Combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology to reveal the key effective compounds and mechanism of Shengxian decoction for ameliorating doxorubicin cardiotoxicity.

Shengxian decoction, a traditional Chinese medicinal prescription, has been shown to alleviate doxorubicin-induced chronic heart failure. This study established an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to separate and characterize the complex chemical compositions of Shengxian decoction, and the absorbed compounds in the bio-samples of the cardiotoxicity rats with chronic heart failure after its oral delivery. Note that 116 chemical compounds were identified from Shengxian decoction in vitro, 81 more than previously detected. Based on the three-dimensional data of these compounds, 28 absorbed compounds were confirmed in vivo. Network pharmacology and molecular docking experiments indicated that timosaponin B-II, timosaponin A-III, gitogenin, and 7,8-didehydrocimigenol were recognized as the key effective compounds to exert effects against doxorubicin cardiotoxicity by acting on targets such as caspase 3, cyclin-dependent kinase 1, cyclin-dependent kinase 4, receptor tyrosine-protein kinase erbB-2, and mitogen-activated protein kinase 1 in p53 and phosphatidylinositol 3-kinase-Akt signaling pathways. This study developed the understanding of the composition of Shengxian decoction for the treatment of doxorubicin cardiotoxicity, as well as a feasible strategy to elucidate the effective constituents in traditional Chinese medicines.

Effects of Natural Products through Inhibiting Endoplasmic Reticulum Stress on Attenuation of Idiopathic Pulmonary Fibrosis.

With ever-increasing intensive studies of idiopathic pulmonary fibrosis (IPF), significant progresses have been made. Endoplasmic reticulum stress (ERS)/unfolded protein reaction (UPR) is associated with the development and progression of IPF, and targeting ERS/UPR may be beneficial in the treatment of IPF. Natural product is a tremendous source of new drug discovery, and accumulating studies have reported that many natural products show potential therapeutic effects for IPF via modulating one or more branches of the ERS signaling pathway. Therefore, this review focuses on critical roles of ERS in IPF development, and summarizes herbal preparations and bioactive compounds which protect against IPF through regulating ERS.

Association between preoperative anxiety states and postoperative complications in patients with esophageal cancer and COPD: a retrospective cohort study.

BACKGROUND: Esophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications. RESULTS: This study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054). CONCLUSION: Preoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.

The effect of scutellaria baicalensis and its active ingredients on major depressive disorder: a systematic review and meta-analysis of literature in pre-clinical research.

Background: Scutellaria baicalensis, the dry root of scutellaria baicalensis georgi, is a traditional Chinese medicine with long. In clinic, scutellaria baicalensis is commonly used in prescription for the treatment of depression. Additionally, numerous pre-clinical studies have shown that Scutellaria baicalensis and its active constituents are effective for depression. In this study, we aims to systematically review the roles of scutellaria baicalensis in depression and summarize the possible mechanism. Methods: A systematic review and meta-analysis were conducted to analyze the existing studies on the effects of scutellaria baicalensis on depression in animal models. Briefly, we searched electronic databases including Pubmed and Embase for preclinical trial studies from inception to September 2023. The items in each study were evaluated by two independent reviewers, and meta-analyses were performed on scutellaria baicalensis-induced behavioral changes in the study. Finally, random effects model is used to collect data. Results: A total of 49 studies were identified, and 13 studies were included in the final analysis. They all reported the different antidepressant effects of scutellaria baicalensis and the underlying biological mechanisms. Among the included 13 studies, the results of eight articles SPT[SMD = -2.80, 95%CI(-4.03, -1.57), p < 0.01], the results of the nine articles OFT[SMD = -2.38, 95%CI(-3.53, -1.23), p < 0.01], and the results of two articles NSFT[SMD = -2.98, 95%CI(-3.94, -2.02), p < 0.01] were significantly different from the control group. The risk of bias was moderate in all studies, however, there was a significant heterogeneity among studies. Conclusion: These results preliminarily suggest that scutellaria baicalensis can alleviate depressive behaviors and modulate underlying mechanisms, which is expected to be a promising antidepressant.

Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species.

The aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

Tyrosine kinase inhibitor-induced hypothyroidism: mechanism and clinical implications.

INTRODUCTION: Since the first experimentally proven tyrosine kinase inhibitor (TKI) imatinib was introduced in the clinical setting, TKIs have attracted widespread attention because of their remarkable therapeutic effects and improvement of survival rates. TKIs are small-molecule, multi-target, anti-cancer agents that target different tyrosine kinases and block downstream signaling. ADVERSE REACTIONS AND CONCERNS: However, with in-depth research on TKI drugs, the adverse reactions-for example, thyroid dysfunction-have become a concern and thus have attracted the attention of numerous researchers. Thyroid dysfunction, especially hypothyroidism, that occurs in high incidence during TKI therapy has a close relationship with treatment efficacy, but the mechanism of TKI-induced thyroid dysfunction is obscure. DISCUSSION: This review discusses the epidemiology, possible mechanisms, and clinical significance of hypothyroidism in cancer patients treated with TKI.

The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.

A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19.

The combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the nirmatrelvir/ritonavir in plasma of patients with COVID-19, providing technical and theoretical support for the TDM. Plasma samples were processed by protein precipitation using acetonitrile, and analytes were separated on an Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 µm) column at 35°C. Acetonitrile and 0.1% formic acid in water (52 : 48) were utilized as the mobile phases at a flow rate of 0.3 mL/min. In the multiple reaction monitoring (MRM) mode, nirmatrelvir and ritonavir were monitored using precursor/product ions: m/z 500.2/110.1 and 721.3/296.1, respectively, with selinexor as the internal standard. The linear range of both analytes was 2.0 ng/mL to 5000 ng/mL with good inter- and intraday precision and accuracy, and the recovery was 92.0%-107% for nirmatrelvir and 85.7%-106% for ritonavir. Finally, this method was successfully applied to monitor the exposure levels of nirmatrelvir/ritonavir in plasma samples from hemodialysis patients.

TrichomeLess Regulator 3 is required for trichome initial and cuticle biosynthesis in Artemisia annua.

Artemisinin is primarily synthesized and stored in the subepidermal space of the glandular trichomes of Artemisia annua. The augmentation of trichome density has been demonstrated to enhance artemisinin yield. However, existing literature lacks insights into the correlation between the stratum corneum and trichomes. This study aims to unravel the involvement of TrichomeLess Regulator 3 (TLR3), which encodes the transcription factor, in artemisinin biosynthesis and its potential association with the stratum corneum. TLR3 was identified as a candidate gene through transcriptome analysis. The role of TLR3 in trichome development and morphology was investigated using yeast two-hybrid, pull-down analysis, and RNA electrophoresis mobility assay. Our research revealed that TLR3 negatively regulates trichome development. It modulates the morphology of Arabidopsis thaliana trichomes by inhibiting branching and inducing the formation of abnormal trichomes in Artemisia annua. Overexpression of the TLR3 gene disrupts the arrangement of the stratum corneum and reduces artemisinin content. Simultaneously, TLR3 possesses the capacity to regulate stratum corneum development and trichome follicle morphology by interacting with TRICHOME AND ARTEMISININ REGULATOR 1, and CycTL. Consequently, our findings underscore the pivotal role of TLR3 in the development of glandular trichomes and stratum corneum biosynthesis, thereby influencing the morphology of Artemisia annua trichomes.

Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

Exploring the Occurrence Mechanism and Early-Warning Model of Phlebitis Induced by Aescinate Based on Metabolomics in Cerebral Infarction Patients.

Objective: This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics. Methods: Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites. Results: Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of >1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher. Conclusion: The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids.

The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Feedback regulation of plant secondary metabolism: Applications and challenges.

Plant secondary metabolites offer resistance to invasion by herbivorous organisms, and are also useful in the chemical, pharmaceutical, cosmetic, and fragrance industries. There are numerous approaches to enhancing secondary metabolite yields. However, a growing number of studies has indicated that feedback regulation may be critical in regulating secondary metabolite biosynthesis. Here, we review examples of feedback regulation in secondary metabolite biosynthesis pathways, phytohormone signal transduction, and complex deposition sites associated with secondary metabolite biosynthesis. We propose a new strategy to enhance secondary metabolite production based on plant feedback regulation. We also discuss challenges in feedback regulation that must be overcome before its application to enhancing secondary metabolite yields. This review discusses recent advances in the field and highlights a strategy to overcome feedback regulation-related obstacles and obtain high secondary metabolite yields.

External Evaluation of Population Pharmacokinetic Models for High-Dose Methotrexate in Adult Patients with Hematological Tumors.

Currently, numerous population pharmacokinetic (popPK) models for methotrexate (MTX) have been published for estimating PK parameters and variability. However, it is unclear whether the accuracy of these models is sufficient for clinical application. The aim of this study is to evaluate published models and assess their predictive performance according to the standards of scientific research. A total of 237 samples from 74 adult patients who underwent high-dose MTX (HDMTX) treatment at Shanghai Changzheng Hospital were collected. The software package NONMEM was used to perform an external evaluation for each model, including prediction-based diagnosis, simulation-based diagnosis, and Bayesian forecasting. The simulation-based diagnosis includes normalized prediction distribution error (NPDE) and visual predictive check (VPC). Following screening, 7 candidate models suitable for external validation were identified for comparison. However, none of these models exhibited excellent predictive performance. Bayesian simulation results indicated that the prediction precision and accuracy of all models significantly improved when incorporating prior concentration information. The published popPK models for MTX exhibit significant differences in their predictive performance, and none of the models were able to accurately predict MTX concentrations in our data set. Therefore, before adopting any model in clinical practice, extensive evaluation should be conducted.

One-Component Dual-Readout Aggregation-Induced Emission Nanobeads for Qualitative and Quantitative Detection of C-Reactive Protein at the Point of Care.

Fluorescent lateral flow immunoassay (LFA) systems are versatile tools for sensitive and quantitative detection of disease markers at the point of care. However, traditional fluorescent nanoparticle-based lateral flow immunoassays are not visible under room light, necessitate an additional fluorescent reader, and lack flexibility for different application scenarios. Herein, we report a dual-readout LFA system for the rapid and sensitive detection of C-reactive protein (CRP) in clinical samples. The system relied on the aggregation-induced emission nanobeads (AIENBs) encapsulated with red AIE luminogen, which possesses both highly fluorescent and colorimetric properties. The AIENB-based LFA in the naked-eye mode was able to qualitatively detect CRP levels as low as 8.0 mg/L, while in the fluorescent mode, it was able to quantitatively measure high-sensitivity CRP (hs-CRP) with a limit of detection of 0.16 mg/L. The AIENB-based LFA system also showed a good correlation with the clinically used immunoturbidimetric method for CRP and hs-CRP detection in human plasma. This dual-modal AIENB-based LFA system offers the convenience of colorimetric testing and highly sensitive and quantitative detection of disease biomarkers and medical diagnostics in various scenarios.

Corrigendum: SbWRKY75- and SbWRKY41- mediated jasmonic acid signaling regulates baicalin biosynthesis.

[This corrects the article DOI: 10.3389/fpls.2023.1213662.].

Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway.

Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway.

Profiling the metabolic disorder and detection of colorectal cancer based on targeted amino acids metabolomics.

BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.