Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury

BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.

Secondary Metabolites of Entomopathogenic Fungi, Biological Alternative for the Control of Agricultural Pests and Disease: Present and Perspectives

The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it has been reported that these are sensitive to the environmental conditions. For this reason, biopesticides products have been formulated based on secondary metabolites, recently. These biomolecules participate as biological control agent, such as: cyclic depsipeptides, amino acids, polyketides, polyphenols and terpenoids, affecting their morphology, life cycle and insect behavior. The use of secondary metabolites of entomopathogenic fungi opens the possibility of application in a more efficient way for the control of agricultural pests in a compatible with the environment and human health;therefore, it is important to know, analyzing the type of molecules, their effects, and their different methods of application.

Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalfields.However,these secondary metabolites obtained from plants are in low amounts,and it is difficult to synthesize them at the industrial level.Despite these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and tested.Secondary metabolites are complex compounds that exhibit chirality.Further,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell cultures.This review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal products.The article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

Casual associations between blood metabolites and colon cancer

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.

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

BACKGROUND 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.AIM To explore baseline serum metabolites characteristics in responders.METHODS 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(FR),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 chromatographytandem 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.RESULTS 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.CONCLUSION 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.

Effects of rearing system and antibiotic treatment on immune function,gut microbiota and metabolites of broiler chickens

Background:In China,cage systems with a high space utilization have gradually replaced ground litter systems,but the disease incidence of chickens in cages is higher.Broilers in the ground litter pens may be stimulated by more environmental microbes during the growth process and show strong immune function and status,but knowledge of which microbes and their metabolites play an immunomodulatory role is still limited.This study aimed to explore the differences and correlations in the immune function,gut microbiota and metabolites and the importance of gut microbiota of broilers raised in cages and ground litter pens.Methods:The experiment involved a 2×2 factorial arrangement,with rearing systems(cages or ground litter pens)and antibiotic treatment(with or without broad-spectrum antibiotics in drinking water)as factors.Results:The results showed that,compared with the cage group,the ground litter broilers had stronger nonspecific immune function(Macrophages%and NO in blood),humoral immune function(IgG in blood,LPS stimulation index in ileum)and cellular immune function(T%,Tc%,ConA stimulation index and cytokines in blood).Antibiotic(ABX)treat-ment significantly reduced nonspecific immune function(Macrophages%and NO in blood,iNOS and Mucin2 mRNA expression in ileum),humoral immune function(IgG in blood and sIgA in ileum)and cellular immune function(T%and cytokines in blood,Th and Tc ratio,TLRs and cytokines mRNA expression in ileum).Furthermore,the ground litter broil-ers had higherαdiversity of microbiota in ileum.The relative abundance of Staphylococcus,Jeotgalicoccus,Jeotgalibaca and Pediococcus in the ileum of ground litter broilers were higher.ABX treatment significantly reduced theαdiversity of ileal microbiota,with less Chloroplast and Mitochondria.In addition,the levels of acetic acid,isobutyric acid,kynurenic acid and allolithocholic acid in the ileum of ground litter broilers were higher.Spearman correlation analysis showed that Jeotgalibaca,Pediococcus,acetic acid,kynurenic acid and allolithocholic acid were related to the immune function.Conclusions:There were more potential pathogens,litter breeding bacteria,short-chain fatty acids,kynurenine,allolithocholic acid and tryptophan metabolites in the ileum of broilers in ground litter pens,which may be the reason for its stronger immune function and status.

Metabolic and transcriptomic analyses elucidate a novel insight into the network for biosynthesis of carbohydrate and secondary metabolites in the stems of a medicinal orchid Dendrobium nobile

Dendrobium nobile is an important medicinal and nutraceutical herb.Although the ingredients of D.nobile have been identified as polysaccharides,alkaloids,amino acids,flavonoids and bibenzyls,our understanding of the metabolic pathways that regulate the synthesis of these compounds is limited.Here,we used transcriptomic and metabolic analyses to elucidate the genes and metabolites involved in the biosynthesis of carbohydrate and several secondary metabolites in the stems of D.nobile.A total of 1005 metabolites and 31,745 genes were detected in the stems of D.nobile.The majority of these metabolites and genes were involved in the metabolism of carbohydrates(fructose,mannose,glucose,xylulose and starch),while some were involved in the metabolism of secondary metabolites(alkaloids,β-tyrosine,ferulic acid,4-hydroxybenzoate and chrysin).Our predicted regulatory network indicated that five genes(AROG,PYK,DXS,ACEE and HMGCR) might play vital roles in the transition from carbohydrate to alkaloid synthesis.Correlation analysis identified that six genes(ALDO,PMM,BGLX,EGLC,XYLB and GLGA) were involved in carbohydrate metabolism,and two genes(ADT and CYP73A) were involved in secondary metabolite biosynthesis.Our analyses also indicated that phosphoenol-pyruvate(PEP) was a crucial bridge that connected carbohydrate to alkaloid biosynthesis.The regulatory network between carbohydrate and secondary metabolite biosynthesis established will provide important insights into the regulation of metabolites and biological systems in Dendrobium species.

Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1^(-/-))and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAPinduced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1^(-/-)mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p4503a11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites:A Randomized,Double-Blind,Placebo-Controlled Clinical Trial

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62)were randomly assigned to receive placebo(N=31)or B.longum CCFM1077(1×1010colony-forming units(CFUs)per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA)sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p<0.01)and LDL-C(p<0.01)in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine)and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms)were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis

BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Polarity-regulated derivatization-assisted LC-MS method for amino-containing metabolites profiling in gastric cancer

Amino-containing compounds,including amino acids,aliphatic amines,aromatic amines,small peptides and catecholamines,are involved in various biological processes and play vital roles in multiple metabolic pathways.Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer.However,the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need.Herein,we established a polarityregulated derivatization method coupled with liquid chromatography-mass spectrometry(LC-MS)for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls,based on our newly designed and synthesized derivatization reagent(S)-3-(1-(diisopropoxyphosphoryl)pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester(3-DP-NHS).Enhanced separation efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization.This method exhibited good linearity,recovery,intra-and inter-day precision and accuracy.Only 5 mL serum is needed for untargeted analysis,enabling 202 amino-containing metabolites to be detected.Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer.Furthermore,ultra high performance liquid chromatography coupled with mass spectrometry(UHPLCMS/MS)analysis quantification revealed increased serum levels of tryptamine and decreased concentrations of arginine and tryptophan in patients with gastric cancer.Receiver operating characteristic(ROC)curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis.This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis,providing new avenues for the treatment of gastric cancer.

Pharmacokinetics of nitrogen-containing metabolites R-gentiandiol and S-gentiandiol in rat plasma after oral administration of swertiamarin

Objective:A chiral resolution method for enantiomers of two chiral nitrogen-containing metabolites R-gentiandiol and S-gentiandiol of swertiamarin in plasma was developed,and the pharmacokinetics of the metabolites were studied.Methods:The metabolites of swertiamarin in vivo were detected by LC-MS/MS using Astec CyclobondⅡCyclodextrin column(4.6 mm×100 mm,5μm),gradient elution with acetonitrile-water as mobile phase,and monitored by multiple reaction monitoring(MRM)method in positive mode.The ion pairs for quantitative analysis are R-gentiandiol(m/z 210.04→192.06),S-gentiandiol(m/z 210.04→192.06)and gentianone(m/z 192.02→162.08).Results:The linear correlation coefficients of the method developed were greater than 0.999,the precision was less than 7.00%,the recovery was 99.57%-102.65%,and the matrix effect was 90.94%-91.34%.The peak t_(max)of R-gentiandiol and S-gentiandiol in rat plasma after oral administration of swertiamarin were(1.63±0.23)h and(1.58±0.21)h,t_(1/2)was(6.23±0.52)h and(5.46±0.38)h,C_(max)was(86.79±20.81)ng/mL and(60.72±18.95)ng/mL,and the AUC_(0-24)were(1094.58±86.37))(ng·h)/mL and(724.67±58.38)(ng·h)/mL,respectively.Conclusion:The method was highly sensitive with good accuracy and precision,and it was successfully applied for chiral resolution and pharmacokinetics study of R-gentiandiol and S-gentiandiol in plasma.The method developed and experimental results will provide scientific basis for the study of pharmacodynamics and pharmacodynamic material basis of swertiamarin,and lay a foundation for clinical application and resource development of TCM monomer.

Blue light induces leaf color change by modulating carotenoid metabolites in orange-head Chinese cabbage(Brassica rapa L.ssp. pekinensis)

Carotenoids are involved in the formation of plant leaf color as well as photosystem photoprotection. This study showed that blue light significantly induced up-regulation of the total carotenoid content in the inner leaves of orange-head Chinese cabbage(OHCC). Furthermore, the transcriptomic analysis revealed that blue light treatment induced upregulation of genes in photosynthesis(BrHY5-2, BrCOP1 and BrDET1) and the methylerythritol 4-phosphate pathways(BrGGPS, BrDXS and BrHDR) upstream of the carotenoid metabolic pathway. Carotenoid metabolomic analysis revealed that the accumulation of several orange and red carotenoids(lycopene, zeaxanthin, β-carotene, lutein, and β-cryptoxanthin) after blue light treatment contributed to the deepening of the leaf coloration, suggesting that short-term blue light treatment could be used to boost nutritional quality. The light signal gene BrHY5-2 participated in the blue light-induced transcriptional regulation of carotenoid biosynthesis in OHCC. Overexpression of BrHY5-2 in Arabidopsis significantly increased the total carotenoid content and the sensitivity to blue light. The above findings revealed new insights about blue-light-induced carotenoid synthesis and accumulation in OHCC lines. They suggested a new engineering approach to increase the nutritional value of vegetables.

Analysis of Differential Metabolites in Selenium-enriched Rice Based on Extensive Non-targeted Metabolome

[Objectives]Selenium(Se)-enriched rice is the main type of Se-enriched agricultural product developed in China,and this study aimed to understand the impact of selenium application on the metabolites in rice.[Methods]Se-enriched rice was prepared by foliar application of a sodium selenite aqueous solution,and high-throughput analysis of differential metabolites in Se-enriched rice was conducted based on extensive non-targeted metabolome.[Results]There were significant differences in metabolites between Se-enriched rice and ordinary rice,and a total of 535 differential metabolites were identified.Among them,420 metabolites in Se-enriched rice were upregulated,accounting for 78.5%,far higher than downregulated metabolites.The enrichment differences of three KEGG metabolic pathways,including cysteine and methionine metabolism,zeatin biosynthesis,and arachidonic acid metabolism,reached a significant level,indicating that selenium enrichment had a significant regulatory effect on the metabolism of sulfur-containing amino acids,the synthesis of natural cytokinin zeatin,and arachidonic acid bioactive components in rice.[Conclusions]The results can provide a theoretical basis for the production of Se-enriched rice.

Study on Marine actinomycetes and analysis of their secondary metabolites

Actinomycetes are relatively prevalent bacteria in the ocean,constituting 9% of the total number of marine bacteria.The advancement of science and technology has led to a more profound exploration of marine actinomycetes.These studies hold immense significance in comprehending the distribution and adaptation of marine actinomycetes within the oceanic environment,as well as uncovering new secondary metabolites.Based on differing lifestyles,marine actinomycetes can be categorized as free-living or co-epiphytic.The activity and metabolism of actinomycetes vary across diverse marine settings,including the deep sea,benthic regions,and marine organisms.Due to their distinctive biological traits and genetic background,these marine actinomycetes inevitably generate metabolites possessing unique structures.Research methodologies concerning marine actinomycetes predominantly encompass traditional pure culture techniques,molecular biology approaches,and the integration of metagenomics and bioinformatics.The exploration of varied methodologies proves pivotal for the analysis of metabolite processes.Through the cultivation of marine actinomycetes,numerous compounds featuring novel structures and significant activities have been isolated,furnishing a substantial foundation for new drug investigations.These encompass,but are not restricted to,peptides,antibiotics,terpenoids,ketones,quinones,macrolides,and pigments.The potential applications of marine actinomyces and their secondary metabolites extend beyond antibacterial and anti-tumor effects,exhibiting promising prospects in antifungal and antiviral domains.This paper provides a comprehensive review of the classification,resources,research methodologies,and habitats of marine actinomycetes.Furthermore,it delves into the classification of secondary metabolites and their functional activities,facilitating a more exhaustive analysis of the secondary metabolites produced by marine actinomycetes.

Variation of microbiological and small molecule metabolite profiles of Nuodeng ham during ripening by high-throughput sequencing and GC-TOF-MS

The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years(the first,second and third year sample)were analyzed by high-throughput sequencing technology and gas chromatography-time of flight mass spectrography(GC-TOF-MS)to study the effects of microorganisms and small molecular metabolites on the quality of ham in different processing years.The results showed that the dominant bacteria phyla of Nuodeng ham in different processing years were Proteobacteria and Firmicutes,the dominant fungi phyla were Ascomycota and Basidiomycota,while Staphylococcus and Aspergillus were the dominant bacteria and fungi of Nuodeng ham,respectively.Totally,252 kinds of small molecular metabolites were identified from Nuodeng ham in different processing years,and 12 different metabolites were screened through multivariate statistical analysis.Further metabolic pathway analysis showed that 23 metabolic pathways were related to ham fermentation,of which 8 metabolic pathways had significant effects on ham fermentation(Impact>0.01,P<0.05).The content of L-proline,phenyllactic acid,L-lysine,carnosine,taurine,D-proline,betaine and creatine were significantly positively correlated with the relative abundance of Staphylococcus and Serratia,but negatively correlated with the relative abundance of Halomonas,Aspergillus and Yamadazyma.

Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Microbial metabolites in non-alcoholic fatty liver disease

The prevalence of non-alcoholic fatty liver disease(NAFLD) is rising exponentially worldwide. The spectrum of NAFLD includes non-alcoholic fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and even hepatocellular carcinoma. Evidence shows that microbial metabolites play pivotal roles in the onset and progression of NAFLD. In this review, we discuss how microbederived metabolites, such as short-chain fatty acids, endogenous ethanol, bile acids and so forth, contribute to the pathogenesis of NAFLD.