PubMed

J Adv Res. 2025 Mar 16:S2090-1232(25)00184-5. doi: 10.1016/j.jare.2025.03.024. Online ahead of print.ABSTRACTINTRODUCTION: Dill (Anethum graveolens) is a significant medicinal herb belonging to the Apiaceae family. Owing to its high levels of volatile organic compounds (VOCs), dill is commonly utilized for essential oil extraction and medicine purpose. However, the biosynthesis of the crucial VOC in dill remains obscure.OBJECTIVES: Identify the key VOCs related to the flavor formation in dill and dissect the regulatory mechanism of their synthesis.METHODS: The dill chromosomal-level genome was constructed by PacBio HiFi, Hi-C, and BGISEQ second generation sequencing and assembly. The VOCs in dill leaves were identified through GC-MS. The potential mechanism involved in regulating the VOC accumulation in dill flavor formation was analyzed by multi-omics analysis.RESULTS: A 1.17 Gb chromosome-scale genome of dill with a contig N50 of 10.78 Mb was constructed. A total of 46,538 genes were annotated across 11 assembled chromosomes. Comparative genomics analysis suggested that transposable element insertions, especially LTR-Gypsy, have contributed to the evolution and expansion of the dill genome. The flavor formation of dill was mainly attributed to terpenoids, especially α-phellandrene, β-ocimene, and o-cymene. The contribution of expansion and replication of terpenoid synthesis pathway genes, especially terpene synthase (TPS), to the abundant terpenoid production of dill was identified. Differential gene expression patterns observed at various developmental stages and tissues provided key candidate genes for the regulation of terpenoid synthesis, as well as transcription factors. The difference accumulation of esters and aromatics also affected the flavor formation of dill. The key genes implicated in the synthesis of anethole, namely AIS and AMT were further identified.CONCLUSION: This study constructed the chromosome level genome and identified the main VOCs and related key genes in flavor formation of dill, shedding lights on our understanding of terpenoid biosynthesis but also offered guidance for future genetic research on molecular breeding in Anethum graveolens.PMID:40101871 | DOI:10.1016/j.jare.2025.03.024

Cell Rep Med. 2025 Mar 11:102028. doi: 10.1016/j.xcrm.2025.102028. Online ahead of print.ABSTRACTThe commensal gut microbiota has a role in the pathogenesis of extra-intestinal autoimmune diseases such as multiple sclerosis (MS) with unknown mechanisms. Deoxycholic acid (DCA) and lithocholic acid (LCA) are secondary bile acid metabolites (BAMs) produced from primary bile acids by gut microbiota that play key immune regulatory functions by promoting FOXP3+ regulatory T (Treg) cell differentiation at the expense of Th17 cells. Here, we show that bacteria releasing enzymes responsible for secondary BAMs production are under-represented in the gut of MS patients, resulting in significantly reduced intestinal concentration of DCA and immune dysregulation with increased percentage of Th17 cells. We validated our human findings in a preclinical model of MS by showing that DCA/LCA administration prevents experimental autoimmune encephalomyelitis (EAE) by dampening Th17 cell differentiation and the effector phenotype of myelin-reactive T cells. Our data highlight the key role of immune regulatory BAMs for the prevention of central nervous system (CNS) autoimmunity.PMID:40101713 | DOI:10.1016/j.xcrm.2025.102028

Poult Sci. 2025 Mar 5;104(5):104971. doi: 10.1016/j.psj.2025.104971. Online ahead of print.ABSTRACTAreca nut extract (ANE) has a variety of pharmacological effects on animals. Here, we investigated the influence of ANE on the slaughter performance and immune function of Jiaji ducks. One hundred and fifty 42-day-old healthy Jiaji ducks were randomly divided into 2 groups (5 replicates of 15 ducks each), named DCK group (control) and DNT group (treatment), respectively. Ducks in the DCK group were fed a basal diet and ducks in the DNT group were fed a basal food supplemented with 0.08 g ANE per kg of basal diet. Additionally, using proteomics, untargeted metabolomics, and metagenomics, we analyzed the impact of ANE on the protein profile of the spleen, the composition of plasma metabolites, and the structure of the cecal microbiota. The results showed that the dietary inclusion of ANE significantly increased the slaughter rate of Jiaji ducks. Proteomic analysis revealed 78 differentially expressed proteins in the spleens of ANE-treated birds, including 54 proteins up-regulated and 24 proteins down-regulated in the DNT group, mainly enriched in cell adhesion molecules and glutathione metabolic pathways. Untargeted metabolomic analysis revealed that 117 serum metabolites were differentially regulated between the ANE and DCK groups; meanwhile, KEGG pathway analysis indicated that these metabolites were mainly involved in arachidonic acid metabolism, phospholipase D signaling pathway and eicosanoids. Furthermore, a metagenomic analysis showed that the genus Methanobrevibacter was significantly downregulated in the ANE supplementation group. Combined, the results of the metagenomic and metabolomic analyses showed that the relative abundance of Prevotella was significantly lower in the ANE group than in the DCK group and that Prevotella was negatively correlated with the levels of the anti-inflammatory compound hydrocinnamic acid and the lipid metabolism regulator ganoderic acid A. This study provides a reference for the application of ANE as a supplement in the diet of Jiaji ducks.PMID:40101514 | DOI:10.1016/j.psj.2025.104971

Food Chem. 2025 Mar 14;479:143863. doi: 10.1016/j.foodchem.2025.143863. Online ahead of print.ABSTRACTCordyceps militaris (C. militaris) strain is highly prone to degeneration during subculture. The morphological changes in colonies and fruiting bodies during subculture were observed and the metabolites changes were analyzed using metabolic profiling. The results showed that an obvious degeneration occurred in strain beginning from the fifth generation. Antioxidant enzymes activities gradually declined and MDA content slowly increased during subculture. LC-MS results indicated 121 metabolites were identified. K-means clustering analysis results suggested the 5th and 7th clusters had the greatest number of metabolites, mainly including organic acids and derivatives, nucleoside compounds, steroid compounds, fatty acids and their derivatives, and some peptide compounds. Furthermore, the characteristic metabolites levels progressively declined during subculture, which led to the degeneration. The reduced L-glutathione content in the 7th generations was significantly higher than that in the 1st generations, suggesting that C. militaris cells enhanced their synthesis capacity to counter oxidative damage during subculture.PMID:40101383 | DOI:10.1016/j.foodchem.2025.143863

Food Chem. 2025 Mar 13;479:143719. doi: 10.1016/j.foodchem.2025.143719. Online ahead of print.ABSTRACTThe aging of Doenjang enhances its flavor and complexity, making it highly valued by consumers. However, most previous studies have focused on aging periods of two years or less. Additionally, many analyzed samples are produced in laboratories or restricted to specific regions, limiting our understanding of long-term metabolic changes. In this study, we analyzed 49 traditional Doenjang samples aged from 1 to 30 years using CE-TOF/MS with both untargeted and targeted metabolomics to identify aging markers and metabolite profiles. The aging process significantly influenced the metabolites, increasing lactate, 13 amino acids, and four biogenic amines (histamine, tyramine, putrescine, and 2-phyenylethylamine), while reducing concentrations of arginine and tryptophan. These metabolic changes effectively distinguished short-term-aged Doenjang (1-2 years) from long-term-aged Doenjang (7-30 years). This integrated targeted and untargeted metabolomics provides better understanding into metabolic changes occurring during Doenjanbg maturation with practical applications for optimizing its safety and quality.PMID:40101381 | DOI:10.1016/j.foodchem.2025.143719

Biopreserv Biobank. 2025 Mar 7. doi: 10.1089/bio.2024.0160. Online ahead of print.ABSTRACTBiobanking is crucial for advancing medical research and personalized medicine, offering high-quality biospecimens for studies on biomarkers, drug development, and diagnostics. Despite its global potential, challenges such as fragmented governance and varying standards hinder biorepository collaboration, particularly in South Africa (SA). A unified national biobank network could enhance research and healthcare by improving biospecimen access, ethical governance, and collaboration. Global biobank networks offer models for standardization, data sharing, and international cooperation. SA can benefit from these models by creating a centralized biobank platform, promoting capacity building, and fostering regional and global partnerships. To address the challenges SA faces regarding biobanking, the Medical Biobanks Cluster established a network named Medical Biorepositories of SA (MBirSA), which seeks to build a cohesive network of medical biorepositories in SA. Through this network, it plans to foster an inclusive culture of biospecimen and data protocol harmonization, while encouraging adherence to legal, ethical, and quality best practices and standards. The network aims to bring stakeholders together, increasing visibility and transparency, and encouraging sector-wide collaboration. MBirSA also aims to offer training to build capacity in global best practices, aid in the development of dependable biorepository infrastructure, and promote research partnerships to enhance healthcare advancements.PMID:40101279 | DOI:10.1089/bio.2024.0160

Anal Chem. 2025 Mar 18. doi: 10.1021/acs.analchem.4c06061. Online ahead of print.ABSTRACTNewborn screening (NBS) is one of the United States' largest, most successful preventative public health initiatives, improving outcomes for newborns with inborn errors of metabolism. Most disorders on the Recommended Uniform Screening Panel are screened using triple-quadrupole mass spectrometry and flow injection analysis. While these methods are sensitive and well suited for high-throughput quantitative applications, the breadth of measured analytes is limited to a relatively small number of biomarkers, which often have considerable overlaps between healthy and diseased populations. High-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics is now capable of profiling thousands of metabolites, making it well suited for exploratory and biomarker discovery studies. To this end, we developed a robust workflow for performing nontargeted LC-MS analysis on dried bloodspot (DBS) specimens with coverage across many metabolic pathways relevant to NBS. HILIC chromatography enabled quantitation of amino acid and acylcarnitine species while also retaining lipid species, such as lyso-phosphatidylcholines. We analyzed 810 newborn-derived DBS samples across a wide range of newborn birthweights, identifying correlations with metabolites that help to better account for the lower accuracy observed for some NBS markers (e.g., isovalerylcarnitine). Additionally, we leveraged this nontargeted workflow to capture new biomarkers and metabolic phenotypes in newborns associated with parenteral nutrition administration and maternal nicotine exposure. Two critical biomarkers were identified as useful additions to targeted screening panels: N-acetyltyrosine as a qualitative marker for parenteral nutrition administration and N-acetylputrescine as a quantitative marker for controlling birthweight variability.PMID:40100766 | DOI:10.1021/acs.analchem.4c06061

Am J Physiol Lung Cell Mol Physiol. 2025 Mar 18. doi: 10.1152/ajplung.00422.2024. Online ahead of print.ABSTRACTExcessive uncontrolled airway narrowing is the main cause of the symptoms in asthma, yet the reasons behind this problem are still elusive. As mechanistic studies of isolated airways from asthmatic individuals are almost impossible to perform, the aim of this study was to investigate the contractile responses in intralobular bronchi (ILB) isolated from a guinea asthma model. These distal airways are surrounded by parenchymal tissue and resemble functional characteristics of human bronchi. Isolated ILB were mounted in myographs to measure smooth muscle reactions. To avoid the irreversible post-mortem bronchoconstriction, lungs were filled with ice-cold buffer solution containing 1 µM salbutamol followed by 48 hours incubation of the isolated ILB. Pharmacological characterization of ILB from naïve guinea pigs showed that prostaglandin E2 induced mild relaxation, whereas histamine, carbachol, leukotriene D4, and the thromboxane A2 mimetic U46619 caused robust contractions. Although the responses to contractile agonists (histamine, carbachol and leukotriene D4 ) were similar, the contractile responses to house dust mite (HDM) in ILB from HDM sensitized and challenged guinea pigs were significantly greater than those from sensitized-only control guinea pigs. Similarly to isolated human small airways, the antigen response was abolished by inhibitors to mast cell mediators such as histamine, leukotrienes and prostanoids. This study presents, for the first time, an investigation of bronchial responses using a guinea pig asthma model, examining airways with pathophysiological features similar to those of asthmatic individuals and comparing them to matched controls. Moreover, the results suggest the potential of mast cells in the development of asthma.PMID:40100736 | DOI:10.1152/ajplung.00422.2024

Plant Foods Hum Nutr. 2025 Mar 18;80(2):92. doi: 10.1007/s11130-025-01332-9.ABSTRACTThe aim of this study was to investigate the antihyperuricaemic (HUA) effect of Eucommia folium after preparing a tea made from its leaves (abbreviated as DZ) which has the ability to prevent and treat HUA. In this study, a mouse HUA model was established via gavage of potassium oxonate and hypoxanthine, and this HUA model was treated with DZ to investigate the therapeutic effect of DZ on HUA. This study recruited 30 HUA volunteers, who drank 10 g of DZ daily for four consecutive weeks. The serum HUA levels of UA volunteers were measured once per week to observe the anti-HUA efficacy of DZ at the clinical level. Animal experiments have shown that DZ has therapeutic effects on HUA. DZ effectively reduces the levels of uric acid (UA), creatinine (Cr), and urea nitrogen (BUN) in the serum of HUA mice; decreases xanthine oxidase (XOD) activity in the serum; and alleviates damage to kidney tissues and glomeruli. Metabolomic analysis revealed that DZ affects multiple metabolites, such as orotidine, orotic acid, ureidosuccinic acid, 1-methylhistidine, and other metabolites, and these metabolites are involved mainly in pyrimidine metabolism, histidine metabolism, and riboflavin metabolism. Clinical research revealed that, after DZ was consumed, the UA levels in the HUA volunteers significantly decreased. Our research findings suggest that DZ may have a protective effect against HUA. and is in the same class of traditional Chinese medicines used in medicine and food, with extremely low toxicity and high safety. Therefore, DZ may be suitable for preparation as a functional food with anti HUA effects. CLINICAL TRIAL NUMBER: Not applicable.PMID:40100576 | DOI:10.1007/s11130-025-01332-9

JCI Insight. 2025 Mar 18:e180943. doi: 10.1172/jci.insight.180943. Online ahead of print.ABSTRACTBACKGROUND: Alterations in circulating metabolites have been described in obese metabolic dysfunction-associated steatotic liver disease (MASLD), but data on lean MASLD are lacking. We investigated serum metabolites, including microbial bile acids (BAs) and short-chain fatty acids (SCFAs), and their association with lean and obese MASLD.METHODS: Serum samples from 204 subjects of European descent were allocated to four groups: lean healthy (n=61), lean MASLD (n=49), obese healthy (n=47) and obese MASLD (n=47). LC/MS-based metabolomics was performed followed by linear model analysis. MASLD prediction was assessed based on LASSO regression. Functional effects of significantly altered molecules were confirmed in organotypic 3D primary human liver cultures.RESULTS: Lean MASLD was characterized by elevated isobutyrate, along with higher methionine sulfoxide, propionate and phosphatidylcholines. Patients with obese MASLD had increased sarcosine and decreased lysine and asymmetric dimethylarginine. Using metabolites, sex and body mass index, MASLD vs. healthy could be predicted with a median AUC of 86.5% and 85.6% in the lean and obese subgroups, respectively. Functional experiments in organotypic 3D primary human liver cultures showed that propionate and isobutyrate induced lipid accumulation and altered expression of genes involved in lipid and glucose metabolism.CONCLUSION: Our results indicate that lean MASLD is characterized by a distinct metabolite pattern related to amino acid metabolism, lipids and SCFAs, while metabolic pathways of lipid accumulation are differentially activated by microbial metabolites. Our findings highlight an important role of microbial metabolites in MASLD pathogenesis, with implications for the predictive and mechanistic assessment of liver disease across different weight categories.FUNDING: The work received funding from the Robert Bosch Stiftung, Stuttgart, Germany, the Swedish Research Council [grant numbers 2021-02801, 2023-03015 and 2024-03401], the ERC Consolidator Grant 3DMASH [101170408], Ruth and Richard Julin Foundation for Gastroenterology [grant number 2021-00158], the SciLifeLab and Wallenberg National Program for Data-Driven Life Science [WASPDDLS22:006], and the Novo Nordisk Foundation [NNF23OC0085944 and NNF23OC0084420]. JT was supported by PMU-FFF [grant number E-18/28/148-FEL].PMID:40100312 | DOI:10.1172/jci.insight.180943

Elife. 2025 Mar 18;13:RP96892. doi: 10.7554/eLife.96892.ABSTRACTMass spectrometry imaging (MSI) is a powerful technology used to define the spatial distribution and relative abundance of metabolites across tissue cryosections. While software packages exist for pixel-by-pixel individual metabolite and limited target pairs of ratio imaging, the research community lacks an easy computing and application tool that images any metabolite abundance ratio pairs. Importantly, recognition of correlated metabolite pairs may contribute to the discovery of unanticipated molecules in shared metabolic pathways. Here, we describe the development and implementation of an untargeted R package workflow for pixel-by-pixel ratio imaging of all metabolites detected in an MSI experiment. Considering untargeted MSI studies of murine brain and embryogenesis, we demonstrate that ratio imaging minimizes systematic data variation introduced by sample handling, markedly enhances spatial image contrast, and reveals previously unrecognized metabotype-distinct tissue regions. Furthermore, ratio imaging facilitates identification of novel regional biomarkers and provides anatomical information regarding spatial distribution of metabolite-linked biochemical pathways. The algorithm described herein is applicable to any MSI dataset containing spatial information for metabolites, peptides or proteins, offering a potent hypothesis generation tool to enhance knowledge obtained from current spatial metabolite profiling technologies.PMID:40100251 | DOI:10.7554/eLife.96892

Microbiol Spectr. 2025 Mar 18:e0229524. doi: 10.1128/spectrum.02295-24. Online ahead of print.ABSTRACTIn this study, we describe the combined effects of bedaquiline (BDQ) and the natural product curcumin (CUR) on Mycobacterium abscessus. In both in vitro and in vivo experiments, CUR enhanced BDQ's inhibitory effect. This combination reduced M. abscessus survival under nutrient-deprived, hypoxic, and acidic conditions, accelerated ATP depletion, mitigated BDQ-induced respiratory compensation, and effectively improved infection outcomes in both normal and immunosuppressed mice. Metabolomics analysis revealed that adding CUR to BDQ exacerbated BDQ-dependent downregulation of purine and pyrimidine metabolism and amino acid synthesis. Thus, BDQ-CUR combination therapy could potentially be applied to treat M. abscessus infections.IMPORTANCEMycobacterium abscessus is an emerging pathogen that causes pulmonary infections, particularly in immunocompromised patients. It exhibits natural resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and physicians, thereby raising the need for innovative drug discovery. Here, we describe the combined effects of bedaquiline (BDQ) and curcumin (CUR) on M. abscessus. In vitro and in vivo studies have shown that CUR enhances the inhibitory effect of BDQ. Additionally, we investigated the synergistic effects at the metabolic level. Thus, these findings highlight the potential of BDQ-CUR combination therapy against M. abscessus infections.PMID:40099879 | DOI:10.1128/spectrum.02295-24

J Proteome Res. 2025 Mar 18. doi: 10.1021/acs.jproteome.4c01150. Online ahead of print.ABSTRACTSkeletal muscle wasting is a critical clinical problem associated with several diseases that significantly impair patient outcomes due to the progressive loss of muscle mass and function. This study explores the potential of 3-hydroxybutyrate (3-HB) as a therapeutic agent to counteract muscle atrophy by promoting the proliferation and differentiation of C2C12 myoblasts. Using nuclear magnetic resonance (NMR)-based metabolomics analysis, we uncover the underlying mechanisms by which 3-HB exerts its effects. Our findings demonstrate that 3-HB exerts its effects through two distinct mechanisms: as a metabolic substrate and as a signaling molecule. As a metabolic substrate, 3-HB enhances myoblast energy efficiency by stimulating the expression of G protein-coupled receptor 109a (GPR109a), which subsequently upregulates the 3-HB transporters MCT1 and CD147, the utilization enzyme OXCT1, and phosphorylated AMPK, thereby increasing ATP production. As a signaling molecule, 3-HB activates GPR109a, promoting calcium influx, improving calcium homeostasis, and increasing the expression of Ca2+-related proteins such as CAMKK2. This signaling cascade activates calcineurin (CaN), facilitating NFAT translocation to the nucleus and gene expression that drives myoblast proliferation and differentiation. By elucidating the dual regulatory roles of 3-HB in energy metabolism and cellular signaling, this study not only advances our understanding of muscle physiology but also highlights the potential of 3-HB as a novel therapeutic approach for the prevention or treatment of skeletal muscle atrophy.PMID:40099866 | DOI:10.1021/acs.jproteome.4c01150

J Exp Bot. 2025 Mar 18:eraf122. doi: 10.1093/jxb/eraf122. Online ahead of print.ABSTRACTLinking genotype and phenotype is a fundamental challenge in biology. In this respect, machine learning is playing a pivotal role in systems biology. As a central phenotypic trait, fruit development and its relative growth rate (RGR) result from interactions between gene regulation, metabolism and environment. In the present study, we carried out a multispecies transcriptomic analysis of nine different fruits. To illustrate fruit transcriptomes, transcripts were first compared using multivariate methods, revealing main similar profiles. They were then used as variables to predict four growth traits, i.e. RGR, developmental progress, fruit weight and protein content, using generalised linear models (GLMs) to decipher the mechanisms involving gene expression in development. The predictions were very satisfactory despite disparities when the model did not include the entire panel of fruit species. Based on orthogroups derived from BLAST and annotated consensus sequences from gene ontology (GO) terminology, variables annotated for metabolic processes, especially those involving cell wall carbohydrates and proteins, were found to be the most effective in predicting growth. In addition, predictions were improved for RGR when introducing a seven-day lag between transcript contents and growth traits, suggesting the necessity of considering the proteins produced to enhance phenotypic trait predictions. These original results showed that growth traits can be predicted very well with GLMs based on orthogroups from multi-species transcriptomes.PMID:40099514 | DOI:10.1093/jxb/eraf122

J Neurochem. 2025 Mar;169(3):e70038. doi: 10.1111/jnc.70038.ABSTRACTReactive astrocytes play a critical role in the initiation and progression of epilepsy, but their molecular subtypes and functional characterization are not fully understood. In this study, we report the existence of neurotoxic reactive astrocytes, a recently identified subtype, that contribute to neuronal death in the epileptic brain. In a kainic acid (KA)-induced mouse model of epilepsy, we show that neurotoxic reactive astrocytes are induced by microglia-secreted cytokines, including IL-1α, TNFα, and C1q, and are detectable as early as 7 days post-KA stimulation. These cells exhibit a distinct molecular signature marked by elevated expression of complement 3 and adenosine 2A receptor. Transcriptomics and metabolomics analyses of human brain tissues from temporal lobe epilepsy (TLE) patients and an epileptic mouse model reveal that neurotoxic reactive astrocytes induce neuronal damage through lipid-related mechanisms. Moreover, our results demonstrate that the anti-seizure medication cannabidiol (CBD) and an adenosine 2A receptor antagonist can both suppress the formation of neurotoxic reactive astrocytes, mitigate gliosis, and reduce neuronal loss in a mouse model of epilepsy. Electrophysiological and behavioral studies indicate that cannabidiol attenuates seizure symptoms and enhances memory capabilities in epileptic mice. Our findings suggest that neurotoxic reactive astrocytes are formed at an early stage in both the KA-induced mouse model of epilepsy and TLE patients and can contribute to neuronal loss through releasing toxic lipids. Importantly, cannabidiol emerges as a promising therapeutic drug for targeted intervention against neurotoxic reactive astrocytes in adult epilepsy.PMID:40099400 | DOI:10.1111/jnc.70038

Anim Sci J. 2025 Jan-Dec;96(1):e70045. doi: 10.1111/asj.70045.ABSTRACTIn order to investigate the flavor compounds in the muscles of Tianfu finishing (TF) pigs with different slaughter weight (SW), 12 TF pigs were selected for the experiment. The volatile metabolic profiles of meat specimens from the longissimus dorsi (LD) muscle of TF pigs with different SW were studied by untargeted liquid chromatography-mass spectrometry. Our data revealed that the three types of TF pork showed significantly different profiles of hydrocarbons, alcohols, esters, heterocyclic compounds, and others, which could underpin the nuances of their flavors. A total of 118 differentially expressed metabolites (DEMs) were identified (2 upregulated DEMs and 116 downregulated DEMs). Among the volatile flavor compounds, hydrocarbons, alcohols, ester, and heterocyclic compound in the three groups accounted for 26.71%, 13.01%, 13.01%, and 13.70%, respectively, and their contents decreased with increasing SW. The contents of alcohols, aldehydes, and hydrocarbons in the 150-kg group was significantly higher than those in the 125-kg and 100-kg groups (p < 0.05). Taken together, raising SW to 125 kg, or more, decreased the flavor of TF pork and had no benefits to pork quality attributes. Our results provided insights into the molecular basis for sensory variations among different SW of TF pork.PMID:40099363 | DOI:10.1111/asj.70045

Front Mol Biosci. 2025 Mar 3;12:1433912. doi: 10.3389/fmolb.2025.1433912. eCollection 2025.ABSTRACTBACKGROUND: Moxibustion is a form of therapy that to warm the acupoints located skin by using dried mugwort leaves. It is widely used to treat gouty arthritis (GA). However, the mechanism of moxibustion on improving GA has not been fully revealed. In this study, we explore the mechanism of moxibustion on GA via metabolomics combined with traditional Chinese medicine (TCM) theory.METHODS: Three days before model induction, the rats of moxibustion groups were treated with moxibustion in the ST36 and SP6, and then, a GA rat model induced by monosodium urate (MSU) was established. Biological samples, including joint synovial tissue and serum samples, were collected and measured by histopathological staining, molecular biology assays and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics.RESULTS: We found that moxibustion could reduce the ankle edema induced by MSU crystals, decrease the expression of related proinflammatory genes, decrease the levels of serum IL-18 and IL-1β, and restore the metabolism of glycerol phospholipids, niacin and nicotinamide in GA model rats.CONCLUSION: Moxibustion can regulate the metabolism of GA model rats widely to inhibit inflammation. Our research deepens our understanding of the complex mechanisms of moxibustion and promotes the application of moxibustion in the clinical practice.PMID:40099040 | PMC:PMC11911207 | DOI:10.3389/fmolb.2025.1433912

Front Med (Lausanne). 2025 Mar 3;12:1511275. doi: 10.3389/fmed.2025.1511275. eCollection 2025.ABSTRACTBACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease. The occurrence of COPD is associated with gut microbiota, meticulous metabolism and inflammation. Acupuncture may be effective as an adjunctive therapy for COPD, but the available evidence is limited. This study aims to confirm whether acupuncture therapy has an adjunctive therapeutic effect on COPD and to investigate the relationship between the efficacy and the gut microbiota, metabolomics and inflammation.METHODS: This study is a multicenter randomized controlled trial. A total of 72 patients with stable COPD eligible will be randomized in a 1:1 ratio to receive either manual acupuncture (MA) or sham acupuncture (SA) without puncturing the skin. There will be no changes to the essential medicines used for all patients. The intervention will be 12 weeks, 3 times per week and follow-up will be 52 weeks. The primary outcome will be the change in COPD Assessment Test (CAT) score before and after treatment. Secondary outcomes will include modified Medical Research Council (mMRC), St. George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), and the number of moderate or severe acute exacerbations during follow-up. A total of 36 healthy volunteers will also be recruited as normal control. In addition, feces and blood will be collected from each participant to characterize the gut microbiota, metabolomics, immune cells and inflammatory cytokines. Differences between COPD patients and healthy participants will be observed, as well as changes before and after treatment in MA and SA groups. Ultimately, the correlation among gut microbiota, metabolomics, immune cells, inflammatory cytokines and clinical efficacy in COPD patients will be analyzed.DISCUSSION: This study will evaluate the efficacy and provide preliminary possible mechanisms of acupuncture as an adjunctive therapy in treating COPD. In addition, it will identify biomarkers of the gut microbiota, metabolites, immune cells, and inflammatory cytokines associated with therapeutic efficacy. The results of this study will be published in a peer-reviewed journal.PMID:40098933 | PMC:PMC11911195 | DOI:10.3389/fmed.2025.1511275

Drug Des Devel Ther. 2025 Mar 11;19:1681-1701. doi: 10.2147/DDDT.S503757. eCollection 2025.ABSTRACTBACKGROUND: Non-alcoholic steatohepatitis (NASH), as a progressive form of Non-alcoholic fatty liver disease (NAFLD), poses a significant threat to human health as a prevalent and common condition, with a lack of safe and effective therapeutic options. However, the therapeutic effects and potential mechanisms of Lang Qing Ata (LQAtta) against NASH remain elusive.MATERIALS AND METHODS: The components of LQAtta were identified using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS). Subsequently, we employed network construction and analysis approaches within the field of network pharmacology. By integrating known databases and target prediction algorithms, which encompassed database-based target prediction, protein-protein interaction networks, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, we unveiled the potential key targets and signaling pathways that these bioactive components might engage with. These discoveries were further validated in subsequent mouse models. An HFHC-induced NASH mouse model was used to validate the therapeutic effects and potential mechanisms of LQAtta on NASH.RESULTS: From the UHPLC-MS/MS analysis of LQAtta, a total of 1518 chemical components were identified, with 106 of them being absorbed into the bloodstream. Additionally, based on the acquisition of targets from both LQAtta and the NASH database, a total of 160 common targets were screened. KEGG enrichment analysis indicated that LQAtta may alleviate NASH by modulating pathways such as the Toll-like receptor signaling pathway, the NF-κB signaling pathway, and inflammation-related pathways. In vivo experimental results demonstrated that LQAtta could alleviate liver injury, steatosis, and inflammation induced by NASH, thereby slowing down the disease process. Additionally, LQAtta inhibited the expression and phosphorylation of NF-κB protein, playing a role in preventing NASH.CONCLUSION: In this study, the combination of mass spectrometry analysis, network pharmacology, and animal experiments preliminarily elucidated the potential of LQAtta to treat NASH through NF-κB pathways.PMID:40098906 | PMC:PMC11911237 | DOI:10.2147/DDDT.S503757

Front Nutr. 2025 Mar 3;12:1501263. doi: 10.3389/fnut.2025.1501263. eCollection 2025.ABSTRACTBACKGROUND: This study aimed to investigate the associations between serum lipoprotein subclasses and the long-term risk of gastrointestinal (GI) cancers to enhance our understanding of the etiology of GI cancers.METHODS: This prospective cohort study included 249,450 participants from the UK Biobank. Cox proportional hazard models were used to assess the association between 17 serum lipoprotein subclasses with the risk of GI cancers. Restricted cubic spline (RCS) analysis was employed to assess the corresponding dose-response relationships. Additionally, Mendelian randomization (MR) analysis was used to evaluate the causal relationships between the lipoproteins and the risk of GI cancers.RESULTS: A total of 4,787 cases of GI cancers were recorded over a median follow-up period of 12.92 years. Our results revealed that the majority of the high-density lipoprotein (HDL) subclasses, such as very large-, large-, and medium-HDL-particles, were positively associated, while several low-density lipoprotein (LDL) subclasses were negatively associated with the risk of overall GI cancer. Additionally, RCS analysis revealed a linear dose-response relationship between elevated levels of most lipoprotein particles and the risk of overall GI cancer development. Additionally, subgroup analysis indicated a significant sex-dependent interaction between lipoprotein particles and the risk of GI cancers. However, MR analysis revealed a different causal relationships between lipoprotein and GI cancers at the genetic level.CONCLUSION: In this large-scale metabolomics study, we identified several associations between lipoprotein subclasses and the long-term risk of GI cancers. However, further research is needed to fully elucidate their roles in the mechanisms of cancer development.PMID:40098742 | PMC:PMC11912509 | DOI:10.3389/fnut.2025.1501263