Metabolomics for the diagnosis of bladder cancer: A systematic review

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

Review on analytical technologies and applications in metabolomics

Over the past decade,the swift advancement of metabolomics can be credited to significant progress in technologies such as mass spectrometry,nuclear magnetic resonance,and multivariate statistics.Currently,metabolomics garners widespread application across diverse fields including drug research and development,early disease detection,toxicology,food and nutrition science,biology,prescription,and chinmedomics,among others.Metabolomics serves as an effective characterization technique,offering insights into physiological process alterations in vivo.These changes may result from various exogenous factors like environmental conditions,stress,medications,as well as endogenous elements including genetic and protein-based influences.The potential scientific outcomes gleaned from these insights have catalyzed the formulation of innovative methods,poised to further broaden the scope of this domain.Today,metabolomics has evolved into a valuable and widely accepted instrument in the life sciences.However,comprehensive reviews focusing on the sample preparation and analytical methodologies employed in metabolomics within the life sciences are surprisingly scant.This review aims to fill that gap,providing an overview of current trends and recent advancements in metabolomics.Particular emphasis is placed on sample preparation,sophisticated analytical techniques,and their applications in life science research.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics

Objective:To investigate the mechanism of action of Wuzi Yanzong pill(WYP)in rats with oligoasthenozoospermia(OAZ)via metabolomics and to provide a possible basis for improving this WYP-based treatment.Methods:A rat model of OAZ was established by treating male SpragueeDawley rats with glucosides from Tripterygium wilfordii Hook.F.Seventy-two rats were randomly divided into six groups:control,L-carnitine(positive control),model,and low-,medium-,and high-dose WYP groups.Rats in the experimental groups were treated with WYP for 4 weeks.At the end of the treatment period,sperm cell quality(density,motility,and viability)was assessed using a semen analysis system,mitochondrial membrane potential(MMP)was assessed using flow cytometry,and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ.Further,serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment.Results:A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group.WYP-M and WYP-H treatments significantly improved sperm cell density,motility,and viability compared with those in the model group(all P<.05).Compared with the model group,both WYP-M and WYP-H treatments increased MMP values(P=.006 and P=.021 respectively),while there was no significant difference in the L-carnitine group.L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group.Further,44 differential metabolites and four metabolic pathways,especially autophagy pathway,related to OAZ were identified via metabolomics.Conclusions:WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation.These findings can be employed to improve the efficacy of WYP in humans.

Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a“multi-omics”platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China.Interestingly,our previous work has found that R.crenulate extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced colitis.Thus,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against colitis.The chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were identified.Meanwhile,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds.The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis.The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid metabolism.Correspondingly,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

Characterization of squash polysaccharide and the anti-diabetic effect on type 2 diabetic rat revealed by urine metabolomics analysis

The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-F1,SPS-F2 and SPS-F3)isolated and purified from squash.SPS-F1(molecular weight(Mw)=12.30 kDa)and SPS-F2(Mw=19.40 kDa)were likely to contain HG and RG-I domain of pectic polysaccharide,respectively.SPS-F2(Mw=270.4 kDa)was mainly composed of rhamnose,galactose and arabinose.The treatment with SPS decreased body weight gain,glucose and TG levels in type 2 diabetes rats.Besides,25 differential metabolites were identified based on urinary metabolomics analysis,which are crucial to the anti-diabetic effect of SPS.The regulation of nicotinamide N-oxide,histamine,cis-aconitate,citrate,L-malic acid,3-(3-hydroxyphenyl)propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism,gut microbiota and inflammation.Study of surface plasmon resonance revealed the binding kinetics with galectin-3(Gal-3)and fibroblast growth factor 2(FGF2).The K_(D)values of SPS-F2 and SPS-F3 to Gal-3 were 4.97×10^(-3)and 1.48×10^(-3)mol/L,indicating a weak binding affinity.All 3 fractions showed moderate binding to FGF2 and the affinity was SPS-F3>SPS-F2>SPS-F1.Thus,the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.

Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

Transcriptomics integrated with metabolomics reveals the mechanism of CaCl_(2)-HCl electrolyzed water-induced glucosinolate biosynthesis in broccoli sprouts

Glucosinolates are important phytochemicals in Brassicaceae.We investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli sprouts.The results showed that CHEW treatment significantly decreased reactive oxygen species(ROS)and malondialdeh yde(MDA)contents in broccoli sprouts.On the the 8^(th)day,compared to tap water treatment,the the total glucosinolate content of broccoli sprouts with CHEW treatment increased by 10.6%and calcium content was dramatically enhanced from 14.4 mg/g DW to 22.7 mg/g DW.Comparative transcriptome and metabolome analyses revealed that CHEW treatment activated ROS and calcium signaling transduction pathways in broccoli sprouts and they interacted through MAPK cascades.Besides,CHEW treatment not only promoted the biosynthesis of amino acids,but also enhanced the expression of structural genes in glucosinolate synthesis through transcription factors(MYBs,bHLHs,WRKYs,etc.).The results of this study provided new insights into the regulatory network of glucosinolates biosynthesis in broccoli sprouts under CHEW treatment.

Analysis of flavor and widely metabolomics differences in black sesame before and after processing

The objective of this study was to determine the differences of aroma and taste in three black sesame originsbefore and after processing via flavor and widely metabolomics.By analyzing the sensory characteristics and metabolites of raw and treated black sesame from China,Vietnam,and Myanmar,treated Chinese sesame have the most significant change in hardness after thermal processing,low viscosity and was easy to chew.The electronic nose could distinguish between raw and treated sesame due to the aroma distribution.The reason of treated sesame from China was“fragrant”is due to the highest content(2545.50μg/kg)of total pyrazines including 2,5-dimethylpyrazine,2-ethyl-5-methylpyrazine,2,3,5-trimethylpyrazine,3-ethyl-2,5-dimethylpyrazine.933 metabolites were detected via a wide targeted metabolomics in the taste of raw and treated sesame.Based on the analysis of metabolites related to bitterness,145 substances were selected.The main bitter contributors may be amino acids,dipeptides and organic acids.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Analysis of metabolic characteristics of metabolic syndrome in elderly patients with gastric cancer by non-targeted metabolomics

BACKGROUND The relationship between metabolic syndrome(MetS)and gastric cancer(GC),which is a common metabolic disease,has attracted much attention.However,the specific metabolic characteristics of MetS in elderly patients with GC remain unclear.AIM To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques.METHODS In this study,125 patients with nonfrail nonmeal GC were selected as the control group,and 50 patients with GC in the frail group were selected as the frail group.Sixty-five patients with GC combined with MetS alone were included in the MetS group,and 50 patients with GC combined with MetS were included in the MetS group.Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry.Multivariate statistical analysis was performed by principal component analysis,orthogonal partial least squares,pattern recognition analysis,cluster analysis,and metabolic pathway annotation.RESULTS A total of 125 different metabolites,including amino acids,glycerophospholipids,sphingolipids,fatty acids,sugars,nucleosides and nucleotides,and acidic compounds,were identified via nontargeted metabolomics techniques.Compared with those in the control group,there were 41,32,and 52 different metabolites in the MetS group,the debilitated group,and the combined group,respectively.Lipid metabolites were significantly increased in the MetS group.In the weak group,amino acids and most glycerol phospholipid metabolites decreased significantly,and fatty acids and sphingosine increased significantly.The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds.The alanine,aspartic acid,and glutamate metabolic pathways were obviously enriched in the asthenic group,and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group.CONCLUSION Elderly GC patients with simple frailty,simple combined MetS,and frailty combined with MetS have different metabolic characteristics,among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients,and comprehensive supplementation of fat and protein should be considered.Many kinds of metabolites,such as amino acids,lipids,nucleotides,and acidic compounds,are abnormally abundant in patients with MetS combined with fthenia,which may be related to tumor-related metabolic disorders.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study

BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia,which has increased the global medical burden and is also the main cause of death in most countries.AIM To understand the knowledge structure of global development status,research focus,and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23,2023,and the relevant information was analyzed using CiteSpace6.2.2R(CiteSpace),VOSviewer6.1.18(VOSviewer),and Bibliometrix software under R language.RESULTS A total of 3123 publications were included from 2002 to 2022.In the past two decades,the number of publications and citations in this field has continued to increase.The United States,China,Germany,the United Kingdom,and other relevant funds,institutions,and authors have significantly contributed to this field.Scientific Reports and PLoS One are the journals with the most publications and the most citations.Through keyword co-occurrence and cluster analysis,the closely related keywords are"insulin resistance","risk","obesity","oxidative stress","metabolomics","metabolites"and"biomarkers".Keyword clustering included cardiovascular disease,gut microbiota,metabonomics,diabetic nephropathy,molecular docking,gestational diabetes mellitus,oxidative stress,and insulin resistance.Burst detection analysis of keyword depicted that"Gene","microbiota","validation","kidney disease","antioxidant activity","untargeted metabolomics","management",and"accumulation"are knowledge frontiers in recent years.CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention.Diabetic nephropathy,diabetic cardiovascular disease,and kidney disease are key diseases for future research in this field.Gut microbiota,molecular docking,and untargeted metabolomics are key research directions in the future.Antioxidant activity,gene,validation,mass spectrometry,management,and accumulation are at the forefront of knowledge frontiers in this field.

Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

Kick-start for metabolomics in liver disease

It is not complicated for the clinician to diagnose a patient with advanced fibrosis or liver cirrhosis when he has already presented some decompensation of his liver disease.However,it is in the earliest stages when the patient's prognosis can be modified the most.Since liver disease is generally asymptomatic,not invasive markers are of great relevance.In the era of omics,it is time for metabolomics to accompany genomics and proteomics,which are more established in the diagno-stics and prognostics clinical toolbox.Metabolomics,understood as the compre-hensive evaluation of the metabolites present in the organism in a specific phys-iological situation,has undoubted advantages in the study and identification of serum markers relevant to a specific pathology.Last year,I read with interest two articles published in this journal:“Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet”by Dai et al and“Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways”by Ferrasi et al.Both papers illuminate the power of metabolomics to provide us with new tools in the management of liver disease.In this editorial,I comment on these studies and others,and note how they can contribute to our understanding of liver disease in more than one way.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.

Metabolomics in liver diseases: A novel alternative for liver biopsy?

Hepatitis C virus(HCV)remains a significant public health problem as it can cause acute and chronic hepatitis.Chronic HCV infection is a major cause of liver fibrosis,and evaluation of liver fibrosis is essential because the prognosis of patients with chronic HCV infection is closely related to the stage of fibrosis.Liver fibrosis is traditionally evaluated based on pathological analysis of biopsy specimens,which is considered the gold standard.Nevertheless,liver biopsy is invasive and susceptible to sampling error and inter-and intraobserver variation in pathological interpretation;it is also costly.Therefore,noninvasive diagnostic investigations have been developed,including the use of fibrotic markers,scoring systems based on routine blood tests,and transient elastography with magnetic resonance imaging or ultrasonography.Recently,metabolomics,an emerging technology,has been used to detect the fibrosis stage.In this editorial,I comment on the article titled“Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways”by Ferrasi et al published in the recent issue of the World Journal of Hepatology.I discuss previous studies on the use of metabolome analysis for the diagnosis of HCV-related liver fibrosis and the potential development of biopsy-free diagnostic techniques.