Serum Metabolomics Study of Papillary Thyroid Carcinoma Based on HPLC-Q-TOF-MS/MS

This study examined metabolite profile differences between serum samples of thyroid papillary carcinoma (PTC) patients and healthy controls, aiming to identify candidate biomarkers and pathogenesis pathways in this cancer type. Serum samples were collected from PTC patients (n = 80) and healthy controls (n = 80). Using principal component analysis (PCA), partial least squares discrimination analysis(PLS-DA), orthogonal partial least square discriminant analysis (OPLS-DA), t-tests, and the volcano plot, a model of abnormal metabolic pathways in PTC was constructed. PCA, PLS-DA, and OPLS-DA analysis revealed differences in serum metabolic profiles between the PTC and control group. OPLS-Loading plot analysis, combined with Variable importance in the projection (VIP)>1, Fold change (FC) > 1.5, and p < 0.05 were used to screen 64 candidate metabolites. Among them, 22 metabolites, including proline betaine, taurocholic acid, L-phenylalanine, retinyl beta-glucuronide, alpha-tocotrienol, and threonine acid were upregulated in the PTC group; meanwhile, L-tyrosine, L-tryptophan, 2-arachidonylglycerol, citric acid, and other 42 metabolites were downregulated in this group. There were eight abnormal metabolic pathways related to the differential metabolites, which may be involved in the pathophysiology of PTC. Six metabolites yielded an area under the receiver operating curve of >0.75, specifically, 3-hydroxy-cis-5-tetradecenoylcarnitine, aspartylphenylalanine, l-kynurenine, methylmalonic acid, phenylalanylphenylalanine, and l-glutamic acid. The Warburg effect was observed in PTC. The levels of 3-hydroxy-cis-5-tetradecenoylcarnitine, aspartylphenylalanine, l-kynurenine, methylmalonic acid, phenylalanine, and L-glutamic acid may help distinguish PTC patients from healthy controls. Aspartic acid metabolism, glutamic acid metabolism, urea cycle, and tricarboxylic acid cycle are involved in the mechanism of PTC.

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Analysis of Serum Metabolomics in Rats with Osteoarthritis by Mass Spectrometry

Molecules ◽

10.3390/molecules26237181 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7181

Author(s):

Jingtong Zhao ◽

Meng Liu ◽

Tongfei Shi ◽

Mohan Gao ◽

Yuqian Lv ◽

...

Keyword(s):

Mass Spectrometry ◽

Metabolic Pathways ◽

Acid Metabolism ◽

Principal Component ◽

Male Rats ◽

Control Group ◽

Liquid Chromatography Mass Spectrometry ◽

Disease Mechanisms ◽

Periarticular Tissue ◽

Serum Metabolomics

Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.

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Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

10.21203/rs.3.rs-526582/v1 ◽

2021 ◽

Author(s):

Yanjuan Liu ◽

Qi Zeng ◽

Wen Xiao ◽

Fang Chen ◽

Lianhong Zou ◽

...

Keyword(s):

Amino Acid ◽

Metabolic Pathways ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Dynamic Change ◽

Sepsis Group ◽

Control Group ◽

Multivariate Statistical ◽

Xuebijing Injection ◽

Kegg Pathway Analysis

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

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The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/6207183 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Yanyan Xu ◽

Yiwei Zhao ◽

Jiabin Xie ◽

Xue Sheng ◽

Yubo Li ◽

...

Keyword(s):

Metabolic Pathways ◽

Acid Metabolism ◽

Safety Evaluation ◽

Rat Plasma ◽

Leguminous Plant ◽

Control Group ◽

Kidney Toxicity ◽

Flight Mass Spectrometry ◽

Liver And Kidney ◽

Tof Ms

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.

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Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension

Cephalalgia ◽

10.1177/0333102416650705 ◽

2016 ◽

Vol 37 (6) ◽

pp. 525-531 ◽

Cited By ~ 10

Author(s):

Bedia Samancı ◽

Yavuz Samancı ◽

Erdem Tüzün ◽

Güneş Altıokka-Uzun ◽

Esme Ekizoğlu ◽

...

Keyword(s):

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension ◽

Oligoclonal Bands ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Childbearing Age ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Tnf Α

Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1β, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1β level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1β ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1β, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.

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Changes in Amino Acid and Acylcarnitine Plasma Profiles for Distinguishing Patients with Multiple Sclerosis from Healthy Controls

Multiple Sclerosis International ◽

10.1155/2020/9010937 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Marat F. Kasakin ◽

Artem D. Rogachev ◽

Elena V. Predtechenskaya ◽

Vladimir J. Zaigraev ◽

Vladimir V. Koval ◽

...

Keyword(s):

Multiple Sclerosis ◽

Amino Acid ◽

Discriminant Analysis ◽

Clinical Decision ◽

Partial Least Square ◽

Least Square ◽

Control Group ◽

Healthy Controls ◽

Linear Discriminant ◽

Tandem Mass Spectrometric

McDonald criteria and magnetic resonance imaging (MRI) are used for the diagnosis of multiple sclerosis (MS); nevertheless, it takes a considerable amount of time to make a clinical decision. Amino acid and fatty acid metabolic pathways are disturbed in MS, and this information could be useful for diagnosis. The aim of our study was to find changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls. We have applied a targeted metabolomics approach based on tandem mass-spectrometric analysis of amino acids and acylcarnitines in dried plasma spots followed by multivariate statistical analysis for discovery of differences between MS (n=16) and control (n=12) groups. It was found that partial least square discriminant analysis yielded better group classification as compared to principal component linear discriminant analysis and the random forest algorithm. All the three models detected noticeable changes in the amino acid and acylcarnitine profiles in the MS group relative to the control group. Our results hold promise for further development of the clinical decision support system.

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Urine metabolomics of rats with chronic atrophic gastritis

PLoS ONE ◽

10.1371/journal.pone.0236203 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0236203

Author(s):

Guo-Xiu Zu ◽

Qian-Qian Sun ◽

Jian Chen ◽

Xi-Jian Liu ◽

Ke-Yun Sun ◽

...

Keyword(s):

Atrophic Gastritis ◽

Metabolic Pathways ◽

Wistar Rats ◽

Acid Metabolism ◽

Chronic Atrophic Gastritis ◽

Control Group ◽

Liquid Chromatography Mass Spectrometry ◽

Model Group ◽

Rat Urine ◽

Pathological Model

Background/aim To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). Materials and methods Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. Results Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. Conclusion By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

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Serum Metabolites as an Indicator of Developing Gestational Diabetes Mellitus Later in the Pregnancy: A Prospective Cohort of a Chinese Population

Journal of Diabetes Research ◽

10.1155/2021/8885954 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Mengyuan Tian ◽

Shujuan Ma ◽

Yiping You ◽

Sisi Long ◽

Jiayue Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Early Pregnancy ◽

Pantothenic Acid ◽

Maternal Serum ◽

Control Group ◽

Healthy Controls ◽

Serum Samples ◽

Serum Metabolites

Objective. Gestational diabetes mellitus (GDM) is a common metabolic disorder with onset during pregnancy. However, the etiology and pathogenesis of GDM have not been fully elucidated. In this study, we used a metabolomics approach to investigate the relationship between maternal serum metabolites and GDM in early pregnancy. Methods. A nested case-control study was performed. To establish an early pregnancy cohort, pregnant women in early pregnancy ( 10 ‐ 13 + 6 weeks) were recruited. In total, 51 patients with GDM and 51 healthy controls were included. Serum samples were analyzed using an untargeted high-performance liquid chromatography mass spectrometry metabolomics approach. The relationships between metabolites and GDM were analyzed by an orthogonal partial least-squares discriminant analysis. Differential metabolites were evaluated using a KEGG pathway analysis. Results. A total of 44 differential metabolites were identified between GDM cases and healthy controls during early pregnancy. Of these, 26 significant metabolites were obtained in early pregnancy after false discovery rate ( FDR < 0.1 ) correction. In the GDM group, the levels of L-pyroglutamic acid, L-glutamic acid, phenylacetic acid, pantothenic acid, and xanthine were significantly higher and the levels of 1,5-anhydro-D-glucitol, calcitriol, and 4-oxoproline were significantly lower than those in the control group. These metabolites were involved in multiple metabolic pathways, including those for amino acid, carbohydrate, lipid, energy, nucleotide, cofactor, and vitamin metabolism. Conclusions. We identified significant differentially expressed metabolites associated with the risk of GDM, providing insight into the mechanisms underlying GDM in early pregnancy and candidate predictive markers.

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Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery

10.21203/rs.3.rs-661365/v1 ◽

2021 ◽

Author(s):

Biao Qi ◽

Yanyu Zhang ◽

Yuhao Zhang ◽

Guoqiang Fei ◽

Ling lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Biomarker Discovery ◽

Multiple Reaction Monitoring ◽

Control Group ◽

Healthy Controls ◽

Serum Samples ◽

Multivariate Statistical ◽

Lysine Degradation

Abstract Acute ischemic stroke (AIS) is characterized by a sudden blockage of one of the main arteries supplying blood to the brain, leading to insufficient oxygen and nutrients for brain cells to function properly. Unfortunately, metabolic alterations in the biofluids with AIS are still not well understood. In this study, we performed high-throughput target metabolic analysis on 44 serum samples, including 22 from AIS patients and 22 from healthy controls. Multiple reaction monitoring analysis of 180 common metabolites revealed a total of 29 metabolites changed significantly (VIP>1, P <0.05). Multivariate statistical analysis unraveled a strikingly separation between AIS patients and healthy controls. Comparing AIS with Control group, the contents of argininosuccinic acid, beta-D-glucosamine, glycerophosphocholine, L-abrine, and L-pipecolic acid were down-regulated in AIS patients. 29 out of 112 detected metabolites, enriched in aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, lysine degradation, phenylalanine, tyrosine and tryptophan biosynthesis metabolic pathways. Collectively, these results will provide a sensitive, feasible diagnostic prospect for AIS patients.

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Therapeutic Effect and Mechanism Study of Rhodiola wallichiana var. cholaensis Injection to Acute Blood Stasis Using Metabolomics Based on UPLC-Q/TOF-MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1514845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 3

Author(s):

Nan Ran ◽

Zhiqiang Pang ◽

Xuewa Guan ◽

Guoqiang Wang ◽

Jinping Liu ◽

...

Keyword(s):

Rat Model ◽

Metabolic Pathways ◽

Acid Metabolism ◽

Blood Stasis ◽

Blood Stasis Syndrome ◽

Inflammatory Factors ◽

Control Group ◽

High Dose ◽

Alpha Linolenic Acid ◽

Model Control

In traditional Chinese medicine theory, blood stasis syndrome (BSS), characterized by blood flow retardation and blood stagnation, is one of the main pathologic mechanisms and clinical syndromes of cardiovascular diseases (CVDs). Rhodiola wallichiana var. cholaensis injection (RWCI) is made from dry roots and stems of RWC via the processes of decoction, alcohol precipitation, filtration, and dilution. Studies indicated the extracts of RWC could alleviate CVDs; however, the mechanism had not been illustrated. In the present study, the acute blood stasis rat model was established to investigate the pathogenesis of BSS and the therapeutic mechanism of RWCI against BSS. Hemorheological parameters (whole blood viscosity and plasma viscosity) and inflammatory factors (TNF-α and IL-6) were used to evaluate the success of the BSS rat model and RWCI efficacy. 14 and 33 differential metabolites were identified from plasma and urine samples using the metabolomics approach based on ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The results of multivariate analysis displayed that there were significant separations among model, control, and treatment groups, but the high-dose RWCI treatment group was closer to the control group. 9 perturbed metabolic pathways were related to BSS’s development and RWCI intervention. 5 metabolic pathways (arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, retinol metabolism, and steroid hormone biosynthesis) showed apparent correlations. These differential metabolites and perturbed metabolic pathways might provide a novel view to understand the pathogenesis of BSS and the pharmacological mechanism of RWCI.

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Plasma Metabolomic Profiling in Workers With Noise-induced Hearing Loss: A Pilot Study

10.21203/rs.3.rs-437429/v1 ◽

2021 ◽

Author(s):

Long Miao ◽

Boshen Wang ◽

Juan Zhang ◽

Lihong Yin ◽

Yuepu Pu

Keyword(s):

Hearing Loss ◽

Acid Metabolism ◽

White Blood Cells ◽

Partial Least Square ◽

Plasma Metabolites ◽

Control Group ◽

Mrna Levels ◽

Noise Induced Hearing Loss ◽

Autophagy Pathway ◽

Potential Biomarkers

Abstract Noise-induced hearing loss (NIHL) remains a leading occupational related disease and is a serious public health problem. Hence, the identification of potential biomarkers for NIHL prevention and diagnosis has become an urgent work. To discover potential metabolic biomarkers of NIHL, plasma metabolomics analysis among 62 NIHL patients and 62 controls was performed using ultrahigh performance liquid chromatography-mass spectrometry (UPLC/MS). Orthogonal partial least square-discriminant analysis (OPLS-DA) model was applied to distinguish metabolite profile alterations in plasma samples between the two groups. The alterations in autophagy pathway were in accordance with previous published studies, therefore, three autophagy-related genes (PI3K, AKT and ATG5) were selected and mRNA levels were detected by RT-qPCR analysis in peripheral white blood cells (WBCs) samples. Compared to the control group, 20 identified plasma metabolites were significantly altered in NIHL patients. Meanwhile, a total of seven metabolic pathways were enriched, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy, choline metabolism, alpha-linolenic acid metabolism and linoleic acid metabolism, and retrograde endocannabinoid signaling pathway. Furthermore, the results indicated that the mRNA levels of three autophagy-related genes (PI3K, AKT and ATG5) were significantly decreased in NIHL cases compared with controls. Taken together, our current study firstly provides evidence that the identified aberrantly altered metabolites might be potential biomarkers of NIHL for noise-exposed workers. In addition, autophagy pathway may be involved in the occurrence and development of NIHL.

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