PubMed

JACC CardioOncol. 2025 Jan 21;7(1):68-69. doi: 10.1016/j.jaccao.2024.11.005. eCollection 2025 Jan.NO ABSTRACTPMID:39896125 | PMC:PMC11782008 | DOI:10.1016/j.jaccao.2024.11.005

JACC CardioOncol. 2024 Dec 3;7(1):56-67. doi: 10.1016/j.jaccao.2024.10.004. eCollection 2025 Jan.ABSTRACTBACKGROUND: Anthracyclines, a highly effective chemotherapy for many pediatric malignancies, cause cardiomyopathy, a major late effect in adult survivors. Biomarkers are needed for early detection and targeted interventions for anthracycline-associated cardiomyopathy.OBJECTIVES: The aim of this study was to determine if serum proteins and/or metabolites in asymptomatic childhood cancer survivors can discriminate symptomatic cardiomyopathy.METHODS: Using an untargeted mass spectrometry-based approach, 867 proteins and 218 metabolites were profiled in serum samples of 75 asymptomatic survivors with subclinical cardiomyopathy and 75 individually matched survivors without cardiomyopathy from SJLIFE (St. Jude Lifetime Cohort Study). Models were developed on the basis of the most influential differentially expressed proteins and metabolites, using conditional logistic regression with a least absolute shrinkage and selection operator penalty. The best performing model was evaluated in 23 independent survivors with severe or symptomatic cardiomyopathy and 23 individually matched cardiomyopathy-free survivors.RESULTS: A 27-protein model identified using conditional logistic regression with a least absolute shrinkage and selection operator penalty discriminated symptomatic or severe cardiomyopathy requiring heart failure medications in independent survivors; 19 of 23 individually matched survivors with and without cardiomyopathy were correctly discriminated with 82.6% (95% CI: 71.4%-93.8%) accuracy. Pathway enrichment analysis revealed that the 27 proteins were enriched in various biological processes, many of which have been linked to anthracycline-related cardiomyopathy.CONCLUSIONS: A risk model was developed on the basis of the differential expression of serum proteins in subclinical cardiomyopathy, which accurately discriminated the risk for severe cardiomyopathy in an independent, matched sample. Further assessment of these proteins as biomarkers of cardiomyopathy risk should be conducted in external larger cohorts and through prospective studies.PMID:39896123 | PMC:PMC11782007 | DOI:10.1016/j.jaccao.2024.10.004

Front Pharmacol. 2025 Jan 17;16:1497988. doi: 10.3389/fphar.2025.1497988. eCollection 2025.ABSTRACTSkin repair and regeneration are crucial processes in restoring the integrity of the skin after injury, with significant implications for medical treatments and plastic surgery. Multiomics, an integrated approach combining genomics, transcriptomics, proteomics, and metabolomics, offers unprecedented insights into the complex molecular and cellular mechanisms involved in skin healing. This review explores the transformative role of multiomics in elucidating the mechanisms of skin repair and regeneration. While genomic studies identify the genetic basis of wound healing, transcriptomics and proteomics uncover the dynamic changes in gene and protein expression, and metabolomics provides a snapshot of metabolic alterations associated with wound healing. Integrative multiomics studies can also identify novel biomarkers and therapeutic targets for skin regeneration. Despite the technical and biological challenges, the future of multiomics in skin research holds great promise for advancing personalized medicine and improving wound healing strategies. Through interdisciplinary collaboration, multiomics has the potential to revolutionize our understanding of skin repair, paving the way for innovative treatments in plastic surgery and beyond.PMID:39896077 | PMC:PMC11782119 | DOI:10.3389/fphar.2025.1497988

Int J Rheum Dis. 2025 Feb;28(2):e70094. doi: 10.1111/1756-185X.70094.ABSTRACTBACKGROUND: Gout is a prevalent metabolic disorder characterized by a multifaceted process of development. Recent research has emphasized a robust correlation between the immune response and gout. Nevertheless, it is still uncertain if this connection is causative. Hence, the objective of this study was to investigate the causal relationship between immune cells and gout, while also analyzing the role of the plasma metabolome as metabolic mediators in this biological process.METHODS: This study explored the causal link between different subtypes of immune cells and gout using two-sample Mendelian randomization (MR). To confirm the reliability of the findings, reverse MR analysis, steiger test and sensitivity tests were conducted. A two-step mediation analysis was used to gain insight into the role of plasma metabolites as intermediate mediators.RESULTS: This two-sample, bidirectional, two-step MR analysis found a nominal causal link between 33 immune cells as well as 47 known plasma metabolites and gout. Reverse MR analysis and sensitivity tests demonstrated the reliability of the MR results. In addition, we found that Tetradecadienedioate (C14:2-DC) played a partially mediating role in the CD4 on activated CD4 regulatory T cell and gout pathways, with a mediating proportion of 13.16%, (95% CI = 0.65%-25.67%, p = 0.034).CONCLUSION: The objective of our research was to investigate the possible causative connection between immune cells and gout. Our findings indicate that certain plasma metabolites may play a role in mediating this association. This study offers novel insights and sources of information that may contribute to the early detection and proactive measures to avoid gout in the future.PMID:39895258 | DOI:10.1111/1756-185X.70094

Cancer Sci. 2025 Feb 2. doi: 10.1111/cas.16430. Online ahead of print.ABSTRACTEarly detection of esophageal cancer is essential for esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examinations are sometimes invasive, which limits their clinical application and compliance, and traditional blood tumor markers are unsuitable for cancer screening. The current study aimed to evaluate the usefulness of sulfur metabolites as new biomarkers for esophageal cancer using blood samples and exhaled breath condensate (EBC), which can be readily obtained and is non-invasive. We collected EBC and plasma samples from 50 patients with esophageal cancer and 30 healthy controls. Sulfur metabolome analysis using tandem mass spectrometry was performed to compare the metabolic profile between the two groups. Supersulfide metabolic profiles were different between the two cohorts. Supersulfide metabolome analysis showed that cysteine hydropersulfide (CysSSH) and homocysteine hydropersulfide (HomoCysSSH) were increased in the plasma of patients with esophageal cancer. Elevated levels of HomoCysSSH could distinguish patients with esophageal cancer from healthy subjects (area under the curve [AUC]: 0.93, sensitivity: 89%, specificity: 96%). Interestingly, we also detected an elevation of supersulfides in the EBC analysis. CysSSH levels significantly increased in the EBC recovered from patients with esophageal cancer (AUC: 0.71, sensitivity: 60%, specificity: 96%). In addition, the observed level was correlated with that of HomoCysSSH in the plasma (r = 0.27). Supersulfides, such as CysSSH and HomoCysSSH, are potential biomarkers for detecting esophageal cancer. CysSSH from EBC may serve as a valuable non-invasive biomarker with similar detection ability but with superior precision and convenience compared with the currently available blood biomarkers.PMID:39895210 | DOI:10.1111/cas.16430

ACS Nano. 2025 Feb 2. doi: 10.1021/acsnano.4c13753. Online ahead of print.ABSTRACTRadiotherapy is crucial in local cancer management and needs advancements. Tumor cells elevate intracellular copper levels to promote growth and resist radiation; thus, targeted copper delivery to mitochondria could enhance radiotherapy by inducing cuproptosis in tumor cells. In this study, we engineered a multifunctional nanoliposome complex, termed Lipo-Ele@CuO2, which encapsulates both copper peroxide (CuO2) and the copper chelator elesclomol, which can delivery Cu ions to the mitochondria. The Lipo-Ele@CuO2 complex induces mitochondria-mediated cuproptosis in tumor cells and synergistically enhances the efficacy of radiotherapy. CuO2 acts as a copper donor and exhibits inherent sensitivity to acidic environments. Additionally, it depletes intracellular glutathione, thereby sensitizing cells to cuproptosis. Leveraging its pH-responsive properties in the acidic tumor microenvironment, the Lipo-Ele@CuO2 facilitate the controlled release of elesclomol, efficiently delivering copper ions to mitochondria at tumor sites. The combined in vitro and in vivo studies demonstrate that Lipo-Ele@CuO2-based therapy significantly improves antitumor efficacy and exhibits excellent safety profiles, effectively inducing cuproptosis in tumor cells and boosting the effectiveness of radiotherapy. Furthermore, metabolomic and transcriptomic analyses reveal that this combination therapy precipitates significant alterations in tumor energy metabolism, notably repressing genes related to iron-sulfur cluster assembly and glycolysis, thereby confirming the induction of cuproptosis. This therapeutic strategy provides a viable approach for addressing clinical radiotherapy resistance and demonstrates significant translational potential.PMID:39895200 | DOI:10.1021/acsnano.4c13753

Small Methods. 2025 Feb 2:e2401906. doi: 10.1002/smtd.202401906. Online ahead of print.ABSTRACTWith the rising incidence of benign prostatic hyperplasia (BPH) due to societal aging, accurate and early diagnosis has become increasingly critical. The clinical challenges associated with BPH diagnosis, particularly the lack of specific biomarkers that can differentiate BPH from other causes of lower urinary tract symptoms (LUTS). Here, matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) metabolomic detection platform utilizing urine and serum samples is applied to explore metabolic information and identify potential biomarkers in designed cohort. The nanoparticle-assisted platform demonstrated rapid analysis, minimal sample consumption, and high reproducibility. Employing a two-step grouping screening approach, the identification of urinary metabolic patterns (UMPs) is automated to distinguish healthy individuals from LUTS group, followed by the use of serum metabolic patterns (SMPs) to accurately identify BPH cases within the LUTS cohort, achieving an area under the curve (AUC) of 0.830 (95% CI: 0.802-0.851). Furthermore, eight BPH-sensitive metabolic markers are identified, confirming their uniform distribution across age groups (p > 0.05). This research contributes valuable insights for the early diagnosis and personalized treatment of BPH, enhancing clinical practice and patient care.PMID:39895158 | DOI:10.1002/smtd.202401906

J Microbiol. 2025 Jan;63(1):e.2409008. doi: 10.71150/jm.2409008. Epub 2024 Dec 20.ABSTRACTTella is a traditional beverage widely accepted by consumers, despite the lack of product consistency owing to its reliance on natural fermentation. This study aimed to identify potential industrial lactic acid bacteria (LAB) starter cultures based on their technological properties. Seven LAB strains isolated from Tella were characterized for their carbohydrate utilization, salt content, temperature, and acid tolerances, growth and acidification rates, and metabolite profiles. Most strains efficiently utilized various carbohydrates, with Lactiplantibacillus plantarum TDM41 showing exceptional versatility. The strains exhibited similar growth characteristics. Principal component analysis of stress tolerance properties revealed that L. plantarum TDM41, Pediococcus pentosaceus TAA01, and Leuconostoc mesenteroides TDB22 exhibited superior tolerance ability. Strong acidification properties were detected in the L. plantarum TDM41, P. pentosaceus TAA01, and Leuconostoc mesenteroides TDB22 strains after 24 h incubation at 30°C. L. plantarum TDM41 displayed the fastest acidification rate throughout the analysis period. All LAB strains produced significant amounts of diverse organic acids, including lactic acid, citric acid, acetic acid, malic acid, and succinic acid, with lactic acid being the primary acid produced by each strain. Overall, strains L. plantarum TDM41 and P. pentosaceus TAA01 prove to be potential candidates for Tella industrial starter cultures and similar cereal products owing to their robust technological properties.PMID:39895073 | DOI:10.71150/jm.2409008

J Agric Food Chem. 2025 Feb 2. doi: 10.1021/acs.jafc.4c10238. Online ahead of print.ABSTRACTMastitis in dairy cows is an inflammatory disease that severely affects the health and lactation functions of dairy cows. Mitochondrial damage is closely related to the inflammatory response. How to effectively alleviate mitochondrial damage is the key to preventing and treating mastitis in dairy cows. In this study, we found elevated levels of inflammatory response and mitochondrial damage accompanied by reduced expression of Sirt5 (Sirtuin5) in cows with mastitis compared with healthy cows. This suggests that Sirt5 plays an important role in mastitis in dairy cows. Subsequently, we further analyzed mammary gland tissue from healthy and mastitis cows by untargeted metabolomics (LC-MS/MS) and screened for the differential metabolite l-glutamic acid (l-Glu). To further validate the effect of l-Glu on mastitis in dairy cows, we conducted a study using MAC-T cells. The results showed that l-Glu was able to ameliorate LPS-induced mitochondrial damage by activating Sirt5 and promoting mitochondrial fusion and the upregulation of mitochondrial membrane potential (MMP) levels. In contrast, l-Glu was unable to protect mitochondrial function after knocking down Sirt5. Furthermore, we found that l-Glu was able to upregulate the expression of nuclear factor E2-related factor (Nrf2) and peroxiredoxin 1 (Prdx1) in LPS-induced MAC-T cells, and promoted the entry of Nrf2 into the nucleus, which was reversed by knocking down Sirt5. Next, we further explored whether l-Glu alleviates mitochondrial damage through the Nrf2/Prdx1 signaling axis by using the Nrf2 inhibitor RA. The results showed that the use of RA promoted LPS-induced mitochondrial damage and blocked the protective effect of l-Glu on mitochondrial function. In conclusion, l-Glu ameliorates mitochondrial damage by targeting Sirt5 to activate the Nrf2/Prdx1 signaling axis and alleviate mastitis in dairy cows. This study provides a new target and theoretical basis for the clinical control of mastitis. l-Glu could be added as a dietary supplement to the diets of dairy cows and maintain mammary gland homeostasis, thereby protecting the health and economic value of dairy cows.PMID:39895052 | DOI:10.1021/acs.jafc.4c10238

J Anim Sci Biotechnol. 2025 Feb 3;16(1):17. doi: 10.1186/s40104-025-01150-8.ABSTRACTBACKGROUND: Meat originating from the spent hen is an important source of poultry meat production; however, multiple factors cause the decline in the meat quality of spent hens. Chinese herbs have been widely used as medicine for a long time to prevent diseases and as nutrient supplements to improve the product quality. This experiment explored the effects of adding 1.0% Chinese herbal formula (CHF, including 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz.) for 120 d to the spent hens' diet through metabolomics, network pharmacology, and microbiome strategies.RESULTS: The results indicated that CHF supplementation improved the meat quality by reducing drip loss (P < 0.05), b* value (P = 0.058), and shear force (P = 0.099) and increasing cooked meat percentage (P = 0.054) and dry matter (P < 0.05) of breast muscle. The addition of CHF improved the nutritional value of breast muscle by increasing (P < 0.05) the content of C18:2n-6, n-6/n-3 polyunsaturated fatty acids (PUFA), total PUFA, PUFA-to-saturated fatty acids (SFA) ratio, and hypocholesterolemic-to-hypercholesterolemic ratio, and tending to increase serine content (P = 0.069). The targeted metabolomics analysis revealed that the biosynthesis of SFA, linoleic acid metabolism, fatty acid degradation, fatty acid elongation, and fatty acid biosynthesis pathways were enriched by CHF supplementation. Furthermore, the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabolism. The CHF supplementation increased the glutathione peroxidase level (P < 0.05) and upregulated gene expression related to the Nrf2 pathway (including HO-1, P < 0.05; Nrf2, P = 0.098; CAT, P = 0.060; GPX1, P = 0.063; and SOD2, P = 0.052) and lipid metabolism (including PPARγ, P < 0.05; SREBP1, P = 0.059; and CPT1A, P = 0.058). Additionally, CHF supplementation increased Firmicutes and decreased Bacteroidetes, Spirochaetes, and Synergistetes abundances (P < 0.05), which may contribute to better meat quality.CONCLUSIONS: Our results suggest that CHF supplementation improved the quality and nutritional value of meat, which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens' diets.PMID:39894829 | DOI:10.1186/s40104-025-01150-8

Eur Urol Focus. 2025 Feb 1:S2405-4569(25)00010-0. doi: 10.1016/j.euf.2025.01.010. Online ahead of print.ABSTRACTMicrobiome-derived or -modulated metabolites (short-chain fatty acids, bile acids, and amino acids) could mediate antitumor immunity. Diet offers an actionable route for manipulating both the microbiome and the metabolome. Diet- and microbiome-directed trials with robust translational correlates are eagerly awaited.PMID:39894735 | DOI:10.1016/j.euf.2025.01.010

Int Dent J. 2025 Feb 1:S0020-6539(25)00012-7. doi: 10.1016/j.identj.2025.01.004. Online ahead of print.NO ABSTRACTPMID:39894724 | DOI:10.1016/j.identj.2025.01.004

Ann Rheum Dis. 2025 Feb 1:S0003-4967(25)00054-8. doi: 10.1016/j.ard.2025.01.009. Online ahead of print.ABSTRACTOBJECTIVES: Osteoarthritis (OA) is linked to disrupted lipid metabolism. We aimed to profile the lipid composition of human articular cartilage, investigate OA-associated lipidome changes, and explore biological effects.METHODS: Lipidomic profiling and computational analyses were performed on human articular chondrocytes (hACs) from non-OA (n = 13) and OA (n = 14) hips. Lipid changes were confirmed in the destabilisation of the medial meniscus (DMM) mouse model. The effect of specific lipids was evaluated by in vitro supplementation and gene silencing.RESULTS: We identified 573 lipid species covering 11 lipid classes in hACs. OA and non-OA hACs showed distinct lipid profiles. Most ceramides and dihydroceramides were increased, while cholesteryl esters, diacylglycerols, triacylglycerols, sphingomyelins, hexosylceramides, and lactosylceramides were predominantly decreased in OA chondrocytes. Most upregulated lipids in OA contained C18:1, C20:4, or C22:4 side chains. Many downregulated lipids contained C18:2 or odd-chain C17:0. Lipid profiling of articular cartilage from the DMM mouse model paralleled changes in OA hACs, including odd-chain C17:0 reduction. Further analysis showed that deficiency in enzyme 2-hydroxyacyl-CoA lyase 1 (HACL1), responsible for odd-chain fatty acid synthesis, leads to accumulation of 2-hydroxy C18:0, precursor of C17:0, which results in a shift in hACs from an anabolic to a catabolic state.CONCLUSIONS: Our study maps the hAC lipid composition and highlights changes in lipid profiles associated with OA. Dysregulation of certain lipids, especially odd-chain fatty acids, linked to a deficiency in the enzyme HACL1, leads to pathological changes. This understanding opens potential avenues for therapies aimed at targeting lipid imbalances to slow down or treat OA.PMID:39894691 | DOI:10.1016/j.ard.2025.01.009

J Adv Res. 2025 Jan 31:S2090-1232(25)00062-1. doi: 10.1016/j.jare.2025.01.043. Online ahead of print.ABSTRACTINTRODUCTION: PER3 deficiency is associated with depression-like behaviors, but the underlying mechanisms remain unclear.OBJECTIVES: This study aims to elucidate the role and mechanism of PER3 in regulating depression-like behaviors in mice.METHODS: Depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Metabolomic analysis was conducted on hippocampal tissues from Per3 knockout mice using chromatography-mass spectrometry. The regulatory role of PER3 on the expression of nicotinamide phosphoribosyltransferase (Nampt) was investigated through co-immunoprecipitation and chromatin immunoprecipitation assays.RESULTS: Metabolomic analysis revealed that Per3 deficiency disrupts mitochondrial function, as evidenced by reduced activities of key tricarboxylic acid (TCA) cycle enzymes (succinate dehydrogenase, citrate synthase, and α-ketoglutarate dehydrogenase), diminished expression of mitochondrial respiratory chain complexes I-V, and decreased nicotinamide adenine dinucleotide (NAD)+ levels in Per3 knockout mice. Supplementation with the NAD+ precursor nicotinamide (NAM) rescued mitochondrial function and alleviated depression-like behaviors in Per3 knockout mice. Similar effects were observed with intraperitoneal administration of the NAMPT activator P7C3-A20, while these effects were abolished by the NAMPT inhibitor FK866. Mechanistically, PER3 was found to regulate Nampt expression by binding to E-box elements within its intronic regions in conjunction with BMAL1. This interaction enhanced NAD+ production, activating SIRT3 to mitigate mitochondrial dysfunction in Per3 knockout mice.CONCLUSIONS: These findings uncover a novel mechanism by which PER3 ameliorates depressive behaviors through the regulation of NAMPT-controlled NAD+ levels and mitochondrial function, underscoring the critical role of PER3 in depression-related pathophysiology.PMID:39894345 | DOI:10.1016/j.jare.2025.01.043

Bone. 2025 Jan 31:117413. doi: 10.1016/j.bone.2025.117413. Online ahead of print.ABSTRACTBone marrow is a complex tissue featuring distinct cellular organization and diverse cell types. Bone marrow adipose tissue (BMAT) is a dynamic component crucial for tissue function and disease processes. This study explores differences between bone marrow-derived mesenchymal stem cells (BM-MSCs) and BMAT-derived mesenchymal stem cells (BMAT-MSCs), isolated from the same cavity, examining their differentiation potential and secretory profiles. BM-MSCs and BMAT-MSCs both exhibit classical mesenchymal characteristics, with over 90 % positivity for markers such as CD105 and CD29. Notably, BMAT-MSCs display significantly higher differentiation potential than BM-MSCs, with enhanced osteogenic and adipogenic capabilities, as indicated by increased calcium accumulation and lipid storage. In Fanconi anemia (FA) and acute myeloid leukemia (AML), osteogenic potential is limited, indicating impaired differentiation under these pathological conditions. Gene expression analysis of adipogenic molecules and metabolic regulators revealed significant differences in expression profile between BM- and BMAT-MSCs, particularly during adipogenic differentiation, indicating distinct characteristics that were more notable in FAs and AMLs. Furthermore, metabolomic profiling of BM plasma, using GC-MS for in-vivo niche reflection, and lipid analysis via LC-qTOF-MS show significant lipidomic alterations in patient samples, highlighting metabolic dysregulation and lipid remodeling. Lipid-mediated signaling and membrane composition changes appear integral to disease mechanisms. In conclusion, this study highlights the distinctive molecular and metabolomic profiles and adaptive mechanisms of BM- and BMAT-MSCs in bone marrow pathologies.PMID:39894290 | DOI:10.1016/j.bone.2025.117413

Mol Metab. 2025 Jan 31:102106. doi: 10.1016/j.molmet.2025.102106. Online ahead of print.ABSTRACTOBJECTIVES: The rapid growth that occurs during Drosophila larval development requires a dramatic rewiring of central carbon metabolism to support biosynthesis. Larvae achieve this metabolic state, in part, by coordinately up-regulating the expression of genes involved in carbohydrate metabolism. The resulting metabolic program exhibits hallmark characteristics of aerobic glycolysis and establishes a physiological state that supports growth. To date, the only factor known to activate the larval glycolytic program is the Drosophila Estrogen-Related Receptor (dERR). However, dERR is dynamically regulated during the onset of this metabolic switch, indicating that other factors must be involved. Here we examine the possibility that the Drosophila ortholog of Hypoxia inducible factor 1α (Hif1α) is also required to activate the larval glycolytic program.METHODS: CRISPR/Cas9 was used to generate new loss-of-function alleles in the Drosophila gene similar (sima), which encodes the sole fly ortholog of Hif1α. The resulting mutant strains were analyzed using a combination of metabolomics and RNAseq for defects in carbohydrate metabolism.RESULTS: Our studies reveal that sima mutants fail to activate aerobic glycolysis and die during larval development with metabolic phenotypes that mimic those displayed by dERR mutants. Moreover, we demonstrate that dERR and Sima/Hif1α protein accumulation is mutually dependent, as loss of either transcription factor results in decreased abundance of the other protein.CONCLUSIONS: These findings demonstrate that Sima/HIF1α is required during embryogenesis to coordinately up-regulate carbohydrate metabolism in preparation for larval growth. Notably, our study also reveals that the Sima-dependent gene expression profile shares considerable overlap with that observed in dERR mutant, suggesting that Sima/HIF1α and dERR cooperatively regulate embryonic and larval glycolytic gene expression.PMID:39894213 | DOI:10.1016/j.molmet.2025.102106

Life Sci. 2025 Jan 31:123438. doi: 10.1016/j.lfs.2025.123438. Online ahead of print.ABSTRACTAIMS: This study aimed to elucidate clinically-relevant classifications of COPD using a targeted metabolomics approach focusing on signaling lipids.MATERIALS AND METHODS: Using a targeted LC-MS/MS platform, 166 metabolites including free fatty acids, prostaglandins, isoprostanes, lysophospholipids, endocannabinoids, and bile acids were profiled in a cohort of 49 COPD patients. The study integrated metabolomic data with clinical parameters to identify key metabolites and related pathways for various COPD classification systems including Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading stages, Koninklijk Nederlands Genootschap voor Fysiotherapie (KNGF, Royal Dutch Society for Physiotherapy) profiles, and Systemic (SYS) subtypes and explored the association of these classification systems.KEY FINDINGS: The GOLD stages showed correlations with 15 metabolites, including lysophospholipids, oxylipins, and bile acids. KNGF profiles were linked to 13 metabolites, predominantly lysophospholipids, while SYS subtypes were associated with 9 metabolites, mainly oxylipins. A specific cluster of oxylipins, including HETEs and HDoHEs, was notably correlated to prognostic factors of COPD.SIGNIFICANCE: This study identified distinct metabolic patterns associated with GOLD stages, KNGF profiles, and SYS subtypes. Additionally, the findings indicate that 14-HDoHE/DHA may serve as a potential biomarker for COPD exacerbation and suggest possible therapeutic targets for COPD, including pathways involving lipoxygenases, G-protein coupled receptors, and the Farnesoid X receptor.PMID:39894160 | DOI:10.1016/j.lfs.2025.123438

Int J Antimicrob Agents. 2025 Jan 31:107457. doi: 10.1016/j.ijantimicag.2025.107457. Online ahead of print.ABSTRACTBACKGROUND: Combination therapy offers a promising option to enhance efficacy and prevent resistance. A comprehensive and quantitative assessment of the last-resort combination of ceftazidime/avibactam and tigecycline is not available.OBJECTIVE: This study systematically investigated the pharmacodynamic interaction between ceftazidime/avibactam and tigecycline in clinical and isogenic Escherichia coli and Klebsiella pneumoniae strains harbouring genes that encode various carbapenemases or ESBLs.METHODS: An adaptive in vitro 'dynamic' checkerboard design and pharmacometric modelling were employed for the evaluation of pharmacodynamic interactions in fifteen bacterial isolates. Additionally, time-kill assays and metabolomic analyses were used to provide mechanistic insights.RESULTS: Antagonistic drug interactions between ceftazidime/avibactam and tigecycline were identified in the majority of tested strains. Time-kill assays confirmed antagonistic interactions, with tigecycline limiting ceftazidime/avibactam total killing. Metabolomic analyses of mono and combined drug exposure to bacteria revealed matching metabolomes in tigecycline alone and the combination with ceftazidime/avibactam, corroborating the identified antagonism between these drugs.CONCLUSIONS: Our study reveals that the antagonistic interaction between ceftazidime/avibactam and tigecycline can undermine ceftazidime/avibactam's efficacy, suggesting limited clinical benefit in combining these antibiotics. Therefore, further research is encouraged to explore this and alternative combinations or approaches that may offer better clinical outcomes.PMID:39894062 | DOI:10.1016/j.ijantimicag.2025.107457

J Hazard Mater. 2025 Jan 27;488:137219. doi: 10.1016/j.jhazmat.2025.137219. Online ahead of print.ABSTRACTPlastic pollution is a global concern, with polystyrene (PS) being a major source of plastic waste. In this study, a PS-degrading bacterial strain, Gordonia sp. PS3, was isolated from the gut of Galleria mellonella larvae. After 40 days, strain PS3 exhibited a 33.59 ± 1.12 % degradation rate of PS-microplastics (PS-MPs). The biodegradation mechanism of PS by strain PS3 was investigated using genomics, molecular docking, and metabolomics. Degradation resulted in a significant decrease in molecular weight, disappearance of characteristic aromatic peaks, and the appearance of new functional groups (e.g., hydroxyl and carbonyl), indicating oxidative depolymerization and enhanced hydrophilicity. Four key enzymes involved in PS degradation were identified, with alkane 1-monooxygenase initiating cleavage of C-C bonds in PS and cytochrome P450 monooxygenase catalyzing oxidation of the aromatic ring. Metabolomics analysis revealed upregulation of proline, branched-chain amino acids, and polyamines, indicating oxidative stress response and energy acquisition during PS degradation. The PS degradation products showed no significant adverse effects on Arabidopsis thaliana growth, and PS residues were less harmful to G. mellonella larvae than untreated PS-MPs. This study presents a novel strain for PS biodegradation and provides new insights into the microbial degradation mechanism of PS and the safety of its degradation products.PMID:39893981 | DOI:10.1016/j.jhazmat.2025.137219

Plant Physiol Biochem. 2025 Jan 29;220:109585. doi: 10.1016/j.plaphy.2025.109585. Online ahead of print.ABSTRACTPolyamines are small, polycationic molecules with amino groups that are present in most living organisms. Studies indicate that polyamines increase general protein synthesis and are essential for efficient translation. While progress has been made in understanding the role of polyamines in translation in bacteria and mammals, their contribution and mode of action in plants remain largely unexplored. In a previous study, we found that putrescine (Put) and the pathogen-associated molecular pattern (PAMP) from bacterial flagellin (flg22) transcriptionally induced ribosome biogenesis in plants. Here we examined the impact of polyamines (Put and spermine, Spm) and flg22 on ribosome complex formation in Arabidopsis. Our results indicate that polyamines, flg22 and their combinations increase the abundance of actively translating polysomes. Riboproteomic analyses revealed that polyamines and flg22 trigger differential changes in the accumulation of ribosomal proteins, which are structurally confined in response to Put. Importantly, Put was found binding to non-translating and actively translating ribosomes, suggesting that this polyamine has a role in functional aspects of translation, such as stabilization and/or remodeling of polysomal complexes. Additional global proteomics analyses in polyamine biosynthesis mutants revealed that lower Put availability triggers changes in proteins associated with ribonucleoprotein complex binding and biogenesis. Overall, our findings highlight the effect of polyamines and flg22 on shaping the ribosomal protein composition of actively translating ribosomes in plants.PMID:39893946 | DOI:10.1016/j.plaphy.2025.109585