PubMed

Nat Cancer. 2024 Oct 30. doi: 10.1038/s43018-024-00831-z. Online ahead of print.ABSTRACTFamilial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis.PMID:39478120 | DOI:10.1038/s43018-024-00831-z

Sci Rep. 2024 Oct 30;14(1):26122. doi: 10.1038/s41598-024-77746-3.ABSTRACTThis research aimed to analyze the volatile compounds emitted during the proliferation of Klebsiella pneumoniae (K. pneumoniae) in the laboratory setting using gas chromatography-ion mobility spectrometry (GC-IMS) and to investigate the potential of volatile metabolomics for detecting carbapenemase-producing strains of K. pneumoniae. The volatile metabolomics of K. pneumoniae were comprehensively analyzed using GC-IMS in tryptic soy broth (TSB) as the culture medium. Afterward, the growth stabilization period (T2) served as the primary time point for analysis, with the introduction of imipenem and carbapenemase inhibitors (avibactam sodium or EDTA) during the exponential growth phase (T0) to further investigate alterations in volatile molecules associated with K. pneumoniae. Standard strains were utilized as references, while clinical strains were employed for validation purposes. At T2, a total of 22 volatile organic compounds (VOCs) associated with K. pneumoniae were identified (3 VOCs found in both monomer and dimer forms). Significant differences in VOCs were observed between carbapenemase-negative and carbapenemase-positive strains, both standard and clinical, following the introduction of imipenem. Furthermore, the addition of avibactam sodium led to distinct changes in the VOC content of strains producing class A carbapenemase, while the addition of EDTA resulted in specific alterations in the volatile metabolic profiles of strains producing class B carbapenemase. GC-IMS demonstrated significant promise for analyzing bacterial volatile metabolomics, and its application in evaluating the volatolomics of K. pneumoniae may facilitate the timely detection of carbapenemase-producing strains.PMID:39478041 | DOI:10.1038/s41598-024-77746-3

NPJ Parkinsons Dis. 2024 Oct 30;10(1):208. doi: 10.1038/s41531-024-00816-w.ABSTRACTPathological forms of α-synuclein contribute to synucleinopathies, including Parkinson's disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.PMID:39477976 | DOI:10.1038/s41531-024-00816-w

Sci Rep. 2024 Oct 30;14(1):26135. doi: 10.1038/s41598-024-75941-w.ABSTRACTThe global aging population has led to a rise in age-related health issues, such as malnutrition, metabolic disorders, and even immune decline. Among these concerns, periodontitis holds particular significance for the well-being of the elderly. This study aimed to investigate the impact of aging on inflammatory resorption of alveolar bone in mice with periodontitis, with a specific focus on alterations in the intestinal microenvironment. To achieve this, we established a D-galactose (D-gal)-induced aging mouse model with periodontitis and employed histopathological staining, oxidative stress, and inflammatory factors analyses to assess the severity of periodontitis and the health status. Additionally, the 16S rRNA sequencing and untargeted metabolomics analysis were employed to investigate alterations in the intestinal microbiota and metabolites. Our results showed that D-gal-induced aging mice with periodontitis experienced more pronounced alveolar bone inflammatory resorption and disruptions in the gut barrier, accompanied by an overall decline in physical condition. The microbial composition and structure of aged mice also underwent significant modifications, with a decreased Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, metabolomics analysis demonstrated that D-gal-induced aging primarily influenced lipids and lipid-like molecules metabolism, and enrichment observed in the rheumatoid arthritis and histidine metabolism pathways. These findings provide further evidence that the aging process exacerbates age-related alveolar bone loss (ABL) through disturbances in intestinal homeostasis.PMID:39477973 | DOI:10.1038/s41598-024-75941-w

Nat Commun. 2024 Oct 30;15(1):9371. doi: 10.1038/s41467-024-53670-y.ABSTRACTThe trillions of microorganisms inhabiting the human gut are intricately linked to human health. While specific microbes have been associated with diseases, microbial abundance alone cannot reveal the molecular mechanisms involved. One such important mechanism is the biosynthesis of functional metabolites. Here, we develop a biosynthetic enzyme-guided disease correlation approach to uncover microbial functional metabolites linked to disease. Applying this approach, we negatively correlate the expression of gut microbial sulfonolipid (SoL) biosynthetic enzymes to inflammatory bowel disease (IBD). Targeted chemoinformatics and metabolomics then confirm that SoL abundance is significantly decreased in IBD patient data and samples. In a mouse model of IBD, we further validate that SoL abundance is decreased while inflammation is increased in diseased mice. We show that SoLs consistently contribute to the immunoregulatory activity of different SoL-producing human microbes. We further reveal that sulfobacins A and B, representative SoLs, act on Toll-like receptor 4 (TLR4) and block lipopolysaccharide (LPS) binding, suppressing both LPS-induced inflammation and macrophage M1 polarization. Together, these results suggest that SoLs mediate a protective effect against IBD through TLR4 signaling and showcase a widely applicable biosynthetic enzyme-guided disease correlation approach to directly link the biosynthesis of gut microbial functional metabolites to human health.PMID:39477928 | DOI:10.1038/s41467-024-53670-y

Ren Fail. 2024 Dec;46(2):2420830. doi: 10.1080/0886022X.2024.2420830. Epub 2024 Oct 30.ABSTRACTAIMS: Diabetic kidney disease (DKD) develops in approximately 40% of patients with type 2 diabetes mellitus (T2DM). The role of folate metabolites in the progression from T2DM to DKD has not been clearly articulated. Our aim was to assess the association of folate metabolites with DKD.METHODS: We conducted a cross-sectional study sourced from the U.S. National Health and Nutrition Examination Survey from 2011 to 2020. Several forms of folate were measured. DKD was defined as diabetes with albuminuria or impaired glomerular filtration rate. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.RESULTS: Of the 3,461 diabetes patients, 1,349 (38.98%) were diagnosed with DKD. Serum total folate and 5-Methyl-THF were negatively associated with DKD, the OR for comparing extreme quintile were both 0.73 (0.57-0.94). However, a positive association of RBC folate, UMFA, Non-5-Methyl-THF, and MeFox with DKD was observed with extreme quintile OR of 1.41 (1.10-1.82), 1.60 (1.24-2.07), 1.53 (1.20-1.96), and 3.45 (2.65-4.50). Furthermore, the ratio of UMFA to 5-Methyl-THF exhibited a positive association with DKD, with extreme quintile OR of 1.94 (1.50-2.50).CONCLUSIONS: Our findings suggested that guidelines and interventions highlighting the importance of promoting 5-Methyl-THF and reducing UMFA might have significant benefit for the management of patients with diabetes.PMID:39477815 | DOI:10.1080/0886022X.2024.2420830

Pestic Biochem Physiol. 2024 Nov;205:106146. doi: 10.1016/j.pestbp.2024.106146. Epub 2024 Sep 24.ABSTRACTFlupyrimin (FLP) is a novel class of insecticide acting on insect nicotinic acetylcholine receptor (nAChR) and shows robust insecticidal activity. However, the toxicological effects of FLP on Spodoptera litura have not been revealed. In this study, the results showed that the larval survival rate decreased significantly with increasing concentration of FLP. The hematoxylin-eosin (HE) staining showed that FLP exposure damages the structure of the larval midgut. Additionally, FLP treatments significantly increased the activities of detoxification (GST and CarE) and digestive (α-Amylase and Trypsin) enzymes and reduced lipase activity. Transcriptome sequencing identified 855, 1493 and 735 differentially expressed genes (DEGs) at 12 h, 24 h and 48 h after exposure to 3 mM FLP, respectively. Gene function enrichment analysis revealed that DEGs were mainly related to fatty acid metabolic, protein processing in the endoplasmic reticulum and drug metabolism-cytochrome P450. The DEGs associated with food digestion and detoxification was validated by reverse-transcription quantitative PCR (RT-qPCR). Furthermore, a total of fifteen energy-related metabolites were identified, among which thirteen metabolisms were significantly influenced after FLP treatment based on 1H NMR-based metabolome analysis, including tyrosine, glucose, trehalose, malate, threonine, proline, glycine, lysine, citrate, alanine, lactate, valine, and leucine. Taken together, these results provide useful information for revealing the toxicological effect of FLP against S. litura.PMID:39477599 | DOI:10.1016/j.pestbp.2024.106146

Pestic Biochem Physiol. 2024 Nov;205:106136. doi: 10.1016/j.pestbp.2024.106136. Epub 2024 Sep 18.ABSTRACTSpodoptera frugiperda is an economic agricultural pest that has invaded many countries around the world and caused huge losses in grain production. Camptothecin (CPT) is one of the botanical compounds with insecticidal activity and has the potential for pest control. However, the effects of CPT on development and metabolism of S. frugiperda remain unknown. In this study, we have investigated the adverse effects of 1.0 and 5.0 mg/kg CPT exposures on the growth and development of S. frugiperda. Our results found that 1.0 and 5.0 mg/kg CPT treatments altered the parameters of the life cycle, including inducing larval mortality, altering the weight of larvae, pupae, and adults, the larval duration, and decreasing the pupation rate and emergence rate. In addition, comparative metabolomics analysis was performed in the larval midgut of S. frugiperda to explore the toxicity mechanism of CPT. A total of 261 and 348 differential metabolites were identified in the groups with 1.0 and 5.0 mg/kg CPT treatments, respectively. Further analysis found that pantothenate and CoA biosynthesis, sulfur relay system, selenocompound metabolism, and fatty acid biosynthesis pathways were significantly altered by 5.0 mg/kg CPT exposure. Our results provided new insight into the toxicological mechanisms of CPT against S. frugiperda and laid the foundation for the field application of CPT in pest control.PMID:39477589 | DOI:10.1016/j.pestbp.2024.106136

J Appl Toxicol. 2024 Oct 30. doi: 10.1002/jat.4715. Online ahead of print.ABSTRACTAs global regulations on synthetic cannabinoids tighten, illicit vendors increasingly turn to new structures of synthetic cannabinoids to evade legal scrutiny. MDA-19, a novel synthetic cannabinoid, exhibited significant agonistic effects on type 2 cannabinoid receptors in vivo and showed emerging trends of abuse in illicit markets. However, research on the toxicological effects of MDA-19 remains scarce. In this study, we examined the effects of MDA-19 on neurodevelopment, behavior, oxidative stress, and metabolomics by exposing zebrafish embryos to MDA-19 solutions with concentrations of 1, 10, and 20 mg/L over 5 days. Results revealed that exposure to 10 and 20 mg/L of MDA-19 accelerated hatching in zebrafish embryos but led to reduced body length without affecting mortality or malformation. Furthermore, exposure to all concentrations of MDA-19 resulted in diminished swimming ability and reduced activity time in zebrafish. Transgenic zebrafish (hb9-GFP) exposed to MDA-19 exhibited impaired development of spinal motor neurons. Notably, exposure to 20 mg/L MDA-19 increased the levels of reactive oxygen species (ROS) in zebrafish and elevated the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while the levels of the lipid oxidation product malondialdehyde (MDA) remained unaffected. Nontargeted metabolomics analyses showed that MDA-19 interfered with multiple metabolic pathways affecting energy metabolism, such as alanine, aspartate, and glutamate metabolism; the citric acid cycle (TCA cycle), pantothenate, and coenzyme A biosynthesis; and purine metabolism. In conclusion, the present study provided the essential evidence for the neurotoxic effects of MDA-19, which was associated with impaired neurodevelopment, dysregulation of oxidative stress homeostasis, and altered energy metabolism.PMID:39477463 | DOI:10.1002/jat.4715

Anticancer Res. 2024 Nov;44(11):4729-4735. doi: 10.21873/anticanres.17299.ABSTRACTBACKGROUND/AIM: Large extracellular vesicles (lEV) offer a unique window into the metabolism of their cells of orign and dysregulation of lipid metabolism has been described in patients with small cell lung cancer (SCLC). Therefore, metabolomic profiling of patients' lEVs may offer insight into cancer metabolism as well as new potential biomarkers for monitoring disease progression.MATERIALS AND METHODS: lEVs were isolated by differential centrifugation from the peripheral blood of SCLC patients and healthy controls. Targeted mass spectrometry was used to analyze the lipid composition of lEVs. After identifying relevant metabolites, biomarker and pathway analysis were conducted.RESULTS: SCLC patients exhibited a distinct metabolic profile compared to healthy controls. The metabolites TG(16:0:_38:3), TG(18:3_35:2), TG(16:0_40:7), Cer(d18:1/26:0), and CE(16:0) are not only able to discriminate between patients and control samples, but are also served as prognostic markers for survival. Patients with high concentrations of these metabolites showed significantly shorter survival times. Pathway analysis revealed alterations in 'sphingolipid metabolism', 'sphingolipid signaling pathway' and 'necroptosis'.CONCLUSION: Metabolic profiling of lEVs in SCLC patients is feasible and reveals a distinct metabolic profile. High concentrations of identified lipids are associated with poor prognosis.PMID:39477327 | DOI:10.21873/anticanres.17299

Anticancer Res. 2024 Nov;44(11):4801-4811. doi: 10.21873/anticanres.17306.ABSTRACTBACKGROUND/AIM: Natural compounds such as propolis have gained wide popularity in the last decades. While its antibacterial, antiviral, and antifungal properties are well known, the anticancer properties of propolis are just beginning to be appreciated. Herein, we comparatively investigate the cytotoxic and radiosensitizing potential of four different ethanolic propolis extracts originating from three different countries (Germany, Ireland, South Africa) in human lung cancer cell models.MATERIALS AND METHODS: Liquid chromatography-mass spectrometry (LC-MS/MS) was applied to characterize the four different propolis extracts. Cytotoxicity and radiation survival were determined by 3D matrix-based clonogenic assays and autophagy was examined by western blotting.RESULTS: We found cytotoxicity in a propolis type-, time- and cell model- dependent manner. In the four ethanolic propolis extracts, Coumaric acid, Caffeic acid phenethyl ester, Pinocembrin and Chrysin presented the major compounds identified. Examining the induction of autophagy using the marker LC3B and autophagy inhibition with chloroquine suggested autophagy to be part of the survival mechanisms upon propolis treatment in a cell model-dependent manner. Combining propolis with X-ray irradiation showed the radiosensitizing potential of propolis in human lung cancer cell models, which clearly presented in a manner dependent on the incubation time of propolis and the cell model treated.CONCLUSION: Propolis treatment showed cytotoxic and radiosensitizing effects of propolis on human lung cancer cells. Since these effects differ greatly between the four propolis extracts studied and originating from different regions, further studies are urgently needed to differentiate propolis species and their anticancer properties in more detail.PMID:39477309 | DOI:10.21873/anticanres.17306

Sci Total Environ. 2024 Oct 28:177248. doi: 10.1016/j.scitotenv.2024.177248. Online ahead of print.ABSTRACTN-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a widely utilized antioxidant in automobile tires and rubber goods, is frequently detected in aquatic ecosystems and poses a potential threat to aquatic organisms. However, research on the impact of 6PPD on aquatic plants is still scarce. Here, we investigated the bioaccumulation of 6PPD in Myriophyllum verticillatum (M. verticillatum) (watermilfoil), and its impacts on biochemical characteristics and metabolomics. 6PPD (10,100 mg/L) significantly inhibited the growth and photosynthetic pigment content of M. verticillatum. After 14 days of exposure to 100 μg/L 6PPD, accumulation levels of 6PPD and its metabolite 6PPDQ in M. verticillatum reached 0.52 mg/kg and 0.09 mg/kg, respectively. Moreover, 6PPD significantly induced the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) enzymes and glutathione (GSH), reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), thereby mitigating oxidative damage in M. verticillatum. Furthermore, metabolic pathway analysis revealed that 6PPD has remarkable effects on amino acid and sugar metabolism. This study provides data support for understanding the toxic effects of 6PPD on aquatic plants and evaluating its potential risks.PMID:39477116 | DOI:10.1016/j.scitotenv.2024.177248

J Dairy Sci. 2024 Oct 28:S0022-0302(24)01249-9. doi: 10.3168/jds.2024-25430. Online ahead of print.ABSTRACTExploring the toxicity and metabolic mechanisms of Aflatoxin B1 (AFB1) in ruminants can help to develop strategies to prevent or reduce the transfer of the toxin and its metabolites to milk and meat. This study aimed to explore the effects of 3 concentrations of dietary AFB1 (0, 50, and 500 μg/kg) on hepatic injury and metabolism in Saanen goats via histological examination, Western blot analysis, as well as integrated multi-omics techniques. Eighteen Saanen goats were assigned to 1 of 3 treatments and the AFB1 challenge lasted for 14 d. Results showed that the liver tissue was enlarged and the relative organ index of the liver was linearly increased with elevated AFB1 levels. The hepatocyte apoptosis rate was significantly increased after AFB1 exposure and the Western blotting results revealed that both the external apoptotic pathway and mitochondrial-mediated intrinsic apoptotic pathway might be involved in AFB1-induced hepatocyte apoptosis. There were 251, 269, 154 significant differentially expressed genes (DEGs) and 340, 596, 127 significant differential metabolites for the control (C; 0 μg/kg) and low-dose (L; 50 μg/kg), C and high-dose (H; 500 μg/kg), L and H comparisons. The DEGs annotated were mainly involved in the cell part, cell, single-organism process, cellular process, binding, and other functional categories. The identified metabolites primarily belonged to glycerophospholipids, prenol lipids, carboxylic acids and derivatives. Integrative analysis of transcriptomics and metabolomics revealed that glycerophospholipids metabolism and choline metabolism in cancer were the most affected pathways related to AFB1 exposure. The identified differential metabolites, DEGs, and pathways might have played a crucial role in the hepatic injury induced by AFB1 in goats.PMID:39477065 | DOI:10.3168/jds.2024-25430

Eur J Pharm Biopharm. 2024 Oct 28:114552. doi: 10.1016/j.ejpb.2024.114552. Online ahead of print.ABSTRACTThis research is based on the incorporation of the methanolic extract of the Usnea ghattensis into poly (caprolactone) (PCL) nanofibers (NFs) to investigate the capacity in reducing reactive oxygen species (ROS). PCL-NFs were fabricated by the electrospinning technique and are investigated as potential dressing material focused on the release of usnic acid (PCL-USNIC NFs), and its encapsulation efficiency and kinetic release were analyzed by high performance liquid chromatography (HPLC). This investigation was performed by analyzing the usnic acid concentration as a function of the distance from the mat center point. The kinetic release analysis is also developed with the usnea ghattensis extract (PCL-USNEA NFs), performing a metabolomic analysis of the released molecules as a function of time by nuclear magnetic resonance (NMR). Usnic acid was revealed as the most relevant compound together with other molecules, such as sucrose, mannitol, arabitol or glycerol that generate a positive matrix effect on the release of usnic acid. Finally, we analize the cytotoxicity and the neuroprotective effect of PCL-USNEA and PCL-USNIC NFs using a human neuroblastoma cell line model. Negligible toxicity was appreciated for both polymeric systems, showing high protective effects in presence of highly oxidative environment (e.g. in presence of H2O2).PMID:39477028 | DOI:10.1016/j.ejpb.2024.114552

J Mol Cell Cardiol. 2024 Oct 28:S0022-2828(24)00172-X. doi: 10.1016/j.yjmcc.2024.10.011. Online ahead of print.ABSTRACTBACKGROUND: Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with severe cardiovascular complications. AF presents a growing global challenge, however, current treatment strategies for AF do not address the underlying pathophysiology. To advance diagnosis and treatment of AF, a deeper understanding of AF root causes is needed. Metabolomics is a fast approach to identify, quantify and analyze metabolites in a given sample, such as human serum or atrial tissue. In the past two decades, metabolomics have enabled research on metabolite biomarkers to predict AF, metabolic features of AF, and testing metabolic mechanisms of AF in animal models. Due to the field's rapid evolution, the methods of AF metabolomics studies have not always been optimal. Metabolomics research has lacked standardization and requires expertise to face methodological challenges.PURPOSE OF THE REVIEW: We summarize and meta-analyze metabolomics research on AF in human plasma and serum, atrial tissue, and animal models. We present the current progress on metabolic biomarkers candidates, metabolic features of clinical AF, and the translation of metabolomics findings from animal to human. We additionally discuss strengths and weaknesses of the metabolomics method and highlight opportunities for future AF metabolomics research.PMID:39476947 | DOI:10.1016/j.yjmcc.2024.10.011

J Chromatogr A. 2024 Oct 19;1737:465459. doi: 10.1016/j.chroma.2024.465459. Online ahead of print.ABSTRACTUnknown impurities, metabolites and harmful pollutants present in pharmaceutical products, biological and environmental samples, respectively are of high concern in terms of their detection and quantification. The targeted analysis aims to quantify known chemical entities, but it lacks the ability to identify unknown components present in a sample. Non-targeted analysis is an analytical approach that can be made applicable to various disciplines of science to effectively search for unknown chemical, biological, or environmental entities that can answer various baffling mysteries of research. It employs various high-end analytical techniques that can specifically screen out multiple unknown compounds from complex mixtures. Non-targeted analysis is also applicable for complex studies such as metabolomics to search unidentified metabolites of new chemical entities. This review critically discusses the current advancements in non-targeted analysis related to the analysis of pharmaceutical, biological, and environmental samples. Various steps like sample collection, handling, preparation, extraction, its analysis using advanced techniques like high-resolution mass spectrometry, liquid chromatography mass spectrometry, and lastly interpretation of the huge amounts of complex data obtained upon analysis of complex matrices have been discussed broadly in this article. Besides the advantages of non-targeted analysis over targeted analysis, limitations, bioinformatics tools, sources of error, and research gaps have been critically analyzed.PMID:39476774 | DOI:10.1016/j.chroma.2024.465459

J Hazard Mater. 2024 Oct 26;480:136326. doi: 10.1016/j.jhazmat.2024.136326. Online ahead of print.ABSTRACTAn investigation was conducted by researchers on how dibutyl phthalate (DBP) and polystyrene microplastics (PS-MP) influence the development of pneumonia using a mouse model. For a duration of five weeks, the mice were subjected to exposure of DBP (30 mg/kg/day) and PS-MP (0.1 mg/day). The findings indicated notable pathological alterations in airway tissues, increased oxidative stress levels, and intensified inflammation, thereby establishing a connection between plastic pollution and pneumonia. Further examination indicated the involvement of ferroptosis and oxidative stress in the progression of the disease. Administration of deferoxamine (DFO) (100 mg/kg) resulted in symptom relief and reduced pathological alterations, as validated by metabolomic investigations. Increased levels of reactive oxygen species (ROS) triggered a Th2-mediated eosinophilic inflammatory response, marked by elevated IL-4 and reduced IFN-γ via the NFκB pathway. Moreover, analyses of the gut microbiome and metabolomics demonstrated that PPD modifies microbial populations and pulmonary metabolism, linking its effects on pneumonia through the gut-lung axis. This research highlights the health hazards associated with plastic pollution and proposes a framework for tackling these issues.PMID:39476687 | DOI:10.1016/j.jhazmat.2024.136326

Ecotoxicol Environ Saf. 2024 Oct 29;287:117262. doi: 10.1016/j.ecoenv.2024.117262. Online ahead of print.ABSTRACTHigh selenium (Se) levels can induce toxicity, inhibit growth, and affect gene expression and metabolite content in plants. However, the molecular mechanism by which high Se stress affects soybean plants remains unclear. This study examined the responses of soybean leaves and roots to high Se stress using transcriptome and metabolome analyses. High Se stress significantly inhibited soybean root growth, reduced leaf area, and affected the antioxidant enzyme system in roots and leaves, resulting in the accumulation of malondialdehyde (MDA). High Se stress increased indoleacetic acid (IAA), abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) in the roots by 3.34-fold, 8.94-fold, 0.25-fold, and 5.65-fold, respectively. Similarly, high Se stress increased IAA, ABA, JA, and SA in the leaves by 1.96-fold, 10.54-fold, 2.03-fold, and 4.22-fold, respectively. In addition, high Se stress affected ion absorption and transport in soybean plants. Transcriptome results showed that there were 10,038 differentially expressed genes (DEGs) in soybean roots and 5811 DEGs in leaves, which affected the expression of antioxidant enzymes, ion transport and hormone-related genes. Metabolome results revealed that there were 277 differentially expressed metabolites (DEMs) in soybean leaves and 312 DEMs in roots. Soybean roots and leaves were significantly enriched in the "β-alanine metabolism" pathway under high Se stress, with differential expression of Aldehyde dehydrogenase (ALDH), Amine oxidase (AO), and other related genes, thereby relieving oxidative stress. This study improves our understanding of the molecular mechanisms underlying the responses of soybean plants to high Se stress and provides a basis for breeding Se-enriched soybean plants.PMID:39476650 | DOI:10.1016/j.ecoenv.2024.117262

Food Chem. 2024 Oct 26;464(Pt 2):141784. doi: 10.1016/j.foodchem.2024.141784. Online ahead of print.ABSTRACTA prolonged diet laden with purine-rich foods represents a significant contributor to renal fibrosis (RF). Eucommia ulmoides Oliver, a plant homologous to food and medicinal materials, has long been employed to recover kidney function. This investigation presents a strategy integrating chemistry, biochemistry, and metabolomics to evaluate bioactive components and efficiency mechanism of crude and salt-stir fried Eucommiae Cortex (EC) extracts against RF. Firstly, 155 chemical components were identified in the EC extracts and the contents of 19 and 27 compounds decreased and increased respectively after salt-stir frying. Secondly, various biochemical indicators displayed that salt-stir fried EC (SEC) extracts had the optimal anti-RF effects in adenine-induced RF model rats, which were associated with the attenuation of TGF-β signaling pathway. Finally, untargeted metabolomics analysis demonstrated that after treatments with EC and SEC extracts, 30 and 32 efficacy biomarkers were significantly restored in the RF + EC and RF + SEC groups respectively, involving five metabolic pathways.PMID:39476582 | DOI:10.1016/j.foodchem.2024.141784

Theriogenology. 2024 Oct 26;231:197-209. doi: 10.1016/j.theriogenology.2024.10.025. Online ahead of print.ABSTRACTPhospholipase A (PLA) in goat semen aggregates with egg yolk in semen diluent, leading to sperm death. The aim of this study is to address the issue of sperm death caused by the interaction between PLA and egg yolk, and to explore the protective effect and metabolic regulation mechanism of the combination of dexamethasone (DXMS) and azithromycin (AZM) on goat sperm under low temperature conditions. At a low temperature of 4 °C, different concentrations of DXMS were added to semen diluents containing 30 μg/mL AZM to detect the quality of goat sperm. The optimal concentration of DXMS was determined to be 20 μg/mL. On the 5th day of storage, antioxidant capacity, total cholesterol (TC) levels, energy metabolism, and metabolomics analysis were performed on the sperm of the 20 μg/mL DXMS group. The results showed that there was no aggregation caused by the interaction between PLA and egg yolk in the group containing 30 μg/mL AZM at 4 °C. 20 μg/mL DXMS significantly improved sperm motility, plasma membrane integrity, acrosome integrity, glutathione peroxidase (GPX) (P < 0.05), catalase (CAT) (P < 0.01), and superoxide dismutase (SOD) activity (P < 0.01). The content of reactive oxygen species (ROS) and Fe2+ significantly decreased (P < 0.01), while the content of ATP (P < 0.01) and TC (P < 0.05) significantly increased. Through metabolomics analysis, a total of 56 differential metabolites (P < 0.05) were screened, including 5a, 6-Anhydrotetracycline, Betamethasone, and 11-Dehydrocorticosterone, mainly enriched in 8 metabolic pathways (P < 0.05), including steroid hormone biosynthesis, glycerophospholipid metabolism, and choline metabolism in cancer. Among them, 5 metabolic pathways are related to lipid metabolism. The results indicate that AZM effectively inhibits the aggregation of PLA and yolk, and the combination of AZM and DXMS enhances the preservation quality of goat sperm during low-temperature preservation by regulating lipid metabolism.PMID:39476552 | DOI:10.1016/j.theriogenology.2024.10.025