PubMed

Water Res. 2024 Jul 30;263:122189. doi: 10.1016/j.watres.2024.122189. Online ahead of print.ABSTRACTA variety of per- and polyfluoroalkyl substances (PFASs) have been released into the environment via wastewater treatment plant (WWTP) effluent, with current target and nontarget analytical methods typically focusing on negatively ionized PFASs while largely overlooking positively ionized ones. In this study, five cationic PFASs, perfluoroalkyl sulfonyl quaternary ammonium substances (PFAQASs), were first identified in surface water impacted by the WWTP effluent, applying a metabolomics-based nontarget analysis method. Environmental behaviors of identified novel PFAQASs were further investigated. In surface water, sediment, and fish (Coilia mystus) samples collected from the Yangtze River, 8:3 PFAQA was consistently the predominant PFAQASs, with the mean concentrations of 90 ng/L (< LOD-558 ng/L), 92 ng/g dw (< LOD-421 ng/g dw), and 2.3 ng/g ww (< LOD-4.6 ng/g ww), respectively. This study highlights the necessity to discover other cationic PFASs in the environment. Among PFAQASs, 8:4 PFAQA (4.2, range 3.4 - 4.6) had the highest mean sediment-water partitioning coefficient (log Koc), followed by 8:3 PFAQA (3.9, 2.8 - 4.5) and 6:3 PFAQA (3.7, 3.3 - 4.1). The log Koc of PFAQASs showed a general increase trend with the increasing carbon chain length. Mean bioaccumulation factor (BAF) values of PFAQASs calculated in the collected fish from the Yangtze River ranged from 1.9 ± 0.32 (4:3 PFAQA) to 2.9 ± 0.34 (8:4 PFAQA). The mean BAF values of PFAQASs generally increased with the carbon chain length. Further studies are warranted to elucidate the environmental fate, potential toxicity, and human exposure implications for these identified novel PFASs.PMID:39096813 | DOI:10.1016/j.watres.2024.122189

Environ Pollut. 2024 Aug 2;360:124646. doi: 10.1016/j.envpol.2024.124646. Online ahead of print.NO ABSTRACTPMID:39096766 | DOI:10.1016/j.envpol.2024.124646

Ecotoxicol Environ Saf. 2024 Aug 2;283:116822. doi: 10.1016/j.ecoenv.2024.116822. Online ahead of print.ABSTRACTAntimony (Sb) poses a significant ecological threat. This study combines biochemical, pathological, transcriptome, and metabolome analyses to assess the short-term (14-day) toxic impact of two Sb levels (25 mg/kg and 125 mg/kg) on earthworms (Eisenia fetida). Higher Sb concentration caused severe intestinal damage, elevated metallothionein (MT) levels, and reduced antioxidant capacity. Metabolome analysis identifies 404 and 1698 significantly differential metabolites in the two groups. Metabolites such as S(-)-cathinone, N-phenyl-1-naphthylamine, serotonin, 4-hydroxymandelonitrile, and 5-fluoropentylindole contributed to the metabolic responses to Sb stress. Transcriptome analysis shows increased chitin synthesis as a protective response, impacting amino sugar and nucleotide sugar metabolism for cell wall synthesis and damage repair. Integrated analysis indicated that 5 metabolite-gene pairs were found in two Sb levels and 11 enriched pathways were related to signal transduction, carbohydrate metabolism, immune system, amino acid metabolism, digestive system, and nervous system. Therefore, the integration of multiomics approaches enhanced our comprehension of the molecular mechanisms underlying the toxicity of Sb in E. fetida.PMID:39096686 | DOI:10.1016/j.ecoenv.2024.116822

Biomed Pharmacother. 2024 Aug 2;178:117216. doi: 10.1016/j.biopha.2024.117216. Online ahead of print.ABSTRACTAIMS: Silicosis is the most common and severe type of pneumoconiosis, imposing a substantial disease burden and economic loss on patients and society. The pathogenesis and key targets of silicosis are not yet clear, and there are currently no effective treatments available. Therefore, we conducted research on mefunidone (MFD), a novel antifibrotic drug, to explore its efficacy and mechanism of action in murine silicosis.METHODS: Acute 7-day and chronic 28-day silicosis models were constructed in C57BL/6J mice by the intratracheal instillation of silica and subsequently treated with MFD to assess its therapeutic potential. The effects of MFD on silica-induced inflammation, pyroptosis, and fibrosis were further investigated using immortalized mouse bone marrow-derived macrophages (iBMDMs).RESULTS: In the 7-day silica-exposed mouse models, MFD treatment significantly alleviated pulmonary inflammation and notably reduced macrophage infiltration into the lung tissue. RNA-sequencing analysis of silica-induced iBMDMs followed by gene set enrichment analysis revealed that MFD profoundly influenced cytokine-cytokine receptor interactions, chemokine signaling, and the toll-like receptor signaling pathways. MFD treatment also markedly reduced the secretion of inflammatory cytokines and chemokines from silica-exposed iBMDMs. Moreover, MFD effectively downregulated the activation of the TLR4-NF-κB/MAPK signaling pathway induced by silica and mitigated the upregulation of pyroptosis markers. Additionally, MFD treatment significantly suppressed the activation of fibroblasts and alveolar epithelial cells co-cultured with silica-exposed mouse macrophages. Ultimately, in the 28-day silica-exposed mouse models, MFD administration led to a substantial reduction in the severity of pulmonary fibrosis.CONCLUSION: MFD mitigates silica-induced pulmonary inflammation and fibrosis in mice by suppressing the TLR4-NF-κB/MAPK signaling pathway and reducing pyroptotic responses in macrophages. MFD could potentially emerge as a novel therapeutic agent for the treatment of silicosis.PMID:39096618 | DOI:10.1016/j.biopha.2024.117216

Metabolomics. 2024 Aug 3;20(5):91. doi: 10.1007/s11306-024-02159-2.ABSTRACTINTRODUCTION: Variation in DNA methylation (DNAm) in adipose tissue is associated with the pathogenesis of obesity and insulin resistance. The activity of enzymes involved in altering DNAm levels is dependent on several metabolite cofactors.OBJECTIVES: To understand the role of metabolites as mechanistic regulators of epigenetic marks, we tested the association between selected plasma metabolites and DNAm levels in the adipose tissue of African Americans.METHODS: In the AAGMEx cohort (N = 256), plasma levels of metabolites were measured by untargeted liquid chromatography-mass spectrometry; adipose tissue DNAm and transcript levels were measured by reduced representation bisulfite sequencing, and expression microarray, respectively.RESULTS: Among the 21 one-carbon metabolism pathway metabolites evaluated, six were associated with gluco-metabolic traits (PFDR < 0.05, for BMI, SI, or Matsuda index) in AAGMEx. Methylation levels of 196, 116, and 180 CpG-sites were associated (P < 0.0001) with S-adenosylhomocysteine (SAH), cystine, and hypotaurine, respectively. Cis-expression quantitative trait methylation (cis eQTM) analyses suggested the role of metabolite-level-associated CpG sites in regulating the expression of adipose tissue transcripts, including genes in G-protein coupled receptor signaling pathway. Plasma SAH level-associated CpG sites chr19:3403712 and chr19:3403735 were also associated with the expression of G-protein subunit alpha 15 (GNA15) in adipose. The expression of GNA15 was significantly correlated with BMI (β = 1.87, P = 1.9 × 10-16) and SI (β = -1.61, P = 2.49 × 10-5).CONCLUSION: Our study suggests that a subset of metabolites modulates the methylation levels of CpG sites in specific loci and, in turn, regulates the expression of transcripts involved in obesity and insulin resistance.PMID:39096438 | DOI:10.1007/s11306-024-02159-2

Metabolomics. 2024 Aug 3;20(5):92. doi: 10.1007/s11306-024-02161-8.ABSTRACTINTRODUCTION: The human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches.OBJECTIVE: This study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics.METHODS: Urine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups.RESULTS: The study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients.CONCLUSION: The metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.PMID:39096437 | DOI:10.1007/s11306-024-02161-8

J Nat Med. 2024 Aug 3. doi: 10.1007/s11418-024-01837-8. Online ahead of print.ABSTRACTThis study established an Orthogonal Partial Least Squares (OPLS) model combining 1H-NMR and GC-MS data to identify characteristic metabolites in complex extracts. Both in metabolomics studies, and natural product chemistry, the reliable identification of marker metabolites usually requires laborious isolation and purification steps, which remains a bottleneck in many studies. Both ginger (GR) and processed ginger (PGR) are listed in the Japanese pharmacopeia. The plant of origin, the rhizome of Zingiber officinale Roscoe, is differently processed for these crude drugs. Notably, the quality of crude drugs is affected by genetic and environmental factors, making it difficult to maintain a certain quality standard. Therefore, characteristic markers for the quality control of GR and PGR are required. Metabolomic analysis using 1H-NMR was able to discriminate between GR and PGR, but there were unidentified signals that were difficult to distinguish based on NMR data alone. Therefore, we combined 1H-NMR and GC-MS analytical data to identify them by OPLS. As a result, αr-curcumene was found to be a useful marker for these identifications. This new approach enabled rapid identification of characteristic marker compounds and reduced the labor involved in the isolation process.PMID:39096421 | DOI:10.1007/s11418-024-01837-8

Metabolomics. 2024 Aug 3;20(5):93. doi: 10.1007/s11306-024-02157-4.ABSTRACTINTRODUCTION: Bovine milk contains a rich matrix of nutrients such as carbohydrates, fat, protein and various vitamins and minerals, the composition of which is altered by factors including dietary regime.OBJECTIVES: The objective of this research was to investigate the impact of dietary regime on the metabolite composition of bovine whole milk powder and buttermilk.METHODS: Bovine whole milk powder and buttermilk samples were obtained from spring-calving cows, consuming one of three diets. Group 1 grazed outdoors on perennial ryegrass which was supplemented with 5% concentrates; group 2 were maintained indoors and consumed a total mixed ration diet; and group 3 consumed a partial mixed ration diet consisting of perennial ryegrass during the day and total mixed ration maintained indoors at night.RESULTS: Metabolomic analysis of the whole milk powder (N = 27) and buttermilk (N = 29) samples was preformed using liquid chromatography-tandem mass spectrometry, with 504 and 134 metabolites identified in the samples respectively. In whole milk powder samples, a total of 174 metabolites from various compound classes were significantly different across dietary regimes (FDR adjusted p-value ≤ 0.05), including triglycerides, of which 66% had their highest levels in pasture-fed samples. Triglycerides with highest levels in pasture-fed samples were predominantly polyunsaturated with high total carbon number. Regarding buttermilk samples, metabolites significantly different across dietary regimes included phospholipids, sphingomyelins and an acylcarnitine.CONCLUSION: In conclusion the results reveal a significant impact of a pasture-fed dietary regime on the metabolite composition of bovine dairy products, with a particular impact on lipid compound classes.PMID:39096405 | DOI:10.1007/s11306-024-02157-4

J Anim Sci. 2024 Aug 3:skae223. doi: 10.1093/jas/skae223. Online ahead of print.ABSTRACTThe study aimed to determine the effects of a postbiotic feeding program consisting of liquid and dry Saccharomyces cerevisiae fermentation product (SCFP) on ruminal fermentation, digestibility, and plasma metabolome of Holstein steers receiving a grain-based diet. Eight Holstein steers (Body weight; BW 467 ± 13.9 kg) equipped with rumen cannulas were used in a crossover design study, with 21 d per period and a 7 d washout period in between periods. Steers were stratified by initial BW and assigned to one of two treatments. The treatments were (1) Control, basal finishing diet only (CON); (2) SCFP, one-day feeding of liquid SCFP (infused into the rumen via the cannula at 11 mL/100 kg BW) followed by daily feeding of dry SCFP (12 g/d, top-dressed). Feed and spot fecal samples were collected during d 17 to 20 for determination of digestibility and fecal excretion of N, P, Cu, and Zn. Digestibility was measured using acid-insoluble ash as an internal marker. Blood samples were collected on d 21 before the morning feeding. Rumen fluid samples were collected on d 0, 1, 2, 3, 5 and 21 via rumen cannula. Results were analyzed with the GLIMMIX procedure of SAS 9.4 (SAS, 2023). Treatment did not affect DMI (P = 0.15) and digestibility (P ≥ 0.62). The fecal output and absorption of Zn, Cu, P, and N were not affected (P > 0.22) by treatment. On d 1, the liquid SCFP supplementation tended to reduce (P = 0.07) ruminal VFA concentration and increased (P < 0.01) the molar proportion of valerate. Feeding SCFP tended to increase total ruminal VFA on d 5 (P = 0.08) and significantly increased total VFA on d 21 (P = 0.05). Ruminal NH3-N was reduced (P = 0.02) on d 21 by supplementing SCFP. Treatment did not affect the production of proinflammatory cytokines, IL-1β (P > 0.19) and IL-6 (P > 0.12) in the whole blood in response to various toll-like receptor stimulants in vitro. Feeding SCFP enriched (P ≤ 0.05) plasma metabolic pathways, including citric acid cycle, pyrimidine metabolism, glycolysis/gluconeogenesis, retinol metabolism, and inositol phosphate metabolism pathways. In summary, supplementing liquid SCFP with subsequent dry SCFP enhanced ruminal total VFA production and reduced NH3-N concentration nitrogen in the rumen. Furthermore, feeding SCFP enriched several important pathways in lipid, protein, and glucose metabolism, which may improve feed efficiency of energy and protein in Holstein steers.PMID:39096210 | DOI:10.1093/jas/skae223

J Pathol. 2024 Aug 3. doi: 10.1002/path.6329. Online ahead of print.ABSTRACTClear cell ovarian carcinoma (CCOC) is an aggressive malignancy affecting younger women. Despite ovarian cancer subtypes having diverse molecular and clinical characteristics, the mainstay of treatment for advanced stage disease remains cytotoxic chemotherapy. Late stage CCOC is resistant to conventional chemotherapy, which means a suboptimal outcome for patients affected. Despite detailed genomic, epigenomic, transcriptomic, and proteomic characterisation, subtype-specific treatment for CCOC has shown little progress. The unique glycogen accumulation defining CCOC suggests altered metabolic pathway activity and dependency. This study presents the first metabolomic landscape of ovarian cancer subtypes, including 42 CCOC, 20 high-grade serous and 21 endometrioid ovarian carcinomas, together comprising the three most common ovarian carcinoma subtypes. We describe a distinct metabolomic landscape of CCOC compared with other ovarian cancer subtypes, including alterations in energy utilisation and cysteine metabolism. In addition, we identify CCOC-specific alterations in metabolic pathways including serine biosynthesis and ROS-associated pathways that could serve as potential therapeutic targets. Our study provides the first in-depth study into the metabolome of ovarian cancers and a rich resource to support ongoing research efforts to identify subtype-specific therapeutic targets that could improve the dismal outcome for patients with this devastating malignancy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.PMID:39096103 | DOI:10.1002/path.6329

Transfusion. 2024 Aug 2. doi: 10.1111/trf.17960. Online ahead of print.ABSTRACTBACKGROUND: The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR.STUDY DESIGN AND METHODS: The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis.RESULTS: B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation.CONCLUSION: The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).PMID:39095932 | DOI:10.1111/trf.17960

J Neuroinflammation. 2024 Aug 2;21(1):190. doi: 10.1186/s12974-024-03175-8.ABSTRACTRetinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a cell surface transmembrane glycoprotein and the primary receptor for hyaluronic acid. It is involved in many pathological processes, but little is known about CD44's retinal functions. CD44 expression is also increased in Müller cells from our Pde6bSTOP/STOP RP mouse model. To gain a more detailed understanding of CD44's role in healthy and diseased retinas, we analyzed Cd44-/- and Cd44-/-Pde6bSTOP/STOP mice, respectively. The loss of CD44 led to enhanced photoreceptor degeneration, reduced retinal function, and increased inflammatory response. To understand the underlying mechanism, we performed proteomic analysis on isolated Müller cells from Cd44-/- and Cd44-/-Pde6bSTOP/STOP retinas and identified a significant downregulation of glutamate transporter 1 (SLC1A2). This downregulation was accompanied by higher glutamate levels, suggesting impaired glutamate homeostasis. These novel findings indicate that CD44 stimulates glutamate uptake via SLC1A2 in Müller cells, which in turn, supports photoreceptor survival and function.PMID:39095775 | DOI:10.1186/s12974-024-03175-8

Metabolomics. 2024 Aug 2;20(5):89. doi: 10.1007/s11306-024-02160-9.ABSTRACTINTRODUCTION: Breeding for oil palm resistance against basal stem rot caused by Ganoderma boninense is challenging and time-consuming. Advanced oil palm gene pools are very limited, hence it is assumed that parental palms have experienced genetic drift and lost their resistance genes against Ganoderma. High-throughput selection criteria should be developed. Metabolomic analysis using 1H nuclear magnetic resonance (NMR) spectroscopy is easy, and the resulting metabolite can be used as a diagnostic tool for detecting disease in various host-pathogen combinations.OBJECTIVES: The objective of this study was to identify metabolite variations in Dura (D) and Pisifera (P) parental palms with different resistance levels against Ganoderma and moderately resistant DxP using 1H NMR analysis.METHODS: Leaf tissues of seven different oil palm categories consisting of: resistant, moderate, and susceptible Dura (D); moderate and susceptible Pisifera (P); resistant Tenera/Pisifera (T/P) parental palms; and moderately resistant DxP variety progenies, were sampled and their metabolites were determined using NMR spectroscopy.RESULTS: Twenty-nine types of metabolites were identified, and most of the metabolites fall in the monosaccharides, amino acids, and fatty acids compound classes. The PCA, PLS-DA, and heatmap multivariate analysis indicated two identified groups of resistance based on their metabolites. The first group consisted of resistant T/P, moderate P, resistant D, and moderately resistant DxP. In contrast, the second group consisted of susceptible P, moderate D, and susceptible D. Glycerol and ascorbic acid were detected as biomarker candidates by OPLS-DA to differentiate moderately resistant DxP from susceptible D and P. The pathway analysis suggested that glycine, serine, and threonine metabolism and taurine and hypotaurine metabolism were involved in the oil palm defense mechanism against Ganoderma.CONCLUSION: A metabolomic study with 1H NMR was able to describe the metabolite composition that could differentiate the characteristics of oil palm resistance against basal stem rot (BSR) caused by G. boninense. These metabolites revealed in this study have enormous potential to become support tools for breeding new oil palm varieties with higher resistance against BSR.PMID:39095669 | DOI:10.1007/s11306-024-02160-9

Metabolomics. 2024 Aug 2;20(5):90. doi: 10.1007/s11306-024-02153-8.ABSTRACTINTRODUCTION: Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways.OBJECTIVES: To prioritize the discovery of bioactive natural products and their biosynthetic pathways from these hundreds of high-confidence linkages, we developed a bioactivity-driven metabologenomics workflow combining quantitative chemical information, antiproliferative bioactivity data, and genome sequences.METHODS: The 110 fungi from our metabologenomics study were tested against multiple cancer cell lines to identify which strains produced antiproliferative natural products. Three strains were selected for further study, fractionated using flash chromatography, and subjected to an additional round of bioactivity testing and mass spectral analysis. Data were overlaid using biochemometrics analysis to predict active constituents early in the fractionation process following which their biosynthetic pathways were identified using metabologenomics.RESULTS: We isolated three new-to-nature stemphone analogs, 19-acetylstemphones G (1), B (2) and E (3), that demonstrated antiproliferative activity ranging from 3 to 5 µM against human melanoma (MDA-MB-435) and ovarian cancer (OVACR3) cells. We proposed a rational biosynthetic pathway for these compounds, highlighting the potential of using bioactivity as a filter for the analysis of integrated-Omics datasets.CONCLUSIONS: This work demonstrates how the incorporation of biochemometrics as a third dimension into the metabologenomics workflow can identify bioactive metabolites and link them to their biosynthetic machinery.PMID:39095664 | DOI:10.1007/s11306-024-02153-8

Sci Rep. 2024 Aug 2;14(1):17927. doi: 10.1038/s41598-024-68522-4.ABSTRACTPlant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI). Individuals with higher healthful PDI had lower BMI and fasting glucose and higher HDL-C, while those with higher unhealthful PDI had higher BMI, triacylglycerol and fasting glucose and lower HDL-C. Unhealthful PDI was associated with higher levels of several amino acids and biogenic amines previously associated with cardiometabolic diseases and an opposite pattern was observed for healthful PDI. Furthermore, healthful PDI was associated with higher levels of glycerophosphocholines containing very long-chain fatty acids. Glutamate, isoleucine, proline, tyrosine, α-aminoadipate and kynurenine had a statistically significant mediation effect on the associations between PDI scores and LDL-C, HDL-C and fasting glucose. These findings contribute to the growing evidence supporting the role of plant-based diets in promoting metabolic health and shed light on the potential mechanisms explaining their beneficial health effects.PMID:39095501 | DOI:10.1038/s41598-024-68522-4

Nat Commun. 2024 Aug 2;15(1):6560. doi: 10.1038/s41467-024-50883-z.ABSTRACTMethanogenic hydrocarbon degradation can be carried out by archaea that couple alkane oxidation directly to methanogenesis, or by syntrophic associations of bacteria with methanogenic archaea. However, metagenomic analyses of methanogenic environments have revealed other archaea with potential for alkane degradation but apparent inability to form methane, suggesting the existence of other modes of syntrophic hydrocarbon degradation. Here, we provide experimental evidence supporting the existence of a third mode of methanogenic degradation of hydrocarbons, mediated by syntrophic cooperation between archaeal partners. We collected sediment samples from a hot spring sediment in Tengchong, China, and enriched Hadarchaeota under methanogenic conditions at 60 °C, using hexadecane as substrate. We named the enriched archaeon Candidatus Melinoarchaeum fermentans DL9YTT1. We used 13C-substrate incubations, metagenomic, metatranscriptomic and metabolomic analyses to show that Ca. Melinoarchaeum uses alkyl-coenzyme M reductases (ACRs) to activate hexadecane via alkyl-CoM formation. Ca. Melinoarchaeum likely degrades alkanes to carbon dioxide, hydrogen and acetate, which can be used as substrates by hydrogenotrophic and acetoclastic methanogens such as Methanothermobacter and Methanothrix.PMID:39095478 | DOI:10.1038/s41467-024-50883-z

J Environ Sci (China). 2025 Feb;148:107-115. doi: 10.1016/j.jes.2024.01.010. Epub 2024 Jan 18.ABSTRACTThe evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.PMID:39095149 | DOI:10.1016/j.jes.2024.01.010

Bioresour Technol. 2024 Jul 31:131187. doi: 10.1016/j.biortech.2024.131187. Online ahead of print.ABSTRACTMetabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.PMID:39094965 | DOI:10.1016/j.biortech.2024.131187

Toxicol Lett. 2024 Jul 31:S0378-4274(24)01062-2. doi: 10.1016/j.toxlet.2024.07.913. Online ahead of print.ABSTRACTA 14-day rat study with plasma metabolomics was conducted to evaluate the toxicity of Benzene. Wistar rats were orally administered Benzene daily at doses of 0, 300 and 1,000mg/kg bw. The study identified liver and kidneys as target organs of Benzene toxicity and found reductions in total white blood cells, absolute lymphocyte and eosinophil cell counts, and increased relative monocyte counts suggesting bone marrow as a target organ. The study also confirmed liver as a target organ using metabolomics, which showed indications of a stress reaction in rats and changes in metabolites suggestive of a metabolic disorder. The metabolomics investigations did not find any other toxicologically relevant modes of action, and the observed metabolite changes were not associated with markers for mitochondrial dysfunction. The study concludes that integration of omics technologies, such as metabolomics, in regulatory toxicity studies is possible, confirms existing knowledge and adds additional information that can be used for mechanistic understanding of observed toxicity.PMID:39094914 | DOI:10.1016/j.toxlet.2024.07.913

Int J Biol Macromol. 2024 Jul 31:134305. doi: 10.1016/j.ijbiomac.2024.134305. Online ahead of print.ABSTRACTAnoectochilus roxburghii polysaccharides exhibit notable hepatoprotective effects, but the underlying substance basis and mechanisms remain unknown. In this study, four new polysaccharides named ARP-1a, ARP-1b, ARP-2a and ARP-2b, were isolated from A. roxburghii. Their structural characteristics were systematically analyzed using HPGPC, HPLC, GC-MS, IR and NMR analysis. ARP-1a, the leading polysaccharide isolated from A. roxburghii, was further evaluated for its hepatoprotective effects on acute liver injury mice induced by CCl4. ARP-1a significantly reduced the serum ALT, AST, TNF-α, IL-1β and IL-6 levels, liver MDA content, and increased the SOD and CAT activities and GSH level in liver. H&E staining revealed that ARP-1a pretreatment could markedly relieve liver injury. Further mechanism exploration indicated that ARP-1a could relieve CCl4-induced oxidative damage through activating the Nrf2 signaling. In addition, metabolomics, lipidomics and 16S rRNA amplicon sequencing were used to elucidate the underlying mechanisms of ARP-1a. Multi-omics analysis indicated that ARP-1a exerted hepatoprotective effect against CCl4-induced acute liver injury by regulating lipid metabolism and modulating the gut microbiota. In conclusion, the above results suggest that ARP-1a can be considered a promising and safe candidate for hepatoprotective drug, as well as a potential prebiotic for maintaining intestinal homeostasis and promoting human intestinal health.PMID:39094884 | DOI:10.1016/j.ijbiomac.2024.134305