PubMed

Poult Sci. 2025 Mar 1;104(5):104956. doi: 10.1016/j.psj.2025.104956. Online ahead of print.ABSTRACTInfectious bronchitis virus (IBV) is a major pathogen that causes significant economic losses in the global poultry industry. Current vaccination strategies provide only partial protection, highlighting the need for more effective prevention and treatment methods. This study aimed to develop a novel compound throat anti-viral (CTA) from natural plants using data from the Traditional Chinese Medicine Inheritance System and identification through liquid chromatography-mass spectrometry. CTA demonstrated substantial anti-IBV effects both in vitro and in vivo studies. In vitro, CTA significantly inhibited IBV multiplication and alleviated the pathological lesions in chicken embryonic kidney cells, tracheal rings, and chicken embryos. In vivo, a seven-day treatment with CTA obtained much milder clinical signs, enhanced growth performance, and better immune organ indices in infected chickens. Additionally, CTA treatment reduced IBV levels in the trachea and lungs and increased specific antibody titers. CTA also maintained body homeostasis, exhibiting strong antioxidant and anti-inflammatory properties that mitigated respiratory tract damage. Metabolomics and network pharmacology analyses, revealed that CTA's antiviral effects are mediated through the FoxO signaling pathway. This study successfully developed an effective prescription database based on the Traditional Chinese Medicine Inheritance System and validated the antiviral efficacy of CTA through comprehensive in vitro and in vivo experiments. The findings elucidated the mechanisms of CTA's action, particularly through the FoxO signaling pathway, and highlighted its potential for clinical application as a novel antiviral treatment for IBV in the poultry industry.PMID:40127563 | DOI:10.1016/j.psj.2025.104956

Environ Sci Technol. 2025 Mar 24. doi: 10.1021/acs.est.4c12333. Online ahead of print.ABSTRACTNanoparticles (NPs) exhibit the potential to enhance plant tolerance to organic pollutant stress, but how they drive endogenous molecules to detoxify contaminants remains to be further investigated. This study clarified the modulatory mechanisms by which foliar or root application of biosynthesized titanium oxide NPs (g-nTiO2) alleviated atrazine (ATZ) toxicity to Lactuca sativa L. Compared with the ATZ-alone group, 10 mg/L g-nTiO2 intensified light-harvesting, photoelectron transfer, and reduced oxidative damage, thereby improving growth and inducing metabolic reprogramming. Specifically, g-nTiO2 activated pathways related to energy supply and defense detoxification, while stabilizing membrane lipid and nitrogen metabolism. Furthermore, the modulation of biomarkers involved in balancing cellular homeostasis and stimulating growth by g-nTiO2 ultimately boosted lettuce resistance to ATZ and physiological performance. Molecular docking analysis revealed that g-nTiO2 enhanced the Phase II metabolism of ATZ by glutathione and amino acids through increasing detoxification enzyme activities by 23-44%, which confirmed the driving role of NPs in alleviating ATZ phytotoxicity to lettuce. Collectively, these findings provide a prospective nanoenabled strategy for mitigating crop sensitivity to pesticide residues for safe and sustainable agricultural production.PMID:40127405 | DOI:10.1021/acs.est.4c12333

PLoS One. 2025 Mar 24;20(3):e0319163. doi: 10.1371/journal.pone.0319163. eCollection 2025.ABSTRACTObesity, a global public health concern, is influenced by various factors, including genetic predispositions. Although many obesity-associated genes have been identified through genome-wide association studies (GWAS), the molecular mechanisms linking these genes to adipose tissue function remain largely unexplored. This study integrates proteomic data on adipocyte fat accumulation with GWAS data on obesity to unravel the roles of the identified key candidate genes - G protein subunit beta 1 (GNB1) and scavenger receptor class B member 2 (SCARB2) - involved in fat accumulation. We utilized RNA interference to knock down GNB1 and SCARB2 in human subcutaneous adipocytes, followed by lipidome and proteome analyses using mass spectrometry. Knockdown of these genes resulted in a reduction in lipid droplet accumulation, indicating their role in adipocyte lipid storage. Digital PCR confirmed effective gene knockdown, with GNB1 and SCARB2 mRNA levels significantly reduced. In total, the lipidomic analysis identified 96 lipid species with significant alterations. GNB1 knockdown resulted in a decrease in cholesterol esters and an increase in phosphatidylcholines, phosphatidylinositols, and ceramides. SCARB2 knockdown also led to an increase in phosphatidylcholines, with a trend towards decreased triacylglycerols. Proteomic analysis revealed significant changes in proteins involved in lipid metabolism and adipocyte function, including PLPP1 and CDH13, which were upregulated following GNB1 knockdown, and HSPA8, which was downregulated. Conversely, SCARB2 knockdown resulted in the downregulation of PLPP1 and METTL7A, and the upregulation of PLIN2, HSPA8, NPC2, and SQSTM1. Our findings highlight the significant roles of GNB1 and SCARB2 in lipid metabolism and adipocyte function, providing insights that could inform therapeutic strategies targeting these regulatory genes in obesity.PMID:40127054 | DOI:10.1371/journal.pone.0319163

Plant Cell Physiol. 2025 Mar 24:pcaf032. doi: 10.1093/pcp/pcaf032. Online ahead of print.ABSTRACTBroomrapes (Phelipanche and Orobanche spp.) and witchweeds (Striga spp.) are parasitic weeds that are increasingly threatening crops worldwide. Seeds of these species rely on host-derived signals such as strigolactones to germinate. While cytokinins were also reported as germination inducers of witchweeds, their role during germination of broomrapes remains unexplored. Our study shows that some but not all cytokinins stimulate Striga hermonthica germination independently of strigolactones, and that high concentrations of bioactive cytokinins trigger Striga seedlings to differentiate into fully extruded embryo-like structures. In contrast, cytokinin free bases but not ribosylated or glycosylated conjugates are extremely potent inhibitors of broomrapes germination. Germination inhibition upon the cytokinin signaling inhibitor PI-55 and inhibitor of cytokinin degradation INCYDE suggest that the cytokinin perception and degradation machinery is conserved in parasitic weeds. In Phelipanche ramosa, gene expression analyses combined with targeted quantification of cytokinin contents revealed that strigolactones first induce an increase in ABA catabolism, then a modification of the cytokinin endogenous pool in favor of inactive conjugates. Overall, this study provides valuable insights into the hormonal interplay governing seed germination in broomrapes and witchweeds, paving the way for future studies aimed at developing novel strategies for parasitic weed control.PMID:40126921 | DOI:10.1093/pcp/pcaf032

Eur J Nutr. 2025 Mar 24;64(3):136. doi: 10.1007/s00394-025-03644-7.ABSTRACTPURPOSE: We aimed to quantify urinary excretion of LNCS (Low- and No-Calorie Sweeteners) and to identify LNCS-associated food consumption in Germany, with special emphasis on exposure to combinations of different LNCS.METHODS: UPLC-MS/MS was used to quantify LNCS metabolites in 24-hour urine samples of 301 participants from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study. Dietary data were assessed via 24 h recall. Spearman rank correlation analysis and multiple linear regression models were used to investigate food groups that contribute to LNCS exposure.RESULTS: Based on the number of samples with quantifiable urinary concentrations and the absolute excretion within a day, cyclamate (88% of samples), saccharin (44%), acesulfame (35%), and aspartame (32%) were most commonly consumed. The consumption of specific food groups, such as table sweeteners, light soft drinks, Radler, protein shakes, and stevia sweeteners, accounted for significant variations in urinary concentrations. Specific combinations of LNCS were observed for these food groups, as well as a considerable exploitation of LNCS-specific ADI (acceptable daily intake).CONCLUSION: Individuals who consume high amounts of specific LNCS-containing, processed foods are exposed to a notable mix of various LNCS. Since data on associations between mixed LNCS exposure and health are lacking, it is an urgent issue to evaluate the potential risks of consuming combinations of diverse LNCS rather than conducting risk assessments of single LNCS.PMID:40126691 | DOI:10.1007/s00394-025-03644-7

Langmuir. 2025 Mar 24. doi: 10.1021/acs.langmuir.5c00183. Online ahead of print.ABSTRACTWith an estimated global cost of $2.5 trillion per year, metal corrosion represents a major challenge across all industrial sectors. Numerous inorganic and organic corrosion inhibitors have been developed, but there are growing concerns about their toxicity and impact on the environment. Here, superior organic corrosion inhibitors based on indole-3-carboxaldehyde, a compound commonly found in the digestive system, and thiosemicarbazones, a safe class of ligands, were designed and studied for mild steel in pH 1 sulfuric acid solutions. Electroanalytical techniques and gravimetric tests revealed inhibition efficiencies as high as 98.9% at 30 °C. Models using Langmuir isotherms gave adsorption equilibrium constants Kads of 2 to 9 × 104 M-1 and corresponding Gibbs free energies of adsorption (ΔGads) as high as -41.44 kJ mol-1, indicating their chemisorption. SEM images confirmed the efficacy of these corrosion inhibitors, as surface features showed limited to no changes after tests. Surface analysis by XPS and LC-MS revealed inhibitor concentrations on the order of 0.7 to 1.8 μg cm-2 for the best compounds, further underlining their performance at low concentrations. Mapping of the surface by MALDI-MS further confirmed the homogeneous coating of the steel surface, with no visible fluctuations in concentrations. As all inhibitors shared the same indole thiosemicarbazone platform, unique structure-performance relationships were drawn from theoretical calculations. Notably, DFT and AIMD explained the differences in performance, highlighting the role of side groups in the distribution of the molecular orbitals and the role of water molecules in enhancing the electronic properties of the organic corrosion inhibitors and promoting their chemisorption.PMID:40126529 | DOI:10.1021/acs.langmuir.5c00183

J Xenobiot. 2025 Mar 4;15(2):39. doi: 10.3390/jox15020039.ABSTRACTThe plastic manufacturing industry has a crucial role in the global economy with a significant impact in a wide range of fields. The chemical risk to which workers are potentially exposed is difficult to characterize and strictly related to both the products and processes adopted. Among the chemicals used, we can cite styrene, phenol, butadiene and phthalates, but nano- and microplastic particles can also be released in the work environment. In this pilot study, we present for the first time an NMR-based metabolomic approach for assessing urinary profiles of workers employed in a plastic manufacturing company. Urine samples from twelve workers and thirteen healthy volunteers were collected and analyzed by NMR spectroscopy. Forty-six urinary metabolites belonging to different chemical classes were univocally identified and quantified. The dataset so obtained was then subjected to multivariate statistical analysis to characterize each profile and highlight any differences. An alteration in some metabolites involved in several pathways, such as amino acid metabolism and NAD metabolism, was found, and a strong impact on gut microflora was also speculated. Ultimately, our work has the objective of adding a tile to the knowledge of biological effects possibly related to occupational exposure even if it is below the threshold limit values.PMID:40126257 | DOI:10.3390/jox15020039

mBio. 2025 Mar 24:e0330224. doi: 10.1128/mbio.03302-24. Online ahead of print.ABSTRACTClostridioides difficile infects the large intestine and can result in debilitating and potentially fatal colitis. The intestinal microbiota is a major factor influencing the severity of disease following infection. Factors like diet that shape microbiota composition and function may modulate C. difficile colitis. Here, we report that mice fed two distinct standard mouse chows (LabDiet 5010 and LabDiet 5053) exhibited significantly different susceptibility to severe C. difficile infection. Both diets are grain-based with comparable profiles of macro and micronutrient composition. Diet 5010-fed mice had severe morbidity and mortality compared to Diet 5053-fed mice despite no differences in C. difficile colonization or toxin production. Furthermore, Diet 5053 protected mice from toxin-induced epithelial damage. This protection was microbiota-dependent as germ-free mice or mice harboring a reduced diversity microbiota fed Diet 5053 were not protected from severe infection. However, cohousing with mice harboring a complex microbiota restored the protective capacity of Diet 5053 but not Diet 5010. Metabolomic profiling revealed distinct metabolic capacities between Diet 5010- and Diet 5053-fed intestinal microbiotas. Diet 5053-mediated protection extended beyond C. difficile infection as Diet 5053-fed mice displayed less severe dextran sodium sulfate-induced colitis than Diet 5010-fed mice, highlighting a potentially broader capacity for Diet 5053 to limit colitis. These findings demonstrate that standard diet formulations in combination with the host microbiota can drive variability in severity of infectious and non-infectious murine colitis systems, and that diet holds therapeutic potential to limit the severity of C. difficile infection through modulating the functional capacity of the microbiota.IMPORTANCEDiet is a major modulator of the microbiota and intestinal health. This report finds that two different standard mouse diets starkly alter the severity of colitis observed in a pathogen-mediated (Clostridioides difficile) and non-infectious (dextran sodium sulfate) mouse colitis experimental systems. These findings in part explain study-to-study variability using these mouse systems to study disease. Since the gut microbiota plays a key role in intestinal homeostasis, diet-derived modulation of the microbiota is a promising avenue to control disease driven by intestinal inflammation and may represent a potential intervention strategy for at-risk patients.PMID:40126017 | DOI:10.1128/mbio.03302-24

ACS Nano. 2025 Mar 24. doi: 10.1021/acsnano.4c18470. Online ahead of print.ABSTRACTSpatial omics is emerging as a focus of life sciences because of its applications in investigating the molecular mechanisms of cancer, mapping cellular distributions, and revealing specific cellular ecological niches. Notably, the in-depth acquisition of spatial omics information relies on highly sensitive, high-resolution, and high-throughput biological analysis tools and techniques. However, conventional methods of omics data acquisition still suffer from some drawbacks such as limited-resolution and low-throughput and are difficult to adapt directly to the collection of high-quality spatial omics data. Recently, an increasing number of advanced nanomaterials and molecular probes are employed in spatial omics due to their excellent optoelectronic properties, biocompatibility, and multifunction. These well-designed innovative nanoscaffolds successfully enhance the key parameters of spatial omics and, thus, increase the spatial resolution, detection sensitivity, and detection throughput. This review summarizes the design and application of functional nanoscaffolds for spatial omics in recent years, with a particular emphasis on nanomaterials and molecular probes. We believe that the present review can inspire and motivate researchers in designing and selecting appropriate materials and probes for high-quality spatial omics, thus promoting the development of spatial omics and life sciences.PMID:40125910 | DOI:10.1021/acsnano.4c18470

Adv Sci (Weinh). 2025 Mar 24:e2411980. doi: 10.1002/advs.202411980. Online ahead of print.ABSTRACTColorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we report that tirzepatide (TZP), a novel polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist for the treatment of diabetes, has a role in attenuating CRC growth. TZP significantly inhibited colon cancer cell proliferation promoted apoptosis in vitro and induced durable tumor regression in vivo under hyperglycemic and nonhyperglycemic conditions across multiple murine cancer models. As glucose metabolism is known to critically regulate colon cancer progression, spatial metabolomics results revealed that glucose metabolites are robustly reduced in the colon cancer regions of the TZP-treated mice. TZP inhibited glucose uptake and destabilized hypoxia-inducible factor-1 alpha (HIF-1α) with reduced expression and activity of the rate-limiting enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK-1). These effects contributed to the downregulation of glycolysis and the tricarboxylic acid (TCA) cycle. TZP also delayed tumor development in a patient-derived xenograft (PDX) mouse model accompanied by HIF-1α mediated PFKFB3-PFK-1 inhibition. Therefore, the study provides strong evidence that glycolysis-blocking TZP, besides its application in treating type 2 diabetes, has the potential for preclinical studies as a therapy for colorectal cancer used either as monotherapy or in combination with other anticancer therapies.PMID:40125821 | DOI:10.1002/advs.202411980

J Agric Food Chem. 2025 Mar 24. doi: 10.1021/acs.jafc.4c13144. Online ahead of print.ABSTRACTPesticide residues on vegetables may affect microbes and metabolites during the fermentation process, leading to effects and potential risks. Here, the enantioselective effects and potential risks of chiral penflufen on pickled cowpea were investigated by using microbiome and metabolomics analyses. Correlation analysis was conducted to construct bacterial-metabolite interaction networks. Penflufen enantiomers were degraded little during the fermentation process. Rac-penflufen treatment significantly decreased the relative abundance of Lactiplantibacillus while increasing Weissella, but the opposite effects were found in R- and S-penflufen treatments. These shifts were linked to content and functional changes of metabolites. R-/S-/Rac-penflufen upregulated rose aroma metabolites (e.g., β-damascenone), while R- and S-penflufen downregulated floral aroma metabolites (e.g., β-ionone, 2-nonenal) and green leaf aroma metabolites (e.g., (E)-2-hexenal). S-Penflufen reduced alcohols and increased esters more significantly, and altered a higher number of volatile organic compounds (VOCs) and chiral amino acids than R-penflufen, showing a greater risk to food flavor and nutritional quality.PMID:40125728 | DOI:10.1021/acs.jafc.4c13144

Front Mol Biosci. 2025 Mar 7;11:1460186. doi: 10.3389/fmolb.2024.1460186. eCollection 2024.ABSTRACTBACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been considered as a key promoting factor in atherosclerosis (AS). Some studies have shown that regulating EMMPRIN expression in bone marrow-derived macrophages (BMDMs) of ApoE-/- mice can affect plaque stability, but the mechanism was not clear.METHODS: AS model mice were built from high-fat-feeding ApoE -/- mice, and were divided into siE group and CON group. The BMDMs and aortas from AS mice were harvested following in vivo treatment with either EMMPRIN short interfering (si)RNA (siEMMPRIN) or negative control siRNA. Transcriptomic and metabolomic profiles were analyzed using RNA-sequencing and Liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. The efficacy of siEMMPRIN was assessed through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB). Immunofluorescence staining was employed to measure EMMPRIN expression within aortic atherosclerotic plaques. Cell proliferation was monitored using the Cell Counting Kit-8 (CCK8), while flow cytometry was utilized to analyze the cell cycle. Additionally, seahorse analysis and oil red O staining were conducted to verify glucose and lipid metabolism, respectively.RESULTS: A total of 3,282 differentially expressed metabolites (DEMs) and 16,138 differentially expressed genes (DEGs) were identified between the CON group and siE group. The nucleotide metabolism and one-carbon (1C) metabolism were identified as major altered pathways at both the transcriptional and metabolic levels. Metabolomic results identified increased levels of glycine, serine, betaine and S-adenosyl-L-methionine (SAM) to S-adenosyl-L-homocysteine (SAH) ratio and decreased levels of dimethylglycine (DMG) and SAH in 1C metabolism, accompanied by the accumulation of nucleotides, nucleosides, and bases in nucleotide metabolism. Transcriptomics results shown that Dnmt, Mthfd2 and Dhfr were downregulated, while Mthfr were upregulated in 1C metabolism. And numerous genes involved in de novo nucleotide synthesis, pentose phosphate pathway (PPP) and dNTP production were significantly inhibited, which may be associated with decreased BMDMs proliferation and cell cycle arrest in the G0/G1 phase in siE group. Multi-omics results also showed changes in glucose and lipid metabolism. Seahorse assay confirmed reduced glycolysis and oxidative phosphorylation (OXPHOS) levels and the Oil Red O staining confirmed the decrease of lipid droplets in siE group.CONCLUSION: The integrated metabolomic and transcriptomic analysis suggested that nucleotide metabolism and 1C metabolism may be major metabolic pathways affected by siEMMPRIN in AS mouse BMDMs. Our study contributes to a better understanding of the role of EMMPRIN in AS development.PMID:40125455 | PMC:PMC11927532 | DOI:10.3389/fmolb.2024.1460186

J Inflamm Res. 2025 Mar 19;18:4103-4120. doi: 10.2147/JIR.S506162. eCollection 2025.ABSTRACTPURPOSE: Injury and inflammatory activate and polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried to explore the mechanisms that regulate macrophage polarization, providing new insights and targets for IVDD treatment. The aim of our study was to evaluate the influence of LT-α on aerobic glycolysis (AG) and polarization in macrophages.METHODS: M0 macrophages were achieved by stimulating THP-1 cells with PMA. M1 macrophages were obtained by IFN-γ and LPS stimulation in M0 macrophages. Energy metabolomics, AG and apoptosis related protein expression, migration and invasion measurement, proliferation was analyzed. Polarization of macrophages, AG associated genes expression, macrophage recruitment was evaluated. NF-κB signaling was ascertained by laser confocal and Western blotting.RESULTS: The propanoate metabolism pathway was enriched in LT-α overexpressing M0 macrophages, and various energy metabolites were detected. Glucose absorption, lactic acid production, and levels of AG proteins were strikingly increased in LT-α overexpression macrophages and remarkably repressed in LT-α knockdown macrophages, accompanied by activated and inactivated NF-κB signaling, respectively. Suppressed migration and invasion ability, restrained proliferation, activated AG, and enhanced apoptosis were observed in nucleus pulposus (NP) cells treated by LT-α overexpressed macrophages, accompanied by reduced macrophage recruitment, with opposite results when treated by LT-α knockdown macrophages. The enhanced M1 polarization and activated AG in LT-α overexpression macrophages were abolished by co-culturing with NF-κB inhibitor.CONCLUSION: LT-α facilitates the AG and M1 polarization of macrophages via activating the NF-κB signaling pathway.PMID:40125079 | PMC:PMC11930265 | DOI:10.2147/JIR.S506162

Biochem Biophys Rep. 2025 Mar 5;42:101967. doi: 10.1016/j.bbrep.2025.101967. eCollection 2025 Jun.ABSTRACTChronic kidney disease (CKD) often follows acute kidney injury, leading to renal fibrosis and progressive renal failure. Spermine, a polyamine with antioxidant and anti-inflammatory properties, helps reduce renal fibrosis and may serve as a biomarker for CKD progression. We used spatially resolved metabonomic analysis with AFADESI-MSI to examine polyamine distribution in kidneys of a folic acid (FA)-induced CKD mouse model. Results showed decreased spermine and increased spermidine levels, associated with elevated spermine oxidase (SMOX) and spermidine/spermine N1-acetyltransferase (SSAT) enzyme expression in CKD. These findings suggest that altered polyamine metabolism contributes to CKD progression and may provide targets for polyamine-based therapies.PMID:40124992 | PMC:PMC11928990 | DOI:10.1016/j.bbrep.2025.101967

Biofilm. 2025 Feb 28;9:100268. doi: 10.1016/j.bioflm.2025.100268. eCollection 2025 Jun.ABSTRACTThe successful sustainable cultivation of the well-known medicinal plant sundew on rewetted peatlands not only leads to the preservation of natural populations, but also provides a basis for the sustainable pharmaceutical use of the plant. The bioactive compounds of sundew, flavonoids and naphthoquinones, show biofilm-inhibiting properties against multidrug-resistant, ESBL-producing E. coli strains and open up new therapeutic possibilities. This study investigates the molecular mechanisms of these compounds in biofilm inhibition through proteomic analyses. Specific fractions of flavonoids and naphthoquinones, as well as individual substances like 7-methyljuglone and 2″-O-galloylhyperoside, are analyzed. Results show that naphthoquinones appear to act via central regulatory proteins such as OmpR and alter the stress response while flavonoids likely affect biofilm formation by creating an iron-poor environment through iron complexation and additionally influence polyamine balance, reducing intracellular spermidine levels. Further investigations including assays for iron complexation and analysis of polyamines confirmed the proteomic data. Safety evaluations through cytotoxicity tests in 3D cell cultures and the Galleria mellonella in vivo model confirm the safety of the extracts used. These findings highlight sundew as a promising candidate for new phytopharmaceuticals.PMID:40124935 | PMC:PMC11930149 | DOI:10.1016/j.bioflm.2025.100268

Front Pharmacol. 2025 Mar 7;16:1553081. doi: 10.3389/fphar.2025.1553081. eCollection 2025.ABSTRACTBACKGROUND AND OBJECTIVE: Ischemic stroke is a cerebrovascular disease with highly incidence. Previous research has demonstrated that apigenin provides protective effects against ischemic stroke. However, it remains unclear whether apigenin can regulate intestinal flora against ischemic stroke.METHODS: In this study, we evaluated the regulatory effects of apigenin on intestinal microbiota using a middle cerebral artery occlusion rat model. The protective impact of apigenin on brain damage in ischemic stroke rats was assessed through Nissl staining, hematoxylin and eosin staining, and immunohistochemistry. Additionally, we employed 16S rRNA sequencing to analyze intestinal contents and utilized non-targeted metabolomics to investigate the effects of apigenin on brain metabolites, thereby exploring its mechanism of action. AMPK levels were detected by Western blot and immunohistochemistry. The kit was used to detect oxidative stress and inflammation.RESULTS: The intervention with apigenin resulted in significant alterations in the intestinal flora, characterized by an increase in the abundance of probiotic species and a decrease in harmful flora, alongside notable changes in brain metabolite profiles. This protective effect is attributed to apigenin's promotion of AMPK expression and enhancement of energy metabolism in the context of ischemic stroke. In addition, apigenin improved oxidative stress and inflammation in ischemic stroke.CONCLUSION: These findings suggest that apigenin exerts a protective effect on ischemic stroke through the AMPK signaling pathway by modulating intestinal flora and associated metabolites. Consequently, apigenin emerges as a therapeutic candidate warranting further investigation.PMID:40124778 | PMC:PMC11925864 | DOI:10.3389/fphar.2025.1553081

Front Chem. 2025 Mar 7;13:1523712. doi: 10.3389/fchem.2025.1523712. eCollection 2025.ABSTRACTToF-SIMS is a high spatial resolution imaging technique for cellular or subcellular analysis of biological samples. Accurate molecular data in single-cell studies depend on proper cell morphology and chemical integrity, highlighting the importance of sample preparation. In this work, we standardized a more efficient freeze-drying method using standard lab materials and improved the sample preparation process. Our comprehensive freeze-drying protocol for cellular samples, encompassing washing, fixation, and drying steps, facilitates the acquisition of enhanced cellular information and ensures high reproducibility. These improvements are poised to significantly advance single-cell mass spectrometry imaging research.PMID:40124708 | PMC:PMC11925917 | DOI:10.3389/fchem.2025.1523712

iScience. 2025 Jan 6;28(3):111761. doi: 10.1016/j.isci.2025.111761. eCollection 2025 Mar 21.ABSTRACTDiapause enables insects to survive unfavorable conditions through metabolic and developmental adjustments. We investigated metabolic regulation during reproductive diapause in the predatory stinkbug Arma chinensis using transcriptomic and metabolomic analyses. Our study revealed 9,254 differentially expressed genes and 493 significantly changed metabolites across diapause stages. Key metabolic pathways including glutathione metabolism, TCA cycle, glycolysis, and lipid metabolism underwent substantial reorganization. The pre-diapause phase showed increased energy consumption and lipid accumulation, while the maintenance phase exhibited restructuring of amino acid and glucose metabolism. We identified stage-specific metabolic signatures and potential regulatory mechanisms, including the roles of glutathione metabolism in redox regulation and insulin signaling in diapause control. This comprehensive characterization of metabolic reprogramming during A. chinensis diapause provides insights for improving biocontrol agent production and storage strategies.PMID:40124477 | PMC:PMC11928864 | DOI:10.1016/j.isci.2025.111761

Front Immunol. 2025 Mar 7;16:1526110. doi: 10.3389/fimmu.2025.1526110. eCollection 2025.ABSTRACTOBJECTIVE: Qingre Huoxue Decoction (QRHXD) is a traditional Chinese herbal prescription widely used in clinical practice with significant therapeutic effects on RA; however, its mechanism of action remains unclear. This study aimed to investigate the efficacy and underlying mechanisms of QRHXD in treating RA through clinical research, multiomics approaches, and animal experiments.METHODS: We conducted a 24-week clinical study in which QRHXD was the primary treatment, collecting serum samples from patients before and after treatment for integrated proteomic and metabolomic analysis to identify potential therapeutic targets. Bioinformatics analysis of differentially expressed proteins (DEPs) and differential metabolites (DMs) was performed using hierarchical clustering, volcano plots, heat maps, Gene Ontology (GO), and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. To validate the identified therapeutic targets, we constructed a collagen-induced arthritis (CIA) mouse model.RESULTS: Clinical research has shown that QRHXD can improve clinical symptoms and relevant indicators in RA patients, including the disease activity score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), visual analogue scale (VAS), patient-reported outcome (PRO), and health assessment questionnaire (HAQ). Proteomics and metabolomics analysis identified 83 DEPs and 54 DMs, including 46 upregulated and 37 downregulated proteins, as well as 11 upregulated and 43 downregulated metabolites. KEGG enrichment analysis revealed that DEPs are primarily associated with fatty acid degradation, ferroptosis, glycerolipid metabolism, and related pathways. The identified DMs are primarily associated with the AMPK signalling pathway, FoxO signalling pathway, glycolysis/gluconeogenesis, MTOR signalling pathway, and so on. GO enrichment analysis indicated that the DEPs were mainly associated with apoptotic mitochondrial changes, protein modification processes, fatty-acyl-CoA binding, and so on. Integrated proteomics and metabolomics analyses revealed a significant increase in fructose-1,6-biphosphatase 1 (FBP1) levels and a reduction in AMP-activated protein kinase (AMPK) levels in patients with RA. QRHXD inhibited FBP1 and activated AMPK signalling. Animal experiments validated the findings from proteomics and metabolomics analyses, demonstrating that QRHXD could also delay bone destruction and reduce inflammatory factor levels in CIA mice.CONCLUSION: QRHXD may reduce the disease activity of RA, attenuate the inflammatory response, and delay bone destruction by inhibiting FBP1 and activating the AMPK signalling pathway.PMID:40124380 | PMC:PMC11926152 | DOI:10.3389/fimmu.2025.1526110

Biomed Chromatogr. 2025 May;39(5):e70058. doi: 10.1002/bmc.70058.ABSTRACTIn this study, Balb/c mice were subjected to chronic unpredictable mild stress (CUMS) and treated with Zhi-zi-chi Decoction (ZZCD). Using a hippocampal lipidomics approach that combined ultra performance liquid chromatography (UPLC)-Q-Exactive Orbitrap MS with multivariate statistical techniques and targeted metabolic pathway analysis, we identified potential lipid metabolites and pathways associated with depression. Meanwhile, anti-inflammatory analyses were conducted in the hippocampus of mice. The chromatograms revealed that most lipids of the same class eluted within the same time period. In the scatter plot, the control and CUMS groups were obviously separated, whereas the ZZCD-treated or fluoxetine-treated groups were positioned between them. In positive and negative ion modes, a comprehensive screening identified 130 differential lipid metabolites, which were classified into 5 groups and 17 types. ZZCD was hypothesized to have a certain call-back efficiency for some differential lipid metabolites. The study identified three target metabolic pathways with certain influence values: glycerophosphate metabolism, linoleic acid metabolism, and α-linolenic acid metabolism. Although ZZCD's inhibitory effect on IL-6 was not significant, it demonstrated good therapeutic effects in reducing central system inflammation associated with IL-1β and TNF-α. The research suggested that the pathogenesis of depression might be closely related to lipid metabolism. ZZCD exhibited antidepressant effects by regulating endogenous lipid metabolism in CUMS mice.PMID:40123576 | DOI:10.1002/bmc.70058