaired intestinal barrier function, promoted boscalid bioaccumulation, and triggered more severe oxidative stress and metabolic disturbances in earthworms. Notably, differences were observed between PE and PLA in their effects on boscalid behavior and earthworm responses. Our study suggests that microplastics may influence the ecological risk of boscalid through potential carrier effects and biological interface interactions and indicates mechanistic differences between conventional and biodegradable microplastics in modulating pesticide toxicity. These findings offer new insights into the environmental risk assessment of combined pollution. Full article

Citrus aurantium L. is a citrus-derived functional food rich in various phenolic compounds, including flavonoids. However, the bioavailability of its phytochemicals and sensory quality remain limited. This study investigated the effects of ultrasound-assisted fermentation by Lactiplantibacillus plantarum on microbial growth, phytochemical transformation, antioxidant activity, and metabolic profiles of C. aurantium. Ultrasound treatments were applied at different fermentation stages and power levels, among which treatment at 100 W during the exponential growth phase (ULP4) exhibited the best overall performance. Compared with conventional fermentation by L. plantarum (LP), ULP4 significantly promoted microbial growth, accelerated acidification, enhanced carbohydrate utilization, and stimulated β-glucosidase activity compared with conventional fermentation. Consequently, total phenolic content, total flavonoid content, and antioxidant capacities were markedly improved. Untargeted full-MS/MS metabolomic analysis revealed extensive metabolic alterations following ultrasound treatment, with 335 metabolites significantly altered between LP and ULP4. Differential metabolites were mainly associated with flavone and flavonol biosynthesis, secondary metabolite biosynthesis, amino acid metabolism, and lipid metabolism. These metabolic changes were closely associated with improved antioxidant properties and functional quality. Overall, ultrasound treatment during the exponential growth phase effectively enhanced microbial metabolism and phytochemical transformation, offering a promising strategy to improve the functional value of fermented C. aurantium products. Full article

Brown algae are important primary producers in coastal ecosystems, where they provide habitat and food for numerous marine species. For humans, they provide raw materials (food, animal feed, and ingredients for pharmaceuticals and cosmetics) as well as ecosystem services such as coastal protection and carbon sequestration. The molecular characterization of brown algae is necessary to understand their role in ecosystems, their biochemical resources, and responses to environmental stresses—knowledge that is crucial for the sustainable use and biotechnological applications of seaweed. Within this context, we analyzed more than 300 primary and secondary metabolites by gas chromatography–mass spectrometry to elucidate the metabolic profiles of seven habitat-forming species of brown algae in the arctic and temperate seas. Metabolite profiles were discussed considering physiological and ecological characteristics of the different algae, thus revealing the taxon-specific biochemical signatures and metabolite patterns contributing to seaweed adaptation to their typical habitats. Three important groups of metabolites representing polyols, phenolic compounds, and organic acids, were analyzed and discussed in more detail. Our study revealed metabolic diversity of species from the same order and genus, thereby indicating a very distinct regulation at the molecular level to meet metabolic needs of the habitat. The knowledge of different compositions of algal extracts can be used to develop specialized applications for humans in cosmetic, medical, or nutritional sectors. Full article

Background: Hypertension-induced vascular injury involves endothelial dysfunction, inflammation, and oxidative stress, leading to vascular remodeling and cardiovascular complications. Flavin-containing monooxygenase 2 (FMO2) has been implicated in redox regulation, but its role in hypertensive vascular injury remains unclear. This study investigated whether KuJiang GanLuoYin (KJGLY) protects against hypertensive vascular injury and whether FMO2-associated Fat mass and obesity-associated protein (FTO)/N6-methyladenosine (m⁶A) signaling is involved. Methods: Spontaneously hypertensive rats (SHRs) were treated with KJGLY for eight weeks. Blood pressure, vascular remodeling, inflammation, oxidative stress, and global m⁶A RNA methylation were assessed. Integrated metabolomic and proteomic analyses were performed to identify treatment-associated molecular alterations and candidate proteins. AAV9-mediated FMO2 knockdown in SHRs and gain- and loss-of-function approaches in angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells were used to examine the functional involvement of FMO2. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based chemical profiling and High-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) quantification were performed to characterize the major constituents of KJGLY. Results: KJGLY significantly reduced blood pressure and alleviated vascular remodeling in SHRs. Metabolomic and proteomic analyses revealed treatment-associated alterations in inflammatory and lipid metabolic pathways and identified FMO2 as a treatment-responsive candidate. KJGLY restored FMO2 expression, reduced FTO abundance and NF-κB activation, increased global m⁶A levels, and attenuated inflammatory and oxidative stress responses in hypertensive aortas. Conversely, AAV9-mediated FMO2 knockdown aggravated vascular injury, enhanced inflammation and oxidative stress, reduced global m⁶A levels, and increased NF-κB activation. Co-immunoprecipitation showed an association between FMO2 and FTO, and MeRIP-qPCR indicated that FMO2 manipulation altered m⁶A enrichment of VCAM-1 mRNA. In Ang II-stimulated endothelial cells, linarin, the most abundant quantified constituent of KJGLY, partially recapitulated the cellular effects of KJGLY, including restoration of FMO2/FTO-associated signaling and attenuation of inflammatory activation. Conclusions: These findings support a functional role for FMO2 in hypertensive vascular injury and suggest that FMO2-associated modulation of FTO/m⁶A signaling may contribute to the vascular protective effects of KJGLY. Linarin recapitulated key protective effects in vitro, although its in vivo contribution to the formula remains to be determined. Full article

Training induces sweat morphology changes in horses from muddy sweat (MS) to foamy sweat (FS) and clear sweat (CS), reflecting physiological adaptation. However, the metabolic mechanisms linking sweat phenotypes to systemic amino acid dynamics remain unclear. This study integrated sweat untargeted metabolomics and plasma amino acid targeted metabolomics to reveal coordinated metabolic remodeling. Six 2-year-old Yili horse stallions underwent 10-week training. Plasma and sweat were sampled pre- and post-race at each stage. LC-MS/MS and UHPLC-MS/MS were used for sweat metabolome and plasma amino acid analysis, followed by multivariate statistics, KEGG enrichment, and correlation network (CNet) analysis. Differential sweat metabolites decreased across stages (45, 127, and 38 for MS vs. FS, MS vs. CS, and FS vs. CS). Pre-race BCAA concentrations were higher in MS than in FS and CS, while glycine was lower. Post-race valine, histidine, and aspartate were elevated only in MS. Pre-race plasma amino acids positively correlated with sweat lipids and organic acids, shifting to negative post-race. ABC transporters, mTOR signaling, and BCAA metabolic pathways were key co-regulators. The MS-to-CS transition reflects metabolic remodeling from acute stress to homeostatic adaptation. Plasma BCAAs and sweat cortisol are potential biomarkers, with ABC transporters and mTOR pathways mediating sweat-plasma metabolic coordination. Full article