scholarly journals Molecular mechanism of oil induced growth inhibition in diatoms using Thalassiosira pseudonana as the model species

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manoj Kamalanathan ◽  
Savannah Mapes ◽  
Jessica Hillhouse ◽  
Noah Claflin ◽  
Joshua Leleux ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Photosynthetic Apparatus ◽  
Enrichment Analysis ◽  
Photosynthetic Electron Transport ◽  
Conclusive Evidence ◽  
Thalassiosira Pseudonana ◽  
Cellular Damage ◽  
Pathway Enrichment Analysis ◽  
Negative Effects ◽  
Oil Exposure

AbstractThe 2010 Deepwater Horizon oil-spill exposed the microbes of Gulf of Mexico to unprecedented amount of oil. Conclusive evidence of the underlying molecular mechanism(s) on the negative effects of oil exposure on certain phytoplankton species such as Thalassiosira pseudonana is still lacking, curtailing our understanding of how oil spills alter community composition. We performed experiments on model diatom T. pseudonana to understand the mechanisms underpinning observed reduced growth and photosynthesis rates during oil exposure. Results show severe impairment to processes upstream of photosynthesis, such as light absorption, with proteins associated with the light harvesting complex damaged while the pigments were unaffected. Proteins associated with photosynthetic electron transport were also damaged, severely affecting photosynthetic apparatus and depriving cells of energy and carbon for growth. Negative growth effects were alleviated when an organic carbon source was provided. Further investigation through proteomics combined with pathway enrichment analysis confirmed the above findings, while highlighting other negatively affected processes such as those associated with ferroxidase complex, high-affinity iron-permease complex, and multiple transmembrane transport. We also show that oxidative stress is not the primary route of negative effects, rather secondary. Overall, this study provides a mechanistic understanding of the cellular damage that occurs during oil exposure to T. pseudonana.

scholarly journals Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guangyu Gao ◽  
Zhen Yao ◽  
Jiaofeng Shen ◽  
Yulong Liu
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Obvious Association

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

scholarly journals A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action of the Wei Pi Xiao Decoction for the Treatment of Gastric Precancerous Lesions

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Liangjun Yang ◽  
Wei Liu ◽  
Zhipeng Hu ◽  
Maoyi Yang ◽  
Jiali Li ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Therapeutic Effect ◽  
Drug Targets ◽  
Precancerous Lesions ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

scholarly journals The System Research of the Molecular Mechanism of Quyushengxin Capsule in the Treatment of Osteonecrosis of the Femoral Head

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Xia Du ◽  
Lintao Zhao ◽  
Yuan Qiao ◽  
Yuan Liu ◽  
Dong Guo
Keyword(s):  
Molecular Docking ◽  
Femoral Head ◽  
Molecular Mechanism ◽  
Enrichment Analysis ◽  
Integrated Approach ◽  
Pathway Enrichment Analysis ◽  
Systems Pharmacology ◽  
Protein Protein Interaction ◽  
Chip Experiment ◽  
Tnf Α

Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that has a risk of eventually developing into a joint collapse and resulting in joint dysfunction. Quyushengxin capsule (QYSXC) is an effective and safe traditional Chinese medicine used in the treatment of ONFH. In this present study, an integrated approach was used to investigate the mechanism of QYSXC in the treatment of ONFH, which contained systems pharmacology, molecular docking, and chip experiment. In the systems pharmacology, target fishing, protein-protein interaction (PPI), Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and herbs-compounds-targets-pathways (H-C-T-P) network construction were performed to study the mechanism of QYSXC in the treatment of ONFH. The results showed that 15 key compounds, 8 key targets, and 8 key signaling pathways were found for QYSXC in the treatment with ONFH. Then, molecular docking was performed to further explore the interaction between some key compounds and key targets. After that, the chip experiment was performed to verify some target factors, including ICAM-1, IL-6, IL-1α, IL-1β, IL-2, IL-4, IL-10, and TNF-α. The results of this work may provide a theoretical basis for further research on the molecular mechanism of QYSXC in the treatment of ONFH.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Determination of Usnic Acid Responsive miRNAs in Breast Cancer Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Usnic Acid ◽  
Enrichment Analysis ◽  
Breast Cancer Cell Lines ◽  
Pathway Enrichment Analysis ◽  
Molecular Heterogeneity ◽  
Proliferative Effect ◽  
Mcf 7

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.

scholarly journals Signature RNAS and related regulatory roles in type 1 diabetes mellitus based on competing endogenous RNA regulatory network analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinghong Shi ◽  
Hanxin Yao
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Network Analysis ◽  
Type 1 Diabetes Mellitus ◽  
Regulatory Network ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Competing Endogenous Rna ◽  
Pathway Enrichment

Abstract Background Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis. Methods Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD). Results In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1). Conclusion The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.

scholarly journals Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1821
Author(s):  
Ujjwal Mukund Mahajan ◽  
Ahmed Alnatsha ◽  
Qi Li ◽  
Bettina Oehrle ◽  
Frank-Ulrich Weiss ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Enrichment Analysis ◽  
Response Prediction ◽  
Ductal Adenocarcinoma ◽  
Pathway Enrichment Analysis ◽  
Metabolome Analysis ◽  
Dismal Prognosis ◽  
Chemotherapeutic Response ◽  
Plasma Metabolome ◽  
Metabolome Profiling

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

scholarly journals Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Yuan ◽  
Shenqiang Hu ◽  
Liang Li ◽  
Chunchun Han ◽  
Hehe Liu ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Lipid Droplets ◽  
Cell Model ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Follicle Development ◽  
Microscopy Analysis ◽  
Stearoyl Coa Desaturase ◽  
Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

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