PubMed

Food Res Int. 2025 Mar;204:115859. doi: 10.1016/j.foodres.2025.115859. Epub 2025 Jan 29.ABSTRACTβ-Casein is the main component of cow's milk protein, with A1 and A2 β-casein being the most common. Of these, A1 β-casein hydrolysate produces BCM-7, which can cause lactose intolerance, while A2 β-casein milk is more gentle on the gut. However, there is limited research on the composition of rumen microbiota, metabolites, and host metabolites in different genotype cows using metagenomics and metabolomics. In this study, we used multi-omics analysis techniques to perform enrichment analysis of differential metabolites, identifying three key metabolic pathways in all three groups: Arachidonic acid metabolism and Tryptophan metabolism. The metabolites in these pathways exhibited unique metabolic characteristics within each group. We then used random forests and ROC to predict key metabolites in these pathways, identifying that the signature metabolites in the A2A2 group were predominantly anti-inflammatory substances, including 12-HETE, PGD2-4d, and Arachidonic Acid. The signature metabolites in the A1A2 group and A2A2 group were Indoleacetaldehyde. The AUC of these signature metabolites was greater than 0.85. Macrogenic linear discriminant analysis (LDA > 2.5) found that the microorganisms with greater contribution were concentrated in the A2A2 group. Compared with the other two groups, g_Bacteroides and g_Parabacteroides were mainly enriched in the A1A2 group. In group A2A2, g_Xanthomonas and g_Acetobacter are mainly enriched. Then, the key microorganisms in A1A2 group were identified by correlation analysis as g_Bacteroides and g_Parabacteroides. The key microorganisms in group A2A2 were g_Acetobacter, g_Xanthomonas and g_Mannheimia, which were consistent with the results of LEfSe analysis. These microorganisms mainly affect the degradation of fiber in the diet, host metabolism and the occurrence of inflammation. In conclusion, our results provide theoretical basis and data support for the study of dairy cows with different genotypes of β-casein, and help to determine the potential biological functions of different genotypes of casein in dairy products and their effects on human health.PMID:39986751 | DOI:10.1016/j.foodres.2025.115859

Chin J Nat Med. 2025 Feb;23(2):182-190. doi: 10.1016/S1875-5364(25)60822-3.ABSTRACTAconitum (Ranunculaceae) has a long-standing history in traditional Chinese medicine (TCM), where it has been widely used to treat conditions such as rheumatoid arthritis (RA), myocardial infarction, and heart failure. However, the potency of Aconitum alkaloids, the primary active components of Aconitum, also confers substantial toxicity. Therefore, assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety. Metabolomics, a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways, provides a comprehensive view of the metabolic state across multiple systems in vivo. This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity, identifying potential sensitive biomarkers, and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM. This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing, aiming to identify more viable methods for characterizing toxic medicinal plants.PMID:39986694 | DOI:10.1016/S1875-5364(25)60822-3

J Nutr Biochem. 2025 Feb 20:109872. doi: 10.1016/j.jnutbio.2025.109872. Online ahead of print.ABSTRACTAgeing disrupts how our bodies process nutrients, leading to deregulation of nutrient-sensing and increased inflammation. Dietary interventions can promote healthy ageing, which demonstrates the importance of both metabolism and the gastrointestinal tract for our health. Bitter taste receptors (TAS2R) present in the intestine are key members of metabolic regulation. TA2R are involved in controlling enterohormonal secretion, detect phenolic compounds in our diet, and potentially have a great impact on the ageing process. Here, we aimed to analyse the potential role of intestinal TAS2R on the ageing process and establish potential impact of these receptors on the biomarkers. Healthy subjects were divided into two age cohorts: young (38.9 ± 6) and aged (63.6 ± 6). TAS2R expression was analysed in the colon. Analyses of metabolomics and of phenolic markers were performed in plasma. Best discriminatory parameters were obtained using three machine-learning methods. Finally, Spearman's rank correlation was performed. The best separators of the age cohorts were docosahexaenoic acid and multiple lipoprotein fractions. Two TAS2R were also identified: TAS2R5 and TAS2R38. TAS2R5 correlated with multiple lipoprotein-derived fractions, inflammatory marker IL-6 and polyunsaturated fatty acids. TAS2R38 was much more selective, correlating with a few parameters, including membrane lipid sphingomyelin, ketone body acetone, and omega acids. Both TAS2R5 and TAS2R38 correlated with β-hydroxybutyrate. The parameters that correlated with TAS2R have known effects on the ageing process. This suggests that TAS2R5 and TASR38 are the bitter receptors most likely to play a role in the development and progress of ageing.PMID:39986633 | DOI:10.1016/j.jnutbio.2025.109872

Transl Res. 2025 Feb 20:S1931-5244(25)00025-8. doi: 10.1016/j.trsl.2025.02.004. Online ahead of print.ABSTRACTInflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, and is usually accompanied by dysbiosis in the gut microbiome, a factor that contributes to disease progression. Excessive production of reactive oxygen species (ROS) because of gut microbiome dysbiosis-one of the hallmark features of IBD-promotes chronic inflammation and facilitates the transformation of normal cells into senescent cells. Cellular senescence is associated with the development of various chronic and age-related diseases. We hypothesise that senolytic agents, specifically dasatinib (D) and quercetin (Q), could have a beneficial effect on both the gut microbiome and intestinal cells in IBD. The modulatory effects of a combination of D+Q was assessed in the M-SHIME model with faecal microbiota sourced from Crohn's disease patients. D+Q significantly modulated butyrate and lactate levels in the samples from specific patients. In addition, metabolomic analysis showed that D+Q positively impacted the abundance of anti-inflammatory bacteria while also significantly reducing the several species of pathogenic bacteria. Findings from a Caco-2 cell/THP1 co-culture model of IBD demonstrated that D+Q exerted strong immunomodulatory effects on the gut epithelium, evidenced by reduced NF-kB activity, and lower levels of the pro-inflammatory markers TNF-α, CXCL-10, and MCP-1. Furthermore, D+Q induced the secretion of anti-inflammatory cytokines, including IL-6 and IL-10. However, it should be noted that D+Q also led to the secretion of the pro-inflammatory cytokines IL-8. These findings suggest that D+Q could offer a novel therapeutic approach for advanced IBD management by modulating both the gut microbiome and inflammatory pathways. The results support the potential repurposing of senotherapeutic agents as a strategy for addressing the chronic inflammation central to IBD pathogenesis.PMID:39986536 | DOI:10.1016/j.trsl.2025.02.004

J Ethnopharmacol. 2025 Feb 20:119519. doi: 10.1016/j.jep.2025.119519. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Achillea alpina L. is a traditional herbal medicine with a long history, which is often used to detoxify and relieve pain. Achillea alpina L. essential oil (AHO) is extracted from the aboveground part of the Achillea alpina L. The role of AHO on the in vivo anti-inflammatory effects remains unclear.AIM OF THE STUDY: To explore the anti-inflammatory effect and interaction mechanism of AHO in zebrafish tail fin model.MATERIALS AND METHODS: The chemical components of AHO were first identified utilizing gas chromatography-mass spectrometry (GC-MS). A zebrafish tail fin model was employed to evaluate the anti-inflammatory effect of AHO by observing the numbers of neutrophils and the expression levels of pro-inflammatory cytokines. The combined application of transcriptomics and metabolomics helped us to explore the potential anti-inflammatory mechanism of AHO, and the expression of core gene was verified by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: The principal constituents of the AHO included bicyclo sesquiphellandrene (11.99%), α-thujene (6.19%), 1-methyl-7-isopropyl naphthalene (5.90%), and β-elemene (5.58%). AHO exhibited potent anti-inflammatory properties by dramatically inhibiting the migration of neutrophils to the tail fin amputation site, along with autophagy linked to inflammation. Moreover, AHO had an excellent regulatory influence on the expression of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and interleukin 1β. Furthermore, transcriptome and metabolomic analyses identified a crucial gene and fourteen significant metabolites influenced by AHO in relation to inflammation. The investigation demonstrated that AHO modulated the inflammatory response via influencing amino acid and glucose metabolism.CONCLUSION: In this study, AHO has excellent anti-inflammatory effects and shown remarkable regulatory effects on the expression of immune cells and pro-inflammatory factors in vivo, which is highlighting the necessity for more research and development as a potential anti-inflammatory drug.PMID:39986357 | DOI:10.1016/j.jep.2025.119519

Lancet Neurol. 2025 Mar;24(3):218-229. doi: 10.1016/S1474-4422(24)00526-X.ABSTRACTBACKGROUND: Through the agnostic screening of patients with uncharacterised disease phenotypes for an upregulation of type I interferon (IFN) signalling, we identified a cohort of individuals heterozygous for mutations in PTPN1, encoding the protein-tyrosine phosphatase 1B (PTP1B). We aimed to describe the clinical phenotype and molecular and cellular pathology of this new disease.METHODS: In this case series, we identified patients and collected clinical and neuroradiological data through collaboration with paediatric neurology and clinical genetics colleagues across Europe (Czechia, France, Germany, Italy, Slovenia, and the UK) and Israel. Variants in PTPN1 were identified by exome and directed Sanger sequencing. The expression of IFN-stimulated genes was determined by quantitative (q) PCR or NanoString technology. Experiments to assess RNA and protein expression and to investigate type 1 IFN signalling were undertaken in patient fibroblasts, hTERT-immortalised BJ-5ta fibroblasts, and RPE-1 cells using CRISPR-Cas9 editing and standard cell biology techniques.FINDINGS: Between Dec 20, 2013, and Jan 11, 2023, we identified 12 patients from 11 families who were heterozygous for mutations in PTPN1. We found ten novel or very rare variants in PTPN1 (frequency on gnomAD version 4.1.0 of <1·25 × 10:sup>-6). Six variants were predicted as STOP mutations, two involved canonical splice-site nucleotides, and two were missense substitutions. In three patients, the variant occurred de novo, whereas in nine affected individuals, the variant was inherited from an asymptomatic parent. The clinical phenotype was characterised by the subacute onset (age range 1-8 years) of loss of motor and language skills in the absence of seizures after initially normal development, leading to spastic dystonia and bulbar involvement. Neuroimaging variably demonstrated cerebral atrophy (sometimes unilateral initially) or high T2 white matter signal. Neopterin in CSF was elevated in all ten patients who were tested, and all probands demonstrated an upregulation of IFN-stimulated genes in whole blood. Although clinical stabilisation and neuroradiological improvement was seen in both treated and untreated patients, in six of eight treated patients, high-dose corticosteroids were judged clinically to result in an improvement in neurological status. Of the four asymptomatic parents tested, IFN signalling in blood was normal (three patients) or minimally elevated (one patient). Analysis of patient blood and fibroblasts showed that tested PTPN1 variants led to reduced levels of PTPN1 mRNA and PTP1B protein, and in-vitro assays demonstrated that loss of PTP1B function was associated with impaired negative regulation of type 1 IFN signalling.INTERPRETATION: PTPN1 haploinsufficiency causes a type 1 IFN-driven autoinflammatory encephalopathy. Notably, some patients demonstrated stabilisation, and even recovery, of neurological function in the absence of treatment, whereas in others, the disease appeared to be responsive to immune suppression. Prospective studies are needed to investigate the safety and efficacy of specific immune suppression approaches in this disease population.FUNDING: The UK Medical Research Council, the European Research Council, and the Agence Nationale de la Recherche.PMID:39986310 | DOI:10.1016/S1474-4422(24)00526-X

J Pharm Biomed Anal. 2025 Feb 21;259:116758. doi: 10.1016/j.jpba.2025.116758. Online ahead of print.ABSTRACTThis study aimed to employ a comprehensive data screening strategy to identify the chromones and coumarins present in Saposhnikovia divaricata (SD). Initially, the five-point mass defect filter (MDF) method was utilized to screen the respective three subclasses of chromones and coumarins for MS1. In comparison to the traditional MDF method, the number of interference peaks was reduced from 3462 to 1053, representing a decrease of 69.58 %. Then, diagnostic fragment ion filtering (DFIF) was used to screen product ions selected by MDF method, which was based on the fragmentation rules of each subclass to screen whether it met the conditions. Finally, we characterized 94 compounds from SD, including 40 chromones and 54 coumarins, among them, 82 chromones and coumarins were identified by combining the above two methods, 12 coumarins were identified by combining MDF and references, they were classified into other coumarins. Twenty one compounds were identified for the first time from SD, and 3 chromones and 7 coumarins were unknown compounds. Through untargeted metabolomics analysis of SD samples from 12 different regions, significant differences were found in SD samples from different areas, and 20 differential metabolites were distinguished, including 13 chromones and 7 coumarins. This study established for the first time a comprehensive strategy combining MDF, DFIF, and untargeted metabolomics to evaluate SD quality. The results indicated that this method is an efficient, accurate, and promising approach for classifying and exploring compounds in complex natural product systems, providing a basis for evaluating the quality of SD from different sources.PMID:39986245 | DOI:10.1016/j.jpba.2025.116758

Phytomedicine. 2025 Feb 16;139:156522. doi: 10.1016/j.phymed.2025.156522. Online ahead of print.ABSTRACTBACKGROUND: Alcohol-related liver disease (ALD) has become an increasingly serious global health issue. In recent years, growing evidence has highlighted the restoration of liver regenerative capacity as an effective therapeutic strategy for improving ALD. Previous studies have demonstrated the protective effect of dihydromyricetin (DMY) in alcohol-induced liver injury, but its pharmacological role in ALD-related liver regeneration impairment remains poorly understood.OBJECTIVE: This study aims to explore the therapeutic potential and molecular mechanisms of DMY in the context of liver regeneration impairment in ALD.METHODS: The classic Lieber-DeCarli alcohol liquid diet was used to establish an ALD model in vivo. DMY (75 and 150 mg/kg/day) and silybin (200 mg/kg) were administered for 7 weeks to assess the hepatoprotective effects of DMY. First, biochemical markers and liver histopathology were used to evaluate liver inflammation and steatosis in ALD mice. Second, we explored the potential molecular mechanisms by which DMY improves ALD through serum untargeted metabolomics, hepatic transcriptomics, and single-cell sequencing data. Furthermore, in vivo and in vitro experiments, combined with Western blotting, dual-luciferase reporter assays, and immunofluorescence, were conducted to elucidate the protective mechanisms underlying DMY's effects on ALD.RESULTS: In vivo studies showed that DMY significantly ameliorated ALT/AST abnormalities, liver inflammation, and steatosis in ALD mice. Multi-omics and bioinformatics analyses revealed that DMY may exert its anti-ALD effects by regulating the miR-155-5p/SIRT1/VDAC1 pathway, thereby mitigating cellular senescence. Notably, knockdown of miR-155 provided partial protection against ethanol-induced liver damage. Additionally, clinical ALD samples and in vivo and in vitro experiments further confirmed that excessive alcohol exposure induces the production of miR-155-5p in liver Kupffer cells. miR-155-5p targets and inhibits SIRT1, promoting the expression of mitochondrial VDAC1, leading to mitochondrial DNA leakage, thereby accelerating hepatocyte senescence and inflammation. However, DMY improved the disruption of the miR-155-5p/SIRT1/VDAC1 pathway and hepatocyte senescence, thereby restoring liver regenerative function and exerting anti-ALD effects.CONCLUSION: In this study, we provide the first evidence that DMY improves liver inflammation and cellular senescence by regulating the miR-155-5p/SIRT1/VDAC1 positive feedback loop, promoting liver regeneration to improve ALD. In summary, our work provides important research evidence and theoretical support for DMY as a promising candidate drug for the prevention and treatment of ALD.PMID:39986231 | DOI:10.1016/j.phymed.2025.156522

Int Immunopharmacol. 2025 Feb 21;151:114305. doi: 10.1016/j.intimp.2025.114305. Online ahead of print.ABSTRACTBACKGROUND: The primary cause of subarachnoid hemorrhage (SAH) is the rupture of intracranial aneurysms. Over-activation of microglia following SAH is a primary driving force in early brain injury (EBI), which is a leading cause of poor outcomes. Silybin is a flavonoid compound extracted from Silybum marianum, a plant belonging to the Asteraceae family. Its anti-inflammatory and antioxidant properties could provide neuroprotective effects. The mechanism of silybin on EBI after SAH is unclear.PURPOSE: To determine the therapeutic effect of silybin on SAH and its underlying mechanisms.METHODS: We used a prechiasmatic autologous arterial blood injection in vivo and hemoglobin in vitro to establish experimental SAH model. Dexamethasone was used as a positive control drug. We evaluated the neuroprotective effect of silybin on the in vivo SAH model by neurological function scores, rotarod test, and open field test, and explored the protective effect of silybin on neuroinflammation and apoptosis after SAH by quantitative polymerase chain reaction (qPCR), western blot (WB), Immunofluorescence (IF) and TUNEL staining. IF staining of CD86 and CD206 was used to assess microglial phenotype polarization. Then we used WB and IF labeling of STING to explore the effect of silybin on the STING pathway after SAH, and used a combination of transcriptomics and non-targeted metabolomics to study the potential mechanism of silybin in detail, and verified the essential genes by qPCR. We also extracted cerebrospinal fluid from SAH patients and detected the expression level of STING in cerebrospinal fluid by enzyme-linked immunosorbent assay (ELISA) to clarify the association between STING and neural function.RESULTS: Results showed that silybin ameliorated neuronal damage and improved short-term neurological function, and reduced inflammatory damage and neuronal apoptosis in SAH mice. Silybin inhibited the expression levels of TNF-α, IL-1β and NLRP3, and promoted the expression levels of CD206, Arg1 and IL-10. Notably, Silybin promoted M2 microglia polarization. Further studies found that silybin reduced the mRNA and protein levels of the stimulator of interferon genes (STING) in microglia. And the use of a specific activator of STING (CMA) disrupted the protective effect of silybin. A total of 358 differential expression genes were identified using transcriptomics, and 150 different metabolites abundance were identified using metabolomic screening. Analysis of the effects of STING on transcriptomics and metabolomics revealed that STING might impact metabolic pathways, including linoleic acid metabolism. The qPCR results confirmed the decreased expression of essential proteins involved in the pathway. Finally, we found that increased STING expression in the cerebrospinal fluid of SAH patients was associated with decreased neurological function scores and poor prognosis.CONCLUSION: Silybin had a therapeutic effect on SAH. The underlying mechanism involves linoleic acid metabolism, which is associated with the differential genes and metabolites detected in the study. This study presented a pharmacological rationale for using silybin to treat SAH.PMID:39986195 | DOI:10.1016/j.intimp.2025.114305

Food Chem. 2025 Feb 15;476:143423. doi: 10.1016/j.foodchem.2025.143423. Online ahead of print.ABSTRACTMeat products are highly perishable and have a short shelf life. The effects of using a molecular hydrogen-producing magnesium-incorporated coating (H2-P-Mg) on the color, pHysicochemical properties, deterioration, biogenic amines, free amino acid profile, and volatilomic profile of beef meatballs were evaluated. The meatballs were coated with different films as follows: group A (uncoated), group B (whey protein coating), group C (whey protein coating +7 % thyme extract), group D (whey protein coating +7 % thyme extract + Mg), and group E (whey protein coating + Mg). At the end of storage, group E samples showed higher color scores and lower pH (5.89) and Eh7 (+260 mV) values. At the end of storage, the H2-P-Mg coating (groups D and E) showed an inhibitory effect on TBARS (58-64 %) and biogenic amines (15.38-25.87 %). The concentrations of putrescine, histamine, cadaverine, and tyramine were reduced by about 15, 20, 22, and 26 % in Mg-coated samples compared to the control. Group E showed higher levels of histidine, tyrosine, and lysine. Group D had the lowest levels of ketones and aldehydes. The use of H2-P-Mg as an edible coating can bring numerous nutritional, safety, and technological benefits to meat technology.PMID:39986070 | DOI:10.1016/j.foodchem.2025.143423

Food Chem. 2025 Feb 12;476:143400. doi: 10.1016/j.foodchem.2025.143400. Online ahead of print.ABSTRACTLiubao tea (LBT) with longer storage year is believed to have better sensory quality. The aroma characteristics and fungal community succession during the storage process of LBT were studied using LBT stored for 2-15 years as materials. The results showed that the aroma characteristics of LBT showed significant changes in 3 stages. After 10 years of storage, the sensory quality of LBT was notably improved, with herbal aroma beginning to emerge and a distinctly woody aroma. In addition, fungi were involved in the transformation of substances to affect the aroma quality during the storage of LBT. Aspergillus and Penicillium may help reduce musty and green odors and enhancing woody and herbal odors based on correlation analysis. This study provided useful information on the key aroma compounds and core functional microorganisms that drive the aroma characteristics formation of LBT during storage.PMID:39986067 | DOI:10.1016/j.foodchem.2025.143400

Ecotoxicol Environ Saf. 2025 Feb 21;292:117915. doi: 10.1016/j.ecoenv.2025.117915. Online ahead of print.ABSTRACTCyanobacterial harmful algal blooms (cHABs), normally dominated by Microcystis aeruginosa, pose a threat to aquatic ecosystems due to the release of various harmful metabolites. Cadmium (Cd), a heavy metal commonly found in surface water and sediments, often coincides with cHABs in eutrophic lakes. However, the ecotoxicological effects of Cd on M. aeruginosa and the potential for combined toxicity are not yet fully understood. In this study, we determined the effective concentrations of cadmium from 10 % (EC10) to 50 % (EC50) for M. aeruginosa based on cell density inhibition. We then conducted a combined analysis focusing on the impact of a low dose Cd (EC10, 139 μg/L) on the physiological factors, transcriptome and both intracellular and extracellular metabolites of M. aeruginosa. We found that Cd treatment decreased M. aeruginosa chlorophyll a content by 24.5 %, which coincided with the suppression of genes linked to ribosomal and photosynthesis pathways. However, Cd exposure stimulated the synthesis and extracellular release of cellular compounds by enhancing amino acid and carbohydrate metabolism. This led to elevated extracellular levels of amino acids, organic acids, and secondary metabolites - including peptides, lipids, benzenoids, terpenes, sterols, and glycosides - which could serve as potential toxic metabolites of cyanobacteria. These changes were driven by the activation of osmoregulatory mechanisms, antioxidant-related amino acids, and ATP-binding cassette transport and secretion systems. Our research indicated that low Cd concentrations could stimulate the synthesis and release of toxic metabolites and exacerbate cHAB threats in eutrophic lakes, underscoring the importance of addressing multiple stressors in freshwater environments.PMID:39986053 | DOI:10.1016/j.ecoenv.2025.117915

Ecotoxicol Environ Saf. 2025 Feb 21;292:117905. doi: 10.1016/j.ecoenv.2025.117905. Online ahead of print.ABSTRACTCadmium (Cd) contamination in soils poses a critical environmental challenge, jeopardizing both agricultural productivity and food safety. The utilization of plant growth-promoting rhizobacteria (PGPR) emerges as a promising strategy for mitigating the adverse effects of heavy metal stress on plant health and development. This study investigates the effectiveness of Enterobacter hormaechei X20 in enhancing Cd tolerance in perennial ryegrass, a species renowned for its phytoremediation potential. Strain X20 demonstrated multiple PGPR traits, including phosphate solubilization, indole-3-acetic acid (IAA) production, and siderophore secretion. Under Cd stress, X20 significantly stimulated plant growth, elevated canopy height, and preserved leaf water content. Additionally, X20 inoculation enhanced Cd uptake and reestablished ion homeostasis by augmenting Fe2+, Cu2+, Zn2+, and Mn2+ levels. It also improved photosynthetic efficiency, particularly by optimizing PSII activity, and strengthened antioxidant defense, alleviating oxidative stress. Metabolomic analysis revealed significant modulations in amino acid and sugar metabolism, marked by increased in serine and glycine levels under Cd stress. Furthermore, fructose and glucose levels rose, while sucrose levels declined, reflecting metabolic reprogramming that facilitates stress adaptation. These findings suggest that Enterobacter hormaechei X20 holds great promise as a bioinoculant for enhancing phytoremediation efficiency and plant resilience in Cd-contaminated soils, providing a sustainable strategy for managing heavy metal pollution in agriculture.PMID:39986050 | DOI:10.1016/j.ecoenv.2025.117905

Sci Total Environ. 2025 Feb 21;968:178886. doi: 10.1016/j.scitotenv.2025.178886. Online ahead of print.ABSTRACTThis study focuses on the potential hazards of borneol (BO) to aquatic organisms and human health. BO has antibacterial, anti-inflammatory and antioxidant activities, and is widely used in medicine, cosmetics, and detergents. In this study, zebrafish was used as a model organism to systematically evaluate the effects of BO on the heart, liver, kidney, and nervous system. The effects of BO on metabolites of zebrafish were studied using MALDI-MSI. The results showed that a high concentration of BO (500 μM) could induce morphological abnormalities (swim-bladder loss, spinal curvature, body-length shortening), cardiotoxicity (decreased heart rate, increased SV-BA distance), hepatotoxicity (reduced liver area index), and neurotoxicity (impaired behavioral ability, and dopamine neuron development deficits), but there was no renal toxicity observed in zebrafish. Additionally, MALDI-MSI analysis showed that BO exposure significantly altered the levels of metabolites, including phospholipids, fatty acids, choline, and amino acids. The contents of PC-34:1, PC-34:2, PI-36:4, PE-36:1, LysoPE-22:5, LysoPC-18:1, FA-18:2, phenylalanine, lysine and glutathione were significantly increased, while the contents of PC-38:6 and PC-40:6 were significantly decreased. Notably, BO elicited a significant alteration in the mRNA expression levels of genes associated with phospholipid metabolism, fatty acid metabolism, choline metabolism, and amino acid metabolism (such as elovl5, chpt1, chka, setd7, hgd). This study revealed that BO exerted toxicity on multiple organs and demonstrated that BO causes metabolic dysregulation in zebrafish. These findings provide a novel insight into the toxicity of BO.PMID:39986037 | DOI:10.1016/j.scitotenv.2025.178886

JACC Adv. 2025 Feb 21;4(3):101590. doi: 10.1016/j.jacadv.2025.101590. Online ahead of print.ABSTRACTBACKGROUND: Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar).OBJECTIVES: This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (H4Bip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase.METHODS: We measured preinterventional ADMA levels in 51 patients with PAD in Australia and Germany with mean changes in absolute claudication distance (dACD) as the primary outcome upon orally supplementing the L-arginine precursor, L-citrulline (3 g) twice daily for 12 weeks, and, in one arm, additionally H4Bip (0.45 g) once per day for a further 2 weeks.RESULTS: Preinterventional ADMA levels were pathological (>0.4 μM) in 34 patients. Supplementation with L-citrulline significantly increased the mean plasma levels of both L-citrulline and L-arginine, from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004) and from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001) respectively, when compared with placebo. dACD in % of control was significantly improved by L-citrulline vs placebo (20.11% ± 4.50% vs 5.73% ± 2.74%, respectively; P = 0.011). Further addition of H4Bip increased the mean percentage dACD to 28.15% ± 6.84% (P = 0.021), but only in patients with preinterventional pathological ADMA levels.CONCLUSIONS: L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.PMID:39985883 | DOI:10.1016/j.jacadv.2025.101590

Eur Neuropsychopharmacol. 2025 Feb 21;94:20-21. doi: 10.1016/j.euroneuro.2025.02.004. Online ahead of print.NO ABSTRACTPMID:39985868 | DOI:10.1016/j.euroneuro.2025.02.004

Plant J. 2025 Feb;121(4):e70029. doi: 10.1111/tpj.70029.ABSTRACTLigustrum lucidum, an important ornamental and medicinal plant in the Oleaceae family, has become a globally notorious invasive species because of its high adaptability. However, the lack of a high quality genome has hindered the understanding of the genetic basis for its broad adaptability and the mechanisms of its medicinal component synthesis. In this study, we successfully assembled a gap free telomere to telomere genome of L. lucidum. Through the reconstruction of the phylogenetic tree, we presented evidence that Jasmineae diverged from Oleaceae earlier than Forsythieae, which challenges the existing phylogenetic relationships within Oleaceae. Comparative genomics has found that two rounds of gene family expansions in L. lucidum significantly increased the number of genes related to its biotic and abiotic stress resistances, which may lay the genetic foundation for its broad adaptability. Among the L. lucidum fruits from January to March in our investigation, the results of metabolome show that March may be the optimal harvesting time. By integrating genomic, transcriptomic, and metabolomic data, we identified candidate genes involved in the synthesis of compounds, such as specnuezhenide, salidroside, and oleanolic acid. This study provides valuable genomic resources for comparative genomics studies within Oleaceae and for the genetic research of L. lucidum.PMID:39985810 | DOI:10.1111/tpj.70029

Biochem Genet. 2025 Feb 22. doi: 10.1007/s10528-025-11064-9. Online ahead of print.ABSTRACTThis study employs a comprehensive multi-omics approach to investigate the regulatory roles of specific microRNAs (miRNAs) in Congenital Tooth Agenesis (CTA). A total of 58 miRNAs associated with tooth diseases, cancer, and bone development were initially identified through a literature review and analyzed using bioinformatics. Based on target prediction and network analysis, eight miRNAs with strong connectivity and common target genes were shortlisted for further investigation. Blood samples from 10 CTA patients and 5 healthy controls were analyzed for miRNA expression using stem-loop RT-PCR. Four miRNAs-hsa-miR-218-5p, hsa-miR-15b-5p, hsa-miR-200b-3p, and hsa-let-7a-3p-were identified as significantly differentially expressed, marking their first reported involvement in CTA. Notably, hsa-miR-218-5p and hsa-let-7a-3p emerged as novel regulators with no prior associations with CTA or tooth development. To address the limitations of a small sample size, a multi-omics strategy was employed to validate these findings, integrating miRNA expression data with whole exome sequencing (WES), gene expression panels, and metabolomic profiling. The analysis confirmed the association of these four miRNAs with CTA and highlighted their involvement in critical biological pathways such as Wnt signaling, FGF signaling, and PI3 kinase pathways, which are essential for cellular proliferation, differentiation, and tissue morphogenesis. Importantly, the identification of these miRNAs in blood samples, rather than traditional dental tissues, highlights a minimally invasive approach that could aid in the early detection, therapeutic targeting, and personalized management of dental anomalies.PMID:39985697 | DOI:10.1007/s10528-025-11064-9

Anal Bioanal Chem. 2025 Feb 22. doi: 10.1007/s00216-025-05794-3. Online ahead of print.ABSTRACTThe challenge of robust and automated glycopeptide quantitation from liquid chromatography-mass spectrometry (LC-MS) data has yet to be adequately addressed by commercial software. Recently, open-source tools like Skyline and LaCyTools have advanced the field of label-free MS1 level quantitation. Yet, important steps late in the data processing workflow remain manual. Because manual data curation is time-consuming and error-prone, it presents a bottleneck, especially in an era of emerging high-throughput methodologies and increasingly complex analyses such as antigen-specific antibody glycosylation. We addressed this gap by developing GlycoDash, an R Shiny-based interactive web application designed to democratize label-free high-throughput glycoproteomics data analysis. The software comes in at a stage where analytes have been identified and quantified, but whole measurement and individual analyte signals of insufficient quality for quantitation remain and reduce the quality of the overall dataset. GlycoDash focuses on these challenges by incorporating several options for measurement and metadata linking, spectral and analyte curation, normalization, and repeatability assessment, and additionally includes glycosylation trait calculation, data visualization, and reporting capabilities that adhere to FAIR principles. The performance and versatility of GlycoDash were demonstrated across antibody glycoproteomics data of increasing complexity, ranging from relatively simple monoclonal antibody glycosylation analysis to a clinical cohort with over a thousand measurements. In a matter of hours, these large, diverse, and complex datasets were curated and explored. High-quality datasets with integrated metadata ready for final analysis and visualization were obtained. Critical aspects of the curation strategy underlying GlycoDash are discussed. GlycoDash effectively automates and streamlines the curation of glycopeptide quantitation data, addressing a critical need for high-throughput glycoproteomics data analysis. Its robust performance across diverse datasets and its comprehensive feature toolbox significantly enhance both research and clinical applications in glycoproteomics.PMID:39985669 | DOI:10.1007/s00216-025-05794-3

Bioinformatics. 2025 Feb 22:btaf077. doi: 10.1093/bioinformatics/btaf077. Online ahead of print.ABSTRACTMOTIVATION: Modeling genome-scale metabolic networks (GEMs) helps understand metabolic fluxes in cells at a specific state under defined environmental conditions or perturbations. Elementary Flux Modes (EFMs) are powerful tools for simplifying complex metabolic networks into smaller, more manageable pathways. However, the enumeration of all EFMs, especially within GEMs, poses significant challenges due to computational complexity. Additionally, traditional EFM approaches often fail to capture essential aspects of metabolism, such as co-factor balancing and by-product generation.The previously developed Minimum Network Enrichment Analysis (MiNEA) method addresses these limitations by enumerating alternative minimal networks for given biomass building blocks and metabolic tasks. MiNEA facilitates a deeper understanding of metabolic task flexibility and context-specific metabolic routes by integrating condition-specific transcriptomics, proteomics, and metabolomics data. This approach offers significant improvements in the analysis of metabolic pathways, providing more comprehensive insights into cellular metabolism.RESULTS: Here, I present MiNEApy, a Python package reimplementation of MiNEA, which computes minimal networks and performs enrichment analysis. I demonstrate the application of MiNEApy on both a small-scale and a genome-scale model of the bacterium E. coli, showcasing its ability to conduct minimal network enrichment analysis using minimal networks and context-specific data.AVAILABILITY: MiNEApy can be accessed at: https://github.com/vpandey-om/mineapy.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:39985451 | DOI:10.1093/bioinformatics/btaf077