PubMed

Environ Health Perspect. 2024 Apr;132(4):47005. doi: 10.1289/EHP13435. Epub 2024 Apr 10.ABSTRACTBACKGROUND: Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored.OBJECTIVES: This study aims to investigate the impacts of polymer microspheres on tissue metabolism in mice by assessing the microspheres ability to translocate across the gut barrier and enter into systemic circulation. Specifically, we wanted to examine microsphere accumulation in different organ systems, identify concentration-dependent metabolic changes, and evaluate the effects of mixed microsphere exposures on health outcomes.METHODS: To investigate the impact of ingested microspheres on target metabolic pathways, mice were exposed to either polystyrene (5μm) microspheres or a mixture of polymer microspheres consisting of polystyrene (5μm), polyethylene (1-4μm), and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid) (5μm). Exposures were performed twice a week for 4 weeks at a concentration of either 0, 2, or 4mg/week via oral gastric gavage. Tissues were collected to examine microsphere ingress and changes in metabolites.RESULTS: In mice that ingested microspheres, we detected polystyrene microspheres in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolic differences that occurred in the colon, liver, and brain, which showed differential responses that were dependent on concentration and type of microsphere exposure.DISCUSSION: This study uses a mouse model to provide critical insight into the potential health implications of the pervasive issue of plastic pollution. These findings demonstrate that orally consumed polystyrene or mixed polymer microspheres can accumulate in tissues such as the brain, liver, and kidney. Furthermore, this study highlights concentration-dependent and polymer type-specific metabolic changes in the colon, liver, and brain after plastic microsphere exposure. These results underline the mobility within and between biological tissues of MPs after exposure and emphasize the importance of understanding their metabolic impact. https://doi.org/10.1289/EHP13435.PMID:38598326 | DOI:10.1289/EHP13435

Zhonghua Nan Ke Xue. 2023 Apr;29(4):323-330.ABSTRACTOBJECTIVE: To investigate the difference in the levels of metabolites in the seminal plasma exosomes (SPE) of men with a high sperm DNA fragmentation index (DFI) from those with a low DFI.METHODS: We performed a sperm exosomal metabolomics analysis of 5 healthy married men with DFI ≤15% (the control group) and another 5 with DFI ≥30% and matched in marital status, age and body mass index with the controls (the case group). Using high-performance liquid chromatography and mass spectrum, we examined the metabolites, observed their difference, and analyzed the metabolite enrichment pathway by Kyoto encyclopedia of genes and genomes (KEGG). According to the inclusion and exclusion criteria, we also selected 11 men in the control group and 20 men in the case group, and detected the differences in the seminal plasma amino acid and carnitine between the two groups using liquid measurement systems.RESULTS: After primary and secondary analyses and qualified screening, 23 metabolites related to sperm DNA integrity were obtained, including 9 organic acids, 2 amino acid intermediate metabolites, and 11 acylcarnitine, purine, niacin and other intermediate products. KEGG enrichment analysis showed that 23 metabolites were mainly involved in the sphingoid signaling pathway, niacin and niacinamide metabolic pathway, and arginine and proline metabolic pathway. Further verification revealed no difference in the level of seminal plasma amino acid between the two groups, and significantly lower levels of seminal plasma acylcarnitine, free carnitine, propionylcarnitine, 3-hydroxybutyrylcarnitine and malonylcarnitine, 3-hydroxyisovalerylcarnitine and succinylcarnitine, and isoamyl (enylcarnitine) in the case group than in the controls (P<0.05).CONCLUSION: There are significant differences in the levels of the metabolites organic acids, amino acids and acylcarnitine in the SPE of males with a high DFI from those with a low DFI. The level of seminal plasma acylcarnitine is significantly correlated with sperm DFI, which can be used as an indicator in quantitative and rapid assessment of the degree of sperm DNA damage.PMID:38598216

FASEB J. 2024 Apr 15;38(7):e23611. doi: 10.1096/fj.202302344R.ABSTRACTMutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.PMID:38597925 | DOI:10.1096/fj.202302344R

J Agric Food Chem. 2024 Apr 10. doi: 10.1021/acs.jafc.3c03901. Online ahead of print.ABSTRACTPostbiotics are preparations of inanimate microorganisms and/or their components that are beneficial to host health. Compared with probiotics, the postbiotic dose required for exerting obvious protective effects is unknown. Thus, we conducted a dose-dependent postbiotic intervention study in dextran sulfate sodium (DSS)-induced colitis rats. The trial included five rat groups, including: control without DSS/postbiotic treatment, group C; 7-day DSS treatment, group D; 14-day low, medium, and high probiotic doses (0.1, 0.2, 0.4 g/kg; groups L, M, H, respectively) after DSS induction. We found that postbiotic intervention effectively mitigated the symptoms and inflammation in colitis rats, evidenced by the improved spleen index, less severe colon tissue damage, and changes in serum cytokine levels (decreases in tumor necrosis factor-α and interleukin-1β; increase in interleukin-10) in postbiotic groups compared with group D. Moreover, the therapeutic effect was dose-dependent. Fecal metabolomics analysis revealed that the postbiotic recipients had more anti-inflammatory metabolites, namely, salicyloyl phytophingosine, podophylloxin, securinine, baicalein, and diosmetin. Fecal metagenomics analysis revealed that the postbiotic recipients had more beneficial microbes and less pro-inflammatory bacteria. This study confirmed that postbiotics are effective in alleviating colitis in a dose-dependent manner. Our findings are of interest to food scientists, clinicians, and the health food industry.PMID:38596883 | DOI:10.1021/acs.jafc.3c03901

Front Immunol. 2024 Mar 26;15:1333848. doi: 10.3389/fimmu.2024.1333848. eCollection 2024.ABSTRACTExcessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation in vitro. In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.PMID:38596683 | PMC:PMC11002173 | DOI:10.3389/fimmu.2024.1333848

Front Microbiol. 2024 Mar 26;15:1373344. doi: 10.3389/fmicb.2024.1373344. eCollection 2024.ABSTRACTThe DNA damage inducible SOS response in bacteria serves to increase survival of the species at the cost of mutagenesis. The SOS response first initiates error-free repair followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response. Escherichia coli was grown in batch cultivation in bioreactors to ensure highly controlled conditions, and a low dose of the antibiotic ciprofloxacin was used to activate the SOS response while avoiding extensive cell death. Our results show that expression of genes involved in error-free and error-prone repair were both induced shortly after DNA damage, thus, challenging the established perception that the expression of error-prone repair genes is delayed. By combining transcriptomics and a sub-proteomics approach termed signalomics, we found that the temporal segregation of error-free and error-prone repair is primarily regulated after transcription, supporting the current literature. Furthermore, the heterology index (i.e., the binding affinity of LexA to the SOS box) was correlated to the maximum increase in gene expression and not to the time of induction of SOS genes. Finally, quantification of metabolites revealed increasing pyrimidine pools as a late feature of the SOS response. Our results elucidate how the SOS response is coordinated, showing a rapid transcriptional response and temporal regulation of mutagenesis on the protein and metabolite levels.PMID:38596376 | PMC:PMC11002266 | DOI:10.3389/fmicb.2024.1373344

Front Microbiol. 2024 Mar 26;15:1331130. doi: 10.3389/fmicb.2024.1331130. eCollection 2024.ABSTRACTThe gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/β-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.PMID:38596370 | PMC:PMC11002229 | DOI:10.3389/fmicb.2024.1331130

Front Microbiol. 2024 Mar 26;15:1284402. doi: 10.3389/fmicb.2024.1284402. eCollection 2024.ABSTRACTOBJECTIVE: The primary objective of this study is to investigate the mechanism by which Bacillus coagulans TBC169 accelerates intestinal function recovery in patients who have undergone gynecological laparoscopic surgery, using metabolomics and gut microbiota analysis.METHODS: A total of 20 subjects were selected and randomly divided into two groups: the intervention group (n = 10) receiving Bacillus coagulans TBC169 Tablets (6 pills, 1.05 × 108 CFU), and the control group (n = 10) receiving placebos (6 pills). After the initial postoperative defecation, fecal samples were collected from each subject to analyze their gut microbiota and metabolic profiles by high-throughput 16S rRNA gene sequencing analysis and untargeted metabonomic.RESULTS: There were no statistically significant differences observed in the α-diversity and β-diversity between the two groups; however, in the intervention group, there was a significant reduction in the relative abundance of unclassified_Enterobacteriaceae at the genus level. Furthermore, the control group showed increased levels of Holdemanella and Enterobacter, whereas the intervention group exhibited elevated levels of Intestinimonas. And administration of Bacillus coagulans TBC169 led to variations in 2 metabolic pathways: D-glutamine and D-glutamate metabolism, and arginine biosynthesis.CONCLUSION: This study demonstrated that consuming Bacillus coagulans TBC169 after gynecological laparoscopic surgery might inhibit the proliferation of harmful Enterobacteriaceae; mainly influence 2 pathways including D-glutamine and D-glutamate metabolism, and arginine biosynthesis; and regulate metabolites related to immunity and intestinal motility; which can help regulate immune function, maintain intestinal balance, promote intestinal peristalsis, and thus accelerate the recovery of intestinal function.PMID:38596369 | PMC:PMC11002114 | DOI:10.3389/fmicb.2024.1284402

Front Endocrinol (Lausanne). 2024 Mar 26;15:1370525. doi: 10.3389/fendo.2024.1370525. eCollection 2024.ABSTRACTINTRODUCTION: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT.METHODS: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus.RESULTS: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites.DISCUSSIONS: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.PMID:38596218 | PMC:PMC11002274 | DOI:10.3389/fendo.2024.1370525

Heliyon. 2024 Mar 19;10(7):e27828. doi: 10.1016/j.heliyon.2024.e27828. eCollection 2024 Apr 15.ABSTRACTOBJECTIVE: As a traditional Chinese medicine, leech has obvious pharmacological activities in anticoagulantion and antithrombosis. Whitmania pigra Whitman (WP) is the most commonly used leech in the Chinese market. It is often used in clinical applications after high-temperature processing by talcum powder to remove the fishy taste and facilitate crushing. The anticoagulant and thrombolytic active ingredients are protein and polypeptide, which may denaturate and lose activity after high-temperature processing. The rationality of its processing has been questioned in recent years. This study aims to investigate the effect of talcum powder scalding on the antithrombotic activity of WP in vivo and to discuss its pharmacodynamic mechanism in vivo.METHODS: Raw and talcum-powdered processed WP were administered intragastrically for 14 days, and carrageenan was injected intraperitoneally to prepare a mouse model of tail vein thrombosis. The incidence rate of tail vein thrombosis and the thrombus area under pathological tissue sections were calculated to evaluate the antithrombotic effect between raw and processed WP. Non-targeted metabolomics was conducted using UPLC-Q-TOF/MS technology to analyze the changes of small molecule metabolites in the body after administration of WP.RESULTS: After intragastric administration, both the raw product and the processed product of WP could inhibit the thrombosis induced by carrageenan, and the processed product had a more apparent antithrombotic effect than the raw product. The administration of WP could regulate the changes of some small molecular metabolites, such as amino acids, lipids, and steroids, in Sphingolipid metabolism and Glycerophospholipid metabolism.CONCLUSIONS: Based on the results of pharmacodynamics and metabolomics, processed WP will not reduce the antithrombotic activity of WP. This study provided a scientific basis for the rational use of leeches.PMID:38596067 | PMC:PMC11002550 | DOI:10.1016/j.heliyon.2024.e27828

Mol Genet Metab Rep. 2024 Apr 3;39:101077. doi: 10.1016/j.ymgmr.2024.101077. eCollection 2024 Jun.ABSTRACTFarber Disease is a debilitating and lethal childhood disease of ceramide accumulation caused by acid ceramidase deficiency. The potent induction of a ligand-gated neutral ceramidase activity promoted by adiponectin may provide sufficient lowering of ceramides to allow for the treatment of Farber Disease. In vitro, adiponectin or adiponectin receptor agonist treatments lowered total ceramide concentrations in human fibroblasts from a patient with Farber Disease. However, adiponectin overexpression in a Farber Disease mouse model did not improve lifespan or immune infiltration. Intriguingly, mice heterozygous for the Farber Disease mutation were more prone to glucose intolerance and insulin resistance when fed a high-fat diet, and adiponectin overexpression protected from these metabolic perturbations. These studies suggest that adiponectin evokes a ceramidase activity that is not reliant on the functional expression of acid ceramidase, but indicates that additional strategies are required to ameliorate outcomes of Farber Disease.PMID:38595987 | PMC:PMC11002753 | DOI:10.1016/j.ymgmr.2024.101077

Front Pharmacol. 2024 Mar 26;15:1362464. doi: 10.3389/fphar.2024.1362464. eCollection 2024.ABSTRACTQuercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio and enhanced Cyanobacteria. At the genus level, quercetin downregulated 6 and upregulated 14 bacterial species. Metabolomics analysis revealed that quercetin regulated multiple metabolic pathways, including glycolysis/gluconeogenesis, sphingolipid metabolism, the pentose phosphate pathway, and coenzyme A biosynthesis. This modulation leads to improvements in depression-like phenotypes, anxiety-like phenotypes, and cognitive function, highlighting the therapeutic potential of quercetin in treating depression.PMID:38595919 | PMC:PMC11002179 | DOI:10.3389/fphar.2024.1362464

MethodsX. 2024 Apr 3;12:102695. doi: 10.1016/j.mex.2024.102695. eCollection 2024 Jun.ABSTRACTMetabolomics, a recent addition to omics sciences, studies small molecules across plants, animals, humans, and marine organisms. Nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) are widely used in those studies, including microalgae metabolomics. NMR is non-destructive and highly reproducible but has limited sensitivity, which could be supplemented by joining GC-MS analysis. Extracting metabolites from macromolecules requires optimization for trustworthy results. Different extraction methods yield distinct profiles, emphasizing the need for optimization. The results indicated that the optimized extraction procedure successfully identified NMR and GC-MS-based metabolites in MeOH, CHCl3, and H2O extraction solvents. The findings represented the spectral information related to carbohydrates, organic molecules, and amino acids from the water-soluble metabolites fraction and a series of fatty acid chains, lipids, and sterols from the lipid fraction. Our study underscores the benefit of combining NMR and GC-MS techniques to comprehensively understand microalgae metabolomes, including high and low metabolite concentrations and abundances.•In this study, we focused on optimizing the extraction procedure and combining NMR and GC-MS techniques to overcome the low NMR sensitivity and the different detected range limits of NMR and GC-MS.•We explored metabolome diversity in a tropical strain of the small cells' diatom Cheatoceros tenuissimus.PMID:38595808 | PMC:PMC11001764 | DOI:10.1016/j.mex.2024.102695

Front Plant Sci. 2024 Mar 26;15:1373975. doi: 10.3389/fpls.2024.1373975. eCollection 2024.ABSTRACTProanthocyanidins (PAs), one of the most abundant natural polymers found in plants, are gaining increasing attention because of their beneficial effects for agriculture and human health. The study of PA biosynthesis has been active for decades, and progress has been drastically accelerated since the discovery of key enzymes such as Anthocyanidin Reductase (ANR), Leucoanthocyanidin Reductase (LAR), and key transcription factors such as Transparent Testa 2 (TT2) and Transparent Testa 8 (TT8) in the early 2000s. Scientists raised some compelling questions regarding PA biosynthesis about two decades ago in the hope that addressing these questions would lead to an enhanced understanding of PA biosynthesis in plants. These questions focus on the nature of starter and extension units for PA biosynthesis, the stereochemistry of PA monomers and intermediates, and how and where the polymerization or condensation steps work subcellularly. Here, I revisit these long-standing questions and provide an update on progress made toward answering them. Because of advanced technologies in genomics, bioinformatics and metabolomics, we now have a much-improved understanding of functionalities of key enzymes and identities of key intermediates in the PA biosynthesis and polymerization pathway. Still, several questions, particularly the ones related to intracellular PA transportation and deposition, as well as enzyme subcellular localization, largely remain to be explored. Our increasing understanding of PA biosynthesis in various plant species has led to a new set of compelling open questions, suggesting future research directions to gain a more comprehensive understanding of PA biosynthesis.PMID:38595764 | PMC:PMC11002137 | DOI:10.3389/fpls.2024.1373975

RSC Adv. 2024 Apr 9;14(16):11388-11399. doi: 10.1039/d4ra01646g. eCollection 2024 Apr 3.ABSTRACTCaroxylon volkensii is a wild desert plant of the family Amaranthaceae. This study represents the first report of the metabolomic profiling of C. volkensii by liquid chromatography quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The dereplication study of its secondary metabolites led to the characterization of 66 known compounds. These compounds include catecholamines, tyramine derivatives, phenolic acids, triterpenoids, flavonoids, and others. A new tyramine derivative, alongside other known compounds, was reported for the first time in the Amaranthaceae family. The new derivative and the first-reported compounds were putatively identified through MS/MS fragmentation data. Given the notorious taxonomical challenges within the genus Salsola, to which C. volkensii previously belonged, our study could offer a valuable insight into its chemical fingerprint and phylogenetic relationship to different Salsola species. The antibacterial potential of C. volkensii methanolic extract (CVM) against Pseudomonas aeruginosa was screened. The minimum inhibitory concentration (MIC) of CVM ranged from 32 to 256 μg mL-1. The anti-quorum sensing potential of CVM resulted in a decrease in the percentage of strong and moderate biofilm-forming isolates from 47.83% to 17.39%. It revealed a concentration-dependent inhibitory activity on violacein formation by Chromobacterium violaceum. Moreover, CVM exhibited an in vivo protective potential against the killing capacity of P. aeruginosa isolates. A molecular docking study revealed that the quorum-sensing inhibitory effect of CVM can be attributed to the binding of tyramine conjugates, ethyl-p-digallate, and isorhamnetin to the transcriptional global activator LasR.PMID:38595719 | PMC:PMC11002840 | DOI:10.1039/d4ra01646g

RSC Adv. 2024 Apr 9;14(16):11322. doi: 10.1039/d4ra90032d. eCollection 2024 Apr 3.ABSTRACT[This corrects the article DOI: 10.1039/D3RA00802A.].PMID:38595710 | PMC:PMC11002562 | DOI:10.1039/d4ra90032d

Am J Vet Res. 2024 Apr 13:1-10. doi: 10.2460/ajvr.23.12.0285. Online ahead of print.ABSTRACTOBJECTIVE: To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons.ANIMALS: 48 adult central bearded dragons (Pogona vitticeps).METHODS: Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson's trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics.RESULTS: Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, β-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid.CLINICAL RELEVANCE: Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.PMID:38593838 | DOI:10.2460/ajvr.23.12.0285

Neoplasia. 2024 Apr 8;52:100996. doi: 10.1016/j.neo.2024.100996. Online ahead of print.ABSTRACTPapillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.PMID:38593698 | DOI:10.1016/j.neo.2024.100996

Water Res. 2024 Mar 19;256:121492. doi: 10.1016/j.watres.2024.121492. Online ahead of print.ABSTRACTCyanobacterial blooms, producing toxic secondary metabolites, are becoming increasingly common phenomena in the face of rising global temperatures. They are the world's most abundant photosynthetic organisms, largely owing their success to a range of highly diverse and complex natural products possessing a broad spectrum of different bioactivities. Over 2600 compounds have been isolated from cyanobacteria thus far, and their characterisation has revealed unusual and useful chemistries and motifs including alkynes, halogens, and non-canonical amino acids. Genome sequencing of cyanobacteria lags behind natural product isolation, with only 19% of cyanobacterial natural products associated with a sequenced organism. Recent advances in meta(genomics) provide promise to narrow this gap and has also facilitated the uprise of combined genomic and metabolomic approaches, heralding a new era of discovery of novel compounds. Analyses of the datasets described within this manuscript reveal the asynchrony of current genomic and metabolomic data, highlight the chemical diversity of cyanobacterial natural products. Linked to this manuscript, we make these manually curated datasets freely accessible for the public to facilitate further research in this important area.PMID:38593604 | DOI:10.1016/j.watres.2024.121492

Int J Food Microbiol. 2024 Mar 27;417:110686. doi: 10.1016/j.ijfoodmicro.2024.110686. Online ahead of print.ABSTRACTRosa roxburghii Tratt fruits (RRT) exhibit extremely high nutritional and medicinal properties due to its unique phytochemical composition. Probiotic fermentation is a common method of processing fruits. Variations in the non-volatile metabolites and bioactivities of RRT juice caused by different lactobacilli are not well understood. Therefore, we aimed to profile the non-volatile components and investigate the impact of L. plantarum fermentation (LP) and L. paracasei fermentation (LC) on RRT juice (the control, CG). There were both similarities and differences in the effects of LP and LC on RRT juice. Both of the two strains significantly increased the content of total phenolic, total flavonoid, and some bioactive compounds such as 2-hydroxyisocaproic acid, hydroxytyrosol and indole-3-lactic acid in RRT juice. Interestingly, compared with L. paracasei, L. plantarum showed better ability to increase the content of total phenolic and these valuable compounds, as well as certain bioactivities. The antioxidant capacity and α-glucosidase inhibitory activity of RRT juice were notably enhanced after the fermentations, whereas its cholesterol esterase inhibitory activity was reduced significantly. Moreover, a total of 1466 metabolites were identified in the unfermented and fermented RRT juices. There were 278, 251 and 134 differential metabolites in LP vs CG, LC vs CG, LC vs LP, respectively, most of which were upregulated. The key differential metabolites were classified into amino acids and their derivatives, organic acids, nucleotides and their analogues, phenolic acids and alkaloids, which can serve as potential markers for authentication and discrimination between the unfermented and lactobacilli fermented RRT juice samples. The KEGG enrichment analysis uncovered that metabolic pathways, purine metabolism, nucleotide metabolism and ABC transporters contributed mainly to the formation of unique composition of fermented RRT juice. These results provide good coverage of the metabolome of RRT juice in both unfermented and fermented forms and also provide a reference for future research on the processing of RRT or other fruits.PMID:38593553 | DOI:10.1016/j.ijfoodmicro.2024.110686