PubMed

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

ACS Omega. 2025 Mar 6;10(10):10327-10339. doi: 10.1021/acsomega.4c10160. eCollection 2025 Mar 18.ABSTRACTThe chemodiversity of plants is a valuable resource for drug discovery, and its combination with modern approaches can reduce the time consumption for bioactive metabolite discovery. This study aimed to evaluate the chemical constituents from 18 plant species of different families against leukemia cancer cells and the application of statistical analysis from metabolomic data and molecular networking for the prediction of bioactive metabolites. The samples, extracted by an accelerated solvent extractor using ethanol and water 7:3 (v/v), were analyzed by LC-DAD-MS and evaluated against leukemia cancer cells (Kasumi-1, KG-1, and K-562). Chemical data were aligned, analyzed by statistics, and applied to create the molecular network. Sesbania virgata, Aeschynomene denticulata, Erythroxylum angiufugum, Psidium guineense, Astronium fraxinifolium, Coccoloba ochreolata, Solanum glaucophyllum (S. glaucophyllum), and Paullinia pinnata inhibited K-562 leukemia cancer cell viability by approximately 70% at 100 μg/mL, while Ocotea diospyrifolia showed 35% inhibition for the KG-1 lineage. Alkaloid fractions from S. glaucophyllum and O. diospyrifolia revealed EC50 values ranging from 13.9 to 6.4 μg/mL for K-562 and KG-1 cell lines, effectively inducing cell death with apoptotic characteristics, membrane integrity loss, and signs of late apoptosis. The molecular networking was essential and crucial to complement the statistical analysis, which was performed from 430 features and targeted steroidal and aporphine alkaloids. Boldine revealed EC50 values of 46, 116, and 145 μM for Kasumi, KG-1, and K-562 cancer cell lines, respectively. The findings marked the relevance of a broader chemical data analysis to predict bioactive compounds, emphasizing potential benefits in the search for metabolites against leukemia cancer cells, particularly steroidal and aporphine alkaloids.PMID:40124017 | PMC:PMC11923848 | DOI:10.1021/acsomega.4c10160

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

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

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

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

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

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

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

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