PubMed

J Pharm Pharmacol. 2024 Nov 30:rgae130. doi: 10.1093/jpp/rgae130. Online ahead of print.ABSTRACTOBJECTIVES: The clinical application of Pazopanib (Paz) is often accompanied by hepatotoxicity. However, the mechanisms of hepatic toxicity induced by pazopanib are not entirely clarified.METHODS: Male C57BL/6J mice were treated with pazopanib every day for 2, 4, or 8 weeks. Transcriptomics and metabolomics analyses of liver tissues were performed. In vitro experiments were carried out to estimate cell viability, apoptosis, and autophagy in L02 cells after Paz treatment. We also examined apoptosis and autophagy-related genes under 4-PBA, l-ornithine, nor-NOHA treatments, and HSPA5 knockdown.KEY FINDINGS: Repeated Paz treatment for 8 weeks resulted in more severe hypofunction of the liver in mice. Moreover, Paz treatment inhibited L02 cells cell viability in a dose-dependent manner. We also discovered activation of endoplasmic reticulum stress, apoptosis, and autophagy in Paz-treated L02 cells, as evidenced by the boosted expression of HSPA5, p-IRE1α, ATF4, ATF6, p-eIF2α, LC3, Beclin-1, and a decrease of phosphorylated PI3K, AKT, and mTOR levels. Moreover, 4-PBA, l-ornithine, and HSPA5 knockdown inhibited apoptosis and autophagy, while nor-NOHA weakened the effects of HSPA5 knockdown on apoptosis in Paz-treated L02 cells.CONCLUSIONS: In summary, our study revealed that Paz-induced liver toxicity is related to HSPA5 expression and l-ornithine metabolism pathway in mice.PMID:39673386 | DOI:10.1093/jpp/rgae130

Physiol Plant. 2024 Nov-Dec;176(6):e70015. doi: 10.1111/ppl.70015.ABSTRACTHydrogen sulfide (H2S) functions as a signaling molecule affecting plant growth, development, and stress adaptation. Tall fescue (Festuca arundinacea Schreb.), a bioenergy crop, encounters significant challenges in agricultural production owing to low light by shading. However, the influence of H2S on tall fescue under low light stress (LLS) remains unclear. To examine the role of H2S in acclimation of tall fescue to low light, we conducted combined analyses of physiological traits, metabolomics, and transcriptomics. These results showed that H2S mitigated LLS-induced inhibition of photosynthesis and maintained normal chloroplast ultrastructure by boosting the expression of photosynthesis-related genes, including PsbQ, PsbR, PsaD, PsaK, and PetH, thereby enhancing the synthesis of carbohydrates (sucrose, starch). H2S upregulated the expression of key genes (PFK, PK, IDH, G6PD) connected to glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway to promote carbon metabolism and ensure the supply of carbon skeletons and energy required for nitrogen metabolism. H2S application reverted the LLS-induced accumulation of nitrate nitrogen and the changes in the key nitrogen metabolism enzymes glutamate synthase (GOGAT, EC 1.4.1.13), nitrate reductase (NR, EC 1.6.6.1), glutamine synthetase (GS, EC 6.3.1.2), and glutamate dehydrogenase (GDH, EC 1.4.1.2), thus promoting amino acid decomposition to produce proteins involved in nitrogen assimilation and nitrogen use efficiency as well as specialized metabolism. Ultimately, H2S upregulated the C/N ratio of tall fescue, balanced its carbon and nitrogen metabolism, enhanced shade tolerance, and increased biomass. These results provided new insights into enhancing plant resilience under LLS.PMID:39673341 | DOI:10.1111/ppl.70015

Biol Reprod. 2024 Nov 29:ioae161. doi: 10.1093/biolre/ioae161. Online ahead of print.ABSTRACTThe blastocyst of the European roe deer (Capreolus capreolus) undergoes a period of decelerated growth and limited metabolism. During this period known as embryonic diapause, it floats freely in the uterus encircled by the histotroph. Prior to implantation, reactivation is marked by rapid embryonic growth and conceptus elongation. We hypothesized that the uterine fluid, which is known to undergo changes in its composition to support early embryonic development, contributes to controlling embryonic growth during diapause and elongation. We therefore characterized the pre-implantation uterine fluid metabolome during diapause and at elongation by mass spectrometry and particularly assessed nonpolar lipids, polar metabolites, acylcarnitines, and polyamines. Our results show that triglycerides and diglycerides levels decreased at elongation, likely serving as a source for membrane synthesis rather than for energy production. A functional analysis identified glycolysis as a key pathway during elongation, which may compensate for the energy requirements during this phase. We also observed an increase of sphingomyelin; prostaglandin precursors; and the amino acids asparagine, glutamine, and methionine upon elongation. The sphingolipid and glycerophospholipid metabolism pathways were implicated during elongation. Particularly, spermidine, and to some extent spermine but not putrescine-levels significantly increased in the uterine fluid during elongation, indicating their significance for reactivation and/or proliferation at embryo elongation. We conclude that the roe deer uterine fluid sustained dynamic compositional changes necessary to support the energy- and resource-intensive conceptus elongation. However, it remains to be determined whether these changes are the cause or a consequence of embryo elongation. Studying the metabolic changes and molecular interactions in the roe deer during diapause and elongation not only reveals insights into aspects of its reproductive strategy, but also deepens our knowledge of embryo metabolic demands and developmental velocities across species.PMID:39673258 | DOI:10.1093/biolre/ioae161

Am J Epidemiol. 2024 Nov 28:kwae445. doi: 10.1093/aje/kwae445. Online ahead of print.ABSTRACTMass spectrometry lipidomics is becoming customary to analyse serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known on the consequences of adjusting lipidomics data with lipoprotein measures. We studied two population cohorts with 5,657 and 2,036 participants. LC-MS/MS lipidomics was applied to analyse 24 molecular lipid classes and NMR spectroscopy to quantify seven lipoprotein lipids plus apolipoprotein A-I (apoA-I) and B (apoB). The associations of these measures were analysed via partial Spearman's correlations. The effects of nine different lipoprotein adjustments on these interrelationships were assessed. Multivariable regression modelling with these adjustments was also performed for the associations between the lipidomics data and BMI. These novel large-scale lipidomics data and their associations between the lipoprotein measures were coherent in both population cohorts, confirming the compatibility of the analytical approaches. Simulated data were generated to corroborate the mediation effects. The lipoprotein-related lipid-transport and metabolism inherently mediate the lipidomics associations as evident from the striking effects of the lipoprotein adjustments. These effects and their relevance to the interpretations of lipidomics data are presented and discussed in detail for the first time. The combined lipoprotein lipid adjustments appear prone to overadjustment and arbitrary biases.PMID:39673251 | DOI:10.1093/aje/kwae445

Int J Rheum Dis. 2024 Dec;27(12):e15447. doi: 10.1111/1756-185X.15447.ABSTRACTBACKGROUND: Presently, research examining the impact of plasma metabolites on rheumatoid arthritis (RA) is scarce. We utilized a bidirectional two-sample Mendelian randomization (MR) analysis to explore the potential causal link between 1400 plasma metabolites and RA.METHODS: We performed a two-sample MR analysis to assess the causal association between 1400 plasma metabolites and RA. The primary method of two-sample MR Analysis was the Inverse Variance Weighted (IVW) model, and the secondary methods were the Weighted Median (WM) and MR Egger methods. We conducted sensitivity analyses using Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and Leave-One-Out analyses. Steiger test was used for validation of the metabolites. The main results were validated in the UK Biobank.RESULTS: In the discovery dataset, 60 metabolites were identified as significantly associated with the onset of RA. A notable finding was the strong correlation between Valve levels and RA risk, showing the highest positive correlation (OR [95% CI]: 1.361 (1.112, 1.667), p = 0.0028). Subsequent analysis of the validation dataset revealed 46 metabolites linked to RA, with X-22771 levels displaying the strongest positive association (OR [95% CI]: 1.002 (1.00, 1.004), p = 0.037). Notably, Glycohydrocolate levels exhibited a protective effect on RA in both datasets. Specifically, the effect size in the initial dataset was (OR [95% CI]:0.867 (0.753, 1.000), p = 0.050), whereas in the validation dataset, the effect was weaker (OR [95% CI]: 0.999 (0.997, 1.000), p = 0.048). These findings were further validated through a series of sensitivity analyses, affirming their robustness and reliability.CONCLUSIONS: This study highlights a strong correlation between elevated Valine levels and an increased risk of RA, as well as potential protective effects of Glycohydrohorate in independent datasets.PMID:39673206 | DOI:10.1111/1756-185X.15447

Plant Commun. 2024 Dec 12:101221. doi: 10.1016/j.xplc.2024.101221. Online ahead of print.ABSTRACTCotton (Gossypium hirsutum L.) is one of the world's most important commercial crops. However, the dynamics of metabolite abundance and the potential regulatory networks throughout its life cycle remain poorly understood. In this study, we developed a comprehensive Cotton Metabolism Regulatory Network (CMRN) encompassing various developmental stages, involving 2,138 metabolites and 90,309 genes expressed in upland cotton. By integrating high-resolution spatiotemporal metabolome and transcriptome data, we identified 1,958 differentially accumulated metabolites and 13,597 co-expressed differentially expressed genes between the dwarf mutant pagoda 1 (pag1) and its wild-type counterpart Zhongmiansuo 24 (ZM24). These metabolites and genes were classified into seven clusters based on tissue-specific accumulation patterns and gene expression at different developmental stages. KEGG enrichment analysis revealed significant differential genes and metabolites enrichment in the fatty acid elongation pathway, particularly in fibers. The differential involvement of genes and metabolites in the VLCFA synthesis pathway led to the identification of GhKCS1b_Dt as a key gene. Overexpression of GhKCS1b_Dt significantly promoted fiber elongation, while its silencing dramatically inhibited cotton fiber growth, underscoring its positive regulatory role in fiber elongation. This dataset provides a valuable resource for further research on metabolic pathways and gene regulatory networks, offering new insights for developing future cotton breeding strategies.PMID:39673124 | DOI:10.1016/j.xplc.2024.101221

Clin Transl Med. 2024 Dec;14(12):e70095. doi: 10.1002/ctm2.70095.ABSTRACT : Among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organs appears promising. We hypothesized that using a cell therapy based on extracellular vesicles (EVs) derived from urine progenitor cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR-related kidney damage. We isolated and characterized porcine UPCs and their extracellular vesicles (EVs). Then these were used in an ex vivo porcine kidney preservation model. Kidneys were subjected to warm ischemia (32 min) and then preserved by hypothermic machine perfusion (HMP) for 24 h before 5 h of normothermic machine perfusion (NMP). Three groups were performed (n = 5-6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/EVs + NMP/vehicle, Group 3 (G3): HMP/EVs + NMP/EVs. Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. However, cell damage markers (LDH, ASAT) were decreased in G3 compared with G1, and G3 kidneys displayed a preserved tissue integrity with reduced tubular dilatation and inflammation notably. However, renal function indicators such as creatinine clearance measured for 5 h of normothermic perfusion or NGAL perfusate's level were not modified by EVs injection. Regarding perfusate analysis, metabolomic analyses and cytokine quantification showed an immunomodulation signature in G3 compared with G1 and highlighted potential metabolic targets. In vitro, EVs as well as perfusates from G3 partially recovered endothelial cell metabolic activity after hypoxia. Finally, RNA-seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of EVs therapy. We showed the feasibility/efficacy of UPC-EVs for hypothermic/normothermic kidney conditioning before transplantation, paving the way for combining machine perfusion with EVs-based cell therapy for organ conditioning. HIGHLIGHTS: ·UPCs from porcine urine can be used to generate a cell therapy product based on extracellular vesicles (pUPC-EVs). ·pUPC-EVs injection during HMP and NMP decreases cell damage markers and has an immunomodulatory effect. ·pUPC-EVs-treated kidneys have distinct biochemical, metabolic, and transcriptomic profiles highlighting targets of interest. ·Our results pave the way for combining machine perfusion with EV-based cell therapy for kidney conditioning.PMID:39673122 | DOI:10.1002/ctm2.70095

Metabolomics. 2024 Dec 13;21(1):4. doi: 10.1007/s11306-024-02193-0.ABSTRACTINTRODUCTION/OBJECTIVES: Several observational investigations have observed the possible links between Alzheimer's disease (AD) and metabolic dysfunction associated with fatty liver disease (MAFLD), yet the underlying causal relationships remain undetermined. This study aimed to systemically infer the causal associations between AD and MAFLD by employing a bidirectional network two-sample Mendelian randomization (MR) analysis.METHODS: Genome-wide significant (P < 5 × 10- 8) genetic variants associated with AD and MAFLD were selected as instrumental variables (IVs) from the consortium of FinnGen, MRC-IEU, UK biobank, and genome-wide association studies (GWAS), respectively. The study sample sizes range from 55,134 to 423,738 for AD and from 218,792 to 778,614 for MAFLD. In the forward analysis, AD was set as the exposure factor, and MAFLD was employed as the disease outcome. Causal relationships between AD and MAFLD were evaluated using inverse-variance weighted (IVW), MR Egger regression, the weighted median, and weighted mode. Additionally, the reverse MR analysis was conducted to infer causality between MAFLD and AD. Sensitivity analyses were performed to assess the robustness of causal estimates.RESULTS: In the forward MR analysis, the genetically determined family history of AD was associated with a lower risk of MAFLD (mother's history: ORdiscovery=0.08, 95%CI: 0.03, 0.22, P = 7.91 × 10- 7; ORreplicate=0.83, 95%CI: 0.74, 0.94, P = 3.68 × 10- 3; father's history: ORdiscovery=0.01, 95%CI: 0.01, 0.08, P = 5.48 × 10- 5; ORreplicate=0.79, 95%CI: 0.68, 0.93, P = 4.07 × 10- 3; family history: ORdiscovery=0.84, 95%CI: 0.77, 0.91, P = 6.30 × 10- 5; ORreplicate=0.15, 95%CI: 0.05, 0.41, P = 2.51 × 10- 4) in the primary MAFLD cohort. Consistent findings were observed in an independent MAFLD cohort (all P < 0.05). However, the reverse MR analysis suggested that genetic susceptibility to MAFLD had no causal effects on developing AD.CONCLUSION: Our study demonstrates a causal association between a family history of AD and a lower risk of MAFLD. It suggests that individuals with a history of AD may benefit from tailored metabolic assessments to better understand their risk of MAFLD, and inform the development of preventive strategies targeting high-risk populations.PMID:39673021 | DOI:10.1007/s11306-024-02193-0

Amino Acids. 2024 Dec 13;57(1):2. doi: 10.1007/s00726-024-03434-1.ABSTRACTDipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter.PMID:39673003 | DOI:10.1007/s00726-024-03434-1

Nat Microbiol. 2024 Dec 13. doi: 10.1038/s41564-024-01841-4. Online ahead of print.ABSTRACTTemperature is a key determinant of microbial behaviour and survival in the environment and within hosts. At intermediate temperatures, growth rate varies according to the Arrhenius law of thermodynamics, which describes the effect of temperature on the rate of a chemical reaction. However, the mechanistic basis for this behaviour remains unclear. Here we use single-cell microscopy to show that Escherichia coli exhibits a gradual response to temperature upshifts with a timescale of ~1.5 doublings at the higher temperature. The response was largely independent of initial or final temperature and nutrient source. Proteomic and genomic approaches demonstrated that adaptation to temperature is independent of transcriptional, translational or membrane fluidity changes. Instead, an autocatalytic enzyme network model incorporating temperature-sensitive Michaelis-Menten kinetics recapitulates all temperature-shift dynamics through metabolome rearrangement, resulting in a transient temperature memory. The model successfully predicts alterations in the temperature response across nutrient conditions, diverse E. coli strains from hosts with different body temperatures, soil-dwelling Bacillus subtilis and fission yeast. In sum, our model provides a mechanistic framework for Arrhenius-dependent growth.PMID:39672961 | DOI:10.1038/s41564-024-01841-4

Prep Biochem Biotechnol. 2024 Dec 13:1-11. doi: 10.1080/10826068.2024.2428322. Online ahead of print.ABSTRACTThe microbial agents based on plant growth promoting rhizobacteria (PGPR) have become a hot topic in agricultural research, while the optimization of fermentation conditions for PGPR-based microbial agents still lack systematic research. The single-factor and orthogonal experiments were conducted to determine the optimal fermentation conditions of Pseudomonas synxantha M1. The results indicated that the glycerol and shaker speed was the most significant factors that influence the number of bacteria of P. synxantha M1 fermentation liquid. The viable bacteria count of microbial agent reached 7.1 × 1012 cfu/mL at 36 h, which OD600 value increased by 116.40% compared to before optimization, and promote the growth of highland barley. Significant differences of metabolites of fermentation liquid was observed in different fermentation times, including organic acids, lipids, and organoheterocyclic compounds using liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, the fermentation liquid was found to contain indoleacetic acid, glutathione and xanthine at the end of fermentation, which might contribute for the growth of plants as bioactive substances.PMID:39672807 | DOI:10.1080/10826068.2024.2428322

Pestic Biochem Physiol. 2024 Dec;206:106208. doi: 10.1016/j.pestbp.2024.106208. Epub 2024 Nov 8.ABSTRACTThe high toxicity of thiamethoxam (Thi) to foragers has threatened the development of bee populations and the use of neonicotinoid pesticides. In this study, we explored the mechanism of selective feeding on azadirachtin (Aza) by foragers to reduce the feeding of Aza-Thi and improve foragers' safety. The results showed that foragers under selective feeding significantly reduced the Aza sucrose solution intake. The Thi content in foragers was significantly lower, and the mortality rate was significantly reduced. In order to further analyze the selective feeding of foragers on Aza, the classic proboscis extension response (PER) experiment showed that Aza did not affect the learning ability of foragers, and the expression of related genes was not significantly different from the regular PER foragers. Further analysis of transcriptomics and metabolomics showed that compared with the regular PER foragers, treated with Aza were significantly affected in metabolic pathways and peroxisome and 67 differentially expressed genes (DEGs) were up-regulated and 136 were down-regulated. Differential metabolite analysis showed that metabolites primarily enriched in caffeine metabolism and microbial metabolism in diverse environments, and only dibucaine was up-regulated in response to Aza treatment. It is worth noting that dibucaine was significantly positively correlated with differentially expressed genes. Thus, our findings revealed that Aza does not affect the expression of memory genes in foragers. Aza affected the regular metabolic levels of foragers, leading to selective feeding of foragers on Aza, reduced intake of Aza-Thi, and increased safety for foragers. This study provides a reference for applying Aza to selective mechanisms in foragers.PMID:39672620 | DOI:10.1016/j.pestbp.2024.106208

Pestic Biochem Physiol. 2024 Dec;206:106178. doi: 10.1016/j.pestbp.2024.106178. Epub 2024 Oct 18.ABSTRACTAcetamiprid (ACE) is widely used in agriculture to control pests. However, its accumulation in soil and subsequent translocation to plants can impact plant growth and development through mechanisms that remain unclear. This study evaluated the comprehensive effects of residual ACE from soil on cultivated pak choi and lettuce at environmental levels. Results showed that more than 90 % of ACE residues in the soils dissipated within 14 days. The average root concentration factor (RCF) values of pak choi and lettuce were 1.442 and 0.318, respectively, while the average translocation factor (TF) values were 2.145 for pak choi and 5.346 for lettuce. Seedling height increased by 6.32 % in pak choi but decreased by 8.54 % in lettuce. Furthermore, chlorophyll content decreased by 14.6 % in pak choi and increased by 23.7 % in lettuce. Non-targeted metabolomics analysis showed significant disturbances in carbohydrates, amino acids, and secondary metabolite levels. Additionally, KEGG pathway analysis revealed the down-regulation of amino acid metabolites in both vegetables, alongside an up-regulation of flavone and flavonol biosynthesis in pak choi. This research enhances the understanding of the effects and underlying metabolic mechanism of ACE on different vegetables.PMID:39672607 | DOI:10.1016/j.pestbp.2024.106178

Int J Biol Macromol. 2024 Dec 11:138698. doi: 10.1016/j.ijbiomac.2024.138698. Online ahead of print.ABSTRACTAn imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory response than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory response and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.PMID:39672439 | DOI:10.1016/j.ijbiomac.2024.138698

Environ Pollut. 2024 Dec 11:125522. doi: 10.1016/j.envpol.2024.125522. Online ahead of print.ABSTRACTNanoplastics, as emerging pollutants, have attracted worldwide concern for their possible environmental dangers. The ingestion and accumulation of nanoplastics in crops can contaminate the food chain and have unintended consequences for human health. In this study, we revealed the effects of polystyrene nanoplastics (PS-NPs; 80 nm) at different concentrations (0, 10, 100 mg L-1) on soybean (Glycine max L.) seedling growth, antioxidant enzyme system and secondary metabolism. Using laser confocal microscopy, we demonstrated that the absorption and translocation of PS-NPs in soybean. Plant growth inhibition was observed by changes in plant height, root length, and leaf area after 7 days of exposure to PS-NPs. The effect of PS-NPs on photosynthetic characteristics was reflected by a significant reduction in total chlorophyll content at 10 mg L-1. Activation of the antioxidant system was observed with increased malondialdehyde (MDA) content, and elevated activities of superoxide dismutase (SOD) and catalase (CAT). Non-targeted metabolomics analysis identified a total of 159 secondary metabolites, and exposure to 10 and 100 mg L-1 PS-NPs resulted in the production of 61 and 62 differential secondary metabolites. Metabolomics analysis showed that PS-NPs treatment altered the secondary metabolic profile of soybean leaves through the biosynthesis pathways of flavonoid, flavone flavonol, and isoflavones, which is expected to provide new insights into the tolerance mechanisms of plants to nanoplastics. Overall, the results of this study deepen our understanding of the negative impacts of nanoplastics in agricultural systems, which is crucial for assessing the risks of nanoplastics to ecological security.PMID:39672368 | DOI:10.1016/j.envpol.2024.125522

J Adv Res. 2024 Dec 11:S2090-1232(24)00558-7. doi: 10.1016/j.jare.2024.12.002. Online ahead of print.ABSTRACTINTRODUCTION: Ginseng demonstrates therapeutic potential in treating obesity, with both experimental and clinical studies suggesting its anti-obesity effects are mediated by gut microbiota. Nonetheless, the specific chemical components responsible for this effect remain largely unidentified.OBJECTIVES: This study aims to investigate the anti-obesity effects and mechanisms of ginseng polysaccharides (GP) and ginsenosides (GS), the primary chemical components of ginseng, with a focus on their impact on gut microbiota.METHODS: The impact of GP and GS on high-fat diet (HFD)-induced obesity was assessed using a mouse model. Molecular mechanisms were explored through a combination of chemical analysis, metagenomics, RT-qPCR, ELISA, and biochemical assays.RESULTS: GP or GS administration effectively prevented adiposity in HFD-fed mice, and both effects were mediated by gut microbiota. Chemical analysis revealed diverse glycosyl groups in GP and GS. Metagenomics data suggested that GP-enriched species, e.g., Bacteroides stercorirosoris and Clostridiales bacterium encoded carbohydrate-active enzymes GH35, GH43 and PL9_1, while GS-enriched Sulfurospirillum halorespirans encoded GH16_5. These enzymes facilitated the utilization of glycosyl groups in GP and GS, selectively stimulating bacterial growth and reshaping the gut microbiota. Furthermore, bacterial species enriched by GP or GS encoded specific functional genes involved in short-chain fatty acid (SCFA) synthesis (K00625 and K00925 for GP; K18118, K00100, and K18122 for GS) and intestinal gluconeogenesis (IGN) (K01678, K00024, and K01596 for GP; K18118 and K00278 for GS). Consequently, the SCFA-GLP-1/PYY signaling and IGN were activated by both GP and GS to ameliorate obesity phenotypes.CONCLUSION: GP and GS, containing diverse glycosyl groups, selectively stimulate specific gut bacteria, triggering mechanisms involved in SCFA-GLP-1/PYY signaling and IGN activation to reduce adiposity in HFD-fed mice. The study enhances understanding of the chemical components crucial for the gut microbiota-mediated anti-obesity effect of ginseng. The mechanistic understanding provides valuable insights for developing ginseng-based drugs or health products to combat obesity.PMID:39672231 | DOI:10.1016/j.jare.2024.12.002

J Hazard Mater. 2024 Dec 9;485:136833. doi: 10.1016/j.jhazmat.2024.136833. Online ahead of print.ABSTRACTFine particulate matter (PM2.5) is related to embryo growth arrest (EGA). In this study, we collected demographic information from EGA cases and early pregnancy controls in Taiyuan, China, between 2022 and 2023 and obtained villi and serum samples from these participants. We employed multilevel mixed-effects logistic regression models to estimate the odds ratios (ORs). Subsequently, we examined the associations between PM2.5 and its components and the EGA-related biomarkers in the serum of the case-control groups. Additionally, we performed spatial metabolomics on villi using mass spectrometry imaging. Our results indicated that PM2.5 levels during pregnancy were higher in the EGA group compared to the control, increasing the risk by 17 % (OR=1.17, 95 %CI: 1.06-1.30, p = 0.001). PM2.5 and its components (Ni, Pb, ANY, NAP, ANT, PYR, and BaP) showed significant negative correlations with biomarkers (PAPP-A, VEGF, and PROG). Furthermore, EGA induced histopathological changes in the villi alongside differential spatial distribution of metabolites. Key metabolites, including 2'-deoxyinosine triphosphate, cytidine triphosphate, uridine triphosphate, guanosine-5'-triphosphate, guanosine diphosphate, and deoxyguanosine-5'-triphosphate, were predominantly involved in purine and pyrimidine metabolism pathways. It provides evidence of the association between PM2.5 and EGA and demonstrates the utility of spatial metabolomics in elucidating the metabolic alterations induced by PM2.5 in EGA.PMID:39672068 | DOI:10.1016/j.jhazmat.2024.136833

Food Chem. 2024 Dec 6;468:142394. doi: 10.1016/j.foodchem.2024.142394. Online ahead of print.ABSTRACTPimpinella brachycarpa Nakai is a perennial plant that has been widely used as a traditional medicine. However, the comprehensive analysis of primary and secondary metabolites and antioxidant activities in different organs (flowers, leaves, stems, and roots) has not been extensively studied. A comprehensive analysis using GC-qMS, GC-TOFMS, and HPLC metabolomic analyses identified 66 known metabolites in different organs of P. brachycarpa. The heat map showed that most metabolites were high in flowers and leaves. KEGG enrichment analysis based on plant metabolic pathways showed that six pathways were significantly impacted based on -log p-value and pathway impact scores. The in vitro antioxidant activities, such as DPPH, ABTS, and SOD-like, reducing power activities, IC50 values for DPPH, ABTS, and SOD were highest in flower and leaf extracts. This study elucidated the metabolites and medicinal and edible value of different P. brachycarpa organs, promoting the effective utilisation of different P. brachycarpa organs.PMID:39671916 | DOI:10.1016/j.foodchem.2024.142394

Food Chem. 2024 Dec 6;468:142393. doi: 10.1016/j.foodchem.2024.142393. Online ahead of print.ABSTRACTGhee, a traditional fermented dairy product and dietary staple for inhabitants of the Tibet Plateau, has unclear lipid profiles and flavor formation mechanisms. This study aims to characterize superior ghee varieties and elucidate factors driving the production of beneficial lipids and flavor compounds. Through a comprehensive analysis of lipidomic profiles, volatile organic compound (VOC) release and microbial dynamics during ghee production from Holstein milk (HM) and Jersey milk (JM), A total of 126 differential lipids were identified, primarily associated with glycerophospholipid and sphingolipid metabolism. Additionally, 69 VOCs were detected, with 23 recognized as critical to flavor development. Key microbial species, including Lactococcus, Lactobacillus, Acetobacter, and Lacticaseibacillus, enriched during fermentation, were found to drive both VOC release and free fatty acid (FFA) production, particularly of eicosapentaenoic acid (EPA) and long-chain fatty acids. Notably, ghee derived from JM exhibited higher levels of functional lipids, beneficial FFAs, and critical VOCs compared to Holstein ghee (HG). The fermentation process, supported by microbial activity and enzyme production, significantly enriched these compounds, underscoring the pivotal role of microbes in enhancing both health benefits and flavor. These findings have potential implications for improving the quality of fermented dairy products in the food industry.PMID:39671915 | DOI:10.1016/j.foodchem.2024.142393

J Pharm Biomed Anal. 2024 Dec 4;255:116583. doi: 10.1016/j.jpba.2024.116583. Online ahead of print.ABSTRACTHura crepitans (Euphorbiaceae), is widespread in the Amazon rainforest and on plantations in sub-Saharan Africa. This tree produces an irritating milky latex rich in secondary metabolites, notably daphnane-type diterpenes and cerebrosides. Previous studies have shown that huratoxin, the main daphnane in the latex, significantly and selectively inhibited the growth of colorectal cancer cells through a unique mechanism involving the activation of PKCζ. One major challenge in isolating active molecules from natural products is the accessibility of the resource. This study explores the phytochemical composition and cytotoxic activities of latexes collected in Peru, Benin, and Togo using UHPLC-MS and metabolomics tools to identify a renewable source of bioactive compounds. Significant inter- and intra-continental differences in chemical composition have been highlighted, with daphnanes being concentrated in the Peruvian samples. Extracts form latexes collected in Peru showed cytostatic activity on Caco-2 cells, correlated with the presence of daphnanes, while some African samples exhibited cytotoxic activity on Jurkat and Hela cancer cell lines, leading to the identification of potential other new bioactive compounds such as elasterol and cerebrosides. OBJECTIVE: To compare the composition of different Hura crepitans latex samples and determine their cytotoxic activity in order to identify new bioactive compounds CONCLUSIONS: Inter- and intra-continental variations in the phytochemical composition of latex were observed, leading to significant cytotoxic activities on different cell lines. Daphnanes were identified as responsible for the activity on Caco-2 cells, while elasterol and cerebrosides were putatively associated with the activity on Hela cells.PMID:39671907 | DOI:10.1016/j.jpba.2024.116583