Bioinformatic and Metabolomic Analysis Reveal Intervention Effects of Chicory in a Quail Model of Hyperuricemia

Background. Hyperuricemia (HUA) is a kind of a metabolic disease that seriously threatens human health worldwide. Chicory, a natural herbal medicine, has an obvious effect of reducing uric acid. The aim of this study is to explore the potential components and pharmacological pathways that may play a role in hypouricemia activity of chicory. Bioinformatics and metabonomics were applied to this research. Firstly, component-target network was used to identify possible components related to the pharmacological properties and their corresponding mechanisms pathway of chicory. Afterwards, animal pharmacodynamic experiments were performed. Blood and stool samples were collected for untargeted metabolomic analysis by dint of UHPLC-Q-TOF/MS methods, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. Significant enriched function pathways were used in bioinformatics suggesting that chicory might have the effect of regulation of lipolysis in adipocytes. PLS-DA analysis was applied to discover differentiating metabolites, and pathway enrichment analysis indicated that chicory had powerful effects of glycosylphosphatidylinositol- (GPI-) anchor biosynthesis, inositol phosphate metabolism, glycerophospholipid metabolism, and steroid hormone biosynthesis. Combining bioinformatics and metabolomics results, we consider that chicory may develop on lowering uric acid by adjusting lipid metabolism. In addition, we chose quail as animal model innovatively and discussed the treatment of hyperuricemia with chicory in multiple methods, which may render reference for the research of HUA.

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1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

Disease Markers ◽

10.1155/2016/5803031 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Taijie Lin ◽

Jinping Gu ◽

Caihua Huang ◽

Suli Zheng ◽

Xu Lin ◽

...

Keyword(s):

Intraperitoneal Injection ◽

Ventricular Hypertrophy ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Metabolic Profiles ◽

Metabolic Dysfunction ◽

Sprague Dawley ◽

Mean Pulmonary Arterial Pressure ◽

Pulmonary Arterial

Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH).Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (n=8, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles.Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis.Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

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Metabonomic-Transcriptome Integration Analysis on Osteoarthritis and Rheumatoid Arthritis

International Journal of Genomics ◽

10.1155/2020/5925126 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Ningyang Gao ◽

Li Ding ◽

Jian Pang ◽

Yuxin Zheng ◽

Yuelong Cao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gap Junction ◽

Molecular Mechanisms ◽

Linear Models ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Nf Kappa B ◽

Linear Module ◽

Hedgehog Acyltransferase

Purpose. This study is aimed at exploring the potential metabolite/gene biomarkers, as well as the differences between the molecular mechanisms, of osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. Transcriptome dataset GSE100786 was downloaded to explore the differentially expressed genes (DEGs) between OA samples and RA samples. Meanwhile, metabolomic dataset MTBLS564 was downloaded and preprocessed to obtain metabolites. Then, the principal component analysis (PCA) and linear models were used to reveal DEG-metabolite relations. Finally, metabolic pathway enrichment analysis was performed to investigate the differences between the molecular mechanisms of OA and RA. Results. A total of 976 DEGs and 171 metabolites were explored between OA samples and RA samples. The PCA and linear module analysis investigated 186 DEG-metabolite interactions including Glycogenin 1- (GYG1-) asparagine_54, hedgehog acyltransferase- (HHAT-) glucose_70, and TNF receptor-associated factor 3- (TRAF3-) acetoacetate_35. Finally, the KEGG pathway analysis showed that these metabolites were mainly enriched in pathways like gap junction, phagosome, NF-kappa B, and IL-17 pathway. Conclusions. Genes such as HHAT, GYG1, and TRAF3, as well as metabolites including glucose, asparagine, and acetoacetate, might be implicated in the pathogenesis of OA and RA. Metabolites like ethanol and tyrosine might participate differentially in OA and RA progression via the gap junction pathway and phagosome pathway, respectively. TRAF3-acetoacetate interaction may be involved in regulating inflammation in OA and RA by the NF-kappa B and IL-17 pathway.

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Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

10.21203/rs.3.rs-326163/v1 ◽

2021 ◽

Author(s):

Yaqin Wang ◽

Wenchao Chen ◽

Kun Li ◽

Gang Wu ◽

Wei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Predictive Ability ◽

Principal Component ◽

Enrichment Analysis ◽

Pentose Phosphate ◽

P Value ◽

Pathway Enrichment Analysis ◽

Dodecanoic Acid ◽

Orthogonal Projections ◽

Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

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Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5194016 ◽

2018 ◽

Vol 2018 ◽

pp. 1-20 ◽

Cited By ~ 5

Author(s):

Zhenyan Song ◽

Fang Yin ◽

Biao Xiang ◽

Bin Lan ◽

Shaowu Cheng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Biological Processes ◽

Pathway Enrichment ◽

Study Results ◽

Target Network ◽

Anti Inflammatory

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

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Investigating the Mechanism of Guizhi Fuling Formula in the Treatment of Primary Dysmenorrhea based on Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-151904/v1 ◽

2021 ◽

Author(s):

Lu Sun ◽

Zining Wang ◽

Jian Li ◽

Li Xu ◽

Xiaoou Xue

Keyword(s):

Molecular Docking ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Primary Dysmenorrhea ◽

Potential Mechanism ◽

Protein Protein Interaction ◽

Long Time ◽

Hormone Biosynthesis ◽

Relationship Of

Abstract Background: Primary dysmenorrhea(PD)is the most common gynecologic disorder.Despite the prevalence is high, it is often underdiagnosed,undertreated and normalized even by patients themselves. Guizhi Fuling Formula (GFF) is experientially used for the treatment of PD in a long time. Therefore, the efficiency and potential mechanism are waiting to identify.Methods: We adopted network pharmacology integrated molecular docking strategy in this study.Based on published literatures, the relative compounds of GFF were selected preliminarily. Secondly, the putative targets of PD were obtained by wide-searching DisGeNET, OMIM, Drugbank and GeneCards databases.With protein-protein interaction(PPI) analysis, GO and KEGG pathway enrichment analysis and molecular docking ,we systematically evaluated the relationship of herb ingredients and disease targets.Results: The results showed that 30 ingredients of GFF and 43 hub targets made a difference.Under the further analysis,8 targets(EGFR,AKT1,PTGS2,TNF,ESR1,AHR,CTNNB1,CXCL8) were recognized as key therapeutic targets with excellent binding. The enrichment analyses indicated that the GFF had the potential to influence varieties of biological pathways, especially the pathways in cancer and steroid hormone biosynthesis, which play an important part in the pathogenesis of primary dysmenorrhea.Conclusion: GFF influenced primary dysmenorrhea through the synergistic effect of multiple components, multiple targets, and multiple pathways.This study predictedthe potential mechanism, hope that could made contribution for clinical application and scientific research.

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Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations

Cancers ◽

10.3390/cancers13051136 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1136

Author(s):

Kaya E. Witte ◽

Oliver Hertel ◽

Beatrice A. Windmöller ◽

Laureen P. Helweg ◽

Anna L. Höving ◽

...

Keyword(s):

Human Cancer ◽

Principal Component ◽

Enrichment Analysis ◽

Therapy Resistance ◽

Ribosomal Gene ◽

Pathway Enrichment Analysis ◽

Nanopore Sequencing ◽

Gene Expressions ◽

Metastasis Therapy ◽

Novel Therapeutic Strategies

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

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Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease

Molecules ◽

10.3390/molecules24081499 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1499 ◽

Cited By ~ 3

Author(s):

Yi-wei Sun ◽

Yue Wang ◽

Zi-feng Guo ◽

Kai-cheng Du ◽

Da-li Meng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Large Numbers ◽

Brain Barrier Permeability ◽

Target Network ◽

Synergistic Mechanism

Ohwia caudata (OC)—a traditional Chinese medicine (TCM)—has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer’s disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood–brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound–target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.

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Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.643979 ◽

2021 ◽

Vol 9 ◽

Author(s):

Guo-Bang Li ◽

Hong-Rong Hu ◽

Wen-Feng Pan ◽

Bo Li ◽

Zhi-Ying Ou ◽

...

Keyword(s):

Fatty Acids ◽

Pathogenic Bacteria ◽

Bacterial Species ◽

Disease Onset ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Control Subjects ◽

Sepsis Survivors ◽

Pediatric Sepsis

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

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Multi-omics analysis of m6A modification-related patterns based on m6A regulators and tumor microenvironment infiltration in lung adenocarcinoma

Scientific Reports ◽

10.1038/s41598-021-00272-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xincheng Wu ◽

Zhengping Bai

Keyword(s):

Tumor Microenvironment ◽

Lung Adenocarcinoma ◽

Cytotoxic T Lymphocyte ◽

Principal Component ◽

Enrichment Analysis ◽

Comprehensive Analysis ◽

Survival Advantage ◽

Pathway Enrichment Analysis ◽

Mutation Burden

AbstractEpigenetic modifications, especially N6-methyladenosine (m6A) modification, play a key role in tumor microenvironment (TME) infiltration. However, the regulatory role of m6A modification in the TME of lung adenocarcinoma (LUAD) remains unclear. A total of 2506 patients with LUAD were included in the analysis and divided into different groups according to distinct m6A modification-related patterns based on 23 m6A regulators. A comprehensive analysis was performed to explore TME infiltration in different m6A modification-related patterns. Principal component analysis was performed to obtain the m6Ascore and to quantify m6A modification-related patterns in different individuals. Three distinct m6A modification-related patterns were identified by 23 m6A regulators. The pathway enrichment analysis showed that m6Acluster-A was associated with immune activation; m6Acluster-B was associated with carcinogenic activation; m6Acluster-C was prominently related to substance metabolism. M6Acluster-A was remarkably rich in TME-infiltrating immune cells and patients with this pattern showed a survival advantage. The m6Ascore could predict TME infiltration, tumor mutation burden (TMB), the effect of tumor immunotherapy, and the prognosis of patients in LUAD. High m6Ascore was characterized by increased TME infiltration, reduced TMB, and survival advantage. Patients with a high m6Ascore exhibited significantly improved clinical response to anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA4) immunotherapy. This study explored the regulatory mechanisms of TME infiltration in LUAD. The comprehensive analysis of m6A modification-related patterns may contribute to the development of individualized immunotherapy and the improvement of the overall effectiveness of immunotherapy for LUAD patients.

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Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes

Animals ◽

10.3390/ani11051430 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1430

Author(s):

Fei Zhang ◽

Xiaodong Zhang ◽

Wei Ning ◽

Xiangdong Zhang ◽

Zhenyuan Ru ◽

...

Keyword(s):

High Throughput Sequencing ◽

Enrichment Analysis ◽

Circular Rnas ◽

Pathway Enrichment Analysis ◽

Testicular Development ◽

Adhesion Junctions ◽

Camp Signaling Pathway ◽

Stem Cell Pluripotency ◽

Hormone Biosynthesis ◽

Host Genes

Testicular development is critical for male animals’ reproduction and is tightly regulated by epigenetic factors. Circular RNAs (circRNAs) were recently identified in the testes of humans and bulls. However, the expression profile of circRNAs and their potential biological functions in boar testicular development remain unclear. We identified 34,521 and 31,803 circRNAs in piglet (30 d) and adult (210 d) boar testes by high-throughput sequencing, respectively. Bioinformatics analysis revealed that these circRNAs are widely distributed on autosomes and sex chromosomes. Some of the host genes can generate multiple circRNAs. A total of 2326 differentially expressed circRNAs (DECs) derived from 1526 host genes was found in testicular development, of which 1003 circRNAs were up-regulated in adult boar testes and 1323 circRNAs were down-regulated. Furthermore, gene ontology analysis of host genes of DECs revealed that these circRNAs are mainly involved in regulating spermatogenesis, cilia motility, and hormone biosynthesis. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DECs are markedly enriched to stem cell pluripotency regulation, tight junctions, adhesion junctions, and cAMP signaling pathway. These results indicate that circRNAs are abundantly expressed in boar testes and exhibit dynamic changes during testicular development.

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