scholarly journals Transcriptomic Profiling of Buffalo Spermatozoa Reveals Dysregulation of Functionally Relevant mRNAs in Low-Fertile Bulls

2021 ◽  
Vol 7 ◽  
Author(s):  
Nilendu Paul ◽  
Arumugam Kumaresan ◽  
Mohua Das Gupta ◽  
Pradeep Nag ◽  
Pushpa Rani Guvvala ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Microarray Technology ◽  
Transcriptomic Profile ◽  
Functional Attributes ◽  
Sperm Membrane ◽  
Mrna Microarray ◽  
Primary Localization ◽  
Protamine Deficiency

Although, it is known that spermatozoa harbor a variety of RNAs that may influence embryonic development, little is understood about sperm transcriptomic differences in relation to fertility, especially in buffaloes. In the present study, we compared the differences in sperm functional attributes and transcriptomic profile between high- and low-fertile buffalo bulls. Sperm membrane and acrosomal integrity were lower (P < 0.05), while protamine deficiency and lipid peroxidation were higher (P < 0.05) in low- compared to high-fertile bulls. Transcriptomic analysis using mRNA microarray technology detected a total of 51,282 transcripts in buffalo spermatozoa, of which 4,050 transcripts were differentially expressed, and 709 transcripts were found to be significantly dysregulated (P < 0.05 and fold change >1) between high- and low-fertile bulls. Majority of the dysregulated transcripts were related to binding activity, transcription, translation, and metabolic processes with primary localization in the cell nucleus, nucleoplasm, and in cytosol. Pathways related to MAPK signaling, ribosome pathway, and oxidative phosphorylation were dysregulated in low-fertile bull spermatozoa. Using bioinformatics analysis, we observed that several genes related to sperm functional attributes were significantly downregulated in low-fertile bull spermatozoa. Validation of the results of microarray analysis was carried out using real-time qPCR expression analysis of selected genes (YBX1, ORAI3, and TFAP2C). The relative expression of these genes followed the same trend in both the techniques. Collectively, this is the first study to report the transcriptomic profile of buffalo spermatozoa and to demonstrate the dysregulation of functionally relevant transcripts in low-fertile bull spermatozoa. The results of the present study open up new avenues for understanding the etiology for poor fertility in buffalo bulls and to identify fertility biomarkers.

Identification of key mRNAs and lncRNAs involved in the effects of anti-TWEAK on Osteosarcoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Mingxuan Yang ◽  
Liangtao Zhao ◽  
Xuchang Hu ◽  
Haijun Feng ◽  
Xuewen Kang
Keyword(s):  
Dna Replication ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Type I ◽  
Interferon Signaling ◽  
Nf Kappa B ◽  
Ppi Networks ◽  
Coexpression Networks

Background: Osteosarcoma (OS) is one of the most common primary malignant bone tumors in teenagers. Emerging studies demonstrated TWEAK and Fn14 were involved in regulating cancer cell differentiation, proliferation, apoptosis, migration and invasion. Objective: The present study identified differently expressed mRNAs and lncRNAs after anti-TWEAK treatment in OS cells using GSE41828. Methods: We identified 922 up-regulated mRNAs, 863 downregulated mRNAs, 29 up-regulated lncRNAs, and 58 down-regulated lncRNAs after anti-TWEAK treatment in OS cells. By constructing PPI networks, we identified several key proteins involved in anti-TWEAK treatment in OS cells, including MYC, IL6, CD44, ITGAM, STAT1, CCL5, FN1, PTEN, SPP1, TOP2A, and NCAM1. By constructing lncRNAs coexpression networks, we identified several key lncRNAs, including LINC00623, LINC00944, PSMB8-AS1, LOC101929787. Result: Bioinformatics analysis revealed DEGs after anti-TWEAK treatment in OS were involved in regulating type I interferon signaling pathway, immune response related pathways, telomere organization, chromatin silencing at rDNA, and DNA replication. Bioinformatics analysis revealed differently expressed lncRNAs after antiTWEAK treatment in OS were related to telomere organization, protein heterotetramerization, DNA replication, response to hypoxia, TNF signaling pathway, PI3K-Akt signaling pathway, Focal adhesion, Apoptosis, NF-kappa B signaling pathway, MAPK signaling pathway, FoxO signaling pathway. Conclusion: : This study provided useful information for understanding the mechanisms of TWEAK underlying OS progression and identifying novel therapeutic markers for OS.

scholarly journals Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-κB and MAPK Activities in RAW 264.7 Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hai Yang Yu ◽  
Kyoung-Sook Kim ◽  
Young-Choon Lee ◽  
Hyung-In Moon ◽  
Jai-Heon Lee
Keyword(s):  
Nitric Oxide ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Raw 264.7 Macrophages ◽  
Dendropanax Morbifera ◽  
Cox 2

Oleifolioside A, a new triterpenoid compound isolated fromDendropanax morbiferaLeveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E2(PGE2) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-αand subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

scholarly journals Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Dan Wang ◽  
Mingyue Li ◽  
Jing Li ◽  
Xuechao Wan ◽  
Yan Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cancer Progression ◽  
Regulatory Network ◽  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Ppi Network ◽  
Network Analyses ◽  
Comprehensive Characterization ◽  
Upstream Regulators

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

scholarly journals Circulating miRNA Profiles Associated with Lung Function Decline

2021 ◽  
Author(s):  
Man Cheng ◽  
Yang Xiao ◽  
Zi Ye ◽  
Linling Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Lung Function ◽  
Signaling Pathway ◽  
Respiratory Diseases ◽  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Lung Function Decline ◽  
Expression Levels ◽  
Mirnas Expression

Abstract Background: Lung function decline and miRNAs are known to involve in the pathogenesis process of respiratory diseases. However, the association between miRNA profiles and lung function decline was rarely elucidated. This study aimed to compare the expression pattern of plasma miRNAs among people with rapid lung function decline and healthy controls. Methods: Ten controls and 10 cases with rapid lung function decline in last 3 years were enrolled from the Wuhan-Zhuhai cohort. The miRNA sequencing and bioinformatics analysis were carried out to explore miRNAs expression and possible signal pathways. Pearson correlation analysis was carried out to assess the associations between lung function and miRNAs expression levels.Results: A total of 1209 detected miRNAs were differently expression in the reaseach participants. Among them, 17 miRNAs (miR-6749-5p, miR-6797-3p, miR-4468, miR-4301, miR-629-3p, miR-4713-3p, miR-486-3p, miR-450a-1-3p, miR-4732-5p, miR-514a-5p, miR-193b-5p, miR-6749-5p, miR-3168, miR-4691-5p, miR-6730-5p, miR-184, miR-486-5p) were significantly down-regulated in cases with reduced lung function. The expression levels of these miRNAs, except miR-514a-5p and miR-3168, were significantly correlated with lung function parameters. Through bioinformatics analysis, the Wnt signaling pathway, FoxO signaling pathway, MAPK signaling pathway, Pathway in cancer, inflammatory mediator regulation of TRP channels, and TGF-β signaling pathway maybe involved in mediating the association between 17 identified miRNAs and lung function decline.Conclusions: The plasma miRNA profile of people with rapid lung function decline are different when compared with healthy controls. These miRNAs might become research candidates or biomarkers in the early progression of respiratory diseases.

Interleukin-1 inhibits the induction of insulin-like growth factor-I by growth hormone in CWSV-1 hepatocytes

2005 ◽  
Vol 289 (2) ◽  
pp. G227-G239 ◽  
Author(s):  
Margaret L. Shumate ◽  
Gladys Yumet ◽  
Tamer A. Ahmed ◽  
Robert N. Cooney
Keyword(s):  
Growth Hormone ◽  
Time Course ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Fourfold Increase ◽  
Dna Binding Activity ◽  
Igf I ◽  
Gh Resistance

Sepsis results in hepatic “growth hormone (GH) resistance” with reductions in plasma IGF-I despite a two- to fourfold increase in circulating GH. In this study, we examine the effects of IL-1 on GH receptor (GHR) expression, GH signaling (via the JAK/STAT and MAPK pathways), and the induction of gene expression [IGF-I mRNA and serine protease inhibitor (Spi) 2.1] by GH in CWSV-1 hepatocytes. Incubation of cells with IL-1β (10 ng/ml, 24 h) had no effect on the relative abundance of GHR or signaling proteins JAK2, STAT5b, and ERK1/2 in cell lysates. Baseline phosphorylation of GHR, JAK2, STAT5b, and ERK1/2 was minimal. After GH stimulation, tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2 increased 2- to 10-fold. However, neither the time course nor the magnitude of GHR, JAK2, and ERK1/2 phosphorylation by GH were significantly altered by IL-1. The GH-induced translocation of STAT5b to the nucleus was not prevented by IL-1. Although phosphorylated STAT5 in nuclear extracts from GH + IL-1 cells was decreased by 24% (vs. controls) 15 min after GH stimulation, this did not result in reduced STAT5-DNA binding activity. Pretreatment with IL-1 did not significantly decrease IGF-I mRNA stability. We conclude that IL-1 only minimally affects the time course of JAK2/STAT5 and MAPK signaling by GH. Therefore, an inhibitory effect of IL-1 on IGF-I and Spi 2.1 mRNA synthesis by GH represents the most likely mechanism for IL-1-mediated GH resistance.

scholarly journals Postpartal Subclinical Endometritis Alters Transcriptome Profiles in Liver and Adipose Tissue of Dairy Cows

2014 ◽  
Vol 8 ◽  
pp. BBI.S13735 ◽  
Author(s):  
Haji Akbar ◽  
Felipe C. Cardoso ◽  
Susanne Meier ◽  
Christopher Burke ◽  
Scott Mcdougall ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Bioinformatics Analysis ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Coagulation Cascade ◽  
Fatty Acid Transport ◽  
Vitamin B3 ◽  
Molecular Alterations ◽  
B Cell Receptor Signaling ◽  
Subclinical Endometritis

Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress.

Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise

2006 ◽  
Vol 101 (1) ◽  
pp. 151-163 ◽  
Author(s):  
Motoyuki Iemitsu ◽  
Seiji Maeda ◽  
Subrina Jesmin ◽  
Takeshi Otsuki ◽  
Yoshitoshi Kasuya ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Hypertrophy ◽  
Acute Exercise ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Treadmill Running ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Dna Binding Activity ◽  
Single Bout

Since exercise training causes cardiac hypertrophy and a single bout induces mechanical stress to the heart, the present study aimed to characterize the activation patterns of multiple MAPK signaling pathways in the heart after a single bout of exercise or chronic exercises. The hearts of untrained rats received 5, 15, and 30 min of treadmill running exercise (Ex5 to Ex30) and rested for 0.5, 1, 3, 6, 12, and 24 h (PostEx0.5 to PostEx24) before subjecting them to the following different experiments. Activation of MAPKs (ERK, JNK, and p38) and MAPKKs (MEK1/2, SEK, and MKK3/6) increased immediately after acute exercise in a time-dependent manner, with ERK, JNK, and p38 peaking at Ex15, Ex15, and Ex30, respectively. Expression of immediate early genes ( c-fos, c-jun, and c-myc) was augmented and activator protein-1 DNA binding activity was enhanced in untrained rats immediately after a single bout of exercise. The elevated levels of MAPKs declined to the resting levels within 24 h after exercise. In another set of experiments, following 4, 8, and 12 wk of exercise training, the rats exhibited significant cardiac hypertrophy by week 12. Activation of MAPKs in the 4-wk-trained rats increased after a 30-min single bout of exercise but decreased in the 8-wk group. Finally, the activity of MAPKs signaling in the 12-wk-trained rats exposed to an acute bout of exercise was unaltered. We conclude that exercise induces the activation of multiple MAPK (ERK, JNK, and p38) pathways in the heart, an effect that gradually declines with the development of exercise-induced cardiac hypertrophy.

scholarly journals Prediction of repurposed drugs for treating lung injury in COVID-19

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 609 ◽  
Author(s):  
Bing He ◽  
Lana Garmire
Keyword(s):  
Respiratory Failure ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Bioinformatics Analysis ◽  
Drug Repositioning ◽  
Gene Expression Pattern ◽  
Mapk Signaling ◽  
Efficient Treatment ◽  
Drug Candidates ◽  
Repurposed Drugs

Background: Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Methods: Inhibition of angiotensin-converting enzyme 2 (ACE2) caused by the spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We performed drug repositioning analysis to identify drug candidates that reverse gene expression pattern in L1000 lung cell line HCC515 treated with ACE2 inhibitor. We confirmed these drug candidates by similar bioinformatics analysis using lung tissues from patients deceased from COVID-19. We further investigated deregulated genes and pathways related to lung injury, as well as the gene-pathway-drug candidate relationships. Results: We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19. Further bioinformatics analysis shows that 12 significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues. These include signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and chemokine signaling pathways. All 12 pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares 11 of 12 pathways with COL-3 and common target genes such as RHOA. It also uniquely targets other genes related to lung injury, such as CALR and MMP14. Conclusions: This study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have potential as repurposed drugs for its treatment.

Sign in / Sign up

Export Citation Format

Share Document