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Angelica sinensis (Oliv.) Diels (AS) is a commonly used herbal medicine and culinary spice known for its gastrointestinal protective properties. Angelica sinensis oil (AO) is the main bioactive component of AS. However, the therapeutic effects and mechanisms of AO on the gastrointestinal tract remain unclear. In this study, we aim to investigated the potential of AO in restoring gut microbiota disorder and metabolic disruptions associated with ulcerative colitis (UC). A systematic chemical characterization of AO was conducted using GC×GC-Q TOF-MS. A UC mouse model was established by freely drinking DSS to assess the efficacy of AO. Utilizing 16 S rRNA sequencing in combination with untargeted metabolomics analysis of serum, we identified alterations in gut microbiota, differential metabolites, and pathways influenced by AO in UC treatment, thereby elucidating the therapeutic mechanism of AO in UC management. Pharmacodynamic results indicated that AO effectively inhibited the content of inflammation mediators, such as Interleukin-1β, Interleukin-6 and tumor necrosis factor-α, and proserved colon tissue integrity in UC mice. Furthermore, AO significantly downregulated the abundance of pathogenic bacteria (Bacteroidetes, Proteobacteria, and Desulfobacteriaceae) while increasing the abundance of beneficial bacteria (Firmicutes, Blautia, Akkermansia, and Lachnospiraceae). Metabolomics analysis highlighted significant disruptions in endogenous metabolism in UC mice, with a notable restoration of SphK1 and S1P levels following AO administration. Besides, we discovered that AO regulated the balance of sphingolipid metabolism and protected the intestinal barrier, potentially through the SphK1/MAPK signaling pathway. Overall, this study indicated that AO effectively ameliorates the clinical manifestations of UC by synergistically regulating gut microbe and metabolite homeostasis. AO emerges as a potential functional and therapeutic ingredient for UC treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Mesenchymal stem cell (MSC) therapy offers a promising cure for Crohn's disease (CD), however, its therapeutic effects vary significantly due to individual differences. Therefore, identifying easily detectable biomarkers is essential to assess the efficacy of MSC therapy. In this study, SAMP1/Yit mice were used as a model of CD, which develop spontaneous chronic ileitis, closely resembling the characteristics present in CD patients. Serum metabolic alterations during treatment were analyzed, through the application of differential 12 C-/ 13 C-dansylation labeling liquid chromatography-mass spectrometry. Based on the significant differences and time-varying trends of serum amine/phenol-containing metabolites abundance between the control group, the model group, and the treatment group, four serum biomarkers were ultimately screened for evaluating the efficacy of MSC treatment for CD, namely 4-hydroxyphenylpyruvate, 4-hydroxyphenylacetaldehyde, caffeate, and N-acetyltryptamine, whose abundances both increased in the serum of CD model mice and decreased after MSC treatment. These metabolic alterations were associated with tyrosine metabolism, which was validated by the dysregulation of related enzymes. The discovery of biomarkers may help to improve the targeting and effectiveness of treatment and provide innovative prospects for the clinical application of MSC for CD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1β, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.

Aims: Prediction and early detection of heart failure (HF) is crucial to mitigate its impact on quality of life, survival, and healthcare expenditure. Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance [ 1 H-NMR] spectroscopy) for incident HF., Methods and Results: Leveraging data of 68 311 individuals and >0.8 million person-years of follow-up from the UK Biobank cohort, we (i) fitted per-metabolite Cox proportional hazards models to assess individual metabolite associations, and (ii) trained and validated elastic net models to predict incident HF using the serum metabolome. We benchmarked discriminative performance against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF [PCP-HF]). During a median follow-up of ≈12.3 years, several metabolites showed independent association with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈80% feature reduction). Adding metabolomics to PCP-HF improved predictive performance (Harrel's C: 0.768 vs. 0.755, ΔC = 0.013, [95% confidence interval [CI] 0.004-0.022], continuous net reclassification improvement [NRI]: 0.287 [95% CI 0.200-0.367], relative integrated discrimination improvement [IDI]: 17.47% [95% CI 9.463-27.825]). Models including age, sex and metabolomics performed almost as well as PCP-HF (Harrel's C: 0.745 vs. 0.755, ΔC = 0.010 [95% CI -0.004 to 0.027], continuous NRI: 0.097 [95% CI -0.025 to 0.217], relative IDI: 13.445% [95% CI -10.608 to 41.454]). Risk and survival stratification was improved by integrating metabolomics., Conclusion: Serum metabolomics improves incident HF risk prediction over PCP-HF. Scores based on age, sex and metabolomics exhibit similar predictive power to clinically-based models, potentially offering a cost-effective, standardizable, and scalable single-domain alternative., (© 2024 European Society of Cardiology.)

The study aims to investigate the effects and potential mechanism of raw and processed Aconitum pendulum Busch on rheumatoid arthritis(RA) and analyze their toxicity attenuating and efficacy retaining effects. The bovine type Ⅱ collagen-induced arthritis(CIA) rat model was established. The weight, cardiac index, immune organ index, and arthritis index of the rats were recorded and calculated after administration. ELISA was used to measure the expressions of creatine kinase(CK), cardiac troponin T(cTnT), and multiple factors. The pathological morphological changes in heart tissue and ankle joint tissue were observed by hematoxylin-eosin staining. Connexin 43(Cx43) expression in the hearts of CIA rats was detected via immunohistochemical method. The levels of endogenous metabolites in the serum of CIA rats were detected by UPLC-Q-TOF-MS. Potential biomarkers were screened, and related metabolic pathways were analyzed. The results showed that raw A. pendulum could induce local myocardial fiber degeneration and necrosis, increase the cardiac index, decrease the average positive area of Cx43 expression significantly, and increase the expressions of CK and cTnT in cardiac tissue of rats. Meanwhile, raw A. pendulum could decrease the immune organ index, interleukin-6(IL-6), and other inflammatory cytokine contents in the serum and improve the damaged synovium and joint surface of CIA rats, with toxicity and efficacy coexisting. The Zanba stir-fired A. pendulum could reduce the index of arthritis, immune organ index, and content of IL-6 and inflammatory cytokines in serum and improve damaged synovium and joint surface of CIA rats with no obvious cardiac toxicity, showing significant toxicity attenuating and efficacy retaining effects. A total of 19 potential biomarkers of raw A. pendulum and Zanba stir-fired A. pendulum against RA were screened by serum metabolomics, including glycerophospholipid metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and steroid hormone synthesis. In conclusion, Xizang medicine A. pendulum is preventive and curative for RA. Raw A. pendulum has certain cardiotoxicity, and Zanba stir-fired A. pendulum has significant toxicity attenuating and efficacy retaining effects. The anti-RA mechanism may be related to the regulation of glycerophospholipid and amino acid metabolism.

Prostate cancer (PC) presents great challenges in early diagnosis and often leads to unnecessary invasive procedures as well as over diagnosis and treatment, thus highlighting the need for promising early diagnostic biomarkers. The aim of this review is to provide an up-to-date summary of chronologically existing metabolomics PC biomarkers, their potential to improve clinical PC diagnosis and to reduce the proliferation and monitoring of PC. The systematic research was conducted on PubMed in accordance with PRISMA guidelines to report PC biomarkers. The majority of the studies distinguished malignant from benign prostate and few explored the biomarkers associated with the progression of PC. The present review summarises the primary outcomes of most significant studies to extend our knowledge of PC metabolomics biomarkers. We observed divergent inter-laboratory technical procedures employing different statistical approaches produced abundant information regarding PC metabolites perturbation. Since PC metabolomics is still in its early phase, it is vital that we dig out the most specific, sensitive and accurate metabolic signatures and conduct more studies with milestone findings with comparable sample sizes to validate and corroborate the findings.

Aim: At-risk mental state (ARMS) has been recently attracting attention with respect to the improvement of the management and outcome of psychiatric diseases, such as schizophrenia. Since only a few studies have reported on biological alterations in ARMS, serum metabolomics was carried out in ARMS subjects and healthy controls using liquid chromatography with high-resolution mass spectrometry., Methods: Serum samples were collected from ARMS subjects (n = 24; male: 12; female 12) and age- and sex-matched healthy controls (n = 23 male: 11, female: 12). After serum pre-treatment, liquid chromatography with high-resolution mass spectrometry was performed. Multivariate analyses, such as orthogonal partial least-squares discriminant and volcano plot analyses, were performed., Results: Serum inosine, lactate, taurine, 2,3-dihydroxypropanoate and glutamate levels differed between the two groups. A significant increase in inosine levels was detected in the positive- and negative-ion modes; however, significant differences were not observed in the levels of other purine-related metabolites (hypoxanthine, xanthine and urate) between the two groups., Conclusion: Increased inosine levels may serve as biological markers for ARMS, in addition to alterations in the levels of lactate and certain amino acids., (© 2021 John Wiley & Sons Australia, Ltd.)

Yaobitong capsule (YBTC) has been used for the prevention and treatment of inflammation-related lumbago and leg pain. However, its intervention mechanism still remains unclear. This study was aimed to evaluate the control efficiency of YBTC on adjuvant-induced rheumatoid arthritis (RA) rats by metabonomic method and to explore its possible anti-arthritis mechanism. Taking into account the complexity of endogenous metabolites in serum samples, an integrated metabolomics method based on RP/HILIC-UHPLC-Q-TOF MS was developed, to overcome the limitations of a single chromatographic in this study. The results showed that 32 potential biomarkers of arthritis were identified, primarily related to amino acid metabolism, glucose metabolism, lipid metabolism and nucleotide metabolism. Further receiver operating characteristic analysis revealed that the area under the curve of two down-regulated metabolites (3-Hydroxy-hexadecanoic acid, 2-Oxoarginine) and one up-regulated metabolite (l-Glutamic acid) among 32 biomarkers were 0.906, 0.969 and 1.000, respectively, indicating that high predictive ability of this method for RA. In this study, an integrated serum metabolomics method based on high-resolution mass spectrometry was successfully established for the first time to study the intervention mechanism of YBTC in RA, providing evidence regarding the clinical application of YBTC and a new insight for the prevention of RA in the future., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Renal fibrosis (RF) is a pathological process of progression from chronic kidney disease to end-stage renal disease. Amygdalus mongolica is a traditional Chinese medicine, and our previous studies demonstrated that the n-butanol extract (BUT) and amygdalin extract (AMY) from its seeds can prevent RF. However, the underlying mechanism remains unclear. The present study investigated the exact mechanism of the protective effect of A. mongolica on RF. A renal fibrosis rat model was induced with unilateral ureteral obstruction. Biochemical indicators were measured and combined with histopathology of renal tissue to evaluate the anti-RF effects. A serum metabonomic method was used to clarify the changes in the metabolic profile. The tubulointerstitial damage and fibrosis were significantly improved and metabolic perturbations were restored after treatment with BUT and AMY. Thirty-eight metabolites associated with RF progression and related to the regulation of arginine and proline metabolism, nicotinate and nicotinamide metabolism, and histidine metabolism were identified. They were restored to levels similar to those in controls after treatment. Moreover, no significant differences in efficacy were observed between the BUT and AMY groups. This study reveals and compares the potential mechanisms of the renoprotective effects after treatment with BUT and AMY from a metabolomic perspective.

Context: Baicalin, a major flavonoid extracted from Scutellaria baicalensis Georgi (Lamiaceae), has been shown to exert therapeutic effects on pulmonary fibrosis (PF)., Objective: To use serum metabolomics combined with biochemical and histopathological analyses to clarify anti-PF mechanisms of baicalin on metabolic pathways and the levels of potential biomarkers., Materials and Methods: Forty male Sprague-Dawley rats were randomly divided into the control, PF model, prednisolone acetate-treated (4.2 mg/kg/day) and baicalin-treated (25 and 100 mg/kg/day) groups. A rat model of PF was established using a tracheal injection of bleomycin, and the respective drugs were administered intragastrically for 4 weeks. Histomorphology of lung tissue was examined after H&E and Masson's trichrome staining. Biochemical indicators including SOD, MDA and HYP were measured. Serum-metabonomic analysis based on UPLC-Q-TOF/MS was used to clarify the changes in potential biomarkers among different groups of PF rats., Results: Both doses of baicalin effectively alleviated bleomycin-induced pathological changes, and increased the levels of SOD (from 69.48 to 99.50 and 112.30, respectively), reduced the levels of MDA (from 10.91 to 5.0 and 7.53, respectively) and HYP (from 0.63 to 0.41 and 0.49, respectively). Forty-eight potential biomarkers associated with PF were identified. Meanwhile, the metabolic profiles and fluctuating metabolite levels were normalized or partially reversed after baicalin treatment. Furthermore, baicalin was found to improve PF potentially by the regulation of four key biomarkers involving taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism., Conclusions: These findings revealed the anti-fibrotic mechanisms of baicalin and it may be considered as an effective therapy for PF.

Objective: Graves' disease (GD) related hyperthyroidism (HT) has profound effects on metabolic activity and metabolism of macromolecules affecting energy homeostasis. In this study, we aimed to get a comprehensive understanding of the metabolic changes and their clinical relevance in GD children., Methods: We investigated serum substances from 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We explored the metabolomics using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis, and then analyzed the metabolomic data via multivariate statistical analysis., Results: By untargeted metabolomic analysis, a total of 730 metabolites were identified in all participants, among which 48 differential metabolites between GD and control groups were filtered out, including amino acids, dipeptides, lipids, purines, etc. Among these metabolites, 33 were detected with higher levels, while 15 with lower levels in GD group compared to controls. Pathway analysis showed that HT had a significant impact on aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis, several amino acids metabolism, purine metabolism, and pyrimidine metabolism., Conclusion: In this study, via untargeted metabolomics analysis, significant variations of serum metabolomic patterns were detected in GD children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xia, Qian, Chen, Chen, Xie, Zhang, Wu, Sun, Wang, Liu and Chen.)

Traditional Chinese medicine believes that qi deficiency is important pathogenesis and syndrome of liver cancer and thus is crucial in related research. However, the effect of qi deficiency on the occurrence and development of liver cancer is still unclear. This study aimed to establish a liver cancer model of qi deficiency through the swimming exhaustion and xenograft of human hepatoma HepG2 cells. The effects of qi deficiency on the occurrence and development of liver cancer were investigated by analyzing tumor development, blood routine, histopathology, and serum metabolomics. Results showed that qi deficiency greatly affected the physiology and tumor growth of xenograft mice. Eight potential biomarkers were identified by metabolomics based on ultra-high performance liquid chromatography and tandem quadrupole time-of-flight mass spectrometry. Their main pathways were arachidonic acid metabolism, phenylalanine metabolism, purine metabolism, glycerolipid metabolism, steroid biosynthesis, sphingomyelin metabolism, and fatty acid metabolism pathway. Finally, the effects of qi deficiency on the occurrence and development of liver cancer were comprehensively analyzed, and the mechanism of this process was preliminarily clarified., (© 2021 Wiley-VCH GmbH.)

Long term heat exposure (HE) leads to estrous cycle disorder (ECD) in female rats and damages reproductive function. However, the regulation mechanism of vaginal microorganisms and serum metabolomics remains unclear. This study aimed to explore the effects of microbes on the vaginal secretions of rats with ECD and describe the serum metabolomics characteristics and their relationship with vaginal microorganisms. The alterations in the serum levels of neurotransmitters were used to verify the possible regulatory pathways. The relative abundance, composition, and colony interaction network of microorganisms in the vaginal secretions of rats with ECD changed significantly. The metabolomics analysis identified 22 potential biomarkers in the serum including lipid metabolism, amino acid metabolism, and mammalian target of rapamycin and gonadotropin-releasing hormone (GnRH) signaling pathways. Further, 52 pairs of vaginal microbiota-serum metabolites correlations (21 positive and 31 negative) were determined. The abundance of Gardnerella correlated positively with the metabolite L-arginine concentration and negatively with the oleic acid concentration. Further, a negative correlation was found between the abundance of Pseudomonas and the L-arginine concentration and between the metabolite benzoic acid concentration and the abundance of Adlercreutzia . These four bacteria-metabolite pairs had a direct or indirect relationship with the estrous cycle and reproduction. The glutamine, glutamate, and dopamine levels were significantly uncontrolled. The former two were closely related to GnRH signaling pathways involved in the development and regulation of HE-induced ECD in rats. Serum neurotransmitters partly reflected the regulatory effect of vaginal microorganisms on the host of HE-induced ECD, and glutamatergic neurotransmitters might be closely related to the alteration in vaginal microorganisms. These findings might help comprehend the mechanism of HE-induced ECD and propose a new intervention based on vaginal microorganisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 An, Zhang, Fan, Chen, Wei, Li, Chen, Zhang, Yang and Wang.)

Background: Ischemic stroke is one of the leading causes of death and adult disability. The incidence of ischemic stroke continues to rise in young adults. This study aimed to provide a comprehensive evaluation of metabolic changes and explore possible mechanisms in young ischemic stroke patients without common risk factors., Methods: This study investigated serum metabolomics in 50 young patients with newly suffered ischemic stroke and 50 age-, sex-, and body mass index-matched healthy controls. Liquid chromatography coupled with a Waters Xevo TQ-S mass spectrometer with an electrospray ionization (ESI) source was used to analyze amino acid or bile acid, and free fatty acid or lipid was analyzed by liquid chromatography coupled with a Qtrap5500 mass spectrometer with an ESI source. The metabolomic data were analyzed by performing a multivariate statistical analysis., Results: A total of 197 metabolites, including amino acids, bile acids, free fatty acids, and lipids, were identified in all participants. Multivariate models showed significant differences in serum metabolomic patterns between young patients with ischemic stroke and healthy controls. The stroke patients had increased L-methionine, homocysteine, glutamine, uric acid, GCDCA, and PE (18:0/20:4, 16:0/22:5), and decreased levels of L-citrulline, taurine, PC (16:2/22:6, 16:2/20:5, 15:0/18:2), and SM (d18:1/23:0, d20:0/19:1, d18:1/22:0, d16:0/26:1, d16:0/18:0, d16:0/22:1, d18:1/19:1, d16:0/17:1, d16:1/24:1, d18:1/19:0). Based on the identified metabolites, the metabolic pathways of arginine biosynthesis, glycerophospholipid metabolism, and taurine and hypotaurine metabolism were significantly enriched in the young patients with ischemic stroke., Conclusions: Serum metabolomic patterns were significantly different between young patients with ischemic stroke and healthy controls. Our study is beneficial in providing a further view into the pathophysiology of young patients with ischemic stroke.

Objectives: To provide a comprehensive study of the intervention mechanism and compatible regularity of Chaihu Shu Gan San (CSGS) in a chronic unpredictable mild stress (CUMS)-induced depression model., Methods: Ethological study and ELISA assay were applied to measure the phenotypes of depression after CUMS stimulate and assess the antidepressant activity of fluoxetine, CSGS and its compatibilities. The serum metabolic profile changes were revealed by untargeted Q/TOF MS-based metabolomics followed by multivariate statistical analysis., Key Findings: CSGS exhibits an significant intervention effect on CUMS-induced depression. After the multivariate statistical analysis, 17 potential serum biomarkers were identified and 16 of them could be regulated by CSGS. The intervention of CSGS on CUMS-induced depression involved five key pathways. Moreover, each functional unit (monarch, minister, assistant and guide medicine) in CSGS regulates different metabolites and metabolic pathways to achieve different effects on antidepressant; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of bioactive ingredients in the seven herbs of CSGS., Conclusions: CSGS produced an obvious antidepressant activity. The comprehensive and holistic metabolomics approach could be a powerful tool to study the intervention mechanism and the compatibility rule of traditional Chinese medicine., (© 2020 Royal Pharmaceutical Society.)

Ethnopharmacological Relevance: Renal fibrosis (RF) is a common outcome of various progressive chronic kidney diseases (CKDs) and, thus, seriously endangers human health. As the active ingredient of Amygdalus mongolica, amygdalin inhibits RF. Furthermore, our previous studies demonstrated that n-butanol extract (BUT) and petroleum ether extract (PET), which are effective components of A. mongolica, have an anti-renal fibrosis effect. However, their potential mechanisms of action are unclear and need further verification., Aims of the Study: The aims of this study were to further investigate the effects and potential mechanisms of A. mongolica extracts in the treatment of RF., Materials and Methods: The animals were divided into the control group, RF model group, PET group and BUT group. The RF rat model was established through unilateral ureteral obstruction (UUO). Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), and hydroxyproline (HYP, a routine marker of fibrosis), and the antioxidant index (including superoxide dismutase (SOD) and malondialdehyde (MDA)) were measured to evaluate the anti-RF effects of the extracts of A. mongolica. The histomorphology of renal tissue was observed and scored by HE and Masson staining. A serum metabonomic analysis based on UPLC-Q-TOF/MS was performed to assess the changes in the metabolic profile among the different groups., Results: The results showed that PET and BUT significantly improved tubulointerstitial damage and fibrosis by reducing the levels of Scr, BUN, HYP, and MDA and increasing the level of SOD. Moreover, no significant differences in efficacy were observed between the BUT and PET groups. According to the metabolomics analysis, seventy-four potential biomarkers were identified, and eight crucial biomarkers were further selected. These key biomarkers significantly contributed to RF progression by participating in six metabolic pathways, including pathways involved in arginine and proline metabolism, histidine metabolism, nicotinamide metabolism, pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and amino sugar and nucleotide sugar metabolism. In addition, eight key biomarkers and six crucial biomarkers were restored to levels similar to those observed in controls following the treatment with PET and BUT, respectively., Conclusions: The outcomes of these studies demonstrate the renoprotective effects of A. mongolica extracts in rats with RF and revealed the mechanism underlying these antifibrotic effects on metabolic activity for the first time., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Quantitative assessment of disease activity is important for effective care of patients with Takayasu arteritis (TA). Activated glutaminolysis and reduced glycolytic flux is the hallmark of active inflammation. Based on this, we hypothesize that the circulatory Glutamine/Glucose ratio (QGR) can serve as an indicant of active inflammation in TA. To probe this hypothesis, the serum samples were collected from 45 active and 53 inactive TA patients fulfilling American College of Rheumatology (ACR) criteria and assessed for disease activity according to Indian Takayasu Clinical Activity Score (ITAS) using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. The quantitative profiles of circulatory metabolites implicated in glutaminolysis (Glutamine and Glutamate) and those which estimate glycolytic flux (i.e. glucose and lactate) were measured using high field (800 MHz) NMR spectroscopy. The recorded spectra were analyzed using CHENOMX NMR Suite and the estimated concentration profiles were compared and evaluated for their diagnostic potential using Metaboanalyst. Compared to inactive-TA patients, the sera of active-TA patients were characterized by significantly decreased serum levels of glutamine and lactate suggesting that these patients exhibit activated glutaminolysis and reduced glycolytic activity. This is further supported by significantly decreased QGR and lactate to glucose ratio (LGR) levels in active compared to inactive TA patients. The receiver operating characteristic (ROC) curve analysis revealed satisfactory accuracy, sensitivity and specificity for QGR [with area under ROC curve (AUROC) = 0.76 and 95% confidence interval (CI) = 0.66-0.84) compared to that for LGR (with AUROC = 0.67 and CI = 0.561-0.77). Therefore, we believe that the circulatory QGR has the potential to serve as surrogate marker for the assessment of disease activity in TA patients. However, the use of this ratio in clinical settings will require future studies on large patient cohorts and procedural optimization as well to improve accuracy., Competing Interests: Declaration of Competing Interest On behalf of all authors, the corresponding authors state that there is no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The small blood flukes of genus Schistosoma, which cause one of the most prevalent and serious parasitic zoonosis schistosomiasis, are dependent on immune-related factors of their mammalian host to facilitate their growth and development, and the formation of granulomatous pathology caused by eggs deposited in host's liver and intestinal wall. Schistosome development is hampered in the mice lacking just T cells, and is even more heavily retarded in the severe combined immunodeficient (SCID) mice lacking both T and B lymphocytes. Nevertheless, it's still not clear about the underlying regulatory molecular mechanisms of schistosome growth and development by host's immune system. This study, therefore, detected and compared the serum metabolic profiles between the immunodeficient mice and immunocompetent mice (SCID mice vs. BALB/c mice) before and after S. japonicum infection (on the thirty-fifth day post infection using liquid chromatography-mass spectrometry (LC-MS). Totally, 705 ion features in electrospray ionization in positive-ion mode (ESI+) and 242 ion features in ESI- mode were identified, respectively. First, distinct serum metabolic profiles were identified between SCID mice and BALB/c mice without S. japonicum worms infection. Second, uniquely perturbed serum metabolites and their enriched pathways were also obtained between SCID mice and BALB/c mice after S. japonicum infection, which included differential metabolites due to both species differences and differential responses to S. japonicum infection. The metabolic pathways analysis revealed that arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and purine metabolism were enriched based on the differential serum metabolites between SCID mice and BALB/c mice after S. japonicum infection, which was addressed to be related to the retarded growth and development of S. japonicum in SCID mice. These findings provide new clues to the underlying molecular events of host's systemic metabolic changes on the growth and development of S. japonicum worms, and also provide quite promising candidates for exploitation of drugs or vaccines against schistosome and schistosomiasis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn's disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn's from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn's disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD., Competing Interests: The authors declare no conflict of financial interest.

Chemometric analysis of bioactive compounds revealed that American ginsengs (AGs) from different cultivation regions of China had a difference in quality, which indicates their possible pharmacological difference. A UPLC-Q/TOF-MS-based untargeted metabolomic approach was used to uncover serum metabolite changes in radiated mice pre-administered with AG root decoctions from seven cultivation regions and to further assess their quality difference. OPLS-DA revealed that 51 metabolites (ESI − ) and 110 (ESI⁺) were differentially expressed in sera between the control and the radiated model mice. Heatmap analysis further revealed that AG could not reverse most of these radiation-altered metabolites, which indicates dietary supplement of AG before cobalt radiation had the weak potential to mediate serum metabolites that were altered by the sub-lethal high dose radiation. In addition, 83 (ESI − ) and 244 (ESI⁺) AG altered metabolites were detected in radiated mice under radiation exposure. Both OPLS-DA on serum metabolomes and heatmap analysis on discriminant metabolites showed that AGs from different cultivation regions differentially influenced metabolic alterations in radiated mice, which indicates AGs from different cultivation regions showed the pharmacological difference in modulation of metabolite changes. AGs from Shandong, Shanxi, and Beijing provinces had more similar pharmacological effects than AGs from USA, Canada, Jilin, and Heilongjiang. Finally, 28 important potential biomarkers were annotated and assigned onto three metabolic pathways including lipid, amino acid, and energy metabolisms.

Diet, genetics, and the gut microbiome are determinants of metabolic status, in part through production of metabolites by the gut microbiota. To understand the mechanisms linking these factors, we performed LC-MS-based metabolomic analysis of cecal contents and plasma from C57BL/6J, 129S1/SvImJ, and 129S6/SvEvTac mice on chow or a high-fat diet (HFD) and HFD-treated with vancomycin or metronidazole. Prediction of the functional metagenome of gut bacteria by PICRUSt analysis of 16S sequences revealed dramatic differences in microbial metabolism. Cecal and plasma metabolites showed multifold differences reflecting the combined and integrated effects of diet, antibiotics, host background, and the gut microbiome. Eighteen plasma metabolites correlated positively or negatively with host insulin resistance across strains and diets. Over 1,000 still-unidentified metabolite peaks were also highly regulated by diet, antibiotics, and genetic background. Thus, diet, host genetics, and the gut microbiota interact to create distinct responses in plasma metabolites, which can contribute to regulation of metabolism and insulin resistance., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Recently, the colon has been recognized as an important source of various uremic toxins in patients with end stage renal disease. Medicinal charcoal tablets are an oral adsorbent that are widely used in patients with chronic kidney disease in China to remove creatinine and urea from the colon. A parallel fecal and serum metabolomics study was performed to determine comprehensive metabolic profiles of patients receiving hemodialysis (HD). The effects of medicinal charcoal tablets on the fecal and serum metabolomes of HD patients were also investigated., Methods: Ultra-performance liquid chromatography/mass spectrometry was used to investigate the fecal and serum metabolic profiles of 20 healthy controls and 31 HD patients before and after taking medicinal charcoal tablets for 3 months., Results: There were distinct metabolic variations between the HD patients and healthy controls both in the feces and serum according to multivariate data analysis. Metabolic disturbances of alanine, aspartate and glutamate metabolism, arginine and proline metabolism figured prominently in the serum. However, in the feces, alterations of tryptophan metabolism, lysine degradation and beta-alanine metabolism were pronounced, and the levels of several amino acids (leucine, phenylalanine, lysine, histidine, methionine, tyrosine, and tryptophan) were increased dramatically. Nineteen fecal metabolites and 21 serum metabolites were also identified as biomarkers that contributed to the metabolic differences. Additionally, medicinal charcoal treatment generally enabled the serum and fecal metabolomes of the HD patients to draw close to those of the control subjects, especially the serum metabolic profile., Conclusion: Parallel fecal and serum metabolomics uncovered the systematic metabolic variations of HD patients, especially disturbances in amino acid metabolism in the colon. Medicinal charcoal tablets had an impact on the serum and fecal metabolomes of HD patients, but their exact effects still need to be studied further., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: Sini decoction (SND) is used for cardiovascular disease over thousands of years in China. However, it is still lacking of dose-response relationship of SND in cardiovascular disease at the metabolic level., Purpose: The present study is designed to explore the cardioprotective effects of different dosages of SND pretreatment on the isoproterenol (ISO)-induced myocardial injury and elucidate the mechanism underlying this protective effect., Methods: The cardioprotective effects of different dosages of SND pretreatment on the isoproterenol-induced myocardial injury were compared through a serum metabolomics approach based on ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, the cardioprotective effects were evaluated by serum biochemical analysis and histopathological examination of myocardial tissue. Finally, in view of the fact that these perturbed bile acid and phospholipid metabolisms are connected with NF-κB signaling pathway, nuclear expression of NF-κB p65 and the activation of NF-κB were analyzed by immunohistochemistry, immunoblotting and electrophoretic mobility shift assay (EMSA), respectively., Results: The cardioprotective effect was observed in SND pretreatment groups, especially in low dosage SND group. The results of serum enzyme activities and histopathology were consistent with the above effect. Meanwhile, fifteen latent biomarker candidates were identified involving glucose, phospholipid, bile acid and amino acid metabolisms. Among them, five bile acids including ursodeoxycholic acid, murideoxycholic acid, muricholic acid, hyodeoxycholic acid and cholic acid, were for the first time identified as latent pathological biomarkers related to ISO-induced myocardial injury. Further, different dose SND groups exerted different of inhibition degrees to the activation of NF-κB, which was obvious in the SND-L group., Conclusion: The results revealed that Sini decoction protreatment protects myocardium better at a low dose level and one of possible cardioprotective mechanisms is modulating NF-κB signaling pathway against isoproterenol-induced myocardial injury through regulating phospholipid and bile acid metabolisms., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective and Design: We present in this article 1 H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC)., Material/methods: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). 1 H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation. Receiver operating curve (ROC) and pathway analysis on NMR data were also carried out to validate the findings., Results: Serum metabolites such as glutamine, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), alanine, branch chained amino acids (BCAA), histidine and tyrosine were found to be depleted whereas formate, lactate, 1,2-propanediol were found to be elevated in CC. Metabolic pathways associated with metabolite alteration have also been reported., Conclusions: NMR has been established for disease diagnosis along with identification of metabolic pattern recognition in biofluids. Gallstones cause inflammation of the gallbladder in the form of CC. Inflammation plays a major role in causation of gall bladder cancer and leads the way to malignancy. Metabolic analysis of CC may lead to early diagnosis of disease and its progression to gallbladder cancer.

Yin-Chen-Hao-Tang (YCHT) is a famous Chinese medicine formula which has long been used in clinical practice for treating various liver diseases, such as liver fibrosis. However, to date, the mechanism for its anti-fibrotic effects remains unclear. In this paper, an ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOF-MS)-based metabolomic study was performed to characterize dimethylnitrosamine (DMN)-induced liver fibrosis in rats and evaluate the therapeutic effects of YCHT. Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the YCHT-treated group exhibited a tendency to restore to the controls. Seven significantly changed fibrosis-related metabolites, including unsaturated fatty acids and lysophosphatidylcholines (Lyso-PCs), were identified. Moreover, statistical analysis demonstrated that YCHT treatment could reverse the levels of most metabolites close to the normal levels. These results, along with histological and biochemical examinations, indicate that YCHT has anti-fibrotic effects, which may be due to the suppression of oxidative stress and resulting lipid peroxidation involved in hepatic fibrogenesis. This study offers new opportunities to improve our understanding of liver fibrosis and the anti-fibrotic mechanisms of YCHT.

Background: The gut microbiome plays a key role in the formation of livestock and poultry traits via serum metabolites, and empirical evidence has indicated these traits are sex-linked. Methods: We examined 106 chickens (54 male chickens and 52 female chickens) and analyzed cecal content samples and serum samples by 16S rRNA gene sequencing and non-targeted metabolomics, respectively. Results: The cecal microbiome of female chickens was more stable and more complex than that of the male chickens. Lactobacillus and Family XIII UCG-001 were enriched in male chickens, while Eubacterium_nodatum_group, Blautia, unclassified_Anaerovoraceae, Romboutsia, Lachnoclostridium, and norank_ Muribaculaceae were enriched in female chickens. Thirty-seven differential metabolites were identified in positive mode and 13 in negative mode, showing sex differences. Sphingomyelin metabolites possessed the strongest association with cecal microbes, while 11β-hydroxytestosterone showed a negative correlation with Blautia. Conclusion: These results support the role of sexual dimorphism of the cecal microbiome and metabolome and implicate specific gender factors associated with production performance in chickens. [ABSTRACT FROM AUTHOR]

Background: In modern diets, alcohol consumption has led to an increase in the number of cases of alcohol-related liver disease (ALD). Dihydromyricetin (DMY) is commonly used as a hepatoprotective agent owing to its remarkable efficacy in treating chronic alcoholic liver injury; however, its mechanism of action is unclear. The object of the study is to investigate the effect and mechanism of DMY in alleviating chronic ALD. Methods: A mouse model of chronic ALD was established. Mice were treated with DMY for 56 days, and their biochemical parameters including liver function, blood lipids, and oxidative stress-related indices were measured. Farnesoid X receptor (FXR) expression, NOD-like receptor protein 3 (NLRP3) pathway-related protein expression, and inflammation-related gene expression were determined to elucidate the mechanism of DMY in mice with ALD. Lastly, serum and liver metabolomics-based UHPLC-Orbitrap Exploris MS analyses were used to determine the influence of the metabolism of DMY on mice with ALD. Results: Pharmacodynamic studies showed that DMY could decrease aspartate transaminase, alanine transaminase, triglyceride, and low-density lipoprotein cholesterol levels, improve superoxide dismutase activity, and reduce inflammation in mice with ALD. DMY treatment protects the liver by increasing FXR protein expression and by decreasing NLRP3 pathway-related protein expression and inflammatory gene expression. Metabolomics analysis indicated that ethanol treatment mainly altered metabolism in mice. DMY could regulate 10 metabolites in serum, namely, N-α-acetyllysine, 1-pyrrolinecytosine, glutamyllysine, 5-methylcytosine, N-methylvaline, pyridoxamine, demethoxycurcumin, L-arginine, triacetin, and 15-methylpalmitate. It could also regulate 31 metabolites in the liver, including L-methionine and L-leucine. DMY treatment altered the following important pathways: valine, leucine, and isoleucine biosynthesis; cysteine and methionine metabolism; and valine, leucine, and isoleucine degradation. Correlation analyses using heatmaps revealed that the metabolic parameters are closely related to the pharmacodynamic index. Conclusion: These findings indicated that DMY alleviated ALD by regulating the FXR-NLRP3 signaling pathway and could treat serum and liver metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective To observe the protective effect of Zhilong Huoxue Tongyu Capsule (Zhilong Capsule) on myocardial ischemia reperfusion injury (MIRI) in mice, and explore its regulatory mechanism using metabolomics. Methods Using a random number table method, 30 C57BL/6J mice were randomly divided into the following three groups: sham operation group, model group, and Zhilong Capsule group (6.24 g/kg), with 10 mice in each group. In mice in the model group and the Zhilong Capsule group, a mouse MIRI model was established by ligating the left anterior descending branch, while mice in the sham operation group underwent threading without ligation. The Zhilong Capsule group began modeling one week after pre-administration and continued to receive intragastric administration for two weeks after modeling once daily. The cardiac function, including the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), was assessed by color echocardiography. The myocardial fibrosis and apoptosis were observed by Masson staining and TUNEL staining, respectively. Enzyme-linked immunosorbent assay was used to measure the serum contents of lactate dehydrogenase (LDH) and brain natriuretic peptide (BNP). Liquid chromatography-mass spectrometry combined with multivariate statistical method was performed for serum metabolite detection and identification analysis. Results Compared with the model group, the mice in the Zhilong Capsule group exhibited an increase in LVEF and LVFS, a reduction in cardiac tissue structure disorder, a decrease in myocardial fibrosis, a decrease in cell apoptosis rate, and a decrease in serum LDH and BNP contents (P<0.05). Metabolomics result showed that intervention with Zhilong Capsule significantly regulated 30 differential metabolites related to MIRI. Important metabolic pathways involved 20 pathways related to tyrosine metabolism, arginine and proline metabolism, and vitamin digestion and absorption. Conclusion Zhilong Capsule has a protective effect on MIRI, and it may achieve this effect by regulating pathways related to tyrosine metabolism, arginine and proline metabolism, and vitamin digestion and absorption. [ABSTRACT FROM AUTHOR]

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders. [ABSTRACT FROM AUTHOR]

This study was conducted to explore the potential effect of Yucca schidigera extract (YSE) on the metabolism of beef cattle. Thirty Angus crossbreed steers were selected, with an initial mean body weight of 506.6 ± 33.3 kg, and assigned to two treatments: a diet with no additives (CON group) and a diet supplemented with 1.75 g/kg of YSE (YSE group) (on a dry matter basis). The experiment lasted for 104 days, with 14 days for adaptation. The results showed that adding YSE could significantly improve the average daily gain (ADG) from 1 to 59 d (15.38%) (p = 0.01) and 1 to 90 d (11.38%) (p < 0.01), as well as dry matter digestibility (DMD) (0.84%) (p < 0.05). The contents of alanine aminotransferase, aspartate aminotransferase, and bilirubin and the total antioxidant capacity were increased and blood urea was reduced in the YSE group, compared to the CON group (p < 0.05). Both the glycerophospholipids and bile acids, including phosphocholine, glycerophosphocholine, PC(15:0/18:2(9Z,12Z)), PE(18:0/20:3(5Z,8Z,11Z)), PE(18:3(6Z,9Z,12Z)/P-18:0), LysoPC(15:0), LysoPC(17:0), LysoPC(18:0), LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), deoxycholic acid, glycocholic acid, and cholic acid, were upregulated by the addition of YSE. In summary, YSE may improve the ADG by increasing the blood total antioxidant capacity and glycerophospholipid synthesis, maintaining steers under a healthy status that is beneficial for growth. Furthermore, YSE may also increase the expression of bile acid synthesis, thereby promoting DMD, which, in turn, offers more nutrients available for growth. [ABSTRACT FROM AUTHOR]

To investigate the effect of Bushen Huoxue Recipe (BSHXR) on serum metabolomics in polycystic ovary syndrome rat (PCOSR). In our study, twenty-four 6-week-old Sprague-Dawley (SD) female rats were randomly divided into three groups: treatment group, model group and blank group. The blank group and other groups were gavaged in different ways each morning, and the rats were treated with normal saline or BSHXR containing liquid each afternoon. Liquid chromatography-mass spectrometry (LC-MS) was employed to study serum metabolites in the treatment group after the study as well as in the model and blank groups. There was a tendency to normalize the histomorphology of ovarian pathology and the abnormal sex hormone level of PCOSR was significantly improved after BSHXR treatment. The level of serum metabolites was greatly changed in PCOSR treated with the BSHXR. We identified 32 metabolic targets of BSHXR in PCOSR using LC-MS, and further revealed BSHXR targeted five major metabolic pathway: retrograde endocannabinoid signaling, taurine and hypotaurine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, arginine and proline metabolism. Conclusion: Our study found that BSHXR plays a role in the treatment of PCOS by regulating key metabolic pathways in the PCOSR. [ABSTRACT FROM AUTHOR]

Background: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians. Objective: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB. Materials and Method: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis. Results: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.). Conclusion: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases. Methods: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules were associated with incident diabetes, dyslipidemia, and hypertension over the 6-yr follow-up. Results: Of 624 metabolites, 5 and 102 were associated with MVPA and sedentary behavior at false discovery rate (FDR) <0.05, respectively, after adjusting for socioeconomic and lifestyle factors. The weighted correlation network analysis identified 8 modules from 102 metabolites associatedwith sedentary time. Fourmodules (branched-chain amino acids, erythritol, polyunsaturated fatty acid, creatine)were positively, and the other four (acyl choline, plasmalogen glycerol phosphatidyl choline, plasmalogen glycerol phosphatidyl ethanolamine, urea cycle) were negatively correlated with sedentary time. Among these modules, a higher branched-chain amino acid score and a lower plasmalogen glycerol phosphatidyl choline score were associated with increased risks of diabetes and dyslipidemia. A higher erythritol score was associated with an increased risk of diabetes, and a lower acyl choline score was linked to an increased risk of hypertension. Conclusions: In this study of US Hispanics/Latinos, we identified multiple serum metabolomic signatures of sedentary behavior and their associations with risk of incident diabetes, hypertension, and dyslipidemia. These findings suggest a potential role of circulatingmetabolites in the links between sedentary behavior and cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Introduction: It is essential to understand the underlying changes in the patients' metabolic profiles that may be indicative of the therapy's effectiveness. Aim: To prospectively analyse the clinical efficacy of ozone autohemotherapy in the treatment of acute herpes zoster and investigate its impact on serum metabolomics. Material and methods: A total of 76 patients with acute herpes zoster between May 2018 and June 2020 were enrolled and divided into an experimental group and a control group. The pain location, Numeric Rating Scale (NRS) scores before and after treatment (1 week, 1 month, 3 months, and 6 months post-treatment), medication usage, and Quality of Sleep (QS) scores were prospectively analysed. Additionally, serum metabolomic data were obtained and analysed before and 6 months after the treatment. Results: There were statistically significant differences in the total NRS scores before and after ozone autohemotherapy (p < 0.05). The NRS scores of both groups significantly decreased (p < 0.05). At the 6-month follow-up, no patients were lost, and 83 patients completed the follow-up. The NRS improvement at 1 week, 1 month, 3 months, and 6 months post-treatment in the experimental group was significantly lower than that in the control group (p < 0.05). There was no significant difference in the medication usage (pregabalin or tramadol sustained-release tablets) between the two groups (p > 0.05). One month after treatment, the QS score improvement in the diabetes group was significantly lower than that in the non-diabetes group (p < 0.05). Serum metabolomics analysis revealed three significantly decreased metabolites, namely creatine, adipate, and glucose, after treatment. Conclusions: Ozone autohemotherapy is an effective treatment for acute herpes zoster patients and can rapidly and effectively alleviate pain symptoms in the short term. The changes in serum metabolomics may provide further insights into the treatment mechanism. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is an important cause of end‐stage renal disease with changes in metabolic characteristics. The objective of this study was to study changes in serum metabolic characteristics in patients with DKD and to examine metabolite panels to distinguish DKD from diabetes with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). We recruited 40 type II diabetes mellitus (T2DM) patients with or without DKD from a single center for a cross‐sectional study. Serum metabolic profiling was performed with MALDI‐TOF‐MS using a vertical silicon nanowire array. Differential metabolites between DKD and diabetes patients were selected, and their relevance to the clinical parameters of DKD was analyzed. We applied machine learning methods to the differential metabolite panels to distinguish DKD patients from diabetes patients. Twenty‐four differential serum metabolites between DKD patients and diabetes patients were identified, which were mainly enriched in butyrate metabolism, TCA cycle, and alanine, aspartate, and glutamate metabolism. Among the metabolites, l‐kynurenine was positively correlated with urinary microalbumin, urinary microalbumin/creatinine ratio (UACR), creatinine, and urea nitrogen content. l‐Serine, pimelic acid, 5‐methylfuran‐2‐carboxylic acid, 4‐methylbenzaldehyde, and dihydrouracil were associated with the estimated glomerular filtration rate (eGFR). The panel of differential metabolites could be used to distinguish between DKD and diabetes patients with an AUC value reaching 0.9899–0.9949. Among the differential metabolites, l‐kynurenine was related to the progression of DKD. The differential metabolites exhibited excellent performance at distinguishing between DKD and diabetes. This study provides a novel direction for metabolomics‐based clinical detection of DKD. [ABSTRACT FROM AUTHOR]

Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its antigout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine. [ABSTRACT FROM AUTHOR]

Introduction Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions. Methods Subjects with Qi deficiency and non- Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology. Results QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non- Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non- Qi deficiency subjects. The "herbs-compounds-pathways" diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways. Conclusion Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood. Methods: In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography–tandem mass spectrometry (GC–MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing. Results: The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses. Conclusion: The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM. [ABSTRACT FROM AUTHOR]

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the “Metabolite-TargetComponent” interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF. [ABSTRACT FROM AUTHOR]

Stress is a common factor that reduces production performance. However, the physiology of stress is not fully understood. In this study, 40-day-old rabbits were injected 1.0 mg/kg BW Dexamethasone to induce stress. A metabolomic study on serum of stress-induced rabbits was performed to research the metabolism mechanism of stress by using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC–MS). Clear separations between stress rabbits and control rabbits were observed by principal component analysis (PCA) based on the data obtained using both analytical techniques and 90 significantly changed metabolites were identified as potential biomarkers of stress. Stress rabbits were characterised by altered levels of serum lysophosphatidylcholines, amino acids, phosphatidyl choline, and nucleosides, which were related to multiple perturbed metabolic pathways and contributed to the elucidation of the complex mechanism of stress. These were main linked to three different pathways: pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and biosynthesis of amino acid. In summary, we provided a comprehensive understanding of metabolic alterations in the main stress-targeted tissues, helping to understand the potential mechanisms underlying stress. Stress alters the metabolic composition of serum in rabbits. In rabbits, dexamethasone‐induced chronic stress alters 90 metabolites in serum. [ABSTRACT FROM AUTHOR]

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWDon CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions. [ABSTRACT FROM AUTHOR]

In in vitro fertilization (IVF), it is meaningful to find novel biomarkers predicting ovarian response in advance. The aim of the study was to identify serum metabolomics predicting ovarian response after controlled ovarian stimulation (COS). Blood samples collected at the start of pituitary downregulation and on the fifth day after COS using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were analyzed to quantify metabolites. Demographic data were calculated with SPSS version 22.0 software. Multivariate statistics were used to analyze metabolomics dataset. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic model. Analyses revealed 50 different metabolomics between the pre- and post-COS groups. Compared with baseline, amino acids increased significantly following COS. At baseline, acetylglycine was more abundant in FOI<1 group, while glycine and lipids increased in FOI≥1 group. After COS, glycine, N-acetyl-L-alanine, D-alanine, and 2-aminomuconic acid were higher in those with FOI≥1, but L-glutamine was abundant in FOI<1. ROC curves indicated that combination of glycine, acetylglycine, and lipids predicts different responses to COS (AUC=0.866). Serum metabolism might reflect the response to ovarian stimulation. Higher glycine and PC may be a good predictor for response to COS. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit. Methods: 19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers. Results: Serum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P < 0.05), and Pyruvic acid, D-Ribose, Gamma-Glutamylserine, PE(22:0/24:1(15Z)), Inosinic acid increased (P < 0.05) in EP group. Menawhile, S-Nitrosoglutathione, 5-Thymidylic acid, SN38 glucuronide, PE(22:0/24:0), PC(24:0/24:1(15Z)) and Bisdiphosphoinositol tetrakisphosphate increased significantly in DP group compared to EP group (P < 0.05). For the unique metabolites, bioinformatics analysis results showed that 5-Methoxytryptamine involved in Melatonin Degradation II and Superpathway of Melatonin Degradation is the key metabolite to RA DP. Meanwhile, GABA is the key metabolite in EP group, which involved in Glutamate Dependent Acid Resistance, GABA Receptor Signaling, Glutamate Degradation III (via 4-aminobutyrate) and 4-aminobutyrate Degradation I. Bioinformatics analysis between unique metabolites of RA DP and EP groups with human target genes for RA showed that 5-methoxytryptamine and LysoPC(18:1(9Z)/0:0), the unique metabolites of RA DP, might participate in colorectal cancer metastasis signaling, tumor microenvironment pathway, apoptosis signaling, MYC mediated apoptosis signaling, erythropoietin signaling pathway and LXR/RXR activation. Simultaneously, GABA, LysoPA(18:1(9Z)/0:0) and L-Targinine, the unique metabolites of RA EP, might participate in neuroinflammation signaling pathway, osteoarthritis pathway, glucocorticoid receptor signaling, ILK signaling, IL-17 signaling and HIF1α signaling. Conclusions: The study indicates that serum metabolomics preliminarily revealed the biological basis of RA DP and EP. 5-methoxytryptamine, LysoPC(18:1(9Z)/0:0) and GABA, LysoPA(18:1(9Z)/0:0), L-Targinine might be the predictors to distinguish the DP and EP of RA respectively. These interesting results provide thoughts for further study of traditional medicine patterns of ICD-11. It also contributes to provide strategy for personalized precision treatment of RA and further validation is needed. [ABSTRACT FROM AUTHOR]

Objective: To characterize the serum metabolomic profile and its role in the prediction of poor ovarian response (POR). Patient(s): Twenty-five women with normal ovarian reserve (24-33 years, antral follicle count [AFC] ≥5, anti-Müllerian hormone [AMH] ≥1.2 ng/ml) as the control group and another twenty-five women with POR (19-35 years, AFC <5, AMH < 1.2 ng/ml) as the study group were collected in our study. The serum levels of the women in both groups were determined from their whole blood by untargeted liquid chromatography–mass spectrometry (LC-MS). Multivariate statistical analysis and cell signal pathways analysis were used to reveal the results. Results: A total of 538 different metabolites were finally identified in the two groups. Tetracosanoic acid, 2-arachidonoylglycerol, lidocaine, cortexolone, prostaglandin H2,1-naphthylamine, 5-hydroxymethyl-2-furancarboxaldehyde, 2,4-dinitrophenol, and D-erythrulose1-phosphate in POR were significantly different from control as were most important metabolites in support vector machines (p < 0.05). Metabolomic profiling, together with support vector machines and pathway analysis found that the nicotinate and nicotinamide metabolism pathway, including L-aspartic acid, 6-hydroxynicotinate, maleic acid, and succinic acid semialdehyde, was identified to have significant differences in POR women compared to control women, which may be associated with ovarian reserve. Conclusion: This study indicated that LC–MS-based untargeted metabolomics analysis of serum provided biological markers for women with POR. The nicotinate and nicotinamide metabolism pathway may offer new insight into the complementary prediction and therapeutic potential of POR. The functional associations of these metabolites need further investigation. [ABSTRACT FROM AUTHOR]

Background: Obesity is a public health problem all over the world, and dietary habits are considered one of the important reasons. Methods: In this study, serum metabolites of mice fed a normal or high-fat diet (HFD) were analyzed using UPLC-QTOF-MS. Results: A significant increase in body weight was noted in HFD mice. The HFD and control groups were significantly different from each other on OPLS-DA scores. The major metabolites contributing to obesity were lipid metabolites (phosphatidylcholines, phosphatidylethanolamine, and lysophosphatidylcholines). In addition, this study revealed that glycerophospholipid metabolism, α-linolenic acid metabolism, and linoleic acid metabolism were related to obesity and obesity-associated diseases. Conclusion: These results can be used to better understand obesity and assess its risk, which will provide new ideas for treatment. [ABSTRACT FROM AUTHOR]

Our previous research suggests that supplementation of monoglycerides may reduce diarrhea severity and intestinal and systemic inflammation in weaned pigs infected with Escherichia coli (E. coli) F18. The objective of this study was to investigate the effects of monoglycerides on serum metabolomic profiles of weaned pigs experimentally infected with E. coli F18. Sixty weaned pigs [body weight (BW) = 6.49 ± 0.74 kg; around 21 d old] were individually housed and fed with one of four diets (15 replicates/diet): 1) control diet (CON); 2) CON+0.3% monoglycerides; 3) CON+3,000 mg/kg ZnO and 4) CON+50 mg/kg antibiotics (carbadox). The experiment lasted 28 days with 7 days before and 21 days after the first inoculation [d 0 post-inoculation (PI)]. All piglets were orally challenged with F18 E. coli (1010 CFU/3 mL) for 3 consecutive days. Serum samples were collected on d 5 and 14 PI to analyze untargeted metabolomics by gas chromatography-time of flight-mass spectrometer (GC-TOF-MS). The metabolomics data were analyzed using different modules of a web-based platform, MetaboAnalyst 5.0. Statistical significance was declared at a false discovery rate q < 0.2 and fold change > 2.0. Pathway and metabolite set enrichment analysis were performed on identified metabolites that had a Variable Importance in Projection (VIP) score > 1. On d 5 PI, supplementation of high dose ZnO up-regulated (q < 0.2) pantothenic acid and fructose, compared with control. Supplementation of monoglycerides altered (q < 0.2) the relative abundances of 14 metabolites (7 up-regulated and 7 down-regulated) compared with high dose ZnO, and upregulated (q < 0.2) lactose and cellobiose compared with antibiotics. On d 14 PI, supplementation of high dose ZnO changed (q < 0.2) abundances of 10 metabolites (7 up-regulated and 3 down-regulated) compared with control. Supplementation of monoglycerides up-regulated (q < 0.2) hippuric acid and indole-3-propionic acid, and down-regulated (q < 0.2) 8 metabolites (including glutaric acid, serotonin, mannose, etc.) compared with the high dose ZnO. Citrate cycle, taurine and hypotaurine metabolism, and beta-alanine metabolism were the most (VIP > 1) affected pathways when monoglycerides were compared with high dose ZnO on d 5 PI. TCA cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, and pyrimidine metabolism were the most (VIP > 1) affected metabolic pathways when monoglycerides were compared with high dose ZnO on d 14 PI. Limited differential metabolites were identified when comparing control vs. monoglycerides on d 5 and 14 PI. In conclusion, consistent with performance, diarrhea, and systemic inflammation data, serum metabolomics results indicate that high dose of ZnO supplementation had stronger impacts on the host metabolism of E. coli infected pigs, compared with monoglycerides and antibiotics. [ABSTRACT FROM AUTHOR]

Functional dyspepsia (FD) is an incurable chronic functional gastrointestinal disorder, which has a wide onset and severely affects patients' quality of life and social ability, thus causing a heavy burden on global health and the economy. Zhizhu-kuanzhong Capsule (ZZC), a well-known traditional Chinese medicine is commonly used to treat FD. However, its potential therapeutic mechanisms are rarely known. The purpose is to explore the pharmacological effects of ZZC for FD and to explore its mechanism of action through the integration UHPLC-Q-Exactive Orbitrap-MS of serum metabolomics and biological targets network methods. ZZC significantly callbacked gastrointestinal dysfunction of FD mice. According to the results of the biological targets network and metabolomics, we found 49 active ingredients, 16 key active ingredient target genes, 15 key metabolite target genes, and three key metabolites. KEGG pathway showed that multiple metabolic pathways, such as nicotinate and nicotinamide metabolism pathway, played important roles in the treatment of FD. In this study, the multi-compounds, multi-targets, and multi-mechanisms of ZZC for FD are systematically clarified, which could be mediated by regulating the targets, the pathways, and the levels of metabolites. It provides a new insight to determine the potential pharmacological mechanism of TCM. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations. Methods: Non-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student's t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites. Results: Thirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis. Conclusion: Serum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS. [ABSTRACT FROM AUTHOR]

Diabetes in the elderly increases cognitive impairment, but the underlying mechanisms are still far from fully understood. A non-targeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was performed to screen out the serum biomarkers of diabetic mild cognitive impairment (DMMCI) in rats. Total 48 SD rats were divided into three groups, Normal control (NC) group, high-fat diet (HFD) fed group and type 2 diabetes mellitus (T2DM) group. The T2DM rat model was induced by intraperitoneal administration of streptozotocin (STZ, 35 mg/kg) after 6 weeks of high-fat diet (HFD) feeding. Then each group was further divided into 4-week and 8-week subgroups, which were calculated from the time point of T2DM rat model establishment. The novel object recognition test (NORT) and the Morris water maze (MWM) method were used to evaluate the cognitive deficits in all groups. Compared to the NC-8w and HFD-8w groups, both NOR and MWM tests indicated significant cognitive dysfunction in the T2DM-8w group, which could be used as an animal model of DMMCI. Serum was ultimately collected from the inferior vena cava after laparotomy. Metabolic profiling analysis was conducted using ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to verify the stability of the model. According to variable importance in the project (VIP > 1) and the p-value of t-test (P < 0.05) obtained by the OPLS-DA model, the metabolites with significant differences were screened out as potential biomarkers. In total, we identified 94 differentially expressed (44 up-regulated and 50 down-regulated) endogenous metabolites. The 10 top up-regulated and 10 top down-regulated potential biomarkers were screened according to the FDR significance. These biomarkers by pathway topology analysis were primarily involved in the metabolism of sphingolipid (SP) metabolism, tryptophan (Trp) metabolism, Glycerophospholipid (GP) metabolism, etc. Besides, SP metabolism, Trp metabolism and GP metabolism mainly belonging to the lipid metabolism showed marked perturbations over DMMCI and may contribute to the development of disease. Taken collectively, our results revealed that T2DM could cause cognitive impairment by affecting a variety of metabolic pathways especially lipid metabolism. Besides, serum PE, PC, L-Trp, and S1P may be used as the most critical biomarkers for the early diagnosis of DMMCI. [ABSTRACT FROM AUTHOR]