Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Synergistic inactivation effect of ultrasound and nano-emulsified basil essential oil on the metabolic responses of Salmonella on sprouts

Sun, 02/02/2025 - 12:00
Int J Food Microbiol. 2025 Jan 27;431:111082. doi: 10.1016/j.ijfoodmicro.2025.111082. Online ahead of print.ABSTRACTThis study investigated the effectiveness and mechanisms of ultrasound (US), nano-emulsified basil essential oil (NBEO), and their combination (NBEO_US) in inactivating Salmonella enterica cells inoculated on pea sprouts. The results demonstrated that the combined treatment was more effective than individual treatments in inactivating the target. This led to a decrease of 4.4 to 5.0 log CFU/g. Transmission electron microscopy showed that NBEO_US leads to the disruption of the bacteria morphology. Additionally, the leakage of cell constituents (proteins and nucleotide) demonstrated that NBEO_US disrupted the structural integrity of S. enterica cells. In addition, the metabolomics analysis using 1H NMR showed that NBEO_US had a detrimental effect on energy and amino acid metabolism in bacterial cells, specifically affecting glycolysis and amino acid production. Also, NBEO_US affected the Embden-Meyerhof-Parnas pathway in S. enterica cells by decreasing the activity of hexokinase, phosphofructokinase, and pyruvate kinase. Finally, the application of NBEO_US resulted in a substantial (P < 0.05) increase in the hardness of the treated pea sprouts while simultaneously decreasing their lightness. The present investigation illustrated the synergistic antibacterial mechanism of NBEO_US against S. enterica strains using sprouts as a food model. By understanding the microbiological changes in metabolic pathways induced by the combined treatment, sanitization strategies can be optimized to specifically target critical vulnerabilities, thereby ensuring safer and more efficient production of fresh produce.PMID:39893936 | DOI:10.1016/j.ijfoodmicro.2025.111082

Insights into PUFA and oxylipin production from incubation of Aspergillus novoparasiticus in sugarcane juice

Sun, 02/02/2025 - 12:00
Food Chem. 2025 Jan 26;473:143051. doi: 10.1016/j.foodchem.2025.143051. Online ahead of print.ABSTRACTUnderstanding the metabolism of toxigenic fungi in food is crucial for public health. Fungi of the Aspergillus section Flavi are widespread in tropical and subtropical regions, infecting and producing mycotoxins in peanuts, nuts, cereals, and fruits. Classical Molecular Networking on the Global Natural Products Social Molecular Networking (GNPS) platform was applied to organize and guide the analysis of polyunsaturated fatty acids (PUFAs) and oxylipins, which are strongly associated with chemical communication between fungi and host plants during infection. Dereplication and molecular networking enabled visualization of the metabolome of A. novoparasiticus (ITAL-Y174 strain) incubated in sugarcane juice to mimic the fungal chemical response to plant lipids. The ITAL-Y174 strain produced PUFAs that differed from those of sugarcane. Oxylipins were detected early in the incubation (PGE1, 9,10-DiHOME, 13S-HODE). No known mycotoxins for A. novoparasiticus were detected, and kojic acid was identified, indicating a novel pathway to produce this important industrial natural product.PMID:39893925 | DOI:10.1016/j.foodchem.2025.143051

Liquid and gas-chromatography-mass spectrometry methods for exposome analysis

Sun, 02/02/2025 - 12:00
J Chromatogr A. 2025 Jan 25;1744:465728. doi: 10.1016/j.chroma.2025.465728. Online ahead of print.ABSTRACTMass spectrometry-based methods have become fundamental to exposome research, providing the capability to explore a broad spectrum of chemical exposures. Liquid and gas chromatography coupled with low/high-resolution mass spectrometry (MS) are among the most frequently employed platforms due to their sensitivity and accuracy. However, these approaches present challenges, such as the inherent complexity of MS data and the expertise of biologists, chemists, clinicians, and data analysts to integrate and interpret MS data with other datasets effectively. The "omics" era advances rapidly, driven by developments of AI-based algorithms and an increase in accessible data; nevertheless, further efforts are necessary to ensure that exposomics outputs are comparable and reproducible, thus enhancing research findings. This review outlines the principles of MS-based methods for the exposome analytical pipeline, from sample collection to data analysis. We summarize and review both standard and cutting-edge strategies in exposome research, covering sample preparation, focusing on MS-based platforms, data acquisition strategies, and data annotation. The ultimate goal of this review is to highlight applications that enable the simultaneous analysis of endogenous metabolites and xenobiotics, which can help enhance our understanding of the impact of human exposure on health and disease and support personalized healthcare.PMID:39893915 | DOI:10.1016/j.chroma.2025.465728

A strategy integrated DNA barcoding with metabolomics for screening distinguishable combinatorial chemical quality marker between Pheretima aspergillum and Pheretima vulgaris Chen

Sun, 02/02/2025 - 12:00
J Pharm Biomed Anal. 2025 Jan 29;257:116716. doi: 10.1016/j.jpba.2025.116716. Online ahead of print.ABSTRACTPheretima is an animal-derived traditional Chinese medicines (TCMs). The chemical quality markers of Pheretima used to distinguish different species are still ambiguous. Under this premise, a strategy integrated DNA barcoding with metabolomics is promoted for identifying Pheretima and screening distinguishable combinatorial chemical quality marker (DCQ-marker) between Pheretima aspergillum (P. aspergillum) and Pheretima vulgaris Chen (P. vulgaris). As a result, adenosine, adenine, L-phenylalanine and uridine are successfully selected as DCQ-markers between P. aspergillum and P. vulgaris. This study provides convenient strategy for quickly screening DCQ-marker between P. aspergillum and P. vulgaris. It will be meaningful for further promoting quality control on Pheretima and providing a reference for the quality evaluation of other animal-derived TCMs.PMID:39893778 | DOI:10.1016/j.jpba.2025.116716

Reducing the Bitterness of Rapeseed Protein: Integrating Enzymatic Treatment, Metabolomics, and Sensory Analysis to Elucidate Underlying Mechanisms

Sun, 02/02/2025 - 12:00
J Agric Food Chem. 2025 Feb 2. doi: 10.1021/acs.jafc.4c10442. Online ahead of print.ABSTRACTRapeseed products, such as protein concentrates, hold promise for addressing global protein demands, but their application in food products is limited by their bitter and astringent taste. This study investigates the use of β-glucosidase (BG) and laccase (LAC) enzymatic treatment, individually and combined, to enhance the flavor of rapeseed protein concentrate (RPC). Untargeted metabolomics and sensory analysis reveal that LAC reduces the bitter compound kaempferol 3-O-(2‴-O-sinapoyl-β-D-sophoroside) (K3OSS) as well as a general reduction in other phenolic compounds, which correlates with a significant decrease in bitterness and astringency. In contrast, BG treatment elevates the levels of K3OSS and is accompanied by increased bitterness due to the conversion of precursor compounds to K3OSS. In addition, the synergistic use of both enzymes significantly reduces the concentration of K3OSS, resulting in a lower perception of bitterness. The LC-MS analysis of pure reference compounds treated with LAC and BG confirms that BG-mediated treatment facilitates the breakdown of larger kaempferol glycosides into K3OSS, while LAC treatment promotes polyphenol polymerization. Consequently, LAC treatment seems to be an effective strategy to improve the sensory quality of RPC and make it more suitable for human consumption.PMID:39893689 | DOI:10.1021/acs.jafc.4c10442

The single-berry metabolomic clock paradigm reveals new stages and metabolic switches during grapevine berry development

Sun, 02/02/2025 - 12:00
J Exp Bot. 2025 Feb 2:eraf038. doi: 10.1093/jxb/eraf038. Online ahead of print.ABSTRACTAsynchronicity causes metabolic chimerism in usual grapevine phenological stages, calling for a revisit of berry development at the individual fruit scale. To reveal the dynamics of metabolite composition in grapevine berries without phenological a priori, a dataset of 9,256 ions was obtained on 125 fruits at different stages by non-targeted ultra-performance liquid chromatography coupled to high-resolution mass spectrometry. This large metabolomic dataset was submitted to an analysis workflow combining classification and dimension reduction tools. This led to the clustering of metabolites into 12 specific kinetic patterns and a metabolome-based definition of the pericarp intrinsic clock outperforming expert timing procedures. Such increased temporal resolution enabled the identification of metabolite clusters that are annunciative of the onset of ripening, noticeably characterized by transient lipidic changes and the start of ABA accumulation. We also highlighted a cluster of stilbenes that accumulate during terminal fruit shriveling, after the arrest of phloem unloading. This non-targeted approach enables a more precise characterization of grapevine berry development through the concept of metabolomic clock. The discovery of new metabolic milestones of berry development paves the way toward a better assessment of the impact of environmental changes on the metabolism of non-climacteric fruit, in different genotypes.PMID:39893506 | DOI:10.1093/jxb/eraf038

Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer's disease continuum

Sat, 01/02/2025 - 12:00
Alzheimers Res Ther. 2025 Feb 1;17(1):36. doi: 10.1186/s13195-025-01683-0.ABSTRACTBACKGROUND: Gut microbiota dysbiosis is linked to Alzheimer's disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary.METHODS: Using 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, and cognitive variables across 30 patients with AD, 75 individuals with mild cognitive impairment (MCI), and 61 healthy controls (HC). Furthermore, we assessed the associations between these multi-omics changes using correlation and mediation analyses.RESULTS: There were significant group differences in gut microbial composition, which were driven by 8 microbial taxa (e.g., Staphylococcus and Bacillus) exhibiting a progressive increase in relative abundance from HC to MCI to AD, and 2 taxa (e.g., Anaerostipes) showing a gradual decrease. 26 fecal metabolites (e.g., Arachidonic, Adrenic, and Lithocholic acids) exhibited a progressive increase from HC to MCI to AD. We also observed progressive gray matter atrophy in broadly distributed gray matter regions and gradual micro-structural integrity damage in widespread white matter tracts along the AD continuum. Integration of these multi-omics changes revealed significant associations between microbiota, metabolites, neuroimaging, and cognition. More importantly, we identified two potential mediation pathways: (1) microbiota → metabolites → neuroimaging → cognition, and (2) microbiota → metabolites → cognition.CONCLUSION: Aside from elucidating the underlying mechanism whereby gut microbiota dysbiosis is linked to AD, our findings may contribute to groundwork for future interventions targeting the microbiota-metabolites-brain-cognition pathways as a therapeutic strategy in the AD continuum.PMID:39893498 | DOI:10.1186/s13195-025-01683-0

Lipidomics-based investigation of its impact on the pathogenesis of coronary atherosclerosis: a Mendelian randomization study

Sat, 01/02/2025 - 12:00
Hereditas. 2025 Feb 1;162(1):13. doi: 10.1186/s41065-025-00367-x.ABSTRACTBACKGROUND: Considerable attention has been devoted to investigating the association between lipid metabolites and cardiovascular diseases, particularly coronary atherosclerosis.METHODS: A two-sample MR framework was used to investigate the relationship between lipid metabolites and the risk of coronary atherosclerosis. Two GWAS datasets were examined to take intersections of SNPs from 51,589 cases and 343,079 controls, and 14,334 cases and 346,860 controls to determine genetic susceptibility to coronary atherosclerosis. Random-effects inverse variance weighted (IVW) MR analyses were performed by a series of sensitivity assessments to measure the robustness of our findings and to detect any violations of MR assumptions.RESULTS: Through IVW, MR-Egger and weighted median regression methods, we inferred that these six lipid metabolites: cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, triacylglycerol (53:4), could directly impact the development of atherosclerosis.CONCLUSION: In conclusion, our study comprehensively illustrates a causal relationship between lipid metabolites and the risk of coronary atherosclerosis. Furthermore, cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, and triacylglycerol (53:4) levels are positively correlated with the risk of coronary atherosclerosis. These six lipid metabolites have the potential as new predictors of the risk of atherosclerosis, providing new insights into the treatment and prevention of cardiovascular diseases.PMID:39893493 | DOI:10.1186/s41065-025-00367-x

Comparative transcriptomic and metabolomics analysis of ovary in Nilaparvata lugens after trehalase inhibition

Sat, 01/02/2025 - 12:00
BMC Genomics. 2025 Feb 1;26(1):98. doi: 10.1186/s12864-025-11268-8.ABSTRACTThe fecundity of Nilaparvata lugens (brown planthopper) is influenced by trehalase (TRE). To investigate the mechanism by which trehalose affects the reproduction of N. lugens, we conducted a comparative transcriptomic and metabolomic analysis of the ovaries of N. lugens following injection with dsTREs and validamycin (a TRE inhibitor). The results revealed that 844 differentially expressed genes (DEGs) were identified between the dsGFP and dsTREs injection groups, with 317 up-regulated genes and 527 down-regulated genes. Additionally, 1451 DEGs were identified between the water and validamycin injection groups, with 637 up-regulated genes and 814 down-regulated genes. The total number of DEGs identified between the two comparison groups was 236. The overlapping DEGs were implicated in various biological processes, including protein metabolism, fatty acid metabolism, AMPK signaling, mTOR signaling, insulin/insulin-like growth factor signaling (IIS), the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and the cellular process of meiosis in oocytes. These results suggest that the inhibition of TRE expression may lead to alterations in ovarian nutrient and energy metabolism by modulating glucose transport and affecting amino acid metabolic pathways. These alterations may influence the reproduction of N. lugens by modulating reproductive regulatory signals. These findings provide robust evidence supporting the mechanism through which trehalase inhibition reduces the reproductive capacity of N. lugens.PMID:39893429 | DOI:10.1186/s12864-025-11268-8

Physiological and metabolome characterization of Amaranthus hybridus L. grown under cypermethrin stress: an insight of Jasmonic acid treatment

Sat, 01/02/2025 - 12:00
BMC Plant Biol. 2025 Feb 1;25(1):137. doi: 10.1186/s12870-025-06131-7.ABSTRACTThe indiscriminate use of pesticides compromises physiology and metabolism in crops, posing health risks through residue accumulation in edible tissues. Amaranthus hybridus L., a fast growing, nutritionally and medicinally valuable crop was studied here to assess the impact of cypermethrin (CYP) at recommended (R1, 100 ppm) and double dose (R2, 200 ppm) alongside foliar application of jasmonic acid (JA) at 50 µM, 100 µM, and 200 µM concentrations. CYP at R1 dose induced hormesis, while R2 was toxic, elevating the production of ROS molecules (H2O2, SOR, MDA). JA application upregulated the antioxidant activity of SOD, POD, APX, GST, DHAR, GSH, and proline to alleviate oxidative stress and improve growth indicators, including shoot length, leaf area, chlorophyll content, Fv/Fm ratio, and biomass. JA at 100 µM yielded the highest increase in biomass, 11.52% and 13.7% for R1 and R2 treated plants, respectively and also led to reduced accumulation of CYP residues. The UHPLC-MS analysis of leaf tissue revealed increase in the contents of carotenoids, flavonoids, phenolics, phenylpropanoids, steroids content in the plant group combinedly treated with JA and CYP compared to those treated with CYP alone, indicating a protective and growth-promoting role of JA under pesticide stress conditions. Overall, 100 µM concentration of JA proved to be effective against the stress induced by the either dose of CYP in the study. These insights could offer strategies to reduce pesticide-induced damage in vegetable crops, advancing sustainable agriculture.PMID:39893397 | DOI:10.1186/s12870-025-06131-7

Integrative computational analysis of anti-influenza potential in Caesalpinia mimosoides Lamk hydroethanolic extract

Sat, 01/02/2025 - 12:00
Sci Rep. 2025 Feb 1;15(1):3988. doi: 10.1038/s41598-025-87585-5.ABSTRACTIn a recent study, we used chemical analysis to show that the Caesalpinia mimosoides aqueous extract, which contains a high concentration of simple phenolics, has strong anti-influenza activity. We determined through molecular docking methods that its potential target inhibitor is the neuraminidase. Therefore, our study objectives were to evaluate whether the aqueous-ethanol extract (30% v/v) of this plant species exhibits greater antiviral activity than the aqueous plant extract. The C. mimosoides hydroethanolic extract exhibited potent antioxidant activity in the DPPH assay, with an IC50 value of 15.01 µg/mL, comparable to authentic quercetin (IC50 = 12.72 µg/mL) and approximately 4.91 times greater than standard gallic acid (IC50 = 3.06 µg/mL). Through untargeted metabolomic analyses (UPLC-ESI(±)-QTOF-MS/MS) and subsequent stepwise computational metabolomics analyses, we identified the extract as primarily containing simple phenolics (e.g., gallic acid, ellagic acid, shikimic acid, and chlorogenic acid), flavonoid derivatives (e.g., quercetin, taxifolin, myricitrin, and afzelin), and other bioactive components, including dicarboxylic acids and germacrone. The polyphenol-rich extract showed strong anti-influenza activity, with an IC50 of 2.33 µg/mL against the influenza A/PR/8/34 virus and no cytotoxic effects, as indicated by a CC50 greater than 50 µg/mL. This represents an approximately 3.35-fold increase in effectiveness compared to its corresponding aqueous extract (IC50 = 7.81 µg/mL). Furthermore, the extract demonstrated no hemolytic activity, even at a maximum concentration of 2,000 µg/mL, suggesting its potential as a safe antiviral agent. Molecular docking analyses revealed that the identified phytochemicals can simultaneously interact with the "drug-target binding sites" of neuraminidase (NA) and PB2 subunit of influenza RNA polymerase, indicating their potential polypharmacological effects. The antiviral activity of the ethanolic-aqueous extract against other strains is being explored due to the versatile biological effects of phenolic substances.PMID:39893295 | DOI:10.1038/s41598-025-87585-5

Long noncoding RNA GDIL acts as a scaffold for CHAC1 and XRN2 to promote platinum resistance of colorectal cancer through inhibition of glutathione degradation

Sat, 01/02/2025 - 12:00
Cell Death Dis. 2025 Feb 1;16(1):62. doi: 10.1038/s41419-025-07374-w.ABSTRACTAcquired resistance poses a significant obstacle to the effectiveness of platinum-based treatment for cancers. As the most abundant antioxidant, glutathione (GSH) enables cancer cell survival and chemoresistance, by scavenging excessive reactive oxygen species (ROS) induced by platinum. Therapeutic strategy targeting GSH synthesis has been developed, however, failed to produce desirable effects in preventing cancer progression. Thus, uncovering mechanisms of rewired GSH metabolism may aid in the development of additional therapeutic strategies to overcome or delay resistance. Here, we identify upregulation of long noncoding RNA (lncRNA) GDIL (GSH Degradation Inhibiting LncRNA) in platinum resistant colorectal cancer (CRC) and ovarian cancer cells compared with parental ones. High expression of GDIL in resistant CRC is associated with poor survival and hyposensitivity to chemotherapy. We demonstrate that GDIL boosted GSH levels and enhances clearance of ROS induced by platinum. Metabolomic and metabolic flux analysis further reveals that GDIL promotes GSH accumulation by inhibiting GSH degradation. This is attributed by downregulation of CHAC1, an enzyme that specifically degrades intracellular GSH. Mechanistically, GDIL binds and re-localizes the nuclear protein XRN2 to the cytoplasm, where GDIL further serve as a scaffold for XRN2 to identify and degrade CHAC1 mRNA. Suppression of GDIL with selective antisense oligonucleotide, restored drug sensitivity in platinum resistant cell lines and delayed drug resistance in cell line- and patient-derived xenografts. Thus, lncRNA GDIL is a novel target to promote GSH degradation and augment platinum therapy.PMID:39893168 | DOI:10.1038/s41419-025-07374-w

Combined loss of glyoxalase 1 and aldehyde dehydrogenase 3a1 amplifies dicarbonyl stress, impairs proteasome activity resulting in hyperglycemia and activated retinal angiogenesis

Sat, 01/02/2025 - 12:00
Metabolism. 2025 Jan 30:156149. doi: 10.1016/j.metabol.2025.156149. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Any energy consumption results in the generation of highly reactive dicarbonyls and the need to prevent excessive dicarbonyls accumulation through the activity of several interdependent detoxification enzymes. Glyoxalase 1 (GLO1) knockout zebrafish showed only moderately elevated methylglyoxal (MG) levels, but increased Aldehyde Dehydrogenases (ALDH) activity and increased aldh3a1 expression. Elevated levels of 4-hydroxynonenal (4-HNE) but no MG increase were observed in ALDH3A1KO. The question of whether ALDH3A1 prevents MG formation as a compensatory mechanism in the absence of GLO1 remained unclear.METHODS: To investigate whether ALDH3A1 detoxifies MG as a compensatory mechanism in the absence of GLO1, the GLO1/ALDH3A1 double knockout (DKO) zebrafish was first generated. Various metabolites including advanced glycation end products (AGEs), as well as glucose metabolism and hyaloid vasculature were analyzed in GLO1KO, ALDH3A1KO and GLO1/ALDH3A1DKO zebrafish.RESULTS: In the absence of GLO1 and ALDH3A1, MG-H1 levels were increased. MG-H1 accumulation led to a severe deterioration of proteasome function, resulting in impaired glucose homeostasis and consequently amplified angiogenic activation of the hyaloid and retinal vasculature. Rescue of these pathological processes could be observed by using L-carnosine, and proteasome activator betulinic acid.CONCLUSION: The present data, together with previous studies, suggest that ALDH3A1 and GLO1 are important detoxification enzymes that prevent the deleterious effects of MG-H1 accumulation on proteasome function, glucose homeostasis and vascular function.PMID:39892865 | DOI:10.1016/j.metabol.2025.156149

Integrated gut microbiota and multi-omics analysis revealed the growth differences of female giant freshwater prawn (Macrobrachium rosenbergii)

Sat, 01/02/2025 - 12:00
Comp Biochem Physiol Part D Genomics Proteomics. 2025 Jan 29;54:101432. doi: 10.1016/j.cbd.2025.101432. Online ahead of print.ABSTRACTMacrobrachium rosenbergii (giant freshwater prawn; GFP) holds considerable importance in aquaculture due to its high market demand and economic significance. Female GFP growth varies significantly, however, the processes responsible for these growth disparities remain unknown. In this study, intestinal and hemolymph samples of large (FL), medium (FM), and small (FS) female GFPs were collected to investigate the molecular mechanism of female GFP growth. Through the utilization of 16S rRNA sequencing and liquid chromatography-mass spectrometry metabolomics, significant intestinal flora and metabolites linked to the growth performance of female GFPs were identified. The dominant phyla of the three groups were the same, namely Firmicutes and Proteobacteria. Among groups, small females exhibited the lowest abundance of Proteobacteria (27.26 %) and the highest abundance of Firmicutes (70.10 %). The most abundant genus in each group was Lactococcus. Liquid chromatography-mass spectrometry identified 115 annotated differential metabolites, and essential metabolites related to female GFP growth performance were screened. The concentration of serum metabolites in the larger females exhibited a statistically significant variance compared to that of the smaller females. Through association analysis, we identified key genes, metabolites, and gut microbiota that influence the growth of female GFPs. Likewise, we used multi-omics techniques to establish two relationship models ("gut microbiota-GFP phenotype-metabolite", "gut microbiota-GFP phenotype-transcript"), and three important network association models ("DN5520_c0_g1-CW1-Bacteroides", "DN537746_c0_g1-BW-Roseburia" and "Picolinic acid-phenotype-Roseburia") were further developed. The present study provides novel insights into the mechanisms underlying the variability in individual growth among female GFPs. Our findings offer valuable information for future investigations exploring the correlation between gut flora and host organisms in aquatic environments.PMID:39892364 | DOI:10.1016/j.cbd.2025.101432

Sublethal effects of atrazine concentrations exposure on tadpoles of Dendropsophus minutus: Evaluation of redox status, micronuclei frequencies and comet assay as biomarkers

Sat, 01/02/2025 - 12:00
Aquat Toxicol. 2025 Jan 25;279:107260. doi: 10.1016/j.aquatox.2025.107260. Online ahead of print.ABSTRACTAtrazine (ATZ) is an herbicide that can persist in terrestrial and aquatic environments and potentially cause significant harm to amphibian health. Therefore, the Brazilian National Environment Council (CONAMA) sets the limit concentration of ATZ in waters at 2μg/L. Our study evaluated the genotoxic, mutagenic, and biochemical alterations in Dendropsophus minutus tadpoles in the 25 Gosner stage, to acute exposure (96h) of ATZ (T1 - 0.02µg/L, T2 - 0.04µg/L, T3 - 0.08µg/L, T4 - 2µg/L). The comet assay showed all concentrations caused DNA damage with an increase to T2, T3, and T4. In the micronucleus test (MN) and Erythrocyte Nuclear Abnormality test (ENA), T3 and T4 accumulated more anucleated (AN), binucleated cells (BC) and ENAs. Redox imbalance was not detected. Therefore, we conclude that the concentrations tested are not safe for the health and development of D. minutus tadpoles, and the CONAMA limit needs to be reviewed since all tadpoles presented DNA damage. More studies are necessary to identify other alterations that ATZ can cause in the tadpole health of tropical species. Therefore, implementing public policies aimed at safeguarding the lives of both adult and juvenile amphibians is imperative for the conservation of biodiversity and ecosystem stability.PMID:39892294 | DOI:10.1016/j.aquatox.2025.107260

Screening of key genes involved in endometritis in cows and the regulatory role of CD83 in bovine endometrial epithelial cells

Sat, 01/02/2025 - 12:00
Int Immunopharmacol. 2025 Jan 31;148:114183. doi: 10.1016/j.intimp.2025.114183. Online ahead of print.ABSTRACTEndometritis in dairy cows involves complex molecular regulatory mechanisms. Therefore, uncovering the molecular regulatory mechanisms of endometritis in dairy cows is crucial to understand its development, prevention, and treatment. This study aimed to screen and validate key genes associated with endometritis using transcriptome sequencing of blood samples and previously obtained metabolomic sequencing data. Based on gain-of-function and loss-of-function experiments on the gene, multiple techniques, including qRT-PCR, western blotting, detection of reactive oxygen species (ROS), measurement of mitochondrial membrane potential, EdU assay, flow cytometry, and CCK-8 assay were used to explore the function of the key gene in lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial cells (BEECs). The results identified 536 differentially expressed genes (DEGs) between healthy cows and those with endometritis. These DEGs were significantly enriched in apoptosis and HIF-1 signaling pathways. Weighted gene co-expression network analysis of transcriptomic and metabolomic data identified CD83, CTNNAL1, LRRC25, and NR1H3 as potential key genes for endometritis in dairy cows, with CD83 being more significantly expressed in LPS-induced BEECs. Consequently, in vitro functional studies were performed on CD83. In overexpression experiments, downregulation of the expression of inflammatory markers interleukin (IL)-1β, IL-6, and IL-8 and reduced ROS release primarily indicated the role of CD83 in attenuating the inflammatory response of BEECs. Furthermore, overexpression of CD83 regulated the S/G2 phase transition of BEECs by affecting the mRNA and protein expression of proliferation marker genes, thereby promoting proliferation of BEECs. The increased EdU positivity and the cell proliferation rate further provided evidence for the promotion of cell proliferation after overexpression of CD83. Additionally, overexpression of CD83 attenuated LPS-stimulated mitochondrial damage in BEECs, as well as the downregulation of apoptosis marker gene expression. In contrast, knockdown of CD83 expression showed the opposite trend. In summary, CD83 attenuated the inflammatory response of BEECs, promoted their proliferation, and inhibited apoptosis. This study provided basic data for understanding the mechanisms of endometritis regulation at the gene level in dairy cows.PMID:39892172 | DOI:10.1016/j.intimp.2025.114183

Hazard assessment of airborne and foodborne biodegradable polyhydroxyalkanoates microplastics and non-biodegradable polypropylene microplastics

Sat, 01/02/2025 - 12:00
Environ Int. 2025 Jan 28;196:109311. doi: 10.1016/j.envint.2025.109311. Online ahead of print.ABSTRACTMicroplastics (MP) are ubiquitous in the environment, and are toxic to various living organisms. Proper application of biodegradable plastics may alleviate the hazards of conventional non-biodegradable plastics. In the current study, multi-omics analyses were performed to compare the biodegradable polyhydroxyalkanoates (PHA) and non-biodegradable polypropylene (PP) MP for their toxicity on mouse liver and lung. Airborne PHA MP induced nasal microbiome dysbiosis, pulmonary microbiome alteration, pulmonary and serum metabolome disruption, and hepatic transcriptome disturbances, resulting in mild pulmonary toxicity. By contrast, airborne PP MP caused greater alterations in nasal and pulmonary microbiome, pulmonary and serum metabolome, and hepatic transcriptome, resulting in pulmonary and hepatic toxicity. Both foodborne PHA and PP MP caused intestinal microbiome dysbiosis, while foodborne PHA MP caused slighter intestinal and serum metabolome disruption, hepatic transcriptome disturbances and hepatotoxicity (e.g., lower serum aspartate aminotransferase and alanine aminotransferase) compared to foodborne PP MP. Some potential differential biomarkers were determined between PP and PHA MP exposures, i.e., nasal Allobaculum and pulmonary Alloprevotella for airborne PHA; nasal Lactobacillus and pulmonary Acinetobacter for airborne PP; intestinal Faecalibacterium for foodborne PHA; and intestinal unclassified_Erysipelatoclostridiaceae for foodborne PP. The results show that PHA MP can induce less pulmonary and hepatic toxicity compared to PP MP, suggesting PHA is a potential substitution for PP. The findings can benefit the hazard assessment of airborne and foodborne PHA and PP MP.PMID:39892168 | DOI:10.1016/j.envint.2025.109311

Perturbations in plasma amino acid and lipoprotein subfraction profiles in anorexia nervosa before and after refeeding: A metabolomic cross-sectional and longitudinal analysis

Sat, 01/02/2025 - 12:00
Clin Nutr. 2025 Jan 21;46:107-116. doi: 10.1016/j.clnu.2025.01.014. Online ahead of print.ABSTRACTBACKGROUND: Anorexia nervosa (AN) is a life-threatening eating disorder, which is increasingly being considered a metabo-psychiatric condition. We aimed to assess how the lipoprotein subfraction and plasma metabolome are altered in acutely underweight patients with AN (AcAN), if they change with short-term weight-restoration, and whether these changes point towards altered cardiometabolic risk.METHODS: Using nuclear magnetic resonance spectroscopy, we measured and compared the plasma concentrations of 132 metabolites, aminoacids and lipoprotein subfractions in young female patients with AcAN before (n = 72) versus after (n = 46) a short-term inpatient refeeding program resulting in weight-restoration (longitudinal analysis), as well as versus female healthy control (HC) participants of similar age (n = 74) (cross-sectional analysis).FINDINGS: Patients with AcAN showed elevated plasma cholesterol levels due to higher concentrations of small and dense Low Density Lipoprotein (LDL-6) and of large and less dense High Density Lipoprotein (HDL-1) subfractions compared to HC. Additionally, they had lower plasma concentrations of branched chain amino acids and glucose and higher concentrations of the gluconeogenic amino acids glutamine, alanine and methionine. Refeeding elevated the plasma cholesterol levels further, but with a different pattern compared to AcAN, by increasing the concentrations of the larger and less dense LDL (LDL-1, LDL-2, LDL-3) particles and of smaller and more dense HDL (HDL-2, HDL-3) subfractions. However, refeeding only partially restored the amino acid concentrations.CONCLUSION: Lipoprotein profiles in AcAN point towards a potentially elevated risk for atherosclerosis; an altered lipoprotein profile was also detected after refeeding. Metabolite profiles in AcAN indicate an advanced catabolic state with only partial restoration after refeeding.PMID:39892164 | DOI:10.1016/j.clnu.2025.01.014

Pulsed red light photobiomodulation ameliorates oxytocin-induced primary dysmenorrhea in mice by inhibiting oxidative stress and lipid accumulation

Sat, 01/02/2025 - 12:00
J Photochem Photobiol B. 2025 Jan 31;264:113119. doi: 10.1016/j.jphotobiol.2025.113119. Online ahead of print.ABSTRACTPhotobiomodulation (PBM) has gained attention as a kind of anti-pain or anti-inflammation therapy, yet its efficacy in mitigating the symptoms and underlying metabolic disturbances of primary dysmenorrhea remains underexplored. Here, 630 nm light reduced menstrual pain and prostaglandin F2a/prostaglandin E2 dysregulation, regulated oxidation and lipid peroxidation levels, and improved uterus damage in oxytocin-induced mice. Notably, pulsed wave (PW) treatment exhibited superior efficacy compared to continuous wave application. Hence, this research focused on the effects of 630 nm PW on oxytocin-induced mice by examining changes in the uterine transcriptome and plasma metabolome. Results from integrated analyses revealed significant modifications primarily in antioxidant and lipid metabolism pathways, alongside shifts in biomarkers related to arachidonic acid metabolism. Quantitative real-time PCR confirmed the downregulation of critical genes associated with oxidative stress and inflammation, as well as the suppression of uterine smooth muscle contractions and lipid overaccumulation. These findings support the potential of 630 nm PW PBM as a viable option for clinical interventions in dysmenorrhea management.PMID:39892163 | DOI:10.1016/j.jphotobiol.2025.113119

Untargeted metabolomics and machine learning unveil the exposome and metabolism linked with the risk of early pregnancy loss

Sat, 01/02/2025 - 12:00
J Hazard Mater. 2025 Jan 31;488:137362. doi: 10.1016/j.jhazmat.2025.137362. Online ahead of print.ABSTRACTEarly pregnancy loss (EPL) may result from exposure to emerging contaminants (ECs), although the underlying mechanisms remain poorly understood. This case-control study measured over 2000 serum features, including 37 ECs, 6 biochemicals, and 2057 endogenous metabolites, in serum samples collected from 48 EPL patients and healthy pregnant women. The median total concentration of targeted EC in the EPL group (65.9 ng/mL) was significantly higher than in controls (43.0 ng/mL; p < 0.05). Four machine learning algorithms were employed to identify key molecular features and develop EPL risk prediction models. A random forest model based on chemical data achieved a predictive accuracy of 95 %, suggesting a potential association between EPL and chemical exposure, with phthalic acid esters identified as significant contributors. Ninety-five potential metabolite biomarkers were selected, which were predominantly enriched in pathways related to spermidine and spermine biosynthesis, ubiquinone biosynthesis, and pantothenate and coenzyme A biosynthesis. C17-sphinganine was identified as a leading biomarker with an area under the curve of 0.93. Furthermore, exposure to bis(2-ethylhexyl)phthalate was linked to an increased risk of EPL by disrupting lipid metabolism. These findings indicate that combining untargeted metabolomics with machine learning approaches offers novel insights into the mechanisms of EPL related to EC exposure.PMID:39892135 | DOI:10.1016/j.jhazmat.2025.137362

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