scholarly journals Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 181 ◽  
Author(s):  
Huilin Liu ◽  
Huimin Liu ◽  
Lingyu Zhu ◽  
Ziqi Zhang ◽  
Xin Zheng ◽  
...  

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. It is a complex process, including a broad spectrum of hepatic lesions from fibrosis to cirrhosis. Our previous study suggested that astaxanthin (AST) could alleviate the hepatic inflammation and lipid dysmetabolism induced by ethanol administration. In this study, a total of 48 male C57BL/6J mice were divided into 4 groups: a Con group (fed with a Lieber–DeCarli liquid diet), an AST group (fed with a Lieber–DeCarli liquid diet and AST), an Et group (fed with an ethanol-containing Lieber–DeCarli liquid diet), and a EtAST group (fed with an ethanol-containing Lieber–DeCarli liquid diet and AST). Then, comparative hepatic transcriptome analysis among the groups was performed by Illumina RNA sequencing. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of the top genes were verified by quantitative real-time PCR (qRT-PCR) and Western blot. A total of 514.95 ± 6.89, 546.02 ± 15.93, 576.06 ± 21.01, and 690.85 ± 54.14 million clean reads were obtained for the Con, AST, Et, and EtAST groups, respectively. Compared with the Et group, 1892 differentially expressed genes (DEGs) (including 351 upregulated and 1541 downregulated genes) were identified in the AST group, 1724 differentially expressed genes (including 233 upregulated and 1491 downregulated genes) were identified in the Con group, and 1718 DEGs (including 1380 upregulated and 338 downregulated genes) were identified in the EtAST group. The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes. The findings of this study provide insights for the development of nutrition-related therapeutics for ALD.

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 186
Author(s):  
Guoyong Yan ◽  
Jin Sun ◽  
Zishuai Wang ◽  
Pei-Yuan Qian ◽  
Lisheng He

Barnacles represent one of the model organisms used for antifouling research, however, knowledge regarding the molecular mechanisms underlying barnacle cyprid cementation is relatively scarce. Here, RNA-seq was used to obtain the transcriptomes of the cement glands where adhesive is generated and the remaining carcasses of Megabalanus volcano cyprids. Comparative transcriptomic analysis identified 9060 differentially expressed genes, with 4383 upregulated in the cement glands. Four cement proteins, named Mvcp113k, Mvcp130k, Mvcp52k and Mvlcp1-122k, were detected in the cement glands. The salivary secretion pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes, implying that the secretion of cyprid adhesive might be analogous to that of saliva. Lysyl oxidase had a higher expression level in the cement glands and was speculated to function in the curing of cyprid adhesive. Furthermore, the KEGG enrichment analysis of the 352 proteins identified in the cement gland proteome partially confirmed the comparative transcriptomic results. These results present insights into the molecular mechanisms underlying the synthesis, secretion and curing of barnacle cyprid adhesive and provide potential molecular targets for the development of environmentally friendly antifouling compounds.


2022 ◽  
pp. 1-12
Author(s):  
Zhengfei Ma ◽  
Ping Zhong ◽  
Peidong Yue ◽  
Zhongwu Sun

<b><i>Background:</i></b> Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. <b><i>Methods:</i></b> Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. <b><i>Results:</i></b> In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was &#x3e;0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. <b><i>Conclusion:</i></b> Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Siying He ◽  
Hui Sun ◽  
Yifang Huang ◽  
Shiqi Dong ◽  
Chen Qiao ◽  
...  

Purpose. MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms. Methods. MiRNA expression was initially extracted and pooled by published literature. Microarray data about differentially expressed genes was downloaded from Gene Expression Omnibus (GEO) database and analyzed with the R programming language. Functional and pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network was constructed with the STRING database. The associations between chemicals, differentially expressed miRNAs, and differentially expressed genes were predicted using the online resource. All the networks were constructed using Cytoscape. Results. We found that 35 miRNAs and 301 genes were significantly differentially expressed. Functional enrichment analysis showed that upregulated genes were significantly enriched in extracellular matrix (ECM) organization, while downregulated genes were mainly involved in cell death and apoptotic process. Finally, we concluded the chemical-gene affected network, miRNA-mRNA interacted networks, and significant pathway network. Conclusion. We identified lists of differentially expressed miRNAs and genes and their possible interaction in pterygium. The networks indicated that ECM breakdown and EMT might be two major pathophysiological mechanisms and showed the potential significance of PI3K-Akt signalling pathway. MiR-29b-3p and collagen family (COL4A1 and COL3A1) might be new treatment target in pterygium.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parastoo Modarres ◽  
Farzaneh Mohamadi Farsani ◽  
Amir Abas Nekouie ◽  
Sadeq Vallian

AbstractThe pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.


2021 ◽  
Author(s):  
Parastoo Modarres ◽  
Farzaneh Mohammadi Farsani ◽  
AmirAbas Nekouie ◽  
Sadeq Vallian

Abstract The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes were selected to be differentially expressed in chemo-resistance compared to chemo-sensitive group. Among these genes, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, suggesting this pathway as a novel key regulator of drug-resistance development in AML.


Agronomy ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 283 ◽  
Author(s):  
Xian Zhang ◽  
Ning Tang ◽  
Xiaomeng Liu ◽  
Jiabao Ye ◽  
Jingyi Zhang ◽  
...  

As a traditional spicy condiment, Zanthoxylum armatum var. novemfolius is of high economical and medicinal value. Despite the long history of human cultivation, the molecular mechanisms underlying flower development are still poorly understood in Z. armatum. In this study, we performed de novo transcriptome assembly and comparative analysis of female and male flowers in Z. armatum. A total of 94,771 unigenes were obtained, and 50,605 unigenes were successfully annotated against the public database. Transcriptome data showed that 20,431 annotated unigenes were differentially expressed genes. KEGG enrichment analysis revealed that the most representative pathway was plant hormone signal transduction. Among them, 41, 16, 41, 27, 95, and 40 unigenes were involved in the biosynthesis and signaling of abscisic acid, ethylene, cytokinin, gibberellin, auxin, and jasmonic acid, respectively. Transcription factors also played crucial roles in flower development, such as AGL11, PMADS2, and NAC. These results provided an important basis for characterizing the potential mechanism of flower development and enriching the knowledge of reproduction genetics in Z. armatum.


2021 ◽  
Author(s):  
Charles-Etienne Castonguay ◽  
Cal Liao ◽  
Anouar Khayachi ◽  
Gabrielle Houle ◽  
Jay P Ross ◽  
...  

Essential tremor (ET) is one of the most common movement disorders, affecting nearly 5% of individuals over 65 years old. Despite its high heritability, few genetic risk loci for ET have been identified. Recent advances in pharmacogenomics have generated a wealth of data that led to the identification of molecular signatures in response to hundreds of chemical compounds. Among the different forms of data, gene expression has proven to be quite successful for the inference of drug response in cell models. We sought to leverage this approach in the context of ET where many patients are responsive two drugs: propranolol and primidone. Propranolol- and primidone-specific transcriptomic drug targets, as well as convergent gene targets across both drugs, could provide insights into the pathogenesis of ET and identify possible targets of interest for future treatments. In this study, cerebellar DAOY and neural progenitor cells were treated for 5 days with clinical concentrations of propranolol and primidone, after which RNA-sequencing was used to identify differentially expressed genes. The expression of genes previously implicated in genetic and transcriptomic studies of ET and other movement disorders, such as TRAPPC11, were significantly upregulated by propranolol. Pathway enrichment analysis identified multiple terms related to calcium signalling, endosomal sorting, axon guidance, and neuronal morphology. Convergent differentially expressed genes across all treatments and cell types were also found to be significantly more mutationally constrained, implying that they might harbour rare deleterious variants implicated in disease. Furthermore, these genes were enriched within cell types having high expression of ET related genes in both cortical and cerebellar tissues. Altogether, our results highlight potential cellular and molecular mechanisms associated with tremor reduction and identify relevant genetic biomarkers for drug-responsiveness in ET.


2020 ◽  
Author(s):  
Ali Mohamed Alshabi ◽  
Ibrahim Ahmed Shaikh ◽  
Basavaraj Mallikarjunayya Vastrad ◽  
Chanabasayya Mallikarjunayya Vastrad

Abstract BackgroundThe exact molecular mechanisms of the progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unclear. The current investigation strived to understand and functionally analyze the differentially expressed genes (DEGs) between SARS-CoV-2 infection and mock samples applying extensive bioinformatics analyses.MethodsGSE148729 dataset was downloaded from the Gene Expression Omnibus (GEO) and investigated utilising the limma package in R software to identify DEGs. Pathway and gene ontology (GO) enrichment analysis of the up and down-regulated genes were performed in ToppGene. The HIPPIE database was applied to estimate the interactions of up and down-regulated genes and to construct a protein-protein interaction (PPI) network using Cytoscape software. Receiver operating characteristic (ROC) was utilized for validation.ResultsA total of 928 DEGs (461 up-regulated genes and 467 down-regulated genes) were identified between SARS-CoV-2 infection and mock samples. The up and down-regulated genes were significantly enriched in cytokine-cytokine receptor interaction, and ascorbate and aldarate metabolism. Several significant GO terms, including the response to biotic stimulus and oxoacid metabolic process, were identified. The top hub genes and target genes included JUN, FBXO6, PCLAF, CFTR, TXNIP, PMAIP1, BRI3BP, FAHD1, PROX1, CXCL11, SERHL2 and CFI. ROC curve analysis showed that messenger RNA levels of these ten genes (DDX58, IFITM2, IRF1, PML, SAMHD1, ACSS1, CYP2U1, DDC, PNMT and UGT2A3) exhibited better diagnostic efficiency between SARS-CoV-2 infection and mock.ConclusionsThe current investigation distinguished vital genes and pathways that may be implicated in the progression of SARS-CoV-2 infection, providing a new understanding of the underlying molecular mechanisms of SARS-CoV-2 infection.


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