PubMed

Front Plant Sci. 2025 Mar 7;16:1535384. doi: 10.3389/fpls.2025.1535384. eCollection 2025.ABSTRACTRNA interference (RNAi) is a biotechnological tool used for gene silencing in plants, with both endogenous and exogenous applications. Endogenous approaches, such as host-induced gene silencing (HIGS), involve genetically modified (GM) plants, while exogenous methods include spray-induced gene silencing (SIGS). The RNAi mechanism hinges on the introduction of double-stranded RNA (dsRNA), which is processed into short interfering RNAs (siRNAs) that degrade specific messenger RNAs (mRNAs). However, unintended effects on non-target organisms and GM plants are a concern due to sequence homologies or siRNA-induced epigenetic changes. Regulatory bodies such as the EPA and EFSA emphasize the need for comprehensive risk assessments. Detecting unintended effects is complex, often relying on bioinformatic tools and untargeted analyses like transcriptomics and metabolomics, though these methods require extensive genomic data. This review aims to classify mechanisms of RNAi effects induced by short interfering RNA from different sources in plants and to identify technologies that can be used to detect these effects. In addition, practical case studies are summarized and discussed in which previously unintended RNAi effects in genetically modified plants have been investigated. Current literature is limited but suggests RNAi is relatively specific, with few unintended effects observed in GM crops. However, further studies are needed to fully understand and mitigate potential risks, particularly those related to transcriptional gene silencing (TGS) mechanisms, which are less predictable than post-transcriptional gene silencing (PTGS). Particularly the application of untargeted approaches such as small RNA sequencing and transcriptomics is recommended for thorough and comprehensive risk assessments.PMID:40123947 | PMC:PMC11925957 | DOI:10.3389/fpls.2025.1535384

Food Chem X. 2025 Mar 4;26:102324. doi: 10.1016/j.fochx.2025.102324. eCollection 2025 Feb.ABSTRACTBoletus bainiugan has a unique flavor profile, its quality is correlated with metabolites. Herein, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is utilized to characterize the free amino acid and organic acid of Boletus bainiugan at different drying temperatures. Attenuated total internal reflectance Fourier transform infrared (ATR-FTIR) spectroscopy is employed to identify Boletus bainiugan with various treatment and to predicted compounds. The metabolome includes 72 amino acids and 64 organic acids, wherein, 11 important taste components are analyzed the changes with drying temperatures. The residual convolutional neural network (ResNet) model achieves 100 % accuracy for Boletus bainiugan with distinct treatment. The partial least squares regression (PLSR) model accurately predicted the contents of 11 compounds with an optimal R2 P of 0.975 and a best residual predictive deviation (RPD) of 4.404. The ATR-FTIR spectroscopy coupled with metabolomics can be used as a good tool to estimate the taste enhancers of Boletus bainiugan.PMID:40123875 | PMC:PMC11930190 | DOI:10.1016/j.fochx.2025.102324

Food Chem X. 2025 Mar 4;26:102344. doi: 10.1016/j.fochx.2025.102344. eCollection 2025 Feb.ABSTRACTEffects of red and blue light treatment on physiological quality, microbial loads, redox status and metabolomics profiles of fresh-cut sugarcane in vacuum and plastic packages were investigated during 15 d storage. The results showed that light synergistic vacuum treatment delayed the decrease of pH and the increase of respiration rate and microbial loads, enhanced antioxidant capacities and related enzymes activities. Light treatment was beneficial to 1O2 generation, but had opposite effects on O2 -, H2O2 and malondialdehyde. O2- and H2O2 was negatively associated with CAT, sucrose, fructose, glucose, 2-oxoglutaramate, liquiritigenin and dihydromyricetin, positively with PPO and malondialdehyde. Only phenylacetaldehyde exhibited a negative correlation with 1O2. The biosynthesis of sugars, amino acids and flavonoids were the principal metabolite pathways corresponding to oxidative stress in fresh-cut sugarcane. It could be concluded that the concentration of ROS, especially O2- and H2O2, should be appropriate to kill bacteria and retain the quality of fresh-cut sugarcane.PMID:40123872 | PMC:PMC11930200 | DOI:10.1016/j.fochx.2025.102344

Comput Struct Biotechnol J. 2025 Feb 24;27:928-936. doi: 10.1016/j.csbj.2025.02.020. eCollection 2025.ABSTRACTHigh-content imaging (HCI) enables the characterization of cellular states through the extraction of quantitative features from fluorescence microscopy images. Despite the widespread availability of HCI data, the development of generalizable feature extraction models remains challenging due to the heterogeneity of microscopy images, as experiments often differ in channel count, cell type, and assay conditions. To address these challenges, we introduce uniDINO, a generalist feature extraction model capable of handling images with an arbitrary number of channels. We train uniDINO on a dataset of over 900,000 single-channel images from diverse experimental contexts and concatenate single-channel features to generate embeddings for multi-channel images. Our extensive validation across varied datasets demonstrates that uniDINO outperforms traditional computer vision methods and transfer learning from natural images, while also providing interpretability through channel attribution. uniDINO offers an out-of-the-box, computationally efficient solution for feature extraction in fluorescence microscopy, with the potential to significantly accelerate the analysis of HCI datasets.PMID:40123801 | PMC:PMC11930362 | DOI:10.1016/j.csbj.2025.02.020

Comput Struct Biotechnol J. 2025 Mar 5;27:937-945. doi: 10.1016/j.csbj.2025.03.009. eCollection 2025.ABSTRACTBACKGROUND: High-risk infants are usually treated with empirical antibiotics after birth, regardless of the evidence of infection; however, their gut microbiome and metabolome have seldom been studied. This study investigated the influence of antibiotic exposure on the gut microbiome and associated metabolic pathways in term and preterm infants.METHODS: Thirty-six infants within 10 days of birth who were admitted to a neonatal intensive care unit/newborn nursery unit were divided into four groups based on maturity (gestational age) and use of empirical antibiotics. Genomic DNA was extracted from the fecal samples and underwent high-throughput 16S rRNA amplicon sequencing using the Illumina platforms. Taxonomic classification, diversity analysis, and metagenomic function prediction were performed.RESULTS: Preterm infants with empirical antibiotics showed a significantly decreased population of Firmicutes (p = 0.003) and an increased population of Proteobacteria (p < 0.001) compared to other groups. At the genus level, the populations of Raoultella (p = 0.065) and Escherichia (p = 0.052) showed an increased trend. The change in microbial composition was correlated with increased heme biosynthesis and decreased hemoglobin levels.CONCLUSION: Collectively, our finding suggested that empirical antibiotic exposure in preterm infants alters the gut microbiome, potentially leading to adverse health outcomes. This dysbiosis may affect heme metabolism, increasing the risk of anemia in these vulnerable infants. Therefore, antibiotic use should be carefully tailored to minimize potential harm.PMID:40123796 | PMC:PMC11930222 | DOI:10.1016/j.csbj.2025.03.009

Indian J Clin Biochem. 2025 Apr;40(2):176-190. doi: 10.1007/s12291-024-01187-y. Epub 2024 Feb 9.ABSTRACTThe prognostic biomarkers, or metabolites, have gained relevance due to their significance in predicting clinical and therapeutic outcomes and guiding informed therapy options. This systematic review and meta-analysis aimed to evaluate the prognostic significance of metabolites in non-muscle-invasive bladder cancer (NMIBC) through an array of literature. The PubMed, Web of Science, Embase, and Cochrane Library databases were comprehensively searched for eligible studies published between January 2010 and August 2022, using related keywords and MeSH terms. Two reviewers performed the extraction process, and a third reviewer settled possible controversies. The New Castle Ottawa scale (NOS) was used to determine the quality of selected studies. Pooled hazard ratios (H.R.s) with 95% confidence intervals (C.I.s) were calculated to establish the relationship of metabolites with NMIBC outcomes (recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (O.S.) to establish their prognostic roles. A total of 15 studies, with a sample size of 5491, were included and analyzed in this study. Various metabolites were found to be correlated with the outcomes of the study: PFS (pooled HR, 4.48; 95% CI, 1.70-11.80, p = 0.002), RFS (pooled HR, 2.85; 95% CI, 1.91-4.26; p = 0.00001), and OS (HR, 1.78; 95% CI, 1.07-2.98; p = 0.03). Pretreatment metabolites or markers in NMIBC patients had a relationship with recurrence prediction and disease outcomes in bladder cancer. Therefore, metabolites may equally serve as a critical, independent prognostic predictor for NMIBC patients. This could be considered in most related clinical decisions in bladder cancer.PMID:40123630 | PMC:PMC11928707 | DOI:10.1007/s12291-024-01187-y

Environ Sci Process Impacts. 2025 Mar 24. doi: 10.1039/d4em00736k. Online ahead of print.ABSTRACTPhytoremediation is an effective technology for removing heavy metal cadmium (Cd) from soil without harming the soil; however, it is limited by its long remediation time and low efficiency. In this study, a plant growth regulator (PGR), triacontanol, was sprayed on the leaves of the hyperaccumulator Tagetes patula L. at different growth stages to enhance the accumulation of soil Cd, thereby ultimately enhancing the efficiency of phytoremediation. Results showed that leaves were the main site of Cd accumulation in T. patula, and foliar application of triacontanol increased the leaf biomass and Cd content, with maximum values of 14.69% and 15.44%, respectively. Furthermore, the Cd removal rate in the soil increased to 11.53%. The effect of a single application of triacontanol on Cd accumulation was better than that of two applications, and the bloom period was found to be the best application stage. The proportion of Cd in the cell walls increased, enhancing Cd fixation ability. The photosynthetic efficiency and antioxidant capacity of T. patula improved significantly. In the roots, metabolomic and transcriptomic analyses indicated that triacontanol promoted the metabolism of low-molecular-weight organic acids, leading to an increase in the available and exchangeable Cd in soil, with maximum values of 14.72% and 2.29%, respectively. The upregulation of Cd transport-related genes and pathways in the roots strengthened their ability to absorb Cd and resist Cd stress. These findings systematically elucidated the molecular mechanism of triacontanol-enhanced Cd accumulation in T. patula and provide technical support for its wide application.PMID:40123477 | DOI:10.1039/d4em00736k

Biotechnol J. 2025 Mar;20(3):e202400678. doi: 10.1002/biot.202400678.ABSTRACTGlycosylation is a critical quality attribute in biopharmaceuticals that influences crucial properties, such as biological activity and blood clearance. Current methods for modeling glycosylation typically rely on imprecise or limited data on nucleotide sugar donor (NSD) dynamics. These methods use in vitro transporter kinetics or flux balance analysis, which overlook the key aspects of metabolic regulation. We devised an integrative workflow for absolute subcellular NSD quantification in both cytoplasm and secretory organelles. Using subcellular fractionation, exhaustive sample extraction, and liquid chromatography triple-quadrupole tandem mass spectrometry, we accurately measured NSD concentrations ranging from 1.6 amol/cell to 3 fmol/cell. As expected, NSD concentration profiles aligned closely with the glycan distributions on antibodies, particularly after nutrient pulsing to stimulate NSD production, showcasing method validity. This method enables empirical observation of compartment-specific NSD dynamics. Thus, this study provides novel insights indicating that N-glycosylation, which governs NSD supply, is primarily regulated within the Golgi apparatus (GA). This method offers a novel tool to obtain sophisticated data for a more efficient optimization of glycosylation processes in production cell lines.PMID:40123410 | DOI:10.1002/biot.202400678

Int J Rheum Dis. 2025 Mar;28(3):e70188. doi: 10.1111/1756-185X.70188.ABSTRACTRheumatoid arthritis (RA) is a severe inflammatory autoimmune disease with metabolic changes. RA patients have abnormalities in glycolysis, amino acid metabolism, choline metabolism, and fatty acid synthesis. The differential metabolites in individuals of RA patients and animal models were explored to find the potential biomarkers for the risk prediction, diagnosis, and prognosis of RA in the perspective of metabolism. Moreover, we discussed the changes of related metabolites after treatment with anti-rheumatic drugs, Traditional Chinese Medicine (TCM) and potential metabolites for the treatment of RA to explore promising metabolites. In addition, the immunological mechanism of TCM in the treatment of RA from the perspective of metabolism was also clarified. For the perspectives of research and application of the beneficial metabolites in clinic, relevant technologies and focuses for the future studies in the field have been proposed accordingly.PMID:40123289 | DOI:10.1111/1756-185X.70188

J Pediatr Endocrinol Metab. 2025 Mar 25. doi: 10.1515/jpem-2024-0613. Online ahead of print.ABSTRACTOBJECTIVES: 17α-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene mapped at chromosome 10q, and are required for the synthesis of sex steroids and cortisol. 17α-hydroxylase deficiency causes a decrease in cortisol and androgen with a subsequent overproduction of adrenocorticotrophic hormone (ACTH), gonadotropin, and 11-deoxycorticosterone. However, isolated 17,20-lyase deficiency is a rare condition that results in sex steroid deficiency with normal serum cortisol. This case series aims to report a novel canonical splice site CYB5A variant causing isolated 17,20-lyase deficiency and highlight the utility of steroid metabolomics in diagnosing 17α-hydroxylase and isolated 17,20-lyase deficiencies.CASE PRESENTATIONS: We describe four patients with ambiguous genitalia who were accurately diagnosed through steroid metabolomics using liquid chromatography- mass spectroscopy (LC-MS). Genetic testing identified a novel homozygous likely pathogenic 5' canonical splice site variant, c.129 + 1G>A in intron 1 of CYB5A gene, resulting in isolated 17, 20 lyase deficiency.CONCLUSIONS: Here, we report four patients with 46, XY disorder of sexual development (DSD) from two families with 17α-hydroxylase deficiency and isolated 17,20-lyase deficiency due to cytochrome b5 variant with a variable spectrum of under-virilization who had received inadequate treatment for a prolonged period of time due to incorrect diagnosis.PMID:40123165 | DOI:10.1515/jpem-2024-0613

Metabolomics. 2025 Mar 23;21(2):41. doi: 10.1007/s11306-025-02235-1.ABSTRACTINTRODUCTION: Metabolomic studies which search for acute ischemic stroke (AIS) biomarkers commonly have contradictory findings. Robust methodology is required to understand true metabolome changes after AIS.METHODS: To improve validity, we obtained corroborative evidence on change of serum metabolome after AIS by: (1) focusing on patients with large vessel occlusion (LVO), (2) combining cross-sectional and longitudinal study designs, and (3) performing analysis using different metabolome platforms: Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). In the cross-sectional part we compared serum metabolome of 84 AIS patients and 82 controls using NMR at 48-72 h, while in the longitudinal part we prospectively analyzed serum metabolome using LC-MS on 15 AIS patients at < 24 h, 48-72 h, 5-7 days, 80-120 days. We hypothesized that serum metabolites elevated in cross-sectional part would show rising trajectory in longitudinal part, and vice versa.RESULTS: We found that glycerol, phosphatidylethanolamine (PE), ceramide, phenylalanine and their derivatives had consistent increases, while other key metabolites including histidine, tyrosine, valine, glutamine, phosphatidylcholine (PC), sphingomyelin, fatty acids (FA) had consistent decreases after AIS.CONCLUSION: We identified corroborated changes in metabolome after AIS across different technologies and study designs. These changes correspond to loss of nerve cell membrane integrity and activation of alternative metabolic pathways in the setting of blood brain barrier (BBB) disruption. If proven on a larger sample, our findings may improve prediction of mortality, and functional outcomes after AIS.PMID:40123037 | DOI:10.1007/s11306-025-02235-1

Metabolomics. 2025 Mar 23;21(2):42. doi: 10.1007/s11306-025-02236-0.ABSTRACTINTRODUCTION: Pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6 is involved in 4% of cellular enzymatic activities and its deficiency is responsible for or contributes to several human diseases. The study of underlying mechanisms is still in its infancy and requires suitable model organisms. In Drosophila the deficiency of vitamin B6 produces chromosome aberrations and hallmarks of human diseases including diabetes and cancer. However, the effects of vitamin B6 deficiency have never been examined at a metabolic level.OBJECTIVES: This study evaluates the metabolic changes in vitamin B6 deficient Drosophila larvae with the aim of validating flies as a suitable model for diseases associated to vitamin B6 deficiency.METHODS: To induce vitamin B6 deficiency we fed Drosophila wild type larvae with 4-deoxypyridoxine (4DP), a PLP antagonist. By HPLC analysis we verified that the 4DP treatment was effective in inducing vitamin B6 deficiency. Using an NMR-based metabolomic approach we compared the metabolites in larval extracts from untreated and 4DP-fed larvae.RESULTS: The NMR spectra analysis identified quantitative differences for sixteen metabolites out of forty, including branched chain and aromatic amino acids, glucose, and lipids, thus revealing interesting possible associations with the phenotypes showed by vitamin B6 deficient flies.CONCLUSIONS: Our results validate Drosophila as a suitable model to study in depth the molecular mechanisms underlying human diseases associated with vitamin B6 deficiency and confirmed that 4DP treatment is effective in inducing vitamin B6 deficiency.PMID:40123014 | DOI:10.1007/s11306-025-02236-0

Metabolomics. 2025 Mar 23;21(2):43. doi: 10.1007/s11306-025-02239-x.ABSTRACTINTRODUCTION: Based on distinct triggers, bacterial and allergen-induced inflammatory reactions have different pathophysiology. Metabolomic analysis is high-throughput technique that can provide potential biomarkers to distinguish between these responses.OBJECTIVES: In order to find out the metabolic profiles of two types of inflammation, metabolites were analysed in blood plasma and bronchoalveolar lavage fluid (BALF) of guinea pigs subjected to bacterial lipopolysaccharide (LPS) or allergen ovalbumin (OVA).METHODS: Hydrogen-1 nuclear magnetic resonance (1H NMR) spectroscopy for metabolite analysis was performed in samples of blood plasma and BALF of guinea pigs.RESULTS: Random forest algorithm built on combination of levels of circulating and BALF metabolites resulted in almost ideal discrimination between acute allergic and bacterial inflammation. The differences between inflammation triggered by LPS and OVA were manifested in shift in energy metabolism, metabolism of branched-chain amino acids (BCAAs)/branched-chain keto acids (BCKAs) with alterations in alanine and glutamine, which are linked with both, ammonia homeostasis as well as gluconeogenesis.CONCLUSION: Distinct molecule nutrients are to be utilized during acute bacterial and allergic inflammatory response.PMID:40123009 | DOI:10.1007/s11306-025-02239-x

Sci Rep. 2025 Mar 23;15(1):10012. doi: 10.1038/s41598-025-94759-8.ABSTRACTDiabetic macular edema (DME), a sight-threatening retinopathy, is a leading cause of vision loss in persons with diabetes mellitus. Despite strict control of systemic risk factors, a fraction of patients with diabetes developed DME, suggesting the existence of other potential pathogenic factors underlying DME. This study aimed to investigate the plasma metabotype of patients with DME and to identify novel metabolite markers for DME. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of DME. To match clinical parameters between case and control subjects, patients with DME (DME, n = 30) or those with diabetes but without DME (Control, n = 30) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). A total of 190 distinct metabolites between DME and Control groups were identified (VIP > 1, Fold Change > 1.5 or < 0.667, and P < 0.05). The distinct metabolites between DME and Control groups were enriched in 4 KEGG pathways, namely, Glutamate Metabolism, Carnitine Synthesis, Oxidation of Branched Chain Fatty Acids, and Phytanic Acid Peroxisomal Oxidation. Finally, 4 metabolites were selected as candidate biomarkers for DME, namely, 5-Phospho-beta-D-ribosylamine, Succinic acid, Ascorbyl glucoside, and Glutathione disulfide. The area under the curve for these biomarkers were 0.693, 0.772, 0.762, and 0.771, respectively. This study suggested that impairment in the metabolism and 4 potential metabolites were identified as metabolic dysregulation associated with DME, which might provide insights into potential new pathogenic pathways for DME. 5-Phospho-beta-D-ribosylamine was first identified as a novel metabolite marker, with no previous reports linking it to diabetes or DME. This discovery may offer valuable insights into potential new pathogenic pathways associated with DME.PMID:40122941 | DOI:10.1038/s41598-025-94759-8

BMC Plant Biol. 2025 Mar 24;25(1):375. doi: 10.1186/s12870-025-06410-3.ABSTRACTBACKGROUND: Methyl jasmonate (MeJA) is an effective plant elicitor that enhances secondary metabolism. Chinese chives are prized for their pungent flavor, yet the biosynthetic pathways and regulatory mechanisms of flavor compounds induced by MeJA remain unclear.METHODOLOGY: This study integrated metabolomic and transcriptomic analyses to elucidate how MeJA modulates the biosynthesis of flavor substance precursors in soilless-cultivated Chinese chives.RESULTS: MeJA treatment improved the dry matter content and nutritional quality of Chinese chives. We identified 36 volatile and 183 nonvolatile differentially abundant metabolites between the MeJA-treated and control groups. Gene expression analysis revealed 193 candidate genes associated with flavor formation. Among all the genes, a total of 2,667 DEGs were enriched primarily in metabolic pathways, including secondary metabolite biosynthesis, linoleic acid metabolism, and phenylpropanoid biosynthesis. Furthermore, exogenous MeJA inhibited the synthesis of endogenous jasmonic acid as well as enzyme activity and gene expression related to metabolic pathways. It also promoted the conversion of S-alkyl-L-cysteine to S-alk(en)ylcysteine sulfoxides (CSOs), increasing the accumulation of the flavor precursor CSOs and increasing the levels of S-methyl-L-cysteine. This led to increased concentrations of the key garlic flavor compounds methiin and alliin, intensifying the pungent flavor of Chinese chives. Notably, MeJA-induced AtuFMO1 was associated with enhanced pungent flavor and may be regulated by AtuPHL7 and AP2/ERF-ERF transcription factors.CONCLUSION: In conclusion, exogenous MeJA activates key enzyme-encoding genes involved in the biosynthesis of garlic flavor precursor CSOs, leading to increased accumulation of the spicy compounds Methiin and Alliin. These findings establish AtuFMO1 as a central hub linking hormonal signaling to flavor biosynthesis and provide molecular targets for improving Allium crop flavor and quality through precision horticulture.PMID:40122824 | DOI:10.1186/s12870-025-06410-3

Am J Pathol. 2025 Mar 21:S0002-9440(25)00079-3. doi: 10.1016/j.ajpath.2025.02.007. Online ahead of print.ABSTRACTMetabolic processes within gut microbes generate bioactive metabolites that impact intestinal epithelial barrier function. Using gnotobiotic mice and mass spectrometry-based metabolomics, we identified novel metabolites in host tissues that are of microbial origin. Of those detected, we showed that the gut microbe generated metabolite δ-valerobetaine (δ-VB) is a potent inhibitor of L-carnitine biosynthesis and a modulator of fatty acid oxidation by mitochondria in liver cells. In the current study, we assessed the bioactivity of δ-VB towards gut epithelial barrier function. Germ-free mice are devoid of δ-VB, and we show that administration of δ-VB to germ-free mice also induces the enrichment of transcript sets associated with gut mitochondrial respiration and fatty acid oxidation in colonic tissue. Furthermore, we detected that δ-VB induces the differential expression of genes that function in barrier function in germ-free and conventionally raised mice. Functionally, δ-VB decreased gut barrier permeability and augmented wound healing in cultured gut epithelial cells, and elicited cytoprotective and pro-restitutive effects in a mouse model of colonic injury. We conclude that the microbial derived metabolite δ-VB is a modulator of gut epithelium function, and thus is a molecular target to potentially manage microbiome-host dysbiosis in intestinal health and disease.PMID:40122460 | DOI:10.1016/j.ajpath.2025.02.007

Complement Ther Med. 2025 Mar 21:103165. doi: 10.1016/j.ctim.2025.103165. Online ahead of print.ABSTRACTINTRODUCTION: Fruit juice-antihypertensive drug interactions can lead to subtherapeutic or supratherapeutic outcomes. This systematic review and meta-analysis assess such interactions and their potential clinical relevance.METHODS: PubMed, Scopus, and Science Direct databases were searched from their inception through June 2024. Eligible studies were those that investigated the effects of fruit juice on the pharmacokinetics of antihypertensive drugs. I2 was used to determine heterogeneity among studies and a random effect model was employed for meta-analysis. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022340159).RESULTS: Fifty-one studies were included. Most of them were open-label crossover trials. Grapefruit juice (GFJ), an inhibitor of organic-anion-transporting polypeptide (OATP) transporters and cytochrome P450 (CYP) 3A4, significantly decreased the AUC and Cmax of aliskiren and celiprolol by approximately 80-90%. Conversely, the AUC and Cmax of calcium channel blockers decreased with variable degrees when co-administered with GFJ. Apple and orange juices have comparable effects on certain medications. Most studies had small sample sizes and were of moderate quality. Hemodynamic effects were not assessed in most studies; thus, the clinical significance of these interactions remains uncertain and should be further investigated.CONCLUSION: Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs' bioavailability, depending on the drugs' metabolism route and involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects.PMID:40122403 | DOI:10.1016/j.ctim.2025.103165

J Nutr. 2025 Mar 21:S0022-3166(25)00176-2. doi: 10.1016/j.tjnut.2025.03.024. Online ahead of print.ABSTRACTBACKGROUND: Consuming healthful dietary patterns reduces the risk of developing metabolic diseases and nourishes the intestinal microbiota. Thus, investigating the microbial underpinnings of dietary influences on metabolic health is of clinical interest.OBJECTIVE: To determine the unique contributions of fecal taxa and metabolites in predicting metabolic health markers in adults across various dietary patterns.METHODS: Dietary, metabolic, and fecal microbiota and metabolome data from 118 adults (25-45y) were used for these cross-sectional analyses. The Diet History Questionnaire II assessed adherence to the Dietary Approaches to Stop Hypertension (DASH), Mediterranean diet, Mediterranean-DASH Intervention for Neurocognitive Delay (MIND), and the Healthy Eating Index-2020 (HEI-2020). Metabolic features included waist circumference, blood pressure, and circulating triglyceride (TG), high-density lipoprotein cholesterol (HDL), and glucose concentrations. Microbiota composition was assessed via 16S amplicon sequencing and volatile fatty acid and bile acid concentrations were measured by targeted metabolomics. ANCOM-BC2 and correlation analyses were used to screen for microbiota features independently associated with dietary patterns and metabolic health markers. Then, hierarchical linear regression models were used to evaluate the unique contributions of select microbial features on metabolic markers beyond adherence to dietary patterns.RESULTS: HEI-2020 positively associated with microbiota richness (p = 0.02). Beta diversity varied across all dietary patterns (p < 0.05). DASH diet scores, [Eubacterium] xylanophilum abundance, and deoxycholic acid (DCA) concentration explained the most variance in systolic (R2 = 0.32) and diastolic (R2 = 0.26) blood pressure compared to other dietary patterns and microbial features. TG concentrations were best predicted by MIND diet scores, [E]. eligens abundance, and isobutyrate concentrations (R2 = 0.24).CONCLUSIONS: Integrating fecal taxa and metabolites alongside dietary indices improved metabolic health marker prediction. These results point to a potential role of the intestinal microbiota in underpinning physiological responses to diet and highlight potential microbial biomarkers of metabolic health.PMID:40122388 | DOI:10.1016/j.tjnut.2025.03.024

J Food Prot. 2025 Mar 21:100494. doi: 10.1016/j.jfp.2025.100494. Online ahead of print.ABSTRACTIn food science, fungi demonstrate a paradoxical role: some species contribute positively by improving food's flavor, aroma, and texture, while others undermine food safety and quality, leading to spoilage or contamination through the production of harmful mycotoxins. When fungi colonize food materials, they produce distinct chemical profiles consisting of both primary and secondary metabolites. Metabolomics, a field dedicated to the analysis of small molecular compounds within biological entities, offers valuable insights into fungal metabolic activities and their impact on food safety and quality. This paper explores recent progress in applying metabolomics to investigate fungi within food systems, focusing on the complex interactions between fungi and their environments. Additionally, it identifies promising directions for advancing research in this rapidly evolving domain.PMID:40122345 | DOI:10.1016/j.jfp.2025.100494

Diabetes Res Clin Pract. 2025 Mar 21:112108. doi: 10.1016/j.diabres.2025.112108. Online ahead of print.ABSTRACTAIM: The aims of this study were to compare the metabolic profiles of type 2 diabetes mellitus patients with metformin and insulin monotherapy, to assess the associations of metabolites with major adverse cardiovascular events (MACE) distinctly for metformin-only and insulin-only users, and to test for effect modification by the glucose-lowering treatment.METHODS: We included 3,058 metformin-only and 558 insulin-only users from the UK Biobank. Mean concentrations of 249 metabolites of metformin and insulin users were compared with Cohen's d, their associations with MACE were assessed with Cox regression and interaction terms were tested.RESULTS: Mean VLDL size, HDL size, and concentrations of large and very large HDL molecules differed between insulin-only and metformin-only users. Overall, 75 metabolomic biomarkers were significantly associated with MACE in insulin-only users and 57 in metformin-only users. Significant interaction terms were observed between treatment group and albumin (protective in metformin users only) and 86 lipids/fatty acids, which were all statistically significantly associated with MACE among insulin users only.CONCLUSION: Metformin and insulin users have different metabolic profiles and a consistent pattern emerged that the metabolic profile of metformin users is favorable compared to the one of insulin users due to a lower associated MACE risk.PMID:40122179 | DOI:10.1016/j.diabres.2025.112108