aminoacyl-tRNA Biosynthesis Research Articles

Experimental study on changes in metabolic mechanism of papillary thyroid carcinoma complicated with Hashimoto’s thyroiditis

BackgroundWhether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC. MethodsThe ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis. HMDB was searched to identify potential differential metabolites and final metabolic pathway analysis was performed by MetaboAnalyst 5.0. We analyzed the differential metabolites diagnostic accuracy through receiver operating characteristic (ROC) curves analysis. ResultsSeven different metabolites were screened from HT group and NC group, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine. Logistic regression model combined with ROC analysis of these 7 biomarkers had good discriminability for PTC (area under operating characteristic curve of HT group and NC group were 0.867 and 0.973, respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. ConclusionsThe metabolic profiles of the NC and HT groups had important similarities and differences in PTC. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

Metabolome analysis to investigate the effect of heavy metal exposure and chemoprevention agents on toxic injury caused by a multi-heavy metal mixture in rats

Heavy metal pollution is a significant threat to both the environment and living organisms. This is especially vital considering the persistent and cumulative nature of heavy metal exposure, which can lead to severe and chronic health consequences for individuals. Therefore, implementing effective treatments is critical to addressing the serious public health issues posed by heavy metal pollution. In this study, nontargeted metabolomics was carried out to investigate the metabolic changes associated with long-term low-dose intake of mixed heavy metal pollutants (MHMPs) in liver, kidney, and plasma samples of Sprague-Dawley (SD) rats with and without treatment to reveal the underlying toxic effects of MHMPs and the effects of chemoprevention agents, including epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD), and glutathione (GSH). In the liver, kidney, and plasma, we observed a total of 21, 69, and 16 metabolites, respectively, exhibiting significant differences (P < 0.05, fold change >1.2 or <0.83, and VIP ≥ 1) between the control group and the mixture group. The findings demonstrated that exposure to MHMPs leads to the dysregulation of numerous metabolic pathways, with a particular emphasis on purine metabolism and aminoacyl-tRNA biosynthesis with upregulated renal purine metabolites and downregulated hepatic purine metabolites as well as renal aminoacyl-tRNA biosynthesis-related metabolites. However, the application of chemical protectants was shown to partially restore the metabolic alterations induced by MHMPs, particularly purine metabolism-related metabolites, including hepatic adenine and renal adenine, guanine, guanosine, adenosine monophosphate (AMP), and hypoxanthine. In addition, liver adenosine, kidney inosine and L-phenylalanine were considered the main regulated sites based on their significant correlations with multiple heavy metals. Our study provides crucial insights into the toxicological mechanisms of heavy metal pollution and has the potential to guide the development of effective preventive strategies.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet.

After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear. To explore baseline serum metabolites characteristics in responders. A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk' treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression. As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected. Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Multiplatform Metabolomics to Understand the Imidacloprid-Induced Toxicity in Drosophila.

Neonicotinoids, the class of insecticides used for crop protection, are subjected to vigilance due to their pernicious impacts. Imidacloprid (IMD) is one of the most representative insecticides of the neonicotinoid family, which has shown unfriendly consequences for non-target species. Metabolomics, a multidisciplinary approach, is being used in toxicological research to understand the metabolic responses to toxicant exposure by utilizing modern analytical techniques. Yet, no solitary analytical technique can cover the broad metabolite spectrum, but a multi-technique metabolomics platform can aid in analyzing the majority of the metabolites. In the present study, an effort has been made to identify the differential metabolites in Drosophila after exposure to IMD at 2.5 and 25 ng/mL using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), gas chromatography-MS (GC-MS), and NMR-based untargeted metabolomics. Multivariate pattern recognition analysis helped in identifying/recognizing 19 (LC-HRMS), 7 (GC-MS), and 13 (NMR) differential metabolites mainly belonging to the category of amino acids, sugars, fatty acids, and organic acids. The pathway analysis of differential metabolites predominantly showed impact on aminoacyl-tRNA biosynthesis, amino acid metabolism, and glycerophospholipid metabolism. Among these, arginine and proline metabolism was observed to be the common metabolic pathway perturbed in Drosophila due to IMD exposure. The multiplatform metabolomics based on LC-HRMS, GC-MS, and NMR analysis with an advanced level of statistical analysis can provide insights into potential perturbations in the metabolome of IMD-exposed Drosophila.

Chitosan and its oligosaccharide accelerate colonic motility and reverse serum metabolites in rats after excessive protein consumption

Excessive protein consumption (EPC) could increase the gastrointestinal burden and impair gut motility. The present study was designed to explore the improvement of chitosan (CTS) and chitosan oligosaccharide (COS) on colonic motility and serum metabolites in rats after EPC. The results of in vivo experiments fully proved that CTS and COS could improve gut motility and reverse the serum metabolites in rats as indicated by LC-MS/MS analysis, and the COS group even showed a better effect than the CTS group. Furthermore, short-chain fatty acids (SCFAs), which could promote gut motility, were also increased to alleviate EPC-induced constipation after supplementation with CTS or COS. In addition, CTS and COS could decrease the concentration of ammonia in serum and down-regulate the levels of H2S and indole. In summary, the present study revealed that CTS and COS could produce SCFAs, improve the colonic motility in rats, reverse the levels of valine, adenosine, cysteine, 1-methyladenosine, indole, and uracil, and enhance aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine degradation. The present study provides novel insights into the potential roles of CTS and COS in alleviating the adverse effects of EPC.

Effect of hexavalent chromium on growth performance and metabolism in broiler chicken.

Hexavalent chromium Cr (VI) is one of the most hazardous heavy metals in the environment and is toxic to living organisms causing tissue damage, disruption of the intestinal microbiota and cancer. However, there is little information on the relationship between the Cr (VI) and broiler chickens. The current study was performed to investigate the effect of Cr (VI) on growth performance, serum biochemical analysis, histopathological observations, and metabolomics analysis in broilers. Results show that Cr (VI) exposure significantly decreased the body weight (p < 0.01) and caused liver damages in broilers. With the extension of Cr (VI) action time, the liver appeared obvious pathological changes, including hepatic cord disorder, incomplete hepatocyte additionally, decreased serum biochemical indices of calcium (Ca), phosphorus (P), total protein (TP), phosphatase (ALP), and globin (GLB) significantly (p < 0.01). Moreover, metabolomics analysis indicated that 29 differential metabolites were identified, such as phytosphingosine, L-Serine, 12, 13-DHOME, Alpha-dimorphecolic acid, L-Methionine, L-Phenylalanine, 3-Dehydroshikimate, L-Tyrosine, and N-Acetyl-L-phenylalanine were significantly decreased under the action of Cr (VI) (p < 0.05). These 29 differential metabolites are mainly involved in 35 metabolic pathways, such as aminoacyl-tRNA biosynthesis, phenylalanine metabolism, sphingolipid, and linoleic metabolism. The study revealed that exposure to Cr (VI) resulted in a decrease in growth performance and metabolism, with the hazards and toxicity in broiler chicken. The findings provided new insight and a comprehensive understanding of the relationship between Cr (VI) and broiler chickens.

Autophagy contributes to increase the content of intracellular free amino acids in hard clam (Mercenaria mercenaria) during prolonged exposure to hypersaline environments

Marine bivalves in intertidal zones and land-based seawater ponds are constantly subjected to a wide range of salinity fluctuations due to heavy rainfall, intense drought, and human activities. As osmoconformers, bivalves rely primarily on rapid release or accumulation of free amino acids (FAAs) for osmoregulation. Euryhaline bivalves are capable of withstanding hyposaline and hypersaline environments through regulation of physiology, metabolism, and gene expression. However, current understanding of the molecular mechanisms underlying osmoregulation and salinity adaptation in euryhaline bivalves remains largely limited. In this study, RNA-seq, WGCNA and flow cytometric analysis were performed to investigate the physiological responses of hard clams (Mercenaria mercenaria) to acute short-term hyposalinity (AL) and hypersalinity (AH), and chronic long-term hyposalinity (CL) and hypersalinity (CH) stress. We found that amino acids biosynthesis was significantly inhibited and aminoacyl-tRNA biosynthesis was augmented to decrease intracellular osmolarity during hyposaline exposure. Under CH, numerous autophagy-related genes (ATGs) were highly expressed, and the autophagy activity of gill cells were significantly up-regulated. A significant decrease in total FAAs content was observed in gills after NH4Cl treatment, indicating that autophagy was crucial for osmoregulation in hard clams during prolonged exposure to hypersaline environments. To prevent premature or unnecessary apoptosis, the expression of cathepsin L was inhibited under AL and AH, and inhibitors of apoptosis was augmented under CL and CH. Additionally, neuroendocrine regulation was involved in salinity adaption in hard clams. This study provides novel insights into the physiological responses of euryhaline marine bivalves to hyposaline and hypersaline environments.

Exposure to PM2.5, seminal plasma metabolome, and semen quality among Chinese adult men: Association and potential mediation analyses

Exposure to ambient fine particulate matter (PM2.5) has been linked to a decline in semen quality, but the underlying mechanisms for this association remain unclear. We aimed to examine whether specific metabolites act as mediators in the association between PM2.5 exposure and changes in semen quality. We conducted untargeted metabolomics analysis using LC-MS/MS platforms to identified seminal plasma metabolites associated with various semen quality parameters among 200 Chinese adult men. Additionally, we performed mediation analyses to examine the effects of the seminal plasma metabolites on the association between PM2.5 exposure and semen quality. We identified 140 differential metabolites between the normal and abnormal semen groups, involving two metabolic pathways: Alanine, aspartate and glutamate metabolism, and Aminoacyl-tRNA biosynthesis. We additionally identified 7 specific seminal plasma metabolites that were associated with discrepant metabolic networks related to semen quality. The mediation analysis revealed that D-Aspartate might play a mediating role in the adverse effects of ambient PM2.5 exposure on both total and progressive motility during spermatogenesis period (70–90 days before ejaculation), with a proportion of mediation up to 16% and 17%, respectively. Exposure to PM2.5 was associated with alterations in D-Aspartate levels, which might partially mediate the association between PM2.5 and reduced sperm motility.

Modulation of cellular metabolism and alleviation of bacterial dysbiosis by Aconiti Lateralis Radix Praeparata in non-small cell lung cancer treatment

BackgroundNon-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. PurposeThis article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. MethodsMarker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the anti-NSCLC mechanism of Fuzi. ResultsPharmacological evaluation revealed significant tumour growth inhibition by Fuzi, accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signalling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, α-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota, Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. ConclusionsThis study firstly introduces a novel NSCLC mechanism involving Fuzi, encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.

The Effects of Prolonged Basic Amino Acid Exposures on Mitochondrial Enzyme Gene Expressions, Metabolic Profiling and Insulin Secretions and Syntheses in Rat INS-1 β-Cells.

In order to investigate the chronic effects of basic amino acids (BAA) on β-cell metabolism and insulin secretion, INS-1 β-cells were randomly assigned to cultures in standard medium (Con), standard medium plus 10 mM L-Arginine (Arg), standard medium plus 10 mM L-Histidine (His) or standard medium plus 10 mM L-Lysine (Lys) for 24 h. Results showed that insulin secretion was decreased by the Arg treatment but was increased by the His treatment relative to the Con group (p < 0.05). Higher BAA concentrations reduced the high glucose-stimulated insulin secretions (p < 0.001), but only Lys treatment increased the intracellular insulin content than that in the Con group (p < 0.05). Compared with Arg and Lys, the His treatment increased the mitochondrial key enzyme gene expressions including Cs, mt-Atp6, mt-Nd4l and Ogdh, and caused a greater change in the metabolites profiling (p < 0.05). The most significant pathways affected by Arg, His and Lys were arginine and proline metabolism, aminoacyl-tRNA biosynthesis and pyrimidine metabolism, respectively. Regression analysis screened 7 genes and 9 metabolites associated with insulin releases during BAA stimulations (p < 0.05). Together, different BAAs exerted dissimilar effects on β-cell metabolism and insulin outputs.

Predictive metabolites for incident myocardial infarction: a two-step meta-analysis of individual patient data from six cohorts comprising 7897 individuals from the COnsortium of METabolomics Studies.

Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies. We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors and then performed a fixed effect inverse variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI. On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26-1.56], P < 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67-0.82), P < 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis. In the most comprehensive metabolomic study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings.

Metabolic pathways modulated by coumarin to inhibit seed germination and early seedling growth in Eleusine indica

Coumarin is an allelochemical that is widely present in the plant kingdom and has great potential for weed control. However, its mechanisms of action remain largely unknown. This study employed metabolomic and transcriptomic analyses along with evaluations of amino acid profiles and related physiological indicators to investigate how coumarin inhibits the germination and seedling growth of Eleusine indica by modifying metabolic pathways. At 72 h of germination at 50 and 100 mg L−1 coumarin, E. indica had lower levels of soluble sugar and activities of amylases and higher levels of starch, O2−, H2O2, auxin (IAA) and abscisic acid (ABA) compared to the control. Metabolomic analysis demonstrated that coumarin treatments had a significant impact on the pathways associated with amino acid metabolism and transport and aminoacyl-tRNA biosynthesis. Exposure to coumarin induced significant alterations in the levels of 19 amino acids, with a decrease in 15 of them, including Met, Leu and γ-aminobutyric acid (GABA). Additionally, transcriptomic analysis showed that coumarin significantly disrupted several essential biological processes, including protein translation, secondary metabolite synthesis, and hormone signal transduction. The decrease in TCA cycle metabolite (cis-aconitate, 2-oxoglutarate, and malate) contents was associated with the suppression of transcription for related enzymes. Our findings indicate that the inhibition of germination and growth in E. indica by coumarin involves the suppression of starch conversion to sugars, modification of the amino acid profile, interference of hormone signalling and the induction of oxidative stress. The TCA cycle appears to be one of the most essential pathways affected by coumarin.

Machine learning approaches for biomarker discovery to predict large-artery atherosclerosis

Large-artery atherosclerosis (LAA) is a leading cause of cerebrovascular disease. However, LAA diagnosis is costly and needs professional identification. Many metabolites have been identified as biomarkers of specific traits. However, there are inconsistent findings regarding suitable biomarkers for the prediction of LAA. In this study, we propose a new method integrates multiple machine learning algorithms and feature selection method to handle multidimensional data. Among the six machine learning models, logistic regression (LR) model exhibited the best prediction performance. The value of area under the receiver operating characteristic curve (AUC) was 0.92 when 62 features were incorporated in the external validation set for the LR model. In this model, LAA could be well predicted by clinical risk factors including body mass index, smoking, and medications for controlling diabetes, hypertension, and hyperlipidemia as well as metabolites involved in aminoacyl-tRNA biosynthesis and lipid metabolism. In addition, we found that 27 features were present among the five adopted models that could provide good results. If these 27 features were used in the LR model, an AUC value of 0.93 could be achieved. Our study has demonstrated the effectiveness of combining machine learning algorithms with recursive feature elimination and cross-validation methods for biomarker identification. Moreover, we have shown that using shared features can yield more reliable correlations than either model, which can be valuable for future identification of LAA.

From the perspective of rumen microbiome and host metabolome, revealing the effects of feeding strategies on Jersey Cows on the Tibetan Plateau.

Previous studies have discussed the effects of grazing and house feeding on yaks during the cold season when forage is in short supply, but there is limited information on the effects of these feeding strategies on Jersey cows introduced to the Tibetan Plateau. The objective of this study was to use genomics and metabolomics analyses to examine changes in rumen microbiology and organism metabolism of Jersey cows with different feeding strategies. We selected 12 Jersey cows with similar body conditions and kept them for 60 days under grazing (n=6) and house-feeding (n=6) conditions. At the end of the experiment, samples of rumen fluid and serum were collected from Jersey cows that had been fed using different feeding strategies. The samples were analyzed for rumen fermentation parameters, rumen bacterial communities, serum antioxidant and immunological indices, and serum metabolomics. The results of the study were examined to find appropriate feeding strategies for Jersey cows during the cold season on the Tibetan plateau. The results of rumen fermentation parameters showed that concentrations of acetic acid, propionic acid, and ammonia nitrogen in the house-feeding group (Group B) were significantly higher than in the grazing group (Group G) (P<0.05). In terms of the rumen bacterial community 16S rRNA gene, the Chao1 index was significantly higher in Group G than in Group B (P=0.038), while observed species, Shannon and Simpson indices were not significantly different from the above-mentioned groups (P>0.05). Beta diversity analysis revealed no significant differences in the composition of the rumen microbiota between the two groups. Analysis of serum antioxidant and immune indices showed no significant differences in total antioxidant capacity between Group G and Group B (P>0.05), while IL-6, Ig-M , and TNF-α were significantly higher in Group G than in Group B (P<0.05). LC-MS metabolomics analysis of serum showed that a total of 149 major serum differential metabolites were found in Group G and Group B. The differential metabolites were enriched in the metabolic pathways of biosynthesis of amino acids, protein digestion and absorption, ABC transporters, aminoacyl-tRNA biosynthesis, mineral absorption, and biosynthesis of unsaturated fatty acids. These data suggest that the house-feeding strategy is more beneficial to improve the physiological state of Jersey cows on the Tibetan Plateau during the cold season when forages are in short supply.

Metabolomic profiling of Wilson disease, an inherited disorder of copper metabolism, and diseases with similar symptoms but normal copper metabolism

BackgroundWilson’s disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson’s disease patients (who exhibit similar symptoms but have normal copper levels).ResultsOur pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson’s disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson’s disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson’s disease).ConclusionsOur analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.

Integrating metal-organic framework ZIF-8 with green modifier empowered bacteria with improved bioremediation

Suspended microorganisms often experience diminished efficacy in the bioremediation of polycyclic aromatic hydrocarbons (PAHs). In this study, the potential of zeolite imidazolate framework-8 (ZIF-8) and the eco-friendly modifier citric acid (CA) was harnessed to generate a biomimetic mineralized protective shell on the surface of Bacillus subtilis ZL09–26, resulting in an enhanced capability for PAH degradation. This investigation encompassed the integrated responses of B. subtilis ZL09–26 to ZIF-8 and ZIF-8-CA at both cellular and proteomic levels. The amalgamation of ZIF-8 and CA not only stimulated the growth and bolstered the cell viability of B. subtilis ZL09–26, but also counteracted the toxic effects of phenanthrene (PHE) stress. Remarkably, the bioremediation prowess of B. subtilis ZL09–26@ZIF-8-CA surpassed that of ZL09–26@ZIF-8 and ZL09–26, achieving a PHE removal rate of 94.14 % within 6 days. After undergoing five cycles, ZL09–26@ZIF-8-CA demonstrated an enduring PHE removal rate exceeding 83.31 %. A complex interplay of various metabolic pathways orchestrated cellular responses, enhancing PHE transport and degradation. These pathways encompassed direct PHE biodegradation, central carbon metabolism, oxidative phosphorylation, purine metabolism, and aminoacyl-tRNA biosynthesis. This study not only extends the potential applications of biomineralized organisms but also offers alternative strategies for effective contaminant management.

Fuzi decoction treats chronic heart failure by regulating the gut microbiota, increasing the short-chain fatty acid levels and improving metabolic disorders

Fuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC–MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota. Our results identified 27 in FD-containing serum. FZD increased the Firmicutes-to-Bacteroidetes ratio and the Lactobacillus abundance and affected the β diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine, leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid, butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.

Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington's Disease Brain Tissue.

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington's disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.

Integration of transcriptomic and metabolomic analyses reveal the molecular responses of the mud crab Scylla paramamosain to infection by an undescribed endoparasite Portunion sp.

Portunion is a rare endoparasitic isopod genus, recently observed inhabiting the hemocoel of the commercially important mud crab, Scylla paramamosain. For better understanding of the host-parasite interaction between S. paramamosain and Portunion sp., the metabolomic and transcriptomic changes in the hemolymph of the S. paramamosain were analyzed. We detected a total of 143 and 126 differentially accumulated metabolites in the positive and negative modes, respectively. Pathways related to amino acids and vitamin synthesis, such as Aminoacyl-tRNA biosynthesis, Tyrosine metabolism, Cysteine and methionine metabolism, Vitamin B6 metabolism, and Biotin metabolism were significantly enriched. Based on the transcriptomic data, a total of 942 differentially expressed genes were identified, of which 25 and 36 were significantly related to the immune system and metabolic pathways, respectively. Based on the metabolomic and transcriptomic data, 90 correlated metabolite-gene pairs were selected to build a regulatory network. Common significantly enriched pathways, including Starch and sucrose metabolism, Metabolism of xenobiotics by cytochrome P450, Aminoacyl-tRNA biosynthesis, Nitrogen metabolism, and Galactose metabolism were detected. On the basis of our analysis, the endoparasite Portunion sp. places a heavy metabolic burden on the host, particularly with respect to fundamental resources, such as amino acids, vitamins, carbohydrates, and lipids. In summary, these data provide an overview of the global metabolic and transcriptomic changes of the S. paramamosain resulting from Portunion sp. infection.

Effects of Chinese herbal medicines on growth performance, intestinal flora, immunity and serum metabolites of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatu♂).

The immunomodulatory roles of Chinese herbal Medicine (CHM) in aquatic animals have been well-recorded. However, how CHM impacts the intestinal microbiota and serum metabolism is not fully understood. In this study, the effects of different additive levels of CHM on the growth performance, immunity, intestinal flora and serum metabolism of hybrid grouper (♀Epinephelus fuscoguttatus×♂Epinephelus lanceolatu) were investigated. The addition of 0.5%, 1.0%, 1.5% and 2.0% Chinese herbal medicine compound to feed could significantly improve the weight gain rate (WGR), specific growth rate (SGR) and survival rate (SR) of grouper, reduced feed coefficient, while had no significant difference on morphometric parameter. The most significant improvement for the parameters above was observed in 1.5% group. Different addition levels of CHM could also significantly enhance the activities of ACP, AKP, SOD, CAT and LZM in serum. Accordingly, the supplementation of CHM significantly induced up-regulation of immune genes such as IL-8, IL-1β, TNF-α, Nrf2, Lzm in the liver, spleen and head kidney of grouper, improved the resistance of grouper to V. harveyi as well. The intestinal flora analysis showed that at the phylum level, the main dominant species of intestinal microorganisms were Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, Gemmatimonadota, Desulfobacterota, Fusobacteriota and Myxococcota. At the genus level, the high abundance was Lactobacillus, Streptococcus, Bacteroides, Escherichia, Romboutsia, Sphingomonas and Muribaculaceae. The abundance of probiotics (such as Lachnospiraceae, Lactobacillaceae, Streptococcaceae, etc) in CHM-supplement groups were higher (highest in 1.5% group) compared with control group. Moreover, a total of 11 common differential metabolic pathways were screened by LC-MS metabolism analysis of serum, they were Neuroactive ligand-receptor interaction, Purine metabolism, Linoleic acid, Glycerophospholipid metabolism, Taurine and hypotaurine metabolism, Arginine and proline metabolism, ABC transporters, Aminoacyl-tRNA biosynthesis, Arachidonic acid metabolism, Drug metabolism-cytochrome P450, alpha-Linolenic acid metabolism. Also, three common differential metabolites (PI(20:4(5Z,8Z,11Z,14Z)/18:1(11Z)), PC(20:3(8Z,11Z,14Z)/22:1(13Z)), PC(22:0/20:4(5Z,8Z,11Z,14Z)) associated with intestinal health, growth and disease resistance was found. These data will contributes to a comprehensive understand for the regulatory roles of CHM on fish, which is also beneficial for the disease control and sustainable development of aquaculture.