PubMed

J Hazard Mater. 2025 Apr 4;492:138178. doi: 10.1016/j.jhazmat.2025.138178. Online ahead of print.ABSTRACTPolystyrene (PS) biodegradation by some lepidoptera larvae has been demonstrated, but little is known about the Spodoptera litura and Spodoptera frugiperda (Lepidoptera: Noctuidae). Here we confirmed that PS-fed larvae showed significantly higher survival rates than starvation and antibiotic groups, with S. frugiperda consuming PS more efficiently than S. litura (1.52 vs. 0.56 mg larva⁻¹ day⁻¹). PS-frass characterization revealed oxygen-containing groups (C-O, CO, -OH) with reduced thermal stability and a significant decrease in weight-average molecular weight (S. litura: -6.01 %; S. frugiperda: -8.93 %), evidencing oxidative depolymerization of PS by both species. The gut microbiota (Pedobacter, Achromobacter, Pseudomonas, Acinetobacter, etc.) and functional enzymes (e.g., monooxygenase, dioxygenase, chitinases) were upregulated in PS-fed larvae. Metabolome analysis revealed altered stress responses and reprogrammed metabolic pathways, particularly in lipid and carbohydrate metabolism, which correlated strongly with gut microbiota changes. Overall, we demonstrated the biodegradation of PS by S. litura and S. frugiperda for the first time, and proposed a plausible degradation mechanism mediated by gut microbiota, illustrating both the host and gut microbiomes contributed to PS biodegradation. These findings highlight the feasibility of developing insect-based plastic degradation systems through the isolation of key microbial-enzymatic consortia, offering a sustainable solution for plastic waste management.PMID:40199076 | DOI:10.1016/j.jhazmat.2025.138178

Res Vet Sci. 2025 Apr 4;189:105646. doi: 10.1016/j.rvsc.2025.105646. Online ahead of print.ABSTRACTThe brown seaweed Laminaria digitata, known for its prebiotic qualities, and alginate lyase supplementation, may improve the growth and development of piglets during the critical post-weaning phase. The purpose of this study was to ascertain the effects of 10 % L. digitata and 0.01 % alginate lyase on the proteome and metabolome of the longissimus lumborum muscle in weaned piglets. Findings suggest that the enzyme supplement has a marginal effect on muscle proteome compared to the seaweed diet alone when compared to the control. L. digitata increased the prevalence of proteins related to muscle contraction and structure (such as ACTBL2), while it decreased the presence of glycolytic proteins (like GPI and ALDOC). It also increased the abundance of proteins related to the negative regulation of insulin receptor pathways, such as RABGAP1 and TSC2. Conversely, alginate lyase increased the abundance of proteins associated with fatty acid oxidation (ALOXE3) and calcium balance (WFS1), reflecting the impacts of dietary n-3 polyunsaturated fatty acids and lower calcium in the diet. As for the muscle metabolome, it remained mostly unchanged by dietary treatments, except for mannitol and threonine, which were enriched as a consequence of seaweed inclusion.PMID:40199047 | DOI:10.1016/j.rvsc.2025.105646

Blood Adv. 2025 Apr 8:bloodadvances.2024014476. doi: 10.1182/bloodadvances.2024014476. Online ahead of print.ABSTRACTIncreasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor (CAR) therapy. We conducted whole-genome shotgun sequencing on stool samples (n=117) collected at various times from multiple myeloma patients (n=33) undergoing idecabtagene vicleucel (ide-cel) anti-B cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity post-ide-cel infusion, along with significant differences in bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding was the link between major microbiome disruption, defined as dominant specific taxa (greater than 35% prevalence) and increased facultative pathobionts like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS). Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% compared to those without genus dominance (11.1%, p=0.043). Additionally, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as Flavonifractor plautii being linked to increased indole metabolites and pathways in responders. Our findings uncover novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.PMID:40198765 | DOI:10.1182/bloodadvances.2024014476

Mol Genet Genomics. 2025 Apr 8;300(1):41. doi: 10.1007/s00438-025-02243-9.ABSTRACTPPAR γ, as a widely present receptor in tissues, plays a key role in lipid metabolism, energy balance, inflammatory response, and cell differentiation. It plays an important role in the occurrence and development of various tumors, including prostate cancer, gastric cancer, lung cancer, etc., by regulating lipid metabolism. However, the specific mechanism by which it affects lung cancer growth is not yet clear. To investigate how PPAR γ affects lung cancer cell growth by altering ALDH1A3 levels through its impact on lipid metabolism. Bioinformatics analysis was used to predict the correlation between PPAR γ, ALDH1A3 and lung cancer. Based on the results of bioinformatics analysis, PPAR γ activator (Pioglitazone, Pio) and ALDH1A3 inhibitor (diethylaminobenzaldehyde, DEAB) were used to act on lung cancer cells and observe their growth. After measuring the IC50 value of the drug in vitro experiments, lipid metabolomics analysis was conducted to identify the significant changes in differential metabolites and metabolic pathways under the combined influence of Pio and DEAB. Through bioinformatics analysis, it was found that there were significant differences in the levels of PPAR γ and ALDH1A3 between lung cancer and normal lung tissues, and ALDH1A3 was positively correlated with PPAR γ. AUC analysis found that PPAR γ and ALDH1A3 have good predictive value in the diagnosis and prognosis of lung cancer. GSEA enrichment analysis showed that PPAR γ and ALDH1A3 were significantly correlated with lipid oxidation. Combining relevant literature to demonstrate the inhibitory effect of PPAR γ receptors on lung cancer cells and the ability of PPAR γ activation to inhibit ALDH1A3 levels. Further in vitro CCK-8 and IC50 measurements of lung cancer cells A549 and H1299 were conducted, followed by non targeted lipidomics analysis. It was found that the metabolic pathways upregulated by activation of PPAR γ and inhibition of ALDH1A3 included glycerophospholipid metabolism, cholesterol metabolism, arachidonic acid metabolism, and fat digestion and absorption, with glycerophospholipid metabolism pathway accounting for the highest percentage. Conclusion: PPAR γ activation can inhibit the production of ALDH1A3, alter the glycerophospholipid metabolism pathway, and thus inhibit the proliferation of lung cancer cells. This study confirms that PPAR γ affects lung cancer proliferation by influencing the glycerophospholipid metabolism pathway.PMID:40198404 | DOI:10.1007/s00438-025-02243-9

J Agric Food Chem. 2025 Apr 8. doi: 10.1021/acs.jafc.4c10702. Online ahead of print.ABSTRACTThe Gretchen Hagen 3 genes maintain endogenous hormone homeostasis by conjugating excess hormones with amino acids. Herein, we identified the members of the GH3 family in soybeans and analyzed their phylogeny, gene duplication, structure, domains, conserved motifs, cis-elements in promoter regions for stress responses, and functional characteristics. We found that GH3 genes are induced by pathogens in Group-II. Furthermore, eight out of 16 Group-II genes responded to cyst nematode infection. Overexpression of eight GmGH3 genes can enhance soybean resistance to the cyst nematode. In addition, our metabolomic analysis showed that overexpression of them affected the content of salicylic acid, jasmonic acid, indole-3-acetic acid, and gibberellic acid. Overexpression of GmGH3 in soybean affects the expression of genes involved in plant hormone biosynthesis. This provides valuable insights into the complex molecular mechanisms underlying the interaction between soybeans and cyst nematodes.PMID:40197865 | DOI:10.1021/acs.jafc.4c10702

Pest Manag Sci. 2025 Apr 8. doi: 10.1002/ps.8823. Online ahead of print.ABSTRACTBACKGROUND: Aphid, Aphis gossypii Glover, is a pest that significantly affects cucumbers (Cucumis sativus L.). Phloem protein 2 (PP2) is a conserved phloem lectin. Our previous study showed that the expression of CsPP2-A1 under aphid attack affected the accumulation of flavonoids and total phenolics in cucumber. The novel mechanism of lectin CsPP2-A1 mediating secondary metabolites affecting aphid resistance in cucumbers needs to be investigated.RESULTS: The weight and length of aphids on CsPP2-A1 overexpression (CsPP2-A1-OE) cucumber plants significantly reduced compared to wild-type (WT). Conversely, aphids on CsPP2-A1 RNA interference (CsPP2-A1-RNAi) plants showed the opposite trend. Using secondary metabolomics, small molecular weight secondary metabolites were qualitatively and quantitatively assessed in WT and transgenic cucumber plants after aphid inoculation. The overexpression of CsPP2-A1 resulted in the up-regulation of differential metabolites (DMs) in phenylpropanoid biosynthesis, whereas interference expression of CsPP2-A1 led to a down-regulation of DMs in the flavonoid biosynthesis. Concurrently, it was observed that the CAD activity and the expression of the CsPAL, and CsCAD in OE-2 were up-regulated significantly. A significant reduction in the activities of CHI, F3H, and the expression of CsF3H, CsCHS, CsFLS, and CsCCR was noted in RNAi-2.CONCLUSION: CsPP2-A1 indirectly affects the growth and development of aphids via mediation of phenylpropanoid and flavonoid biosynthesis. The indirect effects of the interaction of CsPP2-A1 with aphids offer insights into plant-insect interaction studies. © 2025 Society of Chemical Industry.PMID:40197847 | DOI:10.1002/ps.8823

Eur Heart J. 2025 Apr 8:ehaf216. doi: 10.1093/eurheartj/ehaf216. Online ahead of print.ABSTRACTA global obesity pandemic, coupled with an increasingly ageing population, is exacerbating the burden of cardiovascular disease. Indeed, clinical and experimental evidence underscores a potential connection between obesity and ageing in the pathogenesis of various cardiovascular disorders. This is further supported by the notion that weight reduction not only effectively reduces major cardiovascular events in elderly individuals but is also considered the gold standard for lifespan extension, in obese and non-obese model organisms. This review evaluates the intricate interplay between obesity and ageing from molecular mechanisms to whole organ function within the cardiovascular system. By comparatively analysing their characteristic features, shared molecular and cell biological signatures between obesity and ageing are unveiled, with the intent to shed light on how obesity accelerates cardiovascular ageing. This review also elaborates on how emerging metabolic interventions targeting obesity might protect from cardiovascular diseases largely through antagonizing key molecular mechanisms of the ageing process itself. In sum, this review aims to provide valuable insight into how understanding these interconnected processes could guide the development of novel and effective cardiovascular therapeutics for a growing aged population with a concerning obesity problem.PMID:40197620 | DOI:10.1093/eurheartj/ehaf216

Hereditas. 2025 Apr 7;162(1):55. doi: 10.1186/s41065-025-00425-4.ABSTRACTBACKGROUND: Breast cancer (BRCA) is a malignancy originating in the breast cells, characterized by a poor overall survival rate. Post-resection, chemotherapy is commonly recommended as a primary therapeutic approach; however, its efficacy remains limited. Recent advancements in lipidomics and metabolomics have provided new insights into the intricate landscape of fatty acid metabolism (FAM) and the fatty acid lipidome in both health and disease. A growing body of evidence suggests that dysregulations in FAM and fatty acid levels play a significant role in cancer initiation and progression. Despite these advances, the precise mechanisms through which FAM mediates the anti-cancer effects of lobaplatin in BRCA remain poorly understood and warrant further investigation.METHODS: GEO and TCGA data were classified into two types. We aimed to show how FAMGs influence immune function, immune checkpoints, and m6a in BRCA. A co-expression analysis discovered that gene expression is strongly connected to pyroptosis. The TCGA gathered information about mRNAsi, gene mutations, CNV, and clinical features.RESULTS: In the low-risk group, overall survival (OS) is longer. GSEA was utilized to identify immune and tumor-related pathways. Most of the FAMG-derived prognostic signatures predominantly modulate immunological and oncogenic signaling pathways, including the Wnt, neurotrophin, chemokine, and calcium signaling cascades. Among the genes involved are CEL, WT1, and ULBP2. Expression levels varied as well. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all pointed to the gene.CONCLUSIONS: The primary objective of this study is to identify and validate BRCA-associated FAMGs that can serve as prognostic indicators and provide insights into immune system function, while also offering evidence to support the development of fatty acid metabolism-related molecularly targeted therapeutics. Consequently, FAMGs and their interactions with the immune system, as well as their role in BRCA, may emerge as promising therapeutic targets.PMID:40197314 | DOI:10.1186/s41065-025-00425-4

Biol Direct. 2025 Apr 7;20(1):47. doi: 10.1186/s13062-025-00637-8.ABSTRACTBACKGROUND: Patients diagnosed with gallbladder carcinoma (GBC) accompanied by hepatic metastasis exhibit unfavorable prognoses generally. Mitochondrial dysfunction promotes cellular transformation and cancer cell survival implicating its importance in cancer development. Previous studies have indicated that dynamin 1 like (DNM1L) is a key mediator of mitochondrial fission. However, whether DNM1L regulates mitochondrial homeostasis in GBC remains unknown.METHODS: The morphological changes of mitochondria were investigated by transmission electron microscopy and mitoTracker red staining. Co-immunoprecipitation assay was performed to detect the interaction of ubiquitin-specific protease-3 (USP3) and DNM1L. The cell-derived xenograft and liver metastasis tumor models were established to validate the function of DNM1L in vivo. The metabolomics data from transcriptomics/metabolomics were analyzed to identify the differentially expressed genes/metabolites of DNM1L in GBC.RESULTS: DNM1L exhibited a marked upregulation in clinical GBC tissues compared to the adjacent tissues, and it promoted proliferation, invasiveness, and migration capability of GBC cells by inducing mitochondrial dysfunction. Mice subcutaneously injected with DNM1L overexpression cells exhibited elevated intrahepatic metastatic nodules within their livers. USP3, a deubiquitinating enzyme, was demonstrated to directly interact with DNM1L and it specifically cleaved the K48-linked polyubiquitin chains to deubiquitinate and stabilize DNM1L. By integrating two omics, we found several altered pathways and speculated that DNM1L disturbed DNA synthesis and glycine, serine, threonine, and pyrimidine metabolism pathways.CONCLUSION: Our findings suggest that DNM1L is a promising clinical target for GBC treatment and that focusing on DNM1L may provide new insights into GBC strategy.PMID:40197257 | DOI:10.1186/s13062-025-00637-8

Comb Chem High Throughput Screen. 2025 Apr 7. doi: 10.2174/0113862073354023250314050225. Online ahead of print.ABSTRACTBACKGROUND: Limited treatments for silicosis necessitate further study of pneumoconiosis characteristics and pathophysiology. This study employs metabolomics to investigate metabolite changes and identify biomarkers for understanding pneumoconiosis pathogenesis.METHODS: We explored pneumoconiosis pathogenesis through the lens of intestinal flora, using 18 healthy SPF male SD rats divided into three groups: control, coal dust, and silica. After dust exposure, metabolite changes were analyzed to identify metabolic markers and pathways. We assessed the relationship between intestinal flora and silicosis, aiming to provide early diagnostic evidence. Rats were exposed to coal dust, silica, or sterile saline for 8 weeks, after which blood, lung tissue, and feces were collected. Lung pathology was assessed, and inflammatory factors (IL-6, IL-11) were measured. 16S rDNA sequencing and UHPLC-QTOFMS metabolomics were used to analyze intestinal flora and fecal metabolites.RESULTS: After 8 weeks of dust exposure, silica-exposed rats showed significantly reduced weight and elevated serum IL-6 and IL-11 levels compared to controls (P < 0.05). Lung tissue pathology revealed normal alveolar structure in controls, whereas silica group rats exhibited lung damage, intensified inflammation, and silicon nodule formation. Coal dust group rats showed lung tissue changes with fibroblast aggregation. α diversity analysis showed a decreased Shannon index and increased Simpson index in the coal dust group, and a decreased Simpson index in the silica group, suggesting altered intestinal flora. β diversity analysis confirmed significant differences in gut microbiota between dust-exposed groups and controls. Metabolomics identified 11 differential metabolites in rat feces, meeting criteria of Fold change > 2, VIP > 1, and P < 0.05, indicating metabolic changes post-exposure.CONCLUSION: Dust exposure disrupts intestinal flora and metabolic state, with potential metabolic markers identified in both coal dust and silica groups, implicating fructose and mannose metabolism in coal dust exposure and sphingolipid metabolism in silica exposure. This study provides new insights into the pathogenesis of pneumoconiosis and potential biomarkers for early diagnosis.PMID:40197198 | DOI:10.2174/0113862073354023250314050225

Curr Mol Med. 2025 Apr 7. doi: 10.2174/0115665240364302250320025755. Online ahead of print.ABSTRACTBACKGROUND: Tissue metabolomics is a promising technology for evaluating in situ changes in disease pathogenesis. It addresses a significant knowledge gap in the study of both degenerated and non-degenerated supraspinatus (SSp) tendons. This study analyzed the metabolomic profiles associated with rotator cuff tears (RCTs).PURPOSE: RCTs cause loss of function and shoulder pain, with the SSp muscle being the most frequently affected. Inflammation and complex metabolic changes may play roles in its etiology. Evaluation of the metabolomic differences between the degenerated and non-degenerated SSp tissues of RCT patients was aimed.METHODS: A cross-sectional study of 14 patients with RCTs, diagnosed through physical examination and magnetic resonance imaging, was conducted. Degenerate and non-degenerate SSp tissue debris were collected during arthroscopy. Untargeted metabolomic analysis of these samples was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS). Metabolic peaks were identified, matched, and normalized before further analysis. Partial least squaresdiscriminant analysis (PLS-DA), heatmap generation, unsupervised volcano plots, and fold-change analyses were conducted. A putative metabolite list was subsequently compiled to elucidate pathways of degeneration. These metabolites were matched with metabolic pathways using the RaMP-DB metabolite set library.RESULTS: The tyrosine metabolism (p=4.93 x10-4), ferroptosis (p=1.25 x10-3), steroidogenesis (p=9.89 x10-4), and cholesterol biosynthesis (p=3.05 x10-3) were altered in the degenerated RCTs.CONCLUSION: These findings suggest that metabolomic alterations may be associated with the development of RCTs, with changes in tyrosine metabolism, ferroptosis, and lipid metabolism potentially contributing to muscle degeneration and inflammation. Identified disruptions in steroidogenesis provide new insights into the role of hormonal factors in RCT development. Understanding these metabolic pathways is clinically relevant in sports medicine, as it enables targeted therapies and personalized treatment strategies, ultimately enhancing recovery and improving outcomes for athletes.PMID:40197183 | DOI:10.2174/0115665240364302250320025755

Physiol Plant. 2025 Mar-Apr;177(2):e70191. doi: 10.1111/ppl.70191.ABSTRACTTiger nuts (Cyperus esculentus) have emerged as a novel oil crop, being utilized as raw materials for obtaining industrial ink. Drought is a serious stress that significantly affects the entire plant and reduces its yield. The seedling stage is crucial as it determines the future growth and yield. Consequently, it is essential to enhance the ability of tiger nuts to mitigate drought at the seedling stage. A comprehensive analysis was conducted on roots and leaves, including their phenotypes, physiological indicators, transcriptomes, and metabolomes. The results revealed that leaves and roots were affected by drought stress, as evidenced by phenotypic data such as leaf area and physiological indicators, including changes in peroxidase and catalase activity, malondialdehyde content, electrolyte leakage, and superoxide anion levels. Drought imposed greater effects on leaves. Phenylpropanoid and flavonoid biosynthesis were identified as candidate pathways using transcriptome and metabolome analysis, Real-Time Quantitative PCR (RT-qPCR), and physiological verifications. However, the response modes of the root and leaf parts differed based on the enriched pathways analysis, indicating that the changes in the content of some metabolites were contrasting between the roots and leaves. The study revealed the molecular mechanisms under drought, particularly the synergistic responses in leaves and roots, providing insights and a theoretical basis for enhancing the drought tolerance of tiger nuts.PMID:40196915 | DOI:10.1111/ppl.70191

J Pediatr Endocrinol Metab. 2025 Apr 8. doi: 10.1515/jpem-2024-0605. Online ahead of print.ABSTRACTOBJECTIVES: Newborns of diabetic and obese/overweight mothers face long-term metabolic risks. Untargeted cord blood metabolomic analysis using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) was performed to explore metabolic alterations and pathways in these high-risk infants.METHODS: Cord blood samples were collected from 46 newborns born to mothers with gestational diabetes (10), obesity (14), overweight (18), type 2 diabetes mellitus (3), type 1 diabetes mellitus (1), and 20 newborns born to healthy mothers. Q-TOF LC/MS was used to investigate the alterations in cord blood metabolomic profiles. Data processing was conducted using MZmine 2.53. Putative metabolites were idendtified using MetaboAnalyst 6.0.RESULTS: Distinct metabolite profiles were observed between diabetes and control groups. Significant identical trend in 19 metabolites were determined in both diabetes and obesity + overweight group vs. control group. Key pathways included steroid and bile acid biosynthesis. Upregulated oxidative stress, clues to sphingophospholipid metabolism, high levels of dihomo-gamma-linolenic acid (DGLA), pantothenic acid, and TRH were detected. The kynurenine pathway was prominent in the diabetes group.CONCLUSIONS: Estrogen metabolites from the 16- and 2-pathways may indicate metabolic risk, with increased downstream flux under diabetic conditions. Accelerated bile acid synthesis may alter fetal metabolic programming, since bile acids play crucial roles in cellular energy regulation and signaling. Elevated pantothenic acid, essential for the production of coenzyme-A, suggests significant alterations in carbohydrate, protein, and fat metabolism. High serum DGLA levels emerge as a potential biomarker for metabolic abnormalities. Increased plasma kynurenines could predict cardiovascular risks. Larger targeted studies are required to validate these metabolic profiles and pathways.PMID:40196912 | DOI:10.1515/jpem-2024-0605

Eur J Prev Cardiol. 2025 Apr 8:zwaf205. doi: 10.1093/eurjpc/zwaf205. Online ahead of print.NO ABSTRACTPMID:40196900 | DOI:10.1093/eurjpc/zwaf205

Heliyon. 2025 Feb 3;11(3):e42360. doi: 10.1016/j.heliyon.2025.e42360. eCollection 2025 Feb 15.ABSTRACT[This retracts the article DOI: 10.1016/j.heliyon.2024.e28296.].PMID:40196790 | PMC:PMC11947705 | DOI:10.1016/j.heliyon.2025.e42360

bioRxiv [Preprint]. 2025 Mar 24:2025.03.24.645021. doi: 10.1101/2025.03.24.645021.ABSTRACTSoil Pseudomonas species, which can thrive on lignin-derived phenolic compounds, are widely explored for biotechnology applications. Yet, there is limited understanding of how the native metabolism coordinates phenolic carbon processing with cofactor generation. Here, we achieve quantitative understanding of this metabolic balance through a multi-omics investigation of Pseudomonas putida KT2440 grown on four common phenolic substrates: ferulate, p- coumarate, vanillate, and 4-hydroxybenzoate. Relative to succinate as a non-aromatic reference, proteomics data reveal >140-fold increase in proteins for transport and initial catabolism of each phenolic substrate, but metabolomics profiling reveals that bottleneck nodes in initial phenolic compound catabolism maintain more favorable cellular energy state. Up to 30-fold increase in pyruvate carboxylase and glyoxylate shunt proteins implies a metabolic remodeling confirmed by kinetic 13 C-metabolomics. Quantitative analysis by 13 C-fluxomics demonstrates coupling of this remodeling with cofactor production. Specifically, anaplerotic carbon recycling via pyruvate carboxylase promotes fluxes in the tricarboxylic acid cycle to provide 50-60% NADPH yield and 60-80% NADH yield, resulting in 2-fold higher ATP yield than for succinate metabolism; the glyoxylate shunt sustains cataplerotic flux through malic enzyme for the remaining NADPH yield. The quantitative blueprint elucidated here explains deficient versus sufficient cofactor rebalancing during manipulations of key metabolic nodes in lignin valorization.PMID:40196702 | PMC:PMC11974891 | DOI:10.1101/2025.03.24.645021

bioRxiv [Preprint]. 2025 Mar 25:2025.03.24.645052. doi: 10.1101/2025.03.24.645052.ABSTRACTAcute respiratory distress syndrome (ARDS) is an often fatal critical illness where lung epithelial injury leads to intrapulmonary fluid accumulation. ARDS became widespread during the COVID-19 pandemic, motivating a renewed effort to understand the complex etiology of this disease. Rigorous prior work has implicated lung endothelial and epithelial injury in response to an insult such as bacterial infection; however, the impact of microorganisms found in other organs on ARDS remains unclear. Here, we use a combination of gnotobiotic mice, cell culture experiments, and re-analyses of a large metabolomics dataset from ARDS patients to reveal that gut bacteria impact lung cellular respiration by releasing metabolites that alter mitochondrial activity in lung epithelium. Colonization of germ-free mice with a complex gut microbiota stimulated lung mitochondrial gene expression. A single human gut bacterial species, Bifidobacterium adolescentis, was sufficient to replicate this effect, leading to a significant increase in mitochondrial membrane potential in lung epithelial cells. We then used genome sequencing and mass spectrometry to confirm that B. adolescentis produces L -lactate, which was sufficient to increase mitochondrial activity in lung epithelial cells. Finally, we found that serum lactate was significantly associated with disease severity in patients with ARDS from the Early Assessment of Renal and Lung Injury (EARLI) cohort. Together, these results emphasize the importance of more broadly characterizing the microbial etiology of ARDS and other lung diseases given the ability of gut bacterial metabolites to remotely control lung cellular respiration. Our discovery of a single bacteria-metabolite pair provides a proof-of-concept for systematically testing other microbial metabolites and a mechanistic biomarker that could be pursued in future clinical studies. Furthermore, our work adds to the growing literature linking the microbiome to mitochondrial function, raising intriguing questions as to the bidirectional communication between our endo- and ecto-symbionts.PMID:40196632 | PMC:PMC11974820 | DOI:10.1101/2025.03.24.645052

bioRxiv [Preprint]. 2025 Mar 25:2025.03.22.644722. doi: 10.1101/2025.03.22.644722.ABSTRACTBACKGROUND: Right atrial (RA) dysfunction is an emerging risk factor for poor outcomes in pulmonary arterial hypertension, however the mechanisms underlying compromised RA function are understudied.OBJECTIVES: Multi-omic analyses defined the cellular and molecular mediators associated with RA dysfunction in pulmonary artery banded (PAB) swine.METHODS: 4-week-old castrated male Yorkshire pigs were subjected to PAB and aged six weeks to induce right heart failure. Cardiac MRI evaluated RA size and function. snRNAseq defined the cell-specific alterations in RA tissue. Mitochondrial proteomics and metabolomics analyses examined the metabolic alterations in RA samples. Inducible pluripotent stem cell-derived atrial cardiomyocytes (iPSC-ACM) were treated with tunicamycin to induce endoplasmic reticulum (ER) stress and mitochondrial structure and function were probed.RESULTS: PAB induced RA dilation/dysfunction and atrial cardiomyocyte hypertrophy. snRNAseq demonstrated PAB altered the cellular composition of the RA defined by increased inflammatory macrophages and an alteration of cardiomyocyte subpopulations. RA cardiomyocytes exhibited ER stress and mitochondrial metabolic enzyme dysregulation. PAB RAs, but not PAB right ventricles, had downregulation of branched chain amino acid degrading enzymes. Metabolomics profiling revealed BCAA and fatty acid metabolism were impaired in the dysfunctional RA. Tunicamycin-induced ER stress disrupted mitochondrial structure/function in iPSC-ACMs.CONCLUSIONS: Multi-omic evaluations demonstrate RA dysfunction is characterized by cardiomyocyte metabolic derangements due to ER dysregulation and an accumulation of pro-inflammatory macrophages.PMID:40196578 | PMC:PMC11974768 | DOI:10.1101/2025.03.22.644722

bioRxiv [Preprint]. 2025 Mar 28:2025.03.27.644723. doi: 10.1101/2025.03.27.644723.ABSTRACTBACKGROUND: Pulmonary arterial hypertension (PAH) is a rare but debilitating condition that causes exercise intolerance and ultimately death. Skeletal muscle derangements contribute to depressed exercise capacity in PAH, but the mechanisms underlying muscle dysfunction including the changes in muscle biology based on fiber type are understudied.METHODS: We evaluated exercise capacity, muscle histopathology, mitochondrial density, mitochondrial proteomics, and metabolomics/lipidomics of quadriceps ( predominately fast fibers ) and soleus ( predominately slow fibers) muscles in the monocrotaline (MCT) rat model of PAH.RESULTS: MCT rats exhibited impaired exercise capacity. Surprisingly, there were divergent atrophic and metabolic remodeling in the quadriceps and soleus muscles of MCT rats. In the quadriceps , there was a mild atrophic response only in type II fibers. In contrast, both type I and II fibers atrophied in the soleus . Both muscles exhibited fibrotic infiltration, but mitochondrial density was reduced in the quadriceps only. Mitochondrial proteomics and tissue metabolomics/lipidomics profiling demonstrated the two muscles exhibited distinct responses as the quadriceps had impairments in oxidative phosphorylation/fat metabolism and storage of triacylglycerides. However, the soleus showed signs of proteasome deficiencies and alterations in phosphatidylcholine/phosphatidylethanolamine homeostasis. Finally, profiling of metabolites/lipids in the serum identified potential novel biomarkers of exercise intolerance in PAH including the dimethylarginine pathway, cysteine, and triacylglycerides.CONCLUSION: Our data suggests differential cachectic and metabolic responses occur in PAH-induced myopathy. We nominate mitochondrial biogenesis and proteasome activation as potential druggable targets for PAH-myopathy.PMID:40196556 | PMC:PMC11974863 | DOI:10.1101/2025.03.27.644723

Front Plant Sci. 2025 Mar 24;16:1530673. doi: 10.3389/fpls.2025.1530673. eCollection 2025.ABSTRACTTo identify candidate genes for breeding oil palm varieties with high flavonoid content through molecular biotechnology, this study analyzed the metabolomes and transcriptomes of oil palm exocarp at different developmental stages using LC-MS/MS and RNA-Seq techniques. The green fruiting type (FS) oil palm exocarp at 95 days (FS1), 125 days (FS2), and 185 days (FS3) after pollination served as the materials. The enzyme genes F3H, CHS, ANS, and DFR were positively correlated with Quercetin-3-O-sambubioside. DFR also showed positive correlations with Afzelechin, Epiafzelechin, and Baimaside. In contrast, F3H, CHS, and ANS were negatively correlated with Hesperetin-7-O-glucoside. Additionally, CYP73A, UGT73C6, FG2-1, and FG2-2 were negatively correlated with Afzelechin, Epiafzelechin, Quercetin-3-O-sambubioside, and Baimaside, while CYP75A was negatively correlated with Epiafzelechin, Quercetin-3-O-sambubioside, and Baimaside. These results suggest that F3H, CHS, ANS, and DFR play a role in promoting Quercetin-3-O-sambubioside* synthesis, with DFR further enhancing the production of Afzelechin, Epiafzelechin, and Baimaside. On the other hand, F3H, CHS, and ANS may inhibit Hesperetin-7-O-glucoside synthesis. Meanwhile, CYP73A, UGT73C6, FG2-1, and FG2-2 appear to suppress the synthesis of multiple flavonoids, including Afzelechin, Epiafzelechin, Quercetin-3-O-sambubioside*, and Baimaside. Lastly, CYP75A is implicated in suppressing Epiafzelechin, Quercetin-3-O-sambubioside*, and Baimaside synthesis. These findings provide a foundation for future molecular breeding efforts targeting flavonoid-rich oil palm varieties.PMID:40196433 | PMC:PMC11973354 | DOI:10.3389/fpls.2025.1530673