PubMed

Life (Basel). 2025 Mar 18;15(3):486. doi: 10.3390/life15030486.ABSTRACTPlants experience various abiotic stresses, among which pollutant stress is one of the most damaging, threatening plant productivity and survival. Thiocyanate (SCN-), a recalcitrant byproduct of industrial processes, poses escalating threats to agroecosystems by disrupting plant hormonal homeostasis, which is critical for stress adaptation. Here, we dissect the regulatory interplay of phytohormones in rice (Oryza sativa L.) under SCN- stress (4.80-124.0 mg SCN/L) through integrated transcriptomic and metabolomic profiling. Quantitative hormonal assays revealed dose- and tissue-specific perturbations in phytohormone homeostasis, with shoots exhibiting higher sensitivity than roots. Transcriptomic analysis revealed that a number of differentially expressed genes (DEGs) mapped in different phytohormone pathways in SCN--treated rice seedlings, and their transcript abundances are tissue-specific. To identify the phytohormones governing rice's sensitivity to SCN- stress, we developed a Total Hormonal Sensitivity Index (THSI) through an integrative multivariate framework, which combines Modified Variable Importance in Projection (VIP(m)) scores to quantify hormonal fluctuations and Total Weighted Contribution Scores (TWCS) at the gene-level from hormonal pathways. This study establishes a system-level understanding of how phytohormonal crosstalk mediates rice's adaptation to SCN- stress, providing biomarkers for phytoremediation strategies in contaminated paddies.PMID:40141830 | DOI:10.3390/life15030486

Life (Basel). 2025 Mar 5;15(3):408. doi: 10.3390/life15030408.ABSTRACTPostpartum dairy cows often face significant challenges due to metabolic disorders. Danggui Buxue Tang (DBT), a botanical drug composed of Astragali radix and Angelica sinensis radix in a 5:1 ratio, has been recognized for its potential to alleviate metabolic disorders. Its regulatory mechanisms on livestock metabolic health have remained unexplored. This study integrated the analyses of serum pharmacochemistry, network pharmacology, serum metabolomics, and fecal microbiota to investigate the regulatory effects of DBT on metabolic adaptation in postpartum dairy cows. Following the oral administration of DBT, levels of blood non-esterified fatty acids and beta-hydroxybutyrate were decreased in multiparous dairy cows one week after calving. Five absorbed prototype metabolites of DBT were identified, specifically formononetin and nicotinic acid, both of which play roles in the regulation of lipid metabolic homeostasis. Furthermore, DBT modified the composition of the gut microbial community and glycerophospholipid levels. Decreases in serum phosphatidylethanolamine and phosphatidylcholine levels were closely correlated with the relative abundance of Bacillus and the concentration of circulating beta-hydroxybutyrate. These findings suggest that DBT contributes positively to metabolic health in postpartum dairy cows by regulating the gut microbiota and glycerophospholipid metabolism, providing new insights into strategies for promoting metabolic adaptation in dairy cows.PMID:40141753 | DOI:10.3390/life15030408

Int J Mol Sci. 2025 Mar 20;26(6):2805. doi: 10.3390/ijms26062805.ABSTRACTBacteriophage therapy is a promising approach for targeting antibiotic-resistant bacteria and modulating gut microbiota in metabolic diseases such as obesity. This study evaluated the impact of a two-phage cocktail on an ex vivo colonic simulation model of gut microbiota derived from obese individuals, both in its normalized state and after enrichment with Enterobacter cloacae, an obesity-related bacteria. Microbiological analyses confirmed that the phage cocktail remained active throughout the colonic regions over three digestion cycles and effectively reduced enterobacterial populations in the enriched microbiota. Metabarcoding of the 16S rRNA gene revealed that phage therapy did not significantly alter the abundance of dominant genera, but selectively reduced E. cloacae across all colonic regions. Alpha diversity was significantly affected only in the enriched microbiota, while beta diversity analysis indicated significant compositional shifts during therapy, with reduced dispersion in the final treatment stage. Short-chain fatty acid profiling demonstrated region- and group-specific metabolic responses, with increased lactic and butyric acid concentrations in the ascending colon of the enriched microbiota following phage treatment. This study provides the first ex vivo evidence that a two-phage cocktail can selectively eliminate E. cloacae while preserving overall microbiota structure and functionality. These findings establish a foundation for future in vivo studies exploring the role of phage therapy in reshaping gut microbial communities and metabolic profiles, highlighting its potential as a precision tool for managing gut dysbiosis in metabolic disorders.PMID:40141446 | DOI:10.3390/ijms26062805

Int J Mol Sci. 2025 Mar 18;26(6):2722. doi: 10.3390/ijms26062722.ABSTRACTGrowing neurochemical evidence highlights cerebral lipid dysregulation as a key factor in the pathophysiology of major depressive disorder (MDD). This review systematically explores the dual roles of lipid species in both normal behavioral regulation and MDD development. By critically examining the recent literature, we classify these lipid species into two functional categories based on their functional neuroactivity: (1) neuroprotective lipids (sphingomyelin, cholesterol, cardiolipin, sphingosine, phosphatidic acid, and phosphatidylserine), which exert neuroprotective effects by modulating membrane fluidity and supporting synaptic vesicle trafficking; and (2) neurotoxic lipids (ceramides, phosphatidylinositol, phosphocholine, and phosphatidylethanolamine), which promote apoptotic signaling cascades and disrupt mitochondrial bioenergetics. An unresolved but critical question pertains to the maintenance of homeostatic equilibrium between these opposing lipid classes. This balance is essential, given their significant impact on membrane protein localization and function, monoaminergic neurotransmitter metabolism, energy homeostasis, and redox balance in neural circuits involved in mood regulation. This emerging framework positions cerebral lipidomics as a promising avenue for identifying novel therapeutic targets and developing biomarker-based diagnostic approaches for MDD treatment.PMID:40141364 | DOI:10.3390/ijms26062722

Int J Mol Sci. 2025 Mar 18;26(6):2719. doi: 10.3390/ijms26062719.ABSTRACTThe aim of this study was to gain insight into the biochemical status of cerebrospinal fluid in the presence of brain death in life-supported patients. The biochemical status was determined via in vitro NMR spectroscopy of cerebrospinal fluid (CSF) obtained by lumbar puncture from 22 patients with confirmed brain death and compared with that of 34 control patients (without neurological diseases). Forty-one NMR signals from raw CSF samples and 20 signals from lipid extracts were analyzed using univariate and multivariate statistical methods. ANOVA revealed significant differences in all analyzed signals. No single biochemical marker was found to predict brain death. The CSF metabolic profiles of patients who died differed significantly from those of patients in the control group. There were many statistically significantly different compounds, including amino acids, ketone bodies, lactate, pyruvate, citrate, guanidinoacetate, choline, and glycerophosphocholine. Analysis of lipids revealed significant differences in cholesterol, estriol, and phosphoethanolamine. Discriminant analysis allows the analysis of metabolic profiles instead of single biomarkers of cerebrospinal fluid compounds. The results of our analysis allowed us to split the groups-the control group, which consisted of patients with a normal biochemical CSF composition, and the brain death group-with confirmed brain death.PMID:40141360 | DOI:10.3390/ijms26062719

Int J Mol Sci. 2025 Mar 17;26(6):2703. doi: 10.3390/ijms26062703.ABSTRACTHeart failure (HF) is a complex, heterogeneous syndrome with rising prevalence and high morbidity and mortality. The pathophysiology and diverse etiologies of HF present significant challenges for developing effective therapies. Omics technologies-including genomics, proteomics, transcriptomics, metabolomics, and epigenomics-have reshaped our understanding of HF at the molecular level, uncovering new biomarkers and potential therapeutic targets. Omics also enable insights into individualized treatment responses, the risks of adverse drug effects, and patient stratification for clinical trials. This review explores how multi-omics can enhance heart failure drug discovery and development across all stages of the therapeutic pipeline: (1) target selection and lead identification, (2) preclinical studies, and (3) clinical trials. By integrating omics approaches throughout the drug development process, we can accelerate the discovery of more effective and personalized therapies for heart failure.PMID:40141349 | DOI:10.3390/ijms26062703

Int J Mol Sci. 2025 Mar 16;26(6):2669. doi: 10.3390/ijms26062669.ABSTRACTPanax quinquefolius is a globally valued medicinal plant rich in bioactive flavonoids, yet the molecular mechanisms underlying their biosynthesis remain poorly understood. In this study, we integrated transcriptomic and metabolomic analyses to investigate tissue-specific flavonoid accumulation and regulatory networks in roots, leaves, and flowers. Metabolomic profiling identified 141 flavonoid metabolites, with flavones, flavonols, and C-glycosylflavones predominantly enriched in aerial tissues (leaves and flowers), while specific glycosides like tricin 7-O-acetylglucoside showed root-specific accumulation. Transcriptome sequencing revealed 15,551-18,946 DEGs across tissues, and the reliability of the transcriptomic data was validated by qRT-PCR. KEGG and GO annotation analyses suggested that these DEGs may play a crucial role in the biosynthesis and metabolism of secondary metabolites. From the DEGs, UGTs and MYB TFs were identified and subjected to correlation analysis. Functional validation through in vitro enzymatic assays confirmed that PqUGT71A1 catalyzes apigenin and naringenin glycosylation at the 7-OH position. Additionally, subcellular localization and yeast one-hybrid assays demonstrated that PqMYB7 and PqMYB13 interact with the PqUGT71A1 promoter and activate its expression.. This study unveils the spatial dynamics of flavonoid metabolism in P. quinquefolius and establishes a MYB-UGT regulatory axis, providing critical insights for metabolic engineering and bioactive compound optimization in medicinal plants.PMID:40141311 | DOI:10.3390/ijms26062669

Int J Mol Sci. 2025 Mar 15;26(6):2661. doi: 10.3390/ijms26062661.ABSTRACTThe mortality rate of breast cancer remains high, despite remarkable advances in chemotherapy. Therefore, it is imperative to identify new treatment options. In the present study, we investigated whether the metabolite ribitol enhances the cytotoxic effect of shikonin against breast cancer in vitro. Here, we screened a panel of small molecules targeting energy metabolism against breast cancer. The results of the study revealed that ribitol enhances shikonin's growth-inhibitory effects, with significant synergy. A significant (p < 0.01) increase in the percentage (56%) of apoptotic cells was detected in the combined treatment group, compared to shikonin single-treatment group (38%), respectively. The combined ribitol and shikonin treatment led to significant arrest of cell proliferation (40%) (p < 0.01) compared to untreated cells, as well as the induction of apoptosis. This was associated with upregulation of p53 (p < 0.05) and downregulation of c-Myc (p < 0.01), Bcl-xL (p < 0.001), and Mcl-1 (p < 0.05). Metabolomic analysis supports the premise that inhibition of the Warburg effect is involved in shikonin-induced cell death, which is likely further enhanced by dysregulation of glycolysis and the tricarboxylic acid (TCA) cycle, afflicted by ribitol treatment. In conclusion, the present study demonstrates that the metabolite ribitol selectively enhances the cytotoxic effect mediated by shikonin against breast cancer in vitro.PMID:40141303 | DOI:10.3390/ijms26062661

Int J Mol Sci. 2025 Mar 14;26(6):2650. doi: 10.3390/ijms26062650.ABSTRACTSeborrheic dermatitis (SD) is a chronic inflammatory skin condition often involving the sebaceous-rich areas, characterized by erythematous scaly lesions. It is frequently observed in individuals with immune dysregulation, suggesting the interplay between the immune system and disease development. An altered immune environment leads to an exaggerated inflammatory response with the activation of innate immunity, involving the participation of mast cells, γδ T cells, and the NOD-LRR-pyrin-domain-containing protein 3 (NLRP3) inflammasome. This review aims to assess the complex relationship between Malassezia and the immune system in the pathogenesis of SD. We will explore how an impaired immune response predisposes the skin to Malassezia overgrowth and infection. We will examine the role of adaptive immunity, particularly T helper cells, in driving chronic inflammation in SD. All actors involved, whether part of innate or adaptive immunity, are responsible for the release of pro-inflammatory cytokines, which contribute to the progression of the disease. Therapeutic strategies aimed at the modulation of the immune response in SD have been tested in clinical trials evaluating the efficacy of immunomodulatory treatments in the management of SD. This review synthesizes insights from immunological studies and clinical trials to present an in-depth analysis of the immune mechanisms underpinning SD, thereby proposing targeted therapeutic strategies for its management.PMID:40141293 | DOI:10.3390/ijms26062650

Int J Mol Sci. 2025 Mar 14;26(6):2651. doi: 10.3390/ijms26062651.ABSTRACTCervical cancer is the fourth leading cause of cancer mortality in women worldwide, with limited therapeutic options for advanced or recurrent cases. In this study, the effects of a recent thieno[2,3-b]pyridine derivative, (E)-3-amino-5-(3-bromophenyl)acryloyl)-N-(3-chloro-2-methylphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide (compound 1), on two cervical cancer cell lines, HeLa and SiHa, are investigated. Cytotoxicity was assessed by MTT assay, apoptosis rates were measured by flow cytometry, and metabolic profiling was performed by GC-MS. The study also examined the expression of eight glycosphingolipids (GSLs) in cancer stem cells (CSCs) and non-CSCs to assess glycophenotypic changes. Compound 1 showed significant cytotoxicity in both cell lines, with apoptosis identified as the primary mechanism of cell death. A significant reduction in the CSC population was observed, particularly in the SiHa cell line. Compound 1 treatment altered GSL expression and decreased GM2 levels in both CSCs and non-CSCs in the SiHa cell line and Gg3Cer levels in the HeLa cell line. Metabolic profiling identified 23 and 21 metabolites in the HeLa and SiHa cell lines, respectively, with significant differences in metabolite expression after treatment. These results underscore the potential of compound 1 as a promising therapeutic candidate for cervical cancer and warrant further investigation in preclinical and clinical settings.PMID:40141292 | DOI:10.3390/ijms26062651

Int J Mol Sci. 2025 Mar 13;26(6):2604. doi: 10.3390/ijms26062604.ABSTRACTNeuropathic pain (NP) is a type of chronic pain resulting from injury or dysfunction of the nerves or spinal cord. Previous studies have shown that the combination of ligustrazine (LGZ) and sinomenine (SIN) exerts a synergistic antinociceptive effect in peripheral and central NP models. On this basis, a comprehensive analgesic evaluation was performed in a chronic constriction injury (CCI)-induced NP model in rats. Sciatic nerve histopathological changes were observed, and 22 cytokines and chemokines levels were analyzed. We also combined network pharmacology and metabolomics to explore their molecular mechanisms. Results showed that the combination of LGZ and SIN significantly alleviated the pain-like behaviors in CCI rats in a time- and dose-dependent manner, demonstrating superior therapeutic effects compared to LGZ or SIN alone. It also improved pathological damage to sciatic nerves and regulated inflammatory cytokine levels. Network pharmacology identified shared and distinct pain-related targets for LGZ and SIN, while metabolomics revealed 54 differential metabolites in plasma, and 17 differential metabolites in CSF were associated with the combined intervention of LGZ and SIN. Finally, through an integrated analysis of the core targets and differential metabolites, tyrosine metabolism, phenylalanine metabolism, and arginine and proline metabolism were identified as potential key metabolic pathways underlying the therapeutic effects of LGZ and SIN in CCI treatment. In conclusion, our study provides evidence to support the clinical application of LGZ and SIN in the treatment of NP.PMID:40141247 | DOI:10.3390/ijms26062604

Int J Mol Sci. 2025 Mar 13;26(6):2599. doi: 10.3390/ijms26062599.ABSTRACTDrought stress seriously threatens human food security, and enhancing crops' drought tolerance is an urgent problem to be solved in breeding. Quinoa is known for its high nutritional value and strong drought tolerance, but its molecular mechanism in response to drought stress is still unclear. In this study, we used drought-tolerant (D2) and drought-sensitive (ZK1) quinoa varieties, and PEG-6000 was used to simulate drought stress in quinoa seedlings. Phenotypic and physiological biochemical indicators were measured during the seedling stage, and LC-MS was used for a metabolite analysis of drought stress to explore the drought tolerance mechanism of quinoa under drought stress. With the intensification of drought stress, chlorophyll content gradually increased, and D2 reached its maximum at W4, an increase of 49.85% compared with W1. The total chlorophyll content, photosynthesis rate, and stomatal conductance of ZK1 were significantly lower than D2 under moderate and severe drought stress. Metabolomic results showed that a total of 1295 positive ion mode (pos) metabolites and 914 negative ion mode (neg) metabolites were identified. Of these, 12(R)-HETE, phosphatidylcholine, monogalactose diester (MGDG), and stachyose up-regulated expression under drought stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that unsaturated fatty acid biosynthesis and glycerophospholipid metabolism pathways were significantly enriched. In summary, our results elucidate that quinoa responds to drought stress by accumulating chlorophyll and sugars, activating unsaturated fatty acid metabolism, and protecting the photosynthetic system. These findings provide new insights for the breeding of drought-tolerant quinoa varieties and the study of drought tolerance mechanisms.PMID:40141239 | DOI:10.3390/ijms26062599

Int J Mol Sci. 2025 Mar 13;26(6):2586. doi: 10.3390/ijms26062586.ABSTRACTGummy stem blight (GSB) is a pervasive disease that causes considerable economic losses in cucurbit crops and poses a significant threat to pumpkin production. However, the molecular interaction mechanisms between pumpkin and the pathogen remain largely unexplored. In our previous research, we isolated and identified Stagonosporopsis cucurbitacearum (Sc) as the primary causative agent of pumpkin stem blight in Northeast China. Through whole-genome analysis, we identified several pathogenic genes associated with Sc infection in pumpkins. In this study, we performed a comprehensive comparative transcriptomic and metabolomic analysis of unvaccinated and Sc-inoculated pumpkins. We observed distinct differences in gene expression profiles, with these genes being significantly enriched in pathways related to plant-pathogen interactions, phytohormone signal transduction, and metabolic processes, including phenylpropanoid biosynthesis. Joint analysis revealed that the phenylpropanoid biosynthesis pathway was activated in Sc-infected pumpkins. Notably, two metabolites involved in the phenylpropanoid and flavonoid biosynthesis pathways, p-coumaric acid and quercetin, exhibited significant upregulation, suggesting their potential roles in conferring resistance to GSB. These findings enhance our understanding of the molecular mechanisms underlying the defense response against GSB infection in pumpkins and may provide valuable insights for developing strategies to control GSB disease.PMID:40141230 | DOI:10.3390/ijms26062586

Int J Mol Sci. 2025 Mar 13;26(6):2578. doi: 10.3390/ijms26062578.ABSTRACTFormononetin (FM), an isoflavone with a range of anti-cancer activities, has not been fully elucidated regarding its anti-hepatocellular carcinoma (HCC) mechanisms. Therefore, this study aims to explore the underlying mechanisms of FM using a comprehensive pharmacology model based on computational technologies and omics technology. A network pharmacology approach was applied to detect the components and targets. A mathematical formula was used to evaluate the network contribution index (CI). Bioinformatics analysis was used to analyze clinical data related to HCC targets corresponding to the core component, and molecular docking simulations were conducted to assess binding activity. The results showed that FM induces oxidative DNA damage through ROS generation and triggers G2/M phase cell cycle arrest via the Chk1/Cdc25C/CDK1/CCNB1 signaling pathway. Subsequently, UPLC-MS/MS was applied for the analysis of differential metabolites and the exploration of distinct metabolic pathways. FM limited the synthesis of glutathione, promoted lipid peroxidation, and facilitated the generation of divalent iron. Finally, a colony formation assay, Western blot, and molecular dynamics simulation methods were executed to further validate the metabolomic results. FM exhibited a strong binding affinity for glutathione peroxidase 4 (GPX4). In addition, FM induces ferroptosis by inhibiting the p53/xCT/GPX4 signaling pathway. In vivo, FM could inhibit tumor growth. Conclusions: FM could induce DNA damage leading to cell cycle arrest and may also induce ferroptosis by regulating glutathione metabolism, thereby intervening in the occurrence and development of HCC, making it a promising candidate for HCC treatment.PMID:40141219 | DOI:10.3390/ijms26062578

Int J Mol Sci. 2025 Mar 12;26(6):2530. doi: 10.3390/ijms26062530.ABSTRACTThe guava tree (Psidium guajava L.) is a tropical plant from the Myrtaceae family. Leaf extracts from this plant have been used in traditional medicine to treat gastrointestinal disorders and exhibit several functional activities that benefit human health. Different varieties of guava trees produce fruits in colors ranging from white to red and present a characteristic metabolic profile in both their leaves and fruits. This study presents a metabolomic characterization of the leaves from two guava varieties: the Caxcana cultivar with yellow fruits and the S-56 accession with pink fruits. Metabolite profiling was conducted using Gas Chromatography-Mass Spectrometry (GC-MS) on methanol extracts, followed by multivariate statistical analysis, including Principal Component Analysis (PCA), and a heat map visualization of compound concentrations in the two varieties. The results identified β-caryophyllene as the major secondary metabolite present in both varieties, with a relative abundance of 16.46% in the Caxcana variety and 23.06% in the S-56 cultivar. Furthermore, in silico analyses, such as network pharmacology and molecular docking, revealed key interactions with proteins such as CB2, PPARα, BAX, BCL2, and AKT1, suggesting potential therapeutic relevance. These findings highlight the pharmacological potential of guava leaf metabolites in natural product chemistry and drug discovery.PMID:40141181 | DOI:10.3390/ijms26062530

Int J Mol Sci. 2025 Mar 12;26(6):2539. doi: 10.3390/ijms26062539.ABSTRACTLicorice (Glycyrrhiza L.) is a globally popular medicinal and edible plant, with nearly 30 species distributed across all continents. The usable part is primarily the root. To understand the metabolic differences among different Glycyrrhiza species, we selected four species and performed comprehensive analyses of their roots. Metabolomic profiling was conducted using UPLC-MS/MS and GC-MS, while transcriptomic analysis was carried out using RNA-sequencing. A total of 2716 metabolites were identified, including flavonoids (527 types) and terpenoids (251 types), among various other components. Subsequently, network pharmacology was employed to explore the medicinal value and potential pharmacological ingredients of these metabolites. Joint analysis of transcriptomic and metabolomic data revealed significant differences in differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) in pairwise comparisons among the four species. These differences were primarily enriched in the isoflavone pathway. Further investigation into the regulatory mechanisms of isoflavone biosynthesis in different Glycyrrhiza species identified key genes and metabolites involved in isoflavone biosynthesis. Finally, we made reasonable predictions of the potential suitable habitats for the four Glycyrrhiza species, aiming to provide new insights for the development and utilization of licorice resources. The results of this study can serve as a basis for the development and utilization of licorice and for in-depth research on the regulation of isoflavone biosynthesis in licorice.PMID:40141180 | DOI:10.3390/ijms26062539

Int J Mol Sci. 2025 Mar 11;26(6):2503. doi: 10.3390/ijms26062503.ABSTRACTInflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota's role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.PMID:40141145 | DOI:10.3390/ijms26062503

Int J Mol Sci. 2025 Mar 10;26(6):2452. doi: 10.3390/ijms26062452.ABSTRACTThe COVID-19 pandemic has stimulated the search for effective preventive and therapeutic agents. In recent years, many studies have considered the effects of different nutrients. This study aimed to investigate the association between serum monolaurin levels and the risk of developing COVID-19 among healthcare workers. In this prospective observational cohort study, 2712 healthcare workers from the University Hospital "Maggiore della Carità" in Novara, Italy were enrolled. Participants underwent blood sampling and were followed up for six months to evaluate the protective role of serum monolaurin against COVID-19 infection. Monolaurin levels were quantified using targeted metabolomic analysis. The study cohort consisted of 1000 individuals with a mean age of 46.4 years, predominantly female. Higher serum monolaurin concentrations were significantly associated with a lower risk of SARS-CoV-2 infection at both 3- and 6-month follow-ups. The optimal cut-off value for serum monolaurin, which provides protective efficacy, was identified as 0.45 µg/mL. Higher serum monolaurin levels appear to be associated with a reduced risk of COVID-19, suggesting its potential as a protective dietary supplement against SARS-CoV-2 infection. This study contributes to the growing body of evidence supporting the role of dietary factors in the management and prevention of infectious diseases and highlights the potential of targeted metabolomics in identifying prophylactic biomarkers.PMID:40141096 | DOI:10.3390/ijms26062452

Int J Mol Sci. 2025 Mar 8;26(6):2426. doi: 10.3390/ijms26062426.ABSTRACTEquine endurance exercise induces physiological changes that alter metabolism and molecular pathways to maintain balance after intense physical activity. However, the specific regulatory mechanisms remain under debate. Identifying differentially expressed genes (DEGs) and differential metabolites (DMs) associated with equine endurance is essential for elucidating these regulatory mechanisms. This study collected blood samples from six Yili horses before and after an 80 km race and conducted transcriptomics and metabolomics analyses, yielding 722 DEGs and 256 DMs. These DEGs were primarily enriched in pathways related to amino acid biosynthesis, cellular senescence, and lipid metabolism/atherosclerosis. The DMs were predominantly enriched in fatty acid biosynthesis and the biosynthesis of unsaturated fatty acids. The integrative transcriptomics and metabolomics analyses of DEGs and DMs highlight functional changes during the endurance race. The findings offer a holistic understanding of the regulatory mechanisms underlying equine endurance and a solid foundation for formulating training programs to optimize horse performance in endurance racing.PMID:40141070 | DOI:10.3390/ijms26062426

Int J Mol Sci. 2025 Mar 7;26(6):2396. doi: 10.3390/ijms26062396.ABSTRACTDrought is one of the main adverse factors affecting the growth and development of wheat. The molecular regulation pathway of Strigolactone (SLs or SL),which induces drought resistance in wheat, needs to be further clarified. In this study, SL and Tis (Strigolactone inhibitor) were sprayed on leaves to clarify the changes in wheat drought resistance and their effect on antioxidant enzyme activity, photosynthesis and other metabolic processes. However, 20 kinds of DOF transcription factors were identified by transcriptome metabolome association analysis, and they were highly enriched on chromosome 2. Moreover, the proline, glycosides, indoleacetic acid, betaine, etc., in wheat are the key factors affecting the change in the drought resistance of wheat. The study initially revealed the mechanism of the involvement of DOF in the SL regulation pathway and revealed its impact on different metabolites of wheat, thus providing a theoretical reference for the subsequent molecular verification and breeding of excellent drought-resistant varieties.PMID:40141041 | DOI:10.3390/ijms26062396