Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

Abstract PURPOSE Lovastatin is an important medicine and it shows a significant effect against glucocorticoid-induced necrosis of the femoral head. This study aimed to investigate the effect of lovastatin on preventing necrosis of the femoral head of by serum metabolomics strategy. METHODS Adult healthy adult Japanese white rabbits were divided into three groups: control group, model group and drug group. The pathologic changes of femoral head were assessed with magnetic resonance imaging and microscope. Metabolomics based on UHPLC-MS/MS was used to analyze the collected serum sample. Data were analyzed using principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). All potential metabolites were identified by comparing with HMDB database, metlin database, lipid maps and chemspider database. RESULTS 11 potential biomarkers were noted and identified as potential biomarkers. The change of biomarkers suggested that lovastatin on preventing necrosis of the femoral head may affect glycerophospholipid metabolism, linoleic acid metabolism, sphingolipid metabolism, alpha-Linolenic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism. CONCLUSION The study suggested that lovastatin could prevent the glucocorticoid-induced necrosis of the femoral head of rabbits. The possible reasons were closely associated with adjusting the lipid metabolism, inhibiting adipogenesis and delaying the osteocyte apoptosis.

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Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

10.21203/rs.3.rs-16772/v3 ◽

2020 ◽

Author(s):

Xiangnan Ren ◽

Zixing Shao ◽

Wu Fan ◽

Zixuan Wang ◽

Kaiyun Chen ◽

...

Keyword(s):

Femoral Head ◽

Least Squares ◽

Partial Least Squares ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Sphingolipid Metabolism ◽

Control Group ◽

Group Model ◽

Alpha Linolenic Acid ◽

Potential Biomarkers

Abstract PURPOSE Lovastatin is an important medicine and it shows a significant effect against glucocorticoid-induced necrosis of the femoral head. This study aimed to investigate the effect of lovastatin on preventing necrosis of the femoral head of by serum metabolomics strategy. METHODS Adult healthy adult Japanese white rabbits were divided into three groups: control group, model group and drug group. The pathologic changes of femoral head were assessed with magnetic resonance imaging and microscope. Metabolomics based on UHPLC-MS/MS was used to analyze the collected serum sample. Data were analyzed using principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). All potential metabolites were identified by comparing with HMDB database, metlin database, lipid maps and chemspider database. RESULTS 11 potential biomarkers were noted and identified as potential biomarkers. The change of biomarkers suggested that lovastatin on preventing necrosis of the femoral head may affect glycerophospholipid metabolism, linoleic acid metabolism, sphingolipid metabolism, alpha-Linolenic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism. CONCLUSION The study suggested that lovastatin could prevent the glucocorticoid-induced necrosis of the femoral head of rabbits. The possible reasons were closely associated with adjusting the lipid metabolism, inhibiting adipogenesis and delaying the osteocyte apoptosis.

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Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

10.21203/rs.3.rs-16772/v2 ◽

2020 ◽

Author(s):

Xiangnan Ren ◽

Zixing Shao ◽

Wu Fan ◽

Zixuan Wang ◽

Kaiyun Chen ◽

...

Keyword(s):

Femoral Head ◽

Least Squares ◽

Partial Least Squares ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Sphingolipid Metabolism ◽

Control Group ◽

Group Model ◽

Alpha Linolenic Acid ◽

Potential Biomarkers

Abstract PURPOSE Lovastatin is an important medicine and it shows a significant effect against glucocorticoid-induced necrosis of the femoral head. This study aimed to investigate the effect of lovastatin on preventing necrosis of the femoral head of by serum metabolomics strategy. METHODS Adult healthy adult Japanese white rabbits were divided into three groups: control group, model group and drug group. The pathologic changes of femoral head were assessed with magnetic resonance imaging and microscope. Metabolomics based on UHPLC-MS/MS was used to analyze the collected serum sample. Data were analyzed using principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). All potential metabolites were identified by comparing with HMDB database, metlin database, lipid maps and chemspider database. RESULTS 11 potential biomarkers were noted and identified as potential biomarkers. The change of biomarkers suggested that lovastatin on preventing necrosis of the femoral head may affect glycerophospholipid metabolism, linoleic acid metabolism, sphingolipid metabolism, alpha-Linolenic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism. CONCLUSION The study suggested that lovastatin could prevent the glucocorticoid-induced necrosis of the femoral head of rabbits. The possible reasons were closely associated with adjusting the lipid metabolism, inhibiting adipogenesis and delaying the osteocyte apoptosis.

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1H-NMR spectroscopy identifies potential biomarkers in serum metabolomic signatures for early stage esophageal squamous cell carcinoma

PeerJ ◽

10.7717/peerj.8151 ◽

2019 ◽

Vol 7 ◽

pp. e8151 ◽

Cited By ~ 3

Author(s):

Yan-Yan Liu ◽

Zhong-Xian Yang ◽

Li-Min Ma ◽

Xu-Qing Wen ◽

Huan-Lin Ji ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Discriminant Analysis ◽

Nmr Spectroscopy ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Least Squares ◽

Partial Least Squares ◽

Early Stage ◽

H Nmr ◽

Potential Biomarkers

Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancies. Here, we used 1H nuclear magnetic resonance spectroscopy (1H-NMR) to identify potential serum biomarkers in patients with early stage ESCC. Methods Sixty-five serum samples from early stage ESCC patients (n = 25) and healthy controls (n = 40) were analysed using 1H-NMR spectroscopy. We distinguished between different metabolites through principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis (OPLS-DA) using SIMCA-P+ version 14.0 software. Receiver operating characteristic (ROC) analysis was conducted to verify potential biomarkers. Results Using OPLS-DA, 31 altered serum metabolites were successfully identified between the groups. Based on the area under the ROC curve (AUROC), and the biomarker panel with AUROC of 0.969, six serum metabolites (α-glucose, choline, glutamine, glutamate, valine, and dihydrothymine) were selected as potential biomarkers for early stage ESCC. Dihydrothymine particularly was selected as a new feasible biomarker associated with tumor occurrence. Conclusions 1H-NMR spectroscopy may be a useful tumour detection approach in identifying useful metabolic ESCC biomarkers for early diagnosis and in the exploration of the molecular pathogenesis of ESCC.

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A Urinary Metabolomics Analysis Based on UPLC-MS and Effects of Moxibustion in APP/PS1 Mice

Current Alzheimer Research ◽

10.2174/1567205017666201109091759 ◽

2020 ◽

Vol 17 (8) ◽

pp. 753-765

Author(s):

Rui He ◽

Juntian Liu ◽

Chang Huang ◽

Jinyi Liu ◽

Herong Cui ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Neurodegenerative Disorder ◽

Principal Component ◽

Sucrose Metabolism ◽

Control Group ◽

Starch Metabolism ◽

Moxibustion Group ◽

Potential Biomarkers

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder with the symptoms of cognitive impairment and decreased learning and memory abilities. Metabolomics can reflect the related functional status and physiological and pathological changes in the process of AD. Moxibustion is a unique method in traditional Chinese medicine, which has been used in the treatment and prevention of diseases for thousands of years. Methods: A total of 32 APP/PS1 mice were randomly divided into the model group, moxibustion group, moxa smoke group and smoke-free moxibustion group (n=8/group), using the random number table method, while eight C57BL/6 mice were used as the control group. The five groups were measured for 20 min/day, 6 days/week, for 4 weeks. After 4 weeks’ experiment, all the mice were placed in metabolic cages to collect urine continuously for 24 hours, for UPLC-MS analysis. Results: Principal component analysis (PCA) was used to identify the different metabolites among the five groups, and partial least squares discriminant analysis (PLS-DA) was performed to reveal the effects on the metabolic variance. Sixteen potential biomarkers were identified among the five groups, primarily related to amino acid metabolism, starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, and aminoacyl biosynthesis. There were 17 differences in the potential metabolites between the control and model groups, involving the metabolism of amino acid, purine, pyrimidine, nicotinic acid and nicotinamide, and biosynthesis of pantothenate and coenzyme A. Fifteen potential biomarkers were identified between the model and moxibustion groups, related to starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, glyoxylate, dicarboxylate anions and some amino acid metabolism. Conclusion: Moxibustion can regulate the metabolism of substance and energy by improving the synthesis and decomposition of carbohydrates and amino acids in APP/PS1 transgenic AD model mice.

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Metabolomic Study of Collagen-Induced Arthritis in Rats and the Interventional Effects of Huang-Lian-Jie-Du-Tang, a Traditional Chinese Medicine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/439690 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 19

Author(s):

Rongcai Yue ◽

Ling Zhao ◽

Yaohua Hu ◽

Peng Jiang ◽

Shuping Wang ◽

...

Keyword(s):

Arachidonic Acid ◽

Fatty Acid ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Control Group ◽

Plasma Samples ◽

Collagen Induced Arthritis ◽

Potential Biomarkers

Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine (TCM) with anti-inflammatory activity. The present study used a metabolomic approach based on LC-Q-TOF-MS to profile rheumatoid-arthritis- (RA-) related metabolic changes and to investigate the interventional mechanisms of HLJDT in collagen-induced arthritis rats. Forty male Wistar rats were randomly divided into five groups: (1) a model group, (2) a normal control group, (3) a dexamethasone group, (4) a HLJDT group, and (5) a group that received 13 components of HLJDT. Plasma samples were collected 8, 15, and 22 days after the rats were injected with bovine type II collagen. By combining variable importance in the projection values with partial least squares discriminant analysis, 18 potential biomarkers were identified in the plasma samples. The biomarkers were primarily involved in glycerophospholipid metabolism, fatty acid metabolism, tryptophan metabolism, linoleic acid metabolism, phenylalanine metabolism, purine metabolism, arachidonic acid metabolism, and bile acid biosynthesis. Using the potential biomarkers as a screening index, the results suggest that HLJDT can potentially reverse the process of RA by partially regulating fatty acid oxidation and arachidonic acid metabolism. This study demonstrates that a metabolomic strategy is useful for identifying potential RA biomarkers and investigating the underlying mechanisms of a TCM in RA treatment.

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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 Lipidomics Profiling Reveals Biomarkers for Papillary Thyroid Cancer Diagnosis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.682269 ◽

2021 ◽

Vol 9 ◽

Author(s):

Nan Jiang ◽

Zhenya Zhang ◽

Xianyang Chen ◽

Guofen Zhang ◽

Ying Wang ◽

...

Keyword(s):

Metabolic Pathways ◽

Acid Metabolism ◽

Normal Subjects ◽

Serum Markers ◽

Arachidonic Acid Metabolism ◽

Proton Nuclear Magnetic Resonance ◽

Papillary Thyroid ◽

Learning Potential ◽

Alpha Linolenic Acid ◽

Potential Biomarkers

The objective of this study was to identify potential biomarkers and possible metabolic pathways of malignant and benign thyroid nodules through lipidomics study. A total of 47 papillary thyroid carcinomas (PTC) and 33 control check (CK) were enrolled. Plasma samples were collected for UPLC-Q-TOF MS system detection, and then OPLS-DA model was used to identify differential metabolites. Based on classical statistical methods and machine learning, potential biomarkers were characterized and related metabolic pathways were identified. According to the metabolic spectrum, 13 metabolites were identified between PTC group and CK group, and a total of five metabolites were obtained after further screening. Its metabolic pathways were involved in glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, Phosphatidylinositol signaling system and the metabolism of arachidonic acid metabolism. The metabolomics method based on PROTON nuclear magnetic resonance (NMR) had great potential for distinguishing normal subjects from PTC. GlcCer(d14:1/24:1), PE-NME (18:1/18:1), SM(d16:1/24:1), SM(d18:1/15:0), and SM(d18:1/16:1) can be used as potential serum markers for the diagnosis of PTC.

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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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Insights into the molecular basis of tick-borne encephalitis from multiplatform metabolomics

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009172 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009172

Author(s):

YanDan Du ◽

ZhiHui Mi ◽

YaPing Xie ◽

DeSheng Lu ◽

HaiJun Zheng ◽

...

Keyword(s):

Disease Progression ◽

Molecular Mechanisms ◽

Global Analysis ◽

Phospholipid Metabolism ◽

System Level ◽

Sphingolipid Metabolism ◽

Control Group ◽

Physiological Changes ◽

Alpha Linolenic Acid ◽

Tick Borne Encephalitis

Background Tick-borne encephalitis virus (TBEV) is the most prevalent arbovirus, with a tentative estimate of 10,000 to 10,500 infections occurring in Europe and Asia every year. Endemic in Northeast China, tick-borne encephalitis (TBE) is emerging as a major threat to public health, local economies and tourism. The complicated array of host physiological changes has hampered elucidation of the molecular mechanisms underlying the pathogenesis of this disease. Methodology/Principle findings System-level characterization of the serum metabolome and lipidome of adult TBEV patients and a healthy control group was performed using liquid chromatography tandem mass spectrometry. By tracking metabolic and lipid changes during disease progression, crucial physiological changes that coincided with disease stages could be identified. Twenty-eight metabolites were significantly altered in the sera of TBE patients in our metabolomic analysis, and 14 lipids were significantly altered in our lipidomics study. Among these metabolites, alpha-linolenic acid, azelaic acid, D-glutamine, glucose-1-phosphate, L-glutamic acid, and mannose-6-phosphate were altered compared to the control group, and PC(38:7), PC(28:3;1), TAG(52:6), etc. were altered based on lipidomics. Major perturbed metabolic pathways included amino acid metabolism, lipid and oxidative stress metabolism (lipoprotein biosynthesis, arachidonic acid biosynthesis, leukotriene biosynthesis and sphingolipid metabolism), phospholipid metabolism and triglyceride metabolism. These metabolites were significantly perturbed during disease progression, implying their latent utility as prognostic markers. Conclusions/Significance TBEV infection causes distinct temporal changes in the serum metabolome and lipidome, and many metabolites are potentially involved in the acute inflammatory response and immune regulation. Our global analysis revealed anti- and pro-inflammatory processes in the host and changes to the entire metabolic profile. Relationships between metabolites and pathologies were established. This study provides important insight into the pathology of TBE, including its pathology, and lays the foundation for further research into putative markers of TBE disease.

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