PubMed

Environ Int. 2023 May 15;176:107977. doi: 10.1016/j.envint.2023.107977. Online ahead of print.ABSTRACTSeveral per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced β-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.PMID:37244004 | DOI:10.1016/j.envint.2023.107977

Physiol Plant. 2023 May 27:e13939. doi: 10.1111/ppl.13939. Online ahead of print.ABSTRACTThe floral colouration of tulip flowers is one of the most prominent traits contributing to its high ornamental value. The molecular mechanisms of petal colouration remain elusive in tulip species. In this study, we performed comparative metabolome and transcriptome analyses using four tulip cultivars with distinguished petal colours. Four types of anthocyanins were identified, including cyanidin derivatives and pelargonidin derivatives. Comparative transcriptome analysis identified 22303 differential expressed genes (DEGs) from the four cultivars, and 2589 DEGs were commonly regulated in three comparison groups (coloured vs white cultivar), including anthocyanins biosynthesis-related genes and regulatory transcription factors. Two basic helix-loop-helix (bHLH) transcription factors, TgbHLH42-1 and TgbHLH42-2, with differential expression levels among cultivars and petal developmental stages, have high homology to TRANSPARENT TESTA 8 (AtTT8) of Arabidopsis. The anthocyanins accumulation in TgbHLH42-1 overexpressing (OE) seedlings was markedly greater than that in wild-type seedlings in the presence of methyl jasmonate (MeJA), but not for TgbHLH42-2 OE seedlings. Both TgbHLH42-1 and TgbHLH42-2 restored pigmentation defects in tt8 mutant seeds after complementation assay. TgbHLH42-1 could interact with MYB protein AtPAP1 to synergistically activate the transcription of AtDFR, whereas TgbHLH42-2 failed to. Silencing TgbHLH42-1 or TgbHLH42-2 individually could not, but simultaneously silencing both TgbHLH42 could reduce the anthocyanin in tulip petals. These results indicate that TgbHLH42-1 and TgbHLH42-2 function partially redundantly to positively regulate anthocyanin biosynthesis during tulip petal colouration. This article is protected by copyright. All rights reserved.PMID:37243848 | DOI:10.1111/ppl.13939

Int Arch Occup Environ Health. 2023 May 27. doi: 10.1007/s00420-023-01987-4. Online ahead of print.ABSTRACTOBJECTIVE: Welding fume exposure is inevitable of welding workers and poses a severe hazard to their health since welding is a necessary industrial process. Thus, preclinical diagnostic symptoms of worker exposure are of great importance. The aim of this study was to screen serum differential metabolites of welding fume exposure based on UPLC-QTOF-MS/MS.METHODS: In 2019, 49 participants were recruited at a machinery manufacturing factory. The non-target metabolomics technique was used to clarify serum metabolic signatures in people exposed to welding fume. Differential metabolites were screened by OPLS-DA analysis and Student's t-test. The receiver operating characteristic curve evaluated the discriminatory power of differential metabolites. And the correlations between differential metabolites and metal concentrations in urine and whole blood were analyzed utilizing Pearson correlation analysis.RESULTS: Thirty metabolites were increased significantly, and 5 metabolites were decreased. The differential metabolites are mainly enriched in the metabolism of arachidonic acid, glycero phospholipid, linoleic acid, and thiamine. These results observed that lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol(PGF1α/16:0) had a tremendous anticipating power with relatively increased AUC values (AUC > 0.9), and they also presented a significant correlation of Mo concentrations in whole blood and Cu concentrations in urine, respectively.CONCLUSION: The serum metabolism was changed significantly after exposure to welding fume. Lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol (PGF1α/16:0) may be a potential biological mediator and biomarker for laborers exposure to welding fume.PMID:37243737 | DOI:10.1007/s00420-023-01987-4

Macromol Biosci. 2023 May 27:e2300016. doi: 10.1002/mabi.202300016. Online ahead of print.ABSTRACTTo provide prominent accessibility of fishmeal to the European population, the currently available, time- and cost-extensive feeding trials, which evaluate fish feed, should be replaced. The current paper reports on the development of a novel 3D culture platform, mimicking the microenvironment of the intestinal mucosa in vitro. The key requirements of the model include sufficient permeability for nutrients and medium size marker molecules (equilibrium within 24 hours), suitable mechanical properties (G' < 10 kPa), and a close morphological similarity to the intestinal architecture. To enable processability with light-based 3D-printing, a gelatin-methacryloyl-aminoethyl-methacrylate (gel-MA-AEMA)-based biomaterial ink was developed and combined with Tween® 20 as porogen to ensure sufficient permeability. To assess the permeability properties of the hydrogels, a static diffusion setup was utilized, indicating that the hydrogel constructs are permeable for a medium size marker molecule (FITC-dextran 4 kg·mol-1 ). Moreover, the mechanical evaluation through rheology evidenced a physiologically relevant scaffold stiffness (G' = 4.83±0.78 kPa). Digital light processing (DLP)-based 3D printing of porogen-containing hydrogels resulted in the creation of constructs exhibiting a physiologically relevant microarchitecture as evidenced through cryo-scanning electron microscopy. Finally, the combination of the scaffolds with a novel Rainbow Trout (Oncorhynchus mykiss) intestinal epithelial cell line (RTdi-MI) evidenced scaffold biocompatibility. This article is protected by copyright. All rights reserved.PMID:37243584 | DOI:10.1002/mabi.202300016

Neurogastroenterol Motil. 2023 May 27:e14615. doi: 10.1111/nmo.14615. Online ahead of print.ABSTRACTBACKGROUND: Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria-driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro-inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions.PURPOSE: Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies.PMID:37243442 | DOI:10.1111/nmo.14615

J Cachexia Sarcopenia Muscle. 2023 May 26. doi: 10.1002/jcsm.13240. Online ahead of print.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, leading to chronic synovial inflammation and local tissue destruction. Extra-articular manifestations may also occur, such as changes in body composition. Skeletal muscle wasting is often observed in patients with RA, but methods for assessing loss of muscle mass are expensive and not widely available. Metabolomic analysis has shown great potential for identifying changes in the metabolite profile of patients with autoimmune diseases. In this setting, urine metabolomic profiling in patients with RA may be a useful tool to identify skeletal muscle wasting.METHODS: Patients aged 40-70 years with RA have been recruited according to the 2010 ACR/EULAR classification criteria. Further, the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) determined the disease activity. The muscle mass was measured by Dual X-ray absorptiometry (DXA) to generate the appendicular lean mass index (ALMI) by summing the lean mass measurements for both arms and legs and dividing them by height squared (kg/height2 ). Finally, urine metabolomic analysis by 1 H nuclear magnetic resonance (1 H-NMR) spectroscopy was performed and the metabolomics data set analysed using the BAYESIL and MetaboAnalyst software packages. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the 1 H-NMR data, followed by Spearman's correlation analysis. The combined receiver operating characteristic curve (ROC) was calculated, as well as the logistic regression analyses to establish a diagnostic model. The significance level at P < 0.05 was set for all analyses.RESULTS: The total set of subjects investigated included 90 patients with RA. Most patients were women (86.7%), with a mean age of 56.5 ± 7.3 years old and a median DAS28-CRP of 3.0 (IQR 1.0-3.0). Fifteen metabolites were identified in the urine samples with high variable importance in projection (VIP scores) by MetaboAnalyst. Of these, dimethylglycine (r = 0.205; P = 0.053), oxoisovalerate (r = -0.203; P = 0.055), and isobutyric acid (r = -0.249; P = 0.018) were significantly correlated with ALMI. Based on the low muscle mass (ALMI ≤6.0 kg/m2 for women and ≤8.1 kg/m2 for men) a diagnostic model have been established with dimethylglycine (area under the curve [AUC] = 0.65), oxoisovalerate (AUC = 0.49), and isobutyric acid (AUC = 0.83) with significant sensitivity and specificity.CONCLUSIONS: Isobutyric acid, oxoisovalerate, and dimethylglycine from urine samples were associated with low skeletal muscle mass in patients with RA. These findings suggest that this group of metabolites may be further tested as biomarkers for identification of skeletal muscle wasting.PMID:37243418 | DOI:10.1002/jcsm.13240

Pharmaceuticals (Basel). 2023 May 9;16(5):719. doi: 10.3390/ph16050719.ABSTRACTAbnormal uterine bleeding (AUB) is a common and frequently occurring disease in gynecology, seriously threatening women's health. Baoyin Jian (BYJ) is a classical prescription for treating AUB. However, the lack of quality control standards of BYJ for AUB have limited the development and applications of BYJ. This experiment aims to explore the mechanism of action and screen the quality markers (Q-markers) of BYJ against AUB through the Chinmedomics strategy to improve the quality standards of Chinese medicine and provide scientific basis for its further development. BYJ has hemostatic effects in rats, as well as the ability to regulate the coagulation system following incomplete medical abortion. According to the results of histopathology, biochemical indexes and urine metabolomics, a total of 32 biomarkers of ABU in rats were identified, 16 of which can be significantly regulated by BYJ. Using traditional Chinese medicine (TCM) serum pharmacochemistry technology, 59 effective components were detected in vivo, of which 13 were highly correlated with efficacy, and 9 components, namely catalpol, rehmannioside D, paeoniflorin, berberine, phellodendrine, baicalin, asperosaponinVI, liquiritin, and glycyrrhizic acid, were screened out as the Q-markers of BYJ based on the "Five Principles" of Q-markers. In sum, BYJ can effectively alleviate abnormal bleeding symptoms and metabolic abnormalities in AUB rats. The study shows that Chinmedomics is an effective tool for screening Q-markers and provides scientific support for the further development and clinical use of BYJ.PMID:37242503 | DOI:10.3390/ph16050719

Pharmaceuticals (Basel). 2023 May 8;16(5):714. doi: 10.3390/ph16050714.ABSTRACTThe gut microbiota and its overall genetic composition, the microbiome, have been the subject of extensive research over the last decade within the fields of genomics, transcriptomics and metabolomics, and their role in various other targeted approaches and advanced technologies has been explored [...].PMID:37242497 | DOI:10.3390/ph16050714

Nutrients. 2023 May 21;15(10):2400. doi: 10.3390/nu15102400.ABSTRACTThis study aimed to identify the serum metabolites associated with sarcopenic risk in Japanese patients with type 2 diabetes, determine the effect of dietary protein intake on the serum metabolic profile, and examine its association with sarcopenia. Ninety-nine Japanese patients with type 2 diabetes were included, and sarcopenic risk was defined as low muscle mass or strength. Seventeen serum metabolites were quantified after gas chromatography-mass spectrometry analysis. The relationship between dietary protein intake and the metabolites concerning sarcopenia was analyzed, and the factors affecting sarcopenic risk were clarified. Twenty-seven patients were classified as being at risk of sarcopenia, the same as the general risk, which was associated with older age, a longer duration of the disease, and a lower body mass index. Low levels of leucine and glutamic acid were significantly associated with low muscle strength (p = 0.002 and p < 0.001, respectively), and leucine was also associated with muscle mass (p = 0.001). Lower levels of glutamic acid had higher odds of sarcopenic risk after being adjusted for age and HbA1c (adjusted OR 4.27, 95% CI 1.07-17.11, p = 0.041), but not for leucine. Leucine and glutamic acid can serve as useful biomarkers for sarcopenia, highlighting potential targets for its prevention.PMID:37242283 | DOI:10.3390/nu15102400

Nutrients. 2023 May 18;15(10):2361. doi: 10.3390/nu15102361.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, not previously ascribed strains from both Lactobacillus and Bifidobacterium genera were proposed as potential probiotics based on their ability to increase epithelial barrier integrity and immunity, promote GLP-1 secretion, and produce metabolites relevant to liver health.PMID:37242245 | DOI:10.3390/nu15102361

Nutrients. 2023 May 17;15(10):2342. doi: 10.3390/nu15102342.ABSTRACTThe important metabolic characteristics of cancer cells include increased fat production and changes in amino acid metabolism. Based on the category of tumor, tumor cells are capable of synthesizing as much as 95% of saturated and monounsaturated fatty acids through de novo synthesis, even in the presence of sufficient dietary lipid intake. This fat transformation starts early when cell cancerization and further spread along with the tumor cells grow more malignant. In addition, local catabolism of tryptophan, a common feature, can weaken anti-tumor immunity in primary tumor lesions and TDLN. Arginine catabolism is likewise related with the inhibition of anti-tumor immunity. Due to the crucial role of amino acids in tumor growth, increasing tryptophan along with arginine catabolism will promote tumor growth. However, immune cells also require amino acids to expand and distinguish into effector cells that can kill tumor cells. Therefore, it is necessary to have a deeper understanding of the metabolism of amino acids and fatty acids within cells. In this study, we established a method for the simultaneous analysis of 64 metabolites consisting of fatty acids and amino acids, covering biosynthesis of unsaturated fatty acids, aminoacyl-tRNA biosynthesis, and fatty acid biosynthesis using the Agilent GC-MS system. We selected linoleic acid, linolenic acid, sodium acetate, and sodium butyrate to treat H460 cells to validate the current method. The differential metabolites observed in the four fatty acid groups in comparison with the control group indicate the metabolic effects of various fatty acids on H460 cells. These differential metabolites could potentially become biomarkers for the early diagnosis of lung cancer.PMID:37242225 | DOI:10.3390/nu15102342

Nutrients. 2023 May 17;15(10):2339. doi: 10.3390/nu15102339.ABSTRACTHuman milk represents an optimal source of nutrition during infancy. Milk also serves as a vehicle for the transfer of growth factors, commensal microbes, and prebiotic compounds to the immature gastrointestinal tract. These immunomodulatory and prebiotic functions of milk are increasingly appreciated as critical factors in the development of the infant gut and its associated microbial community. Advances in infant formula composition have sought to recapitulate some of the prebiotic and immunomodulatory functions of milk through human milk oligosaccharide (HMO) fortification, with the aim of promoting healthy development both within the gastrointestinal tract and systemically. Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on serum metabolite levels relative to breastfed infants. A prospective, randomized, double-blinded, controlled study of infant formulas (64.3 kcal/dL) fortified with varying levels of 2'-FL and galactooligosaccharides (GOS) was conducted [0.2 g/L 2'-FL + 2.2 g/L GOS; 1.0 g/L 2'-FL + 1.4 g/L GOS]. Healthy singleton infants age 0-5 days and with birth weight > 2490 g were enrolled (n = 201). Mothers chose to either exclusively formula-feed or breastfeed their infant from birth to 4 months of age. Blood samples were drawn from a subset of infants at 6 weeks of age (n = 35-40 per group). Plasma was evaluated by global metabolic profiling and compared to a breastfed reference group (HM) and a control formula (2.4 g/L GOS). Fortification of control infant formula with the HMO 2'-FL resulted in significant increases in serum metabolites derived from microbial activity in the gastrointestinal tract. Most notably, secondary bile acid production was broadly increased in a dose-dependent manner among infants receiving 2'-FL supplemented formula relative to the control formula. 2'-FL supplementation increased secondary bile acid production to levels associated with breastfeeding. Our data indicate that supplementation of infant formula with 2'-FL supports the production of secondary microbial metabolites at levels comparable to breastfed infants. Thus, dietary supplementation of HMO may have broad implications for the function of the gut microbiome in systemic metabolism. This trial was registered at with the U.S. National library of Medicine as NCT01808105.PMID:37242222 | DOI:10.3390/nu15102339

Nutrients. 2023 May 10;15(10):2263. doi: 10.3390/nu15102263.ABSTRACTThis study investigated the mechanism of reducing body fat via whey protein diet. Pregnant mice were fed whey or casein, and their offspring were fed by birth mothers. After weaning at 4 weeks, male pups received the diets administered to their birth mothers (n = 6 per group). At 12 weeks of age, body weight, fat mass, fasting blood glucose (FBG), insulin (IRI), homeostatic model assessment of insulin resistance (HOMA-IR), cholesterol (Cho), triglyceride (TG), the expression levels of lipid metabolism-related genes in liver tissues and metabolomic data of fat tissues were measured and compared between the groups. The birth weights of pups born were similar in the two groups. Compared to the pups in the casein group, at 12 weeks of age, pups in the whey group weighed less, had significantly lower fat mass, HOMA-IR and TG levels (p < 0.01, p = 0.02, p = 0.01, respectively), and significantly higher levels of the antioxidant glutathione and the anti-inflammatory 1-methylnicotinamide in fat tissues (p < 0.01, p = 0.04, respectively). No differences were observed in FBG, IRI, Cho levels (p = 0.75, p = 0.07, p = 0.63, respectively) and expression levels of lipid metabolism-related genes. Whey protein has more antioxidant and anti-inflammatory properties than casein protein, which may be its mechanism for reducing body fat.PMID:37242144 | DOI:10.3390/nu15102263

Nutrients. 2023 May 9;15(10):2236. doi: 10.3390/nu15102236.ABSTRACTObesity is a disorder identified by an inappropriate increase in weight in relation to height and is considered by many international health institutions to be a major pandemic of the 21st century. The gut microbial ecosystem impacts obesity in multiple ways that yield downstream metabolic consequences, such as affecting systemic inflammation, immune response, and energy harvest, but also the gut-host interface. Metabolomics, a systematized study of low-molecular-weight molecules that take part in metabolic pathways, represents a serviceable method for elucidation of the crosstalk between hosts' metabolism and gut microbiota. In the present review, we confer about clinical and preclinical studies exploring the association of obesity and related metabolic disorders with various gut microbiome profiles, and the effects of several dietary interventions on gut microbiome composition and the metabolome. It is well established that various nutritional interventions may serve as an efficient therapeutic approach to support weight loss in obese individuals, yet no agreement exists in regard to the most effective dietary protocol, both in the short and long term. However, metabolite profiling and the gut microbiota composition might represent an opportunity to methodically establish predictors for obesity control that are relatively simple to measure in comparison to traditional approaches, and it may also present a tool to determine the optimal nutritional intervention to ameliorate obesity in an individual. Nevertheless, a lack of adequately powered randomized trials impedes the application of observations to clinical practice.PMID:37242119 | DOI:10.3390/nu15102236

Molecules. 2023 May 20;28(10):4207. doi: 10.3390/molecules28104207.ABSTRACTThe plants in the Sideritis genus are postulated to exhibit several important medicinal properties due to their unique chemical composition. To isolate the targeted phytochemical compounds, the selection of a suitable extraction method is of primary importance. In this work, a comparative study on the phytochemical profiles of various Sideritis raeseri and Sideritis scardica extracts has been carried out. An untargeted metabolomics approach based on ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry was applied to investigate the metabolic differences between extracts obtained by conventional extraction and extractions assisted by microwaves, ultrasounds and high pressure. Additionally, the influence of extraction solvents on HPLC antioxidant profiles obtained following the derivatization of analytes with ABTS reagent was evaluated. A total of 102 metabolites have been putatively identified. The major secondary metabolites groups were classified as flavonoids, terpenoids, phenylethanoid glycosides and phenolic acids. The main antioxidants in the extracts were isoscutellarein and hypolaetin derivatives as well as verbascoside and chlorogenic acid. The results showed that 70% ethanol was the most effective extractant for different classes of phytochemicals including antioxidants. In addition, extraction supported with microwaves, ultrasounds or high pressure improved the overall recovery of metabolites by about 3 times compared to the conventional extraction method.PMID:37241947 | DOI:10.3390/molecules28104207

Molecules. 2023 May 12;28(10):4064. doi: 10.3390/molecules28104064.ABSTRACTTesticular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.PMID:37241805 | DOI:10.3390/molecules28104064

Molecules. 2023 May 12;28(10):4050. doi: 10.3390/molecules28104050.ABSTRACTIon mobility-mass spectrometry (IM-MS) is a powerful separation technique providing an additional dimension of separation to support the enhanced separation and characterization of complex components from the tissue metabolome and medicinal herbs. The integration of machine learning (ML) with IM-MS can overcome the barrier to the lack of reference standards, promoting the creation of a large number of proprietary collision cross section (CCS) databases, which help to achieve the rapid, comprehensive, and accurate characterization of the contained chemical components. In this review, advances in CCS prediction using ML in the past 2 decades are summarized. The advantages of ion mobility-mass spectrometers and the commercially available ion mobility technologies with different principles (e.g., time dispersive, confinement and selective release, and space dispersive) are introduced and compared. The general procedures involved in CCS prediction based on ML (acquisition and optimization of the independent and dependent variables, model construction and evaluation, etc.) are highlighted. In addition, quantum chemistry, molecular dynamics, and CCS theoretical calculations are also described. Finally, the applications of CCS prediction in metabolomics, natural products, foods, and the other research fields are reflected.PMID:37241791 | DOI:10.3390/molecules28104050

Molecules. 2023 May 12;28(10):4042. doi: 10.3390/molecules28104042.ABSTRACTNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.PMID:37241783 | DOI:10.3390/molecules28104042

Molecules. 2023 May 9;28(10):3990. doi: 10.3390/molecules28103990.ABSTRACTCrude herbs of Daphne genkwa (CHDG) are often used in traditional Chinese medicine to treat scabies baldness, carbuncles, and chilblain owing to their significant purgation and curative effects. The most common technique for processing DG involves the use of vinegar to reduce the toxicity of CHDG and enhance its clinical efficacy. Vinegar-processed DG (VPDG) is used as an internal medicine to treat chest and abdominal water accumulation, phlegm accumulation, asthma, and constipation, among other diseases. In this study, the changes in the chemical composition of CHDG after vinegar processing and the inner components of the changed curative effects were elucidated using optimized ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Untargeted metabolomics, based on multivariate statistical analyses, was also used to profile differences between CHDG and VPDG. Eight marker compounds were identified using orthogonal partial least-squares discrimination analysis, which indicated significant differences between CHDG and VPDG. The concentrations of apigenin-7-O-β-d-methylglucuronate and hydroxygenkwanin were considerably higher in VPDG than those in CHDG, whereas the amounts of caffeic acid, quercetin, tiliroside, naringenin, genkwanines O, and orthobenzoate 2 were significantly lower. The obtained results can indicate the transformation mechanisms of certain changed compounds. To the best of our knowledge, this study is the first to employ mass spectrometry to detect the marker components of CHDG and VPDG.PMID:37241730 | DOI:10.3390/molecules28103990

J Pers Med. 2023 Apr 29;13(5):776. doi: 10.3390/jpm13050776.ABSTRACTPurine metabolism is an important branch of metabolic reprogramming and has received increasing attention in cancer research. Ovarian cancer is an extremely dangerous gynecologic malignancy for which there are no adequate tools to predict prognostic risk. Here, we identified a prognostic signature consisting of nine genes related to purine metabolism, including ACSM1, CACNA1C, EPHA4, TPM3, PDIA4, JUNB, EXOSC4, TRPM2, and CXCL9. The risk groups defined by the signature are able to distinguish the prognostic risk and the immune landscape of patients. In particular, the risk scores offer promising personalized drug options. By combining risk scores with clinical characteristics, we have created a more detailed composite nomogram that allows for a more complete and individualized prediction of prognosis. In addition, we demonstrated metabolic differences between platinum-resistant and platinum-sensitive ovarian cancer cells. In summary, we have performed the first comprehensive analysis of genes related to purine metabolism in ovarian cancer patients and created a feasible prognostic signature that will aid in risk prediction and support personalized medicine.PMID:37240946 | DOI:10.3390/jpm13050776