PubMed

Sci Rep. 2024 Nov 27;14(1):29523. doi: 10.1038/s41598-024-80985-z.ABSTRACTAcute respiratory distress syndrome (ARDS), with high morbidity and mortality, is a common clinical syndrome of acute respiratory failure caused by diffuse lung inflammation and edema. ARDS can precipitate in various ways. The complex pathophysiology of ARDS involves the activation and dysregulation of multiple metabolisms and immune responses. Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of 179 genetically predicted lipid species and ARDS (375 cases, 406,518 controls) was performed and validated in plasma and pulmonary edema fluid from 24 patients. Furthermore, we used a two-step MR to quantify the effect of immune cell-mediated lipids on ARDS. We identified 8 lipids (Cholesterol, Phosphatidylcholine (14:0_16:0), Phosphatidylcholine (16:0_20:5), Phosphatidylcholine (18:0_18:2), Phosphatidylethanolamine (18:1_18:1), Triacylglycerol (51:2), Triacylglycerol (52:4), and Triacylglycerol (54:3) ) associated with ARDS. The proportions of genetically-predicted lipids mediated by the four types of immune cells were determined. Sensitivity analysis did not reveal any obvious pleiotropy or heterogeneity. Our study demonstrates the power of multivariate genetic analysis in correlated lipidomic data and reveals genetic links between ARDS and lipid species beyond standard lipids.PMID:39604464 | DOI:10.1038/s41598-024-80985-z

Sci Data. 2024 Nov 27;11(1):1293. doi: 10.1038/s41597-024-04066-6.ABSTRACTMost of the species in Paris have important medicinal values in China. Polyphyllins are the key components in Paris, with varying levels and compositions among different species. This study investigated polyphyllin compositions of 206 Paris samples from 16 different producing areas. 9 Paris polyphylla var. yunnanensis, 3 Paris fargesii, and 3 Paris forrestii were selected based on polyphyllin levels and composition for metabolome and transcriptome analysis. A total of 1,243 metabolites were identified among these samples, along with 92.11 Gb of full-length transcriptome data. This study provides potential candidate genes involved in polyphyllins synthesis in Paris, aiming to facilitate the biosynthesis of different polyphyllins.PMID:39604406 | DOI:10.1038/s41597-024-04066-6

NPJ Aging. 2024 Nov 27;10(1):58. doi: 10.1038/s41514-024-00183-z.ABSTRACTThis study investigates why individuals with multimorbidity-two or more chronic conditions-are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating mononuclear cells was measured in 70 participants. Results highlighted four main biological processes associated with multimorbidity: DNA damage with epigenetic changes, mitochondrial energy disruption, cellular aging (senescence) and innate immune response. Histone 2B, its ubiquitination enzymes and AKT3 were upregulated in the multimorbid group. Plasma senescence-associated proteins (IL-1β, GM-CSF) increased with more comorbidities. DNA damage and nucleolar instability were specifically apparent in multimorbid myocardium. We conclude that multimorbidity in cardiovascular patients accelerates biological aging, making them more vulnerable to metabolic stress.PMID:39604391 | DOI:10.1038/s41514-024-00183-z

Phytochem Anal. 2024 Nov 27. doi: 10.1002/pca.3483. Online ahead of print.ABSTRACTINTRODUCTION: Polygoni Multiflori Radix (PMR) is commonly used in traditional medicine as both raw and processed forms. Raw PMR was prepared into processed PMR via processing procedure; however, there is a lack of standardized protocols ensuring the completeness of processing.OBJECTIVE: This aims to develop a strategy based on a metabolomics approach for the comprehensive chemical profiling and comparison of raw and processed PMR and establish a basis for PMR processing standardization.MATERIALS AND METHODS: Methanol extracts of raw and processed PMR were fractionated by centrifugal partition chromatography (CPC) with an optimized two-phase solvent system based on the partition coefficient calculated from the shake-flask method to produce primary (1°Ms)- and secondary metabolites (2°Ms)-enriched fractions. These fractions were profiled by 1D and 2D and selective 1D NMR experiments, spectral fitting, and comparison with reference standards. The profiled compounds were quantified via quantitative 1H NMR (qHNMR) to show the chemical changes, which were correlated with changes in antioxidant effects on H2452 cells.RESULTS: A CPC method was developed to efficiently separate 1°Ms- and 2°Ms-enriched fractions. This method achieved high purity of the major stilbene in PMR in a single run. qHNMR effectively quantified four 2°Ms and twenty-one 1°Ms in both raw and processed PMR, including meso-butane-2,3-diol, which was first reported from processed PMR. Changes in chemical composition of PMR because of processing are highly correlated to the increase of antioxidant activity.CONCLUSION: A convenient and cost-effective strategy for the comprehensive chemical profiling of raw and processed PMR was developed by combining countercurrent separation and qHNMR. This approach will contribute to the standardization of medicinal herbal materials.PMID:39604055 | DOI:10.1002/pca.3483

J Agric Food Chem. 2024 Nov 27. doi: 10.1021/acs.jafc.4c07851. Online ahead of print.ABSTRACTUnderstanding the impacts of pile-fermentation on the taste quality of dark tea (DT) is crucial. Although the large-leaf DT, Yinghong 9 DT, was successfully developed, its taste quality was not systematically studied. This research aims to analyze how pile-fermentation affects taste. Our taste evaluations indicated that pile-fermentation reduces astringency while slightly increasing bitterness. Through untargeted metabolomic analysis, we identified 16 key metabolites associated with these taste changes. The analysis of the dose-overthreshold values affirmed that rutin, isoquercetin, myricetin 3-galactoside, EGCG, DL-C, and ECG were found to lower astringency, while caffeine contributed to the slight increase in bitterness. Additionally, the changes in these metabolites are closely linked to the catalytic effects of microbial extracellular enzymes. These findings provide a theoretical foundation for a deeper understanding of how pile fermentation influences the taste quality of large-leaf DT.PMID:39604007 | DOI:10.1021/acs.jafc.4c07851

Phytomedicine. 2024 Nov 8:156200. doi: 10.1016/j.phymed.2024.156200. Online ahead of print.ABSTRACTBACKGROUND: Chinese yam polysaccharide (SYDT) has been reported to protect renal function and mitigate renal fibrosis in mice with diabetic nephropathy. Based on a multi-omics analysis, the objectives of this study were to determine the effect of SYDT on cisplatin (CDDP)-induced chronic renal interstitial fibrosis (RIF) and the underlying molecular mechanisms using an in vivo model.METHODS: Rats were intraperitoneally injected with a single dose of CDDP and then treated with SYDT or amifostine (AMF). The levels of urinary N-acetyl-β-d-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were detected to assess renal function. Renal tissue damage and fibrosis were evaluated using hematoxylin and eosin (H&E) and Masson's trichrome staining, respectively. In addition, this study applied transcriptomics and metabolomics to predict the possible mechanism of SYDT action, which was verified by several relevant examinations.RESULTS: SYDT significantly protected the renal function, alleviated renal tissue damage and fibrosis, as well as decreased the protein levels of vimentin, α-SMA and CTGF, whereas SYDT significantly increased MMP-1 protein level in renal tissues from rats treated with CDDP. There were 1130 differently expressed genes (DEGs) between the CDDP model and SYDT-M groups proved by transcriptome analysis, indicating that metabolic pathways were likely the primary targets of relevance. Consistent with the transcriptome analysis, metabolome analysis identified 276 differentially expressed metabolites (DEMs) between the SYDT-M and CDDP model groups, with predominant clustering within glycerophospholipid metabolism. Integrative analysis of the transcriptome and metabolome indicated that SYDT inhibited the glycerophospholipid metabolism pathway by regulating the target genes Gpd2, Gpam, Agpat3, Lcat, and Pla2g4b. Notably, integrative analysis showed that the Phospholipase D (PLD) signaling pathway may be the most relevant target. Moreover, related signaling pathway analysis confirmed that SYDT inhibited CDDP-induced RIF in rats by down-regulating the PLD pathway.CONCLUSION: Our study showed that the alleviation of CDDP-induced RIF in vivo can be achieved through the inhibition of glycerophospholipid metabolism and PLD signaling pathways by SYDT.PMID:39603894 | DOI:10.1016/j.phymed.2024.156200

Clin Ther. 2024 Nov 26:S0149-2918(24)00324-2. doi: 10.1016/j.clinthera.2024.10.015. Online ahead of print.ABSTRACTPURPOSE: Females are at increased lifetime risk of stroke and experience worse outcomes compared with males. Tryptophan metabolism through the kynurenine pathway, resulting in decreased tryptophan concentrations, is associated with poor outcomes (larger infarct volume, higher National Institutes of Health Stroke Scale [NIHSS] score, and increased early mortality). This metabolic pathway activity varies by sex in healthy adults. However, evaluation of potential sex differences in tryptophan metabolism after an acute ischemic stroke (AIS) is lacking and could contribute to the disparate outcomes by sex. This study characterized sex differences in tryptophan metabolism via the kynurenine pathway in patients with AIS.METHODS: Whole blood from patients with AIS enrolled in the University of Colorado Health Emergency Medicine Specimen Bank was analyzed using high-throughput mass spectrometry-based metabolomics at the time of arrival to the emergency department and at 12, 24, and 48 hours thereafter. Descriptive statistics characterized the cohort and metabolite levels. Potential sex differences in tryptophan metabolites at individual time points and their change over time were estimated using linear regression models to control for known factors influencing metabolite levels, initial NIHSS score, therapeutic interventions, and time to last known well (or symptom onset). A multivariable linear regression model examined the interaction effect between sex and metabolite level (at 12 hours after admission) on 24-hour NIHSS score while controlling for initial metabolite level, initial NIHSS score, time to last known well, factors influencing metabolite level, and factors influencing neurologic outcomes.FINDINGS: After adjusting for covariates, females with AIS had significantly lower levels of tryptophan at 12 hours after admission compared with males (point estimate, -5.80; P = 0.03). Females and males neither differ in levels of tryptophan, kynurenine, quinolinic acid, or kynurenic acid at any other time point nor did they differ in change in metabolite concentration over time. Only increased quinolinic acid levels across both sexes at 12 hours after admission were associated with increased 24-hour NIHSS scores (point estimate, 0.49; P = 0.0002).IMPLICATIONS: Overall, females and males have similar levels and changes in tryptophan and kynurenine pathway metabolites after an AIS. However, females have lower levels of tryptophan early after a stroke. Increased quinolinic acid levels across both sexes were associated with worsening neurologic function as measured by an NIHSS score. Future evaluation of alternative metabolic pathways downstream of tryptophan is needed to explain differences in tryptophan levels but similar levels of downstream kynurenine metabolites in females and males with AIS.PMID:39603869 | DOI:10.1016/j.clinthera.2024.10.015

Plant Genome. 2024 Nov 27:e20534. doi: 10.1002/tpg2.20534. Online ahead of print.ABSTRACTIodes seguinii is a woody vine known for its potential therapeutic applications in treating rheumatoid arthritis (RA) due to its rich bioactive components. Here, we achieved the first chromosome-level assembly of the nuclear genome of I. seguinii using PacBio HiFi and chromatin conformation capture (Hi-C) sequencing data. The initial assembly with PacBio data produced contigs with an N50 length of 9.71 Mb, and Hi-C data anchored these contigs into 13 chromosomes, achieving a total length of 273.58 Mb, closely matching the estimated genome size. Quality assessments, including BUSCO, long terminal repeat assembly index, transcriptome mapping rates, and sequencing coverage, confirmed the high quality, completeness, and continuity of the assembly, identifying 115.28 Mb of repetitive sequences, 1062 RNA genes, and 25,270 protein-coding genes. Additionally, we assembled and annotated the 150,599 bp chloroplast genome using Illumina sequencing data, containing 121 genes including key DNA barcodes, with maturase K (matK) proving effective for species identification. Phylogenetic analysis positioned I. seguinii at the base of the Lamiales clade, identifying significant gene family expansions and contractions, particularly related to secondary metabolite synthesis and DNA damage repair. Metabolite analysis identified 84 active components in I. seguinii, including the discovery of luteolin, with 119 targets predicted for RA treatment, including core targets like AKT1, toll-like receptor 4 (TLR4), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), TP53, NFKB1, janus kinase 2 (JAK2), BCL2, mitogen-activated protein kinase 1 (MAPK1), and spleen-associated tyrosine kinase (SYK). Key active components such as flavonoids and polyphenols with anti-inflammatory activities were highlighted. The discovery of luteolin, in particular, underscores its potential therapeutic role. These findings provide a valuable genomic resource and a scientific basis for the development and application of I. seguinii, addressing the genomic gap in the genus Iodes and the order Icacinales and underscoring the need for further research in genomics, transcriptomics, and metabolomics to fully explore its potential.PMID:39603810 | DOI:10.1002/tpg2.20534

J Nutr Biochem. 2024 Nov 25:109813. doi: 10.1016/j.jnutbio.2024.109813. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a complex neurodegenerative disease. Nervonic acid is a component of breast milk and is also found in fish oil and specific vegetable oils. Studies have shown that nervonic acid is essential for the development of the human nervous system. In this study, Morris water maze (MWM) test and pathological analysis showed that nervonic acid could improve cognitive deficits and brain nerve damage in AD rats. Then, through sequencing, we found that nervonic acid increased the abundance of beneficial bacteria such as Lactobacillus and Bacteroides, and decreased the abundance of Pseudomonadaceae_Pseudomonas. Not only that, nervonic acid also regulates the production of short-chain fatty acids (SCFA) and the levels of 29 fecal metabolites, and affects the metabolism of linoleic acid, α-linolenic acid, arachidonic acid, and sphingolipid. Finally, we verified the regulatory effect of nervonic acid on metabolic enzyme activity.PMID:39603393 | DOI:10.1016/j.jnutbio.2024.109813

Chemosphere. 2024 Nov 25:143813. doi: 10.1016/j.chemosphere.2024.143813. Online ahead of print.ABSTRACTThe graphene oxide (GO) reduction by microorganisms has garnered considerable interest, yet the specific mechanisms underlying the bacteria secretion of reducing substances for GO reduction remain unclear. This study aims to learn that bacterial extracellular components can reduce graphene oxide through direct (contacting GO) and indirect (not contacting GO) reduction experiments. The subsequent investigation focused on identifying the specific substances secreted by bacteria capable of GO reduction. The results of non-targeted metabolomics revealed differential expression of cacid (L-AA) demonstrates a significant up-regulation. The further experiment involved the supplementation of L-AA in the reduction system of Lysinibacillus sp. with GO, demonstrating enhanced reduction efficacy, with the ID/IG ratio of reduced graphene oxide (rGO) increasing to 1.073 after 4 d of reduction with 0.5 g L-1 L-AA. Therefore, the mediation of GO reduction by L-AA secreted by Lysinibacillus sp. is proposed as a viable mechanism, offering novel insights into microbial GO reduction.PMID:39603357 | DOI:10.1016/j.chemosphere.2024.143813

Exp Eye Res. 2024 Nov 25:110152. doi: 10.1016/j.exer.2024.110152. Online ahead of print.ABSTRACTPathological myopia (PM) is associated with ocular morbidities that cause blindness. PM often occurs in eyes with high myopia (HM) while they are distinctly different. Identifying the differences in metabolites and metabolic pathways between patients with PM and HM may provide information about the pathogenesis of PM, which is currently unknown. This study aimed to reveal the comprehensive metabolic alterations associated with PM. Thirty patients with PM, 27 with simple HM and 27 with low myopia (LM) were enrolled in this study. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed, and a Venn diagram was generated to explore the overlapping differential metabolites and enriched pathways between each set of two groups. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacity of each metabolite marker. A total of 134, 125 and 81 differential metabolites were identified in each comparison. Thirty-two differential metabolites were overlapped between the PM vs HM comparison and the PM vs LM comparison. Of these 32 metabolites, 16 were common to all three comparisons; among these metabolites, high levels of 4-hydroxy-l-glutamic acid and low levels of succinic semialdehyde and 2,3-dinor-8-iso prostaglandin F2α appeared to be risk factors for PM. The remaining 16 metabolites were shared only between the PM versus HM and PM versus LM comparisons, most of which are lipid molecules. Pathway analysis revealed that alanine, aspartate and glutamate metabolism was the key metabolic pathway altered in PM patients. Overall, significant differences in the metabolites and metabolic pathways were observed in patients with PM. The metabolic differences identified in this study included differential factors between PM and HM patients, addressing current gaps in PM research. These findings provide a novel perspective of the molecular mechanism of PM.PMID:39603320 | DOI:10.1016/j.exer.2024.110152

Int J Biol Macromol. 2024 Nov 25:138074. doi: 10.1016/j.ijbiomac.2024.138074. Online ahead of print.ABSTRACTBlue honeysuckle, a new berry with high nutritional value, possesses typical berry postharvest properties, including extreme perishability, rapid quality loss, and high sensitivity to microbial infections. At present, the underlying mechanisms of postharvest quality deterioration, senescence, and low-temperature regulation remain largely unknown. This study aimed to elucidate the metabolic shifts and genetic regulation underlying the preservation or deterioration of blue honeysuckle during storage at room temperature (25 °C) and low temperature (4 °C). Storage at 4 °C inhibited fruit decay and preserved better visual quality, weight, firmness, and total soluble solid and acid contents. We identified 24 key differentially accumulated metabolites that specifically changed during the qualitative shift at room temperature and were effectively regulated by 4 °C. Commonly associated metabolites, sorbitol, succinic acid, malic acid, naringenin, pinobanksin, and taxifolin, characterize the deterioration of blue honeysuckle. These metabolites were integrated with transcriptomic data for weighted correlation network analysis (WGCNA). Regulatory networks were used for the identification of key genes and transcription factors (TFs) influencing sugar, organic acid, flavonoid, and phenolic acid metabolism during storage. The findings provide insight into metabolic regulation and the improvement of flavor in postharvest blue honeysuckle fruit.PMID:39603300 | DOI:10.1016/j.ijbiomac.2024.138074

Cell Rep Methods. 2024 Nov 19:100908. doi: 10.1016/j.crmeth.2024.100908. Online ahead of print.ABSTRACTDetecting strain-specific barcodes with mass spectrometry can facilitate the screening of genetically engineered bacterial libraries. Here, we introduce intact protein barcoding, a method to measure protein-based library barcodes and metabolites using flow injection mass spectrometry (FI-MS). Protein barcodes are based on ubiquitin with N-terminal tags of six amino acids. We demonstrate that FI-MS detects intact ubiquitin proteins and identifies the mass of N-terminal barcodes. In the same analysis, we measured relative concentrations of primary metabolites. We constructed six ubiquitin-barcoded CRISPR interference (CRISPRi) strains targeting metabolic enzymes and analyzed their metabolic profiles and ubiquitin barcodes. FI-MS detected barcodes and distinct metabolome changes in CRISPRi-targeted pathways. We demonstrate the scalability of intact protein barcoding by measuring 132 ubiquitin barcodes in microtiter plates. These results show that intact protein barcoding enables fast and simultaneous detection of library barcodes and intracellular metabolites, opening up new possibilities for mass spectrometry-based barcoding.PMID:39603242 | DOI:10.1016/j.crmeth.2024.100908

Ecotoxicol Environ Saf. 2024 Nov 26;288:117388. doi: 10.1016/j.ecoenv.2024.117388. Online ahead of print.ABSTRACTBenzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo, MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity.PMID:39603220 | DOI:10.1016/j.ecoenv.2024.117388

Ecotoxicol Environ Saf. 2024 Nov 26;288:117375. doi: 10.1016/j.ecoenv.2024.117375. Online ahead of print.ABSTRACTADB-BUTINACA, as a new psychoactive substance, can induce physical and psychological dependence. However, the systemic biological impact of ADB-BUTINACA on hepatic metabolomics remains uncertain. The metabolic spectrum in rat livers following exposure to three varying doses of ADB-BUTINACA (0.1, 1, and 5 mg/kg·bw) were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution quadrupole-orbitrap mass spectrometry and molecular docking techniques. Non-target metabolomic technology demonstrated that ADB-BUTINACA induced significant changes in 42 metabolites and disturbed 11 metabolic pathways especially the taurine and hypotaurine metabolism, β-alanine metabolism, and arachidonic acid metabolism, implicates the potential for ADB-BUTINACA to induce not merely cardiac dysfunction but also neurological anomalies. Molecular docking into the hepatotoxic targets of ADB-BUTINACA unveiled its potential for competitive binding with pantetheinase. This interaction may disrupt the coenzyme A (CoA) synthesis pathway, resulting in energy and lipid metabolism imbalances, and ultimately causing hepatotoxic effects. Cellular experiments confirmed reduced HepG2 cell viability and elevated reactive oxygen species (ROS) levels in HepG2 and Huh7 cells. These findings align with our metabolomic findings, supporting the hypothesis that ADB-BUTINACA induces hepatotoxicity via oxidative stress, as well as disruptions in energy and lipid metabolism. This work not only broadens the knowledge of ADB-BUTINACA' toxicological profile but also contributes to efforts aimed at diagnosing and preventing ADB-BUTINACA-induced hepatotoxicity.PMID:39603218 | DOI:10.1016/j.ecoenv.2024.117375

Poult Sci. 2024 Nov 23;104(1):104567. doi: 10.1016/j.psj.2024.104567. Online ahead of print.ABSTRACTImproving feed efficiency is vital to bolster profitability and sustainability in poultry production. Although several studies have established links between gut microbiota and feed efficiency, the direct effects remain unclear. In this study, two distinct lines of Huiyang bearded chickens, exhibiting significant differences in residual feed intake (RFI), were developed after 15 generations of selective breeding. Fecal microbiota transplantation (FMT) from low RFI (LRFI) chickens to high RFI (HRFI) chickens resulted in a reduction trend in RFI, decreasing from 5.65 to 4.49 in the HRFI recipient chickens (HFMT). Microbiota composition and functional profiles in LRFI and HFMT chickens formed a distinct cluster compared to HRFI chickens. Using 16S rDNA sequencing and RandomForest analysis, Slackia, Peptococcus, Blautia, and Dorea were identified as key microbial markers associated with feed efficiency. Additionally, untargeted metabolomics identified common differential metabolites between HFMT and LRFI vs. HRFI groups. Correlation analysis showed significant correlations between these microbial markers and differential metabolites. These findings provide a foundation for microbiome-based strategies to improve feed efficiency in poultry.PMID:39603188 | DOI:10.1016/j.psj.2024.104567

J Hazard Mater. 2024 Nov 26;483:136656. doi: 10.1016/j.jhazmat.2024.136656. Online ahead of print.ABSTRACTRecent studies have detected microplastics (MPs) in reproductive organs and found that they exert toxic effects on the reproductive system. However, the exact mechanism of action remains unclear. This study evaluates changes in MP levels in patients with cervical cancer as the disease progresses and uses untargeted metabolomics to assess the impact of MP exposure on the metabolomic profiles of cervical invasive cancer tissues. A total of 12 MP types were identified in 101 MP particles, with an average abundance of 2.24 ± 1.61 MP particles/g. Of these, polyethylene (PE, 26.73 %) and polypropylene (PP, 19.80 %) were the most frequently detected. Also, some MPs were observed to have sizes smaller than 20 µm. Notably, MP exposure levels increase as cervical cancer progresses (p < 0.05). Metabolomics analysis revealed that, among the 33 biologically significant metabolites screened, D-Mannose and cis,cis-muconic acid showed the most significant differences. Additionally, the aminosugar and nucleotide sugar metabolism pathways were the most significantly enriched in this experiment, potentially acting as pathways through which MPs may contribute to the pathogenesis of cervical cancer. The metabolites and pathways identified in this study may offer new insights and opportunities for disease research in patients with cervical cancer.PMID:39603134 | DOI:10.1016/j.jhazmat.2024.136656

Aquat Toxicol. 2024 Nov 19;278:107172. doi: 10.1016/j.aquatox.2024.107172. Online ahead of print.ABSTRACTBoth nanoplastic (NP) particles and arsenic (As) are widespread in aquatic environments and pose a combined risk of exposure to aquatic organisms. How the gut of aquatic organisms responds to combined risk of exposure is still unclear. In this study, zebrafish (Danio rerio) were subjected to three distinct As stress environments: only As group (10 μg/L), and As combined with different concentrations of polystyrene (PS) NPs (1 mg/L and 10 mg/L) groups for 21 days via semi-static waterborne exposure. The physiological responses to combined stress, the diversity of gut microorganisms, and the metabolomic response of the gut were investigated. The findings indicated that PSNPs were prevalent in the intestines of zebrafish in the co-exposed group. Furthermore, the administration of 1 mg/L and 10 mg/L of PSNPs in the co-exposed group was observed to elevate As levels in the intestines by 24.88% and 76.95%, respectively, in comparison to As treatment alone. Simultaneous exposure of the gut to PSNPs and As resulted in increased contents/activities of MDA, SOD, CAT, and GST, and a decrease in contents/activities of GSH and GPx, when compared to As exposure alone. Additionally, the combined exposure led to an elevated expression of the Cu/Zn-sod, Mn-sod, gpx, and cat genes. The combined treatment with NPs and As resulted in an increase in the abundance of Proteobacteria and Fusobacteriota at the phylum level, as well as a significant increase in the abundance of Cetobacterium, Rhodococcus, and Bacteroides at the genus level. Non-targeted metabolomics analyses suggest that metabolic pathways affected by co-exposure include glycerophospholipid metabolism, glycerolipid metabolism, ABC transporters and autophagy. The findings of this study are of considerable significance for the evaluation of the toxicological impact of co-existing pollutants.PMID:39603049 | DOI:10.1016/j.aquatox.2024.107172

Tissue Cell. 2024 Nov 26;91:102642. doi: 10.1016/j.tice.2024.102642. Online ahead of print.ABSTRACTOsteoarthritis (OA) is a pervasive degenerative joint disease affecting companion animals, characterized by chronic inflammation and cartilage degradation. However, the effectiveness of chondroitin sulfate (CS) in treating OA in dogs and cats remains controversial. This study aimed to determine the therapeutic effects and molecular mechanisms of CS on lipopolysaccharide (LPS)-induced inflammation in feline and canine articular chondrocytes (FAC and CAC) at the cellular level in vitro. Our findings demonstrated that CS treatment (800 µg/mL) significantly enhanced cell viability and reduced oxidative stress in FAC and CAC, as evidenced by decreased levels of reactive oxygen species and increased activities of antioxidant enzymes. Furthermore, CS treatment effectively suppressed LPS-induced secretion of pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, interleukin-8, interleukin-10, and matrix metalloproteinases-3, and reduced apoptosis, as confirmed by fluorescence staining and flow cytometry. Transcriptomic analysis revealed that CS upregulated neurotrophic signaling pathways, promoting cell survival and proliferation. Metabolomic analysis indicated that CS treatment upregulated metabolites associated with glycerophospholipid and purine metabolism, suggesting enhanced membrane integrity and energy metabolism. Conversely, pathways involved in protein catabolism and arachidonic acid metabolism were downregulated, indicating a reduction in inflammatory mediators. Collectively, these findings elucidate the multifaceted role of CS in modulating chondrocyte metabolism and inflammatory responses, highlighting its potential to alleviate OA.PMID:39603024 | DOI:10.1016/j.tice.2024.102642

Talanta. 2024 Nov 17;284:127234. doi: 10.1016/j.talanta.2024.127234. Online ahead of print.ABSTRACTDetermining the time since deposition (TSD) of bloodstains is important to establish a timeline of bloodshed, while DNA profiling addresses identity (source attribution). Traditionally treated as separate processes, this study integrates TSD estimation into routine DNA profiling by analyzing typically discarded cell lysate (eluates) from spin-column-based DNA extractions. Fluorescence spectroscopy was used to analyze eluates from bloodstains deposited up to 99 weeks. Two excitation-emission matrices (EEMs) were acquired for each sample and deconvoluted using parallel factor analysis (PARAFAC) to identify individual fluorophores. For example, tryptophan demonstrated a time-dependent decrease in fluorescence. Additionally, we observed an accumulation of fluorescent oxidation products (FOX) and advanced glycation end products (AGEs) over TSD. An untargeted metabolomics high-performance liquid chromatography-mass spectrometry workflow was applied to assist with fluorophore identification. Chemometric models were used to estimate TSD from EEM fluorescence data. Boruta feature selection coupled with random forest regression outperformed all other models and achieved high accuracy, with an R2 of 0.993 and root mean square error of prediction (RMSEP) of 2.83 weeks for the full 99-week period, and an R2 of 0.987 and RMSEP of 2.06 weeks for the 1-year timeframe. Comparisons were also made between anticoagulant-free (AC-free) and anticoagulant-treated (AC-treated) bloodstains deposited up to 3 months. We noted differences in fluorescence based on AC treatment, with AC-free blood exhibiting higher FOX and lower AGE fluorescence than AC-treated blood. Our findings demonstrate the effectiveness and feasibility of integrating TSD estimation into routine forensic DNA extractions while maintaining high prediction accuracies.PMID:39603014 | DOI:10.1016/j.talanta.2024.127234