Differences In Metabolic Pathways Research Articles

Longitudinal Profiling of Fasting Plasma Metabolome in Response to Weight-Loss Interventions in Patients with Morbid Obesity.

It is well recognized that patients with severe obesity exhibit remarkable heterogeneity in response to different types of weight-loss interventions. Those who undergo Roux-en-Y gastric bypass (RYGB) usually exhibit more favorable glycemic outcomes than those who receive adjustable gastric banding (BAND) or intensive medical intervention (IMI). The molecular mechanisms behind these observations, however, remain largely unknown. To identify the plasma metabolites associated with differential glycemic outcomes induced by weight-loss intervention, we studied 75 patients with severe obesity (25 each in RYGB, BAND, or IMI). Using untargeted metabolomics, we repeatedly measured 364 metabolites in plasma samples at baseline and 1-year after intervention. Linear regression was used to examine whether baseline metabolites or changes in metabolites are associated with differential glycemic outcomes in response to different types of weight-loss intervention, adjusting for sex, baseline age, and BMI as well as weight loss. Network analyses were performed to identify differential metabolic pathways involved in the observed associations. After correction for multiple testing (q < 0.05), 33 (RYGB vs. IMI) and 28 (RYGB vs. BAND) baseline metabolites were associated with changes in fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c). Longitudinal changes in 38 (RYGB vs. IMI) and 38 metabolites (RYGB vs. BAND) were significantly associated with changes in FPG or HbA1c. The identified metabolites are enriched in pathways involved in the biosynthesis of aminoacyl-tRNA and branched-chain amino acids. Weight-loss intervention evokes extensive changes in plasma metabolites, and the altered metabolome may underlie the differential glycemic outcomes in response to different types of weight-loss intervention, independent of weight loss itself.

Multi-omics analysis on the mechanism of the effect of Isatis leaf on the growth performance of fattening sheep.

This study evaluated the effects of Isatis Leaf (ISL) on the growth performance, gastrointestinal tissue morphology, rumen and intestinal microbiota, rumen, serum and urine metabolites, and rumen epithelial tissue transcriptome of fattening sheep. Twelve 3.5-month-old healthy fattening sheep were randomly divided into two groups, each with 6 replicates, and fed with basal diet (CON) and basal diet supplemented with 80 g/kg ISL for 2.5 months. Gastrointestinal tract was collected for histological analysis, rumen fluid and feces were subjected to metagenomic analysis, rumen fluid, serum, and urine for metabolomics analysis, and rumen epithelial tissue for transcriptomics analysis. The results showed that in the ISL group, the average daily gain and average daily feed intake of fattening sheep were significantly lower than those of the CON group (P < 0.05), and the rumen ammonia nitrogen level was significantly higher than that of the CON group (P < 0.01). The thickness of the reticulum and abomasum muscle layer was significantly increased (P < 0.05). At the genus level, the addition of ISL modified the composition of rumen and fecal microorganisms, and the relative abundance of Methanobrevibacter and Centipeda was significantly upregulated in rumen microorganisms, The relative abundance of Butyrivibrio, Saccharofermentans, Mogibacterium, and Pirellula was significantly downregulated (P < 0.05). In fecal microorganisms, the relative abundance of Papillibacter, Pseudoflavonifractor, Butyricicoccus, Anaerovorax, and Methanocorpusculum was significantly upregulated, while the relative abundance of Roseburia, Coprococcus, Clostridium XVIII, Butyrivibrio, Parasutterella, Macellibacteroides, and Porphyromonas was significantly downregulated (P < 0.05). There were 164, 107, and 77 different metabolites in the rumen, serum, and urine between the ISL and CON groups (P < 0.05). The differential metabolic pathways mainly included thiamine metabolism, niacin and nicotinamide metabolism, vitamin B6 metabolism, taurine and taurine metabolism, beta-Alanine metabolism and riboflavin metabolism. These metabolic pathways were mainly involved in the regulation of energy metabolism and immune function in fattening sheep. Transcriptome sequencing showed that differentially expressed genes were mainly enriched in cellular physiological processes, development, and immune regulation. In summary, the addition of ISL to the diet had the effect of increasing rumen ammonia nitrogen levels, regulating gastrointestinal microbiota, promoting body fat metabolism, and enhancing immunity in fattening sheep.

Mechanistic Insights into Nitrite Degradation by Metabolites of L. plantarum A50: An LC-MS-Based Untargeted Metabolomics Analysis

Nitrites are universally acknowledged natural toxic substances that frequently lead to poisoning in humans and animals. During fermentation, certain microorganisms utilize a portion of the nitrogen element and reduce nitrates to nitrites through specific metabolic pathways. In this study, a highly effective lactic acid bacterial strain, Lactiplantibacillus plantarum A50, was isolated and screened from alfalfa silage for its remarkable ability to degrade nitrites. L. plantarum A50 exhibits exceptional nitrite removal capacity, with a degradation rate of 99.06% within 24 h. Furthermore, L. plantarum A50 demonstrates normal growth under pH values ranging from 4 to 9 and salt concentrations of 5%, displaying excellent tolerance to acidity, alkalinity, and salinity. Additionally, it undergoes fermentation using various carbon sources. Within the first 6–12 h of culture, L. plantarum A50 primarily achieves nitrite degradation through non-acidic processes, resulting in a degradation rate of 82.67% by the 12th hour. Moreover, the metabolites produced by L. plantarum A50 exhibit a synergistic interaction with acidity, leading to a nitrite degradation rate of 98.48% within 24 h. Notably, both L. plantarum A50 and MRS broth were found to degrade nitrites. Consequently, a non-targeted metabolomic analysis using LC-MS was conducted to identify 342 significantly different metabolites between L. plantarum A50 and MRS broth. Among these, lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, and organoheterocyclic compounds emerged as the main constituents. Lipids and lipid-like molecules, derivatives of glucose and galactose, amino acids and their derivatives, as well as organoheterocyclic compounds, are likely to play a role in nitrite elimination. Through the enrichment analysis of differential metabolic pathways using KEGG, nine distinct pathways were identified. These pathways provide essential nutrients, maintain cellular structure and function, participate in substance transport, regulate metabolic activities, and enhance resistance against pathogenic microorganisms in L. plantarum A50.

Metabolomic analysis of hydroxycinnamic acid inhibition on Saccharomyces cerevisiae.

Ferulic acid (FA) and p-coumaric acid (p-CA) are hydroxycinnamic acid inhibitors that are mainly produced during the pretreatment of lignocellulose. To date, the inhibitory mechanism of hydroxycinnamic acid compounds on Saccharomyces cerevisiae has not been fully elucidated. In this study, liquid chromatography-mass spectrometry (LC-MS) and scanning electron microscopy (SEM) were used to investigate the changes in S. cerevisiae cells treated with FA and p-CA. In this experiment, the control group was denoted as group CK, the FA-treated group was denoted as group F, and the p-CA-treated group was denoted as group P. One hundred different metabolites in group F and group CK and 92 different metabolites in group P and group CK were selected and introduced to metaboanalyst, respectively. A total of 38 metabolic pathways were enriched in S. cerevisiae under FA stress, and 27 metabolic pathways were enriched in S. cerevisiae under p-CA stress as identified through Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. The differential metabolites involved included S-adenosine methionine, L-arginine, and cysteine, which were significantly downregulated, and acetyl-CoA, L-glutamic acid, and L-threonine, which were significantly upregulated. Analysis of differential metabolic pathways showed that the differentially expressed metabolites were mainly related to amino acid metabolism, nucleotide metabolism, fatty acid degradation, and the tricarboxylic acid cycle (TCA). Under the stress of FA and p-CA, the metabolism of some amino acids was blocked, which disturbed the redox balance in the cells and destroyed the synthesis of most proteins, which was the main reason for the inhibition of yeast cell growth. This study provided a strong scientific reference to improve the durability of S. cerevisiae against hydroxycinnamic acid inhibitors. KEY POINTS: • Morphological changes of S. cerevisiae cells under inhibitors stress were observed. • Changes of the metabolites in S. cerevisiae cells were explored by metabolomics. • One of the inhibitory effects on yeast is due to changes in the metabolic network.

Study on the chronic inflammatory injury caused by Ageratina adenophora on goat liver using metabolomics

Ageratina adenophora (A. adenophora) is an invasive plant that is harmful to animals. The plants toxic effects on the liver have been studied in detail, however, the inflammation aspects of the hepatotoxicity are rarely discussed in literature. Therefore, in this study, we investigated the level of inflammation and the associated changes in liver metabolism caused by A. adenophora ingestion. Goat were fed with A. adenophora powder which accounts for 40% of the forage for 90 d. After the feeding period, the liver tissues were collected and the level of inflammation was detected using H & E staining and the changes in metabolites by LC-MS/MS. The results indicated that A. adenophora changes the liver metabolites, The test group shown 153 different metabolites in liver of which 71 were upregulated and 82 down regulated. We also found two differential metabolic pathways: neuroactive ligand-receptor interaction and pyrimidine metabolism. The changes in the pathway suggested an association with inflammation and with pathological processes such as oxidative stress and apoptosis. In addition, we observed an increase in the levels of serum liver function indexes (AST and ALT), indicating the liver injury. Furthermore, inflammatory cell infiltration and cell degeneration were observed in histopathological sections.In conclusion, this study reveals that A. adenophora causes chronic inflammation and upregulate metabolites related to inflammation in the liver. The study complements the research content of A. adenophora hepatotoxicity and provides a basis for further research by analyzing changes in the liver metabolites.

Effect of feeding a dried distillers' grains with solubles diet on the metabolism of the intestinal wall in Guanling crossbred cattle: a preliminary assessment.

Dried distillers' grains with solubles (DDGS)-based diets are nutritious and can improve the inflammations and intestinal immunity in livestock. However, there is limited research examining the effect of feeding DDGS-based diets on changes in intestinal metabolites and related pathways in livestock. In this study, six Guanling crossbred cattle (Guizhou Guanling Yellow cattle × Simmental cattle) were selected and divided into a basal diet (BD) group and an experimental group fed with DDGS replacing 25% of the daily ration concentrates (DDGS) (n=3), respectively. Fresh jejunum (J), ileum (I) and cecum (C) tissues were collected for metabolomic analysis. Differential metabolites and metabolic pathways were explored by means of univariate and multivariate statistical analysis. In comparison to the J-BD group, 123 differential metabolites (VIP > 1, p < 0.05) were identified in the J-DDGS group, which (top 20) were mainly divided into superclasses, including lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. Compared with the I-BD group, 47 differential metabolites were obtained in the I-DDGS group, which were mainly divided into superclasses, including lipids and lipid-like molecules and organic acids and derivatives. The C-DDGS vs. C-BD comparison revealed 88 differential metabolites, which were mainly divided into superclasses, including lipids and lipid-like molecules, organic oxygen compounds, and nucleosides. A total of 34 significant metabolic pathways were found (p < 0.05, -log(p) > 1.3). Among them, 3 significant pathways were significantly enriched in the J-DDGS group, 11 significant pathways were significantly enriched in the I-DDGS group, and 20 significant pathways were significantly enriched in the C-DDGS group. Importantly, primary bile acid biosynthesis, linoleic acid metabolism, and arachidonic acid metabolism correlated with intestinal inflammation and immunity by regulating gut microbiota, prostaglandin synthesis, and cell signaling. The data suggest that DDGS-fed cattle unregulated three metabolic pathways mentioned above and that a DDGS-based diet was able to maintain a balance of these three metabolic pathways, thus resulting in improvement of intestinal inflammation and enhanced immunity in cattle. In conclusion, the DDGS diet has the potential to improve intestinal inflammation and enhance the immunity of Guanling crossbred cattle by regulating the metabolic patterns of lipids and lipid-like molecules, organic acids and derivatives, and related metabolic pathways. These results allude to potential metabolic regulatory mechanisms of DDGS diets and also provide a theoretical basis for the application of DDGS in livestock feed.

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.

Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS. We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.

Identification of urine biomarkers predictive of prolonged QTc interval in multidrug-resistant tuberculosis patients treated with bedaquiline.

The most frequent adverse event associated with bedaquiline (BDQ) is the QTc interval prolongation; however, there was no biomarkers that could be used to predict the occurrence of QTc prolongation in BDQ-treated patients. In this study, we employed the ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to generate metabolic profiling for the discovery of potential predictive urine biomarkers of QTc prolongation in these patients. Untargeted metabolomic technique was used to concentrate the differential metabolic pathway, and targeted metabolomic technique was subsequently performed to identify predictive biomarkers for QTc prolongation. A total of 45 rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) patients were enrolled in our study, including 15 RR/MDR-TB patients with QTc interval prolongation (QIP) and 30 RR/MDR-TB patients with QTc interval un-prolongations (QIU). Untargeted technique revealed that the lipid metabolism was the most differential metabolic pathway between two groups. Further targeted technique identified four differential metabolites, including betaine, LPE (18:2), LPE (20:3), and LPE (20:4). The combined analysis of metabolisms revealed that the combined use of LPE (20:3) and LPE (20:4) had the best performance for predicting the occurrence of QTc prolongation in TB patients, yielding a sensitivity of 87.4% and a specificity of 78.5%. In addition, with the progression of BDQ treatment, the LPEs exhibited persistent difference in the BDQ-treated TB patients experiencing QTc interval prolongation. In conclusion, our data demonstrate that the combined use of LPE (20:3) and LPE (20:4) yields promising performance for predicting the occurrence of QTc interval prolongation in BDQ-treated patients.

EMPathways2: Estimation of Enzyme Expression and Metabolic Pathway Activity Using RNA-Seq Reads.

In this chapter, we outline an approach to analyzing metatranscriptomic data, focusing on the assessment of differential enzyme expression and metabolic pathway activities using a novel bioinformatics software tool, EMPathways2. The analysis pipeline commences with raw data originating from a sequencer and concludes with an output of enzyme expressions and an estimate of metabolic pathway activities. The initial step involves aligning specific transcriptomes assembled from RNA-Seq data using Bowtie2 and acquiring gene expression data with IsoEM2. Subsequently, the pipeline proceeds to quality assessment and preprocessing of the input data, ensuring accurate estimates of enzymes and their differential regulation. Upon completion of the preprocessing stage, EMPathways2 is employed to decipher the intricate relationships between genes, enzymes, and pathways. An online repository containing sample data has been made available, alongside custom Python scripts designed to modify the output of the programs within the pipeline for diverse downstream analyses. This chapter highlights the technical aspects and practical applications of using EMPathways2, which facilitates the advancement of transcriptome data analysis and contributes to a deeper understanding of the complex regulatory mechanisms underlying living systems.

Insights from metagenomics into gut microbiome associated with acute coronary syndrome therapy.

Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy.

Analysis of cerebrospinal fluid metabolites affected by WenDanTang based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry.

WenDanTang (WDT) is a Chinese herbal formula used to treat various diseases, including neurodegenerative diseases. However, the neuroprotective metabolic pathways and the components involved in this process are not fully understood. In this study, we examined the neuroprotective metabolic pathways of WDT in rat brains using cerebrospinal fluid metabolomics and ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Twelve rats were randomly divided into a WDT (administrated with WDT solution) and a control group. The ultra-high-performance liquid chromatography technique was used to explore the components of the WDT solution and cerebrospinal fluid, and secondary mass spectra of cerebrospinal fluid were used to identify possible brain-incorporating components after WDT. The results of the differential metabolism analysis showed that eight metabolites were typically altered (all p < 0.05). By comparing the secondary mass spectra of the cerebrospinal fluid of rats and WDT solution, two possible brain-incorporating components of WDT, stachydrine and α-methoxyphenylacetic acid, were identified. The data also suggested that WDT affects nucleotide metabolism, glutathione metabolism, and B-vitamin metabolic pathways, the central differential metabolic pathways. These data suggest that WDT protects neurons through its active components, such as stachydrine, and regulates biochemical metabolism to affect the brain's energy metabolism and antioxidant capacity.

Effect of low-voltage electrostatic field-assisted partial freezing on large yellow croaker protein properties and metabolomic analysis during storage.

Large yellow croaker is highly perishable during storage because of high protein and moisture content. The degradation of the fish is mainly attributed to microbial growth and enzyme activity, so it is important to find an efficient storage method to extend its shelf life. This study investigated the effect of a low-voltage electrostatic field combined with partial freezing treatment on the physicochemical properties of myofibrillar protein (MP) and metabolomic analysis of large yellow croaker during preservation. The samples in chilled storage (C), partial freezing storage (PF) and 6 kV/m low-voltage electrostatic field partial freezing storage (LVEF-PF) were analyzed during an 18 day storage period. In comparison with the C and PF groups, LVEF-PF delayed the oxidation of MP by inhibiting the formation of carbonyl groups (2.25 nmol/mg pro), and maintaining higher sulfhydryl content (29.73 nmol/mg pro). Fourier transform infrared (FTIR) spectroscopy and fluorescence spectroscopy analysis also demonstrated that the LVEF-PF treatment maintained the stability of the protein structure by increasing the a-helix ratio (19.88%) and reducing the random coil ratio (17.83%). Scanning electron microscopy showed that, compared with the LVEF-PF group, there was more degeneration and aggregation of MP in the C and PF groups after 18 days' storage. The results of untargeted metabolomic analysis showed that 415 kinds of differential metabolites were identified after storage, and the difference levels of differential metabolites were least between the samples treated with LVEF-PF stored on the ninth day and the fresh samples. The main differential metabolic pathways during storage were amino acid metabolism and lipid metabolism. The LVEF-PF treatment could maintain the stability of myofibrillar protein in large yellow croaker during storage. These results showed a potential application of the LVEF-PF method for aquatic product preservation. © 2023 Society of Chemical Industry.

Proteomics and Metabolomics Analysis Reveal the Regulation Mechanism of Linoleate Isomerase Activity and Function in Propionibacterium acnes.

Conjugated linoleic acid (CLA) holds significant application prospects due to its anticancer, anti-atherosclerosis, lipid-lowering, weight-loss, and growth-promoting functions. The key to its efficient production lies in optimizing the biocatalytic performance of linoleic acid isomerase (LAI). Here, we constructed a Propionibacterium acnes mutant library and screened positive mutants with high linoleate isomerase activity. The proteomics and metabolomics were used to explore the mechanism in the regulation of linoleic acid isomerase activity. High-throughput proteomics revealed 104 differentially expressed proteins unique to positive mutant strains of linoleic acid isomerase of which 57 were upregulated and 47 were downregulated. These differentially expressed proteins were primarily involved in galactose metabolism, the phosphotransferase system, starch metabolism, and sucrose metabolism. Differential metabolic pathways were mainly enriched in amino acid biosynthesis, including glutamate metabolism, the Aminoacyl-tRNA biosynthesis pathway, and the ABC transporter pathway. The upregulated metabolites include dl-valine and Acetyl coA, while the downregulated metabolites include Glutamic acid and Phosphoenolpyruvate. Overall, the activity of linoleic acid isomerase in the mutant strain was increased by the regulation of key proteins involved in galactose metabolism, sucrose metabolism, and the phosphotransferase system. This study provides a theoretical basis for the development of high-yield CLA food.

Effects of partial reduction of polystyrene micro-nanoplastics on the immunity, gut microbiota and metabolome of mice

Microplastic (MP) and nanoplastic (NP) could cause gut microbiota alterations. Although micro/nanoplastic (MNP) degradation is attracting increasing scientific interest, the evaluation of MNP reduction in gut needs to be further investigated. This study aimed to determine whether partial reduction of polystyrene MNP in gut could affect the immunity, gut microbiota and metabolome of mice. Serum eotaxin/CCL11 was at a lower level in the mice exposed to 200 μg and 500 μg NP (i.e., 2NP and 5NP groups, respectively) compared to those exposed to 500 μg MP (i.e., 5 MP group), while serum IL-2 and IL-4 were both greater in the 5NP group compared to the 5 MP group. The gut bacterial alpha diversity, fungal diversity and evenness were all similar among the MNP and control groups. However, the gut fungal richness was greater in both the 5NP and 5 MP groups compared to the control group. The gut bacterial and fungal compositions were both different between the MNP and control groups. Multiple gut bacteria and fungi showed different levels between the 2NP and 5NP groups, as well as between the 2NP and 5 MP groups. Increased Staphylococcus and decreased Glomus were determined in the 2NP group compared to both the 5NP and 5 MP groups. A Lactobacillus phylotype was found as the sole gatekeeper in the bacterial network of the 2NP group, while a Bifidobacterium phylotype contributed most to the stability of the bacterial networks of both the 5NP and 5 MP groups. Multiple differential gut metabolic pathways were found between the 2NP and 5NP/5 MP groups, and mTOR signaling pathway was largely upregulated in the 2NP group compared to both the 5NP and 5 MP groups. The relevant results could help with the evaluation of partial reduction of MNP in gut.

Lipid characteristics of lung tissue in silicosis rat model were studied based on lipid metabolomics

Silicosis is a common occupational disease caused by the long-term inhalation of large amounts of silica dust. Lipid metabolism plays an important role in the progression of silicosis, but its contributing mechanism remains unclear. The aim of this study was to investigate the differential lipid metabolites and active metabolic pathways in silicosis rat lung tissue. We first constructed a silicosis rat model, and randomly divided 24 male SD rats into control group (C), silicosis group for 1 week (S1W), silicosis group for 2 weeks (S2W) and silicosis group for 4 weeks (S4W) with 6 rats in each group. 1 mL SiO2 suspension (50 mg/mL) or normal saline were injected into the trachea, and the rats were killed at 1 week, 2 weeks and 4 weeks, respectively. The lung tissue pathology of the rats was observed by HE staining and VG staining, and the plasma TC and FC levels were detected by the kit. Western blot was used to detect the expression of lipid-related factors CD36, PGC1α and LXR. In addition, lipidomics analysis of lung tissue samples was performed using UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze lipid enrichment, and verified the expression of differential gene CHPT1 in the metabolic pathway. HE and VG staining showed that the number of nodules and fibrosis increased in a time-dependent manner in the silicosis model group, and the levels of TC, FC and CE in silicosis plasma increased. Western blot results showed that PGC1α and LXR decreased in the silicosis model group, while CD36 expression increased. In addition, metabolomics screened out 28 differential metabolites in the S1W group, 32 in the S2W group, and 22 in the S4W group, and found that the differential metabolites were mainly enriched in metabolic pathways such as glycerophospholipid metabolism and ether lipid metabolism, and the expression of differential gene CHPT1 in the metabolic pathway was decreased in the silicosis model group. These results suggest that there are significant changes in lipid metabolites in lung tissue in silicosis rat models, and glycerophospholipid metabolism was significantly enriched, suggesting that glycerophospholipids play an important role in the progression of silicosis. The differential metabolites and pathways reported in this study may provide new ideas for the pathogenesis of silicosis.

Integrated metabolomic and lipidomic analysis revealed the protective mechanisms of Erzhi Wan on senescent NRK cells through BRL cells

Ethnopharmacological relevanceErzhi Wan (EZW), as a prescription of traditional Chinese medicine, has been used for tonifying the liver and kidney. Although past studies have shown that EZW has potential anti-aging effect, the mechanisms associated with cellular metabolomics and lipidomics are not fully understood. Aim of the studyThis study aimed to evaluate the anti-aging effect of EZW and investigate the mechanisms associated with cellular metabolomics and lipidomics. Materials and methodsEZW solution at dosage of 3.6 g/kg in Sprague-Dawley rats was orally administered twice a day for 7 days and serum containing EZW was then collected. NRK cell senescence model induced by D-galactose was established in vitro, and non-contact co-culture cell assay was performed between senescent NRK cells and BRL cells intervened by serum containing EZW. The anti-aging effect of EZW on NRK cells was evaluated by metabolites identification, differential metabolites screening and metabolic pathways analysis through cellular metabolomics with GC-MS and lipidomics with UHPLC-Q-Exactive Orbitrap/MS. ResultsSerum containing EZW indicated a protective effect through intervening BRL cells in non-contact co-culture system with D-gal-induced senescent NRK cells. For metabolic profiles, 71 endogenous metabolites were identified, among which 24 significantly differential metabolites were screened as metabolomics potential biomarkers. For lipidic profiles, 64 lipid components were identified in NRK cell samples under positive ion mode, among which 24 potential biomarkers of lipids were screened, mainly including PC and PE. 127 lipid components were identified in NRK cell samples under negative ion mode, among which 59 potential biomarkers of lipids were screened, including FA, PC, PE, PI and PS. Metabolic pathway analysis demonstrated that the identified differential metabolites found mainly involved in amino acids metabolism, energy metabolism and phospholipid biosynthesis pathways. ConclusionSerum containing EZW exhibited protective effect on D-gal-induced senescent NRK cells through intervening BRL cells by mainly regulating amino acids metabolism, energy metabolism and phospholipid biosynthesis pathways to possess its anti-aging function, providing a theoretical basis for clinical treatment of EZW.

A Preliminary Study on the Plasma Metabolomic Profiles of Patients Suffering From Acute Diquat Poisoning

To analyze the plasma metabolomic features of patients suffering from acute diquat (DQ) poisoning and to explore the molecular mechanism and potential biomarkers of DQ poisoning. A total of 7 patients suffering from acute DQ poisoning were enrolled in the DQ poisoning group. The poisoning of these patients occurred within a 12-h window at the time of enrollment. Meanwhile, 7 healthy immediate family members of the patients were enrolled as the normal controls. Liquid chromatography-mass spectrometry (LC-MS) was used to perform non-targeted metabolomic profiling of the plasma samples and to screen and identify differential metabolites and metabolic pathways. A total of 104 metabolites were screened and identified (P<0.05 and the variable importance in the projection [VIP]>1). Compared with those of the control group, 61 metabolites, such as sorbitol and galactitol, were up-regulated, and 43 metabolites, such as myo-inositol and gamma-glutamylcysteine, were down-regulated in the DQ poisoning group. Pathway enrichment analysis revealed changes in 11 metabolic pathways, including those for galactose metabolism and linoleic acid metabolism (P<0.05). Metabolomics analysis of plasma samples from DQ poisoning patients shows that DQ mainly interferes with the metabolism of energy, amino acids, and lipids, thus causing metabolic disorders. Some potential biomarkers closely associated with oxidative stress and organ damage of the liver, kidney, and nervous system have been identified.

Potential nervous threat of nanoplastics to Monopterus albus: Implications from a metabolomics study

Nanoplastics, as a new class of environmental pollutants, have been frequently detected in environmental media and organisms. Monopterus albus (M. albus) is an important economic aquatic product with a high dietary consumption. However, the potential biological effects of nanoplastics on M. albus remain unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) at different concentrations (0, 0.5, 1, 5 and 10 mg/L) on M. albus were investigated using an untargeted metabolomics approach. The results showed that 59, 44, 24, and 31 individual differential metabolites and 16, 9, 6, and 2 significant differential metabolic pathways were significantly changed in 0.5, 1, 5, and 10 mg/L respectively, indicating the greater effect of PS-NPs at the relatively low concentrations. After further analysis, there are four same significant differential metabolic pathways for the 0.5 and 1 mg/L groups, i.e., ABC transporters, cAMP signaling pathway, Neuroactive ligand-receptor interaction, and Synaptic vesicle cycle. In addition, there was one mutual differential metabolic pathway (Neuroactive ligand-receptor interaction) among the four groups, indicative of the probably universal nervous influence of nanoplastics on M. albus. In a word, the current work suggests that PS-NPs might affect the nervous systems of M. albus through disturbing their liver metabolism, and nanoplastics at relatively low concentrations may possess a greater effect, which provides significant information for assessing the toxic effect and exposure risk of nanoplastics to organisms in aquatic environment.

Eleven metabolism‑related genes composed of Stard5 predict prognosis and contribute to EMT phenotype in HCC

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with a high mortality and poor survival rate. Abnormal tumor metabolism is considered a hallmark of HCC and is a potential therapeutic target. This study aimed to identify metabolism-related biomarkers to evaluate the prognosis of patients with HCC.MethodThe Cancer Genome Atlas (TCGA) database was used to explore differential metabolic pathways based on high and low epithelial-mesenchymal transition (EMT) groupings. Genes in differential metabolic pathways were obtained for HCC metabolism-related molecular subtype analysis. Differentially expressed genes (DEGs) from the three subtypes were subjected to Lasso Cox regression analysis to construct prognostic risk models. Stard5 expression in HCC patients was detected by western blot and immunohistochemistry (IHC), and the role of Stard5 in the metastasis of HCC was investigated by cytological experiments.ResultsUnsupervised clustering analysis based on metabolism-related genes revealed three subtypes in HCC with differential prognosis. A risk prognostic model was constructed based on 11 genes (STARD5, FTCD, SCN4A, ADH4, CFHR3, CYP2C9, CCL14, GADD45G, SOX11, SCIN, and SLC2A1) obtained by LASSO Cox regression analysis of the three subtypes of DEGs. We validated that the model had a good predictive power. In addition, we found that the high-risk group had a poor prognosis, higher proportion of Tregs, and responded poorly to chemotherapy. We also found that Stard5 expression was markedly decreased in HCC tissues, which was associated with poor prognosis and EMT. Knockdown of Stard5 contributed to the invasion and migration of HCC cells. Overexpression of Stard5 inhibited EMT in HCC cells.ConclusionWe developed a new model based on 11 metabolism-related genes, which predicted the prognosis and response to chemotherapy or immunotherapy for HCC. Notably, we demonstrated for the first time that Stard5 acted as a tumor suppressor by inhibiting metastasis in HCC.

Research on sweat metabolomics of athlete's fatigue induced by high intensity interval training.

Objective: Sweat is an important specimen of human metabolism, which can simply and non-invasively monitor the metabolic state of the body, and its metabolites can be used as biomarkers for disease diagnosis, while the changes of sweat metabolites before and after exercise-induced fatigue are still unclear. Methods: In this experiment, high-performance chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) was used to metabolomic 28 sweat samples before and after exercise-induced fatigue of 14 long-distance runners, also IsoMS PRO and SPSS22.0 software were used to analyze the metabolite changes and differential metabolic pathways. Results: A total of 446 metabolites with high confidence were identified, and the sweat metabolome group before and after high-intensity interval exercise-induced fatigue was obvious, among which the upregulated differential metabolites mainly included hypoxanthine, pyruvate, several amino acids, etc., while the downregulated differential metabolites mainly included amino acid derivatives, vitamin B6, theophylline, etc. Conclusion: The change of hypoxanthine concentration in sweat can be used as a good biomarker for the diagnosis of exercise-induced fatigue, while the change of pyruvate content in sweat can be used as a discriminant index for the energy metabolism mode of the body before and after exercise. The main metabolic pathways involved in differential metabolites produced before and after HIIT exercise-induced fatigue are purine metabolism and amino acid metabolism.