Seminal plasma AnnexinA2 protein is a relevant biomarker for stallions which require removal of seminal plasma for sperm survival upon refrigeration†

Abstract Some stallions yield ejaculates that do not tolerate conservation by refrigeration prior to artificial insemination (AI), showing improvement after removal of most of the seminal plasma (SP) by centrifugation. In this study, the SP-proteome of 10 different stallions was defined through high-performance liquid chromatography with tandem mass spectrometry and bioinformatic analysis in relation to the ability of the ejaculates to maintain semen quality when cooled and stored at 5°C. Stallions were classified into three groups, depending on this ability: those maintaining good quality after direct extension in a commercial extender (good), stallions requiring removal of seminal plasma (RSP) to maintain seminal quality (good-RSP), and stallions, unable to maintain good semen quality even after RSP (poor). Pathway enrichment analysis of the proteins identified in whole equine SP using human orthologs was performed using g: profiler showing enriched Reactome and the Kyoto Encyclopedia of Genes and Genomes pathways related to hexose metabolism, vesicle mediated transport, post translational modification of proteins and immune response. Specific proteins overrepresented in stallions tolerating conservation by refrigeration included a peroxiredoxin-6 like protein, and transcobalamin-2, a primary vitamin B12-binding, and transport protein. Also, the protein involved in protein glycosylation, ST3 beta-galactoside alpha-2,3-sialyltransferase 1 was present in good stallions. These proteins were nearly absent in poor stallions. Particularly, annexinA2 appeared as to be the most powerful discriminant variable for identification of stallions needing RSP prior to refrigeration, with a P = 0.002 and a q value = 0.005. Overall this is the first detailed study of the equine SP-proteome, showing the potential value of specific proteins as discriminant bio-markers for clinical classification of stallions for AI.

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Identification of Differentially Expressed Genes and associated pathways common to Eyelid and Non-Ocular Basal Cell Carcinoma to understand the Molecular Biology of BCC

10.1101/2021.05.01.442022 ◽

2021 ◽

Author(s):

Perumal Jayaraj ◽

Seema Sen ◽

Pranjal Vats ◽

Shefali Dahiya ◽

Vanshika Mohindroo

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Expression Profiles ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Malignant Neoplasms ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Pathway Enrichment

Background: Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive. Objective: This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers. Material and method: The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively. Results: A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC. Conclusion: The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non- Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC. Keywords: Basal cell carcinoma (BCC), Cancer, Microarray, Ophthalmology, Tumour marker

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Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.637489 ◽

2021 ◽

Vol 9 ◽

Author(s):

Rui Chang ◽

Ying Zhu ◽

Jing Xu ◽

Lin Chen ◽

Guannan Su ◽

...

Keyword(s):

High Performance ◽

Area Under The Curve ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Multivariate Statistical ◽

Flight Mass Spectrometry ◽

Laboratory Biomarkers ◽

Vkh Disease

The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.

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Metabolite Changes in the Aqueous Humor of Patients With Retinal Vein Occlusion Macular Edema: A Metabolomics Analysis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.762500 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaojing Xiong ◽

Xu Chen ◽

Huafeng Ma ◽

Zheng Zheng ◽

Yazhu Yang ◽

...

Keyword(s):

Macular Edema ◽

Retinal Vein Occlusion ◽

Aqueous Humor ◽

High Performance ◽

Coenzyme A ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Roc Curve Analysis ◽

Vein Occlusion ◽

Coenzyme A Biosynthesis

Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

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Comprehensive bioinformatic analysis identified m6A methylation as an important regulator in mediating immune response during idiopathic pulmonary arterial hypertension

10.21203/rs.3.rs-64337/v1 ◽

2020 ◽

Author(s):

Na Liu ◽

Yunhong Zeng ◽

Ting Huang ◽

Wanyun Zuo ◽

Yunbin Xiao ◽

...

Keyword(s):

Immune Response ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Immune Cell ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Pathway Enrichment Analysis ◽

Protein Protein Interaction ◽

M1 Macrophage ◽

Pulmonary Arterial

Abstract BackgroundDespite its functional importance in various fundamental bioprocesses, studies of N6-methyladenosine (m6A) in the pulmonary arterial hypertension (PAH) are lacking. Here we studied the potential relevance of m6A RNA methylation and immune response in PAH development.MethodsWe constructed a monocrotaline (MCT) induced PAH rat model and performed Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The 18 idiopathic PAH (IPAH) microarray data obtained from the GEO database was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). CIBERSORT was used to investigate the effect of m6A methylation on immune cell infiltration during PAH.ResultsA differential pattern of m6A abundance, mainly up-methylation, was observed in the lung tissues of rats with MCT induced PAH. By WGCNA, multi-list pathway enrichment analysis and protein-protein interaction (PPI) analysis, we found that m6A methylation modification may play important roles in mediating immune response during PAH. CYBERSORT algorithm indicated that the m6A methylation can drive monocyte to form M1 macrophage, which may be mediated by CCR5 and CXCL9.ConclusionCollectively, m6A landscape is altered in PAH. We summarize newly discovered m6A in controlling immune response, which caused activation of M1 macrophage during PAH. It’s provided a novel insight into the therapeutic mechanisms of PAH.

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Bioinformatic analysis reveals hub genes and pathways that promote melanoma metastasis

10.21203/rs.3.rs-25246/v4 ◽

2020 ◽

Author(s):

Wenxing Su ◽

Yi Guan ◽

Biao Huang ◽

Juanjuan Wang ◽

Yuqian Wei ◽

...

Keyword(s):

Differentially Expressed Gene ◽

Primary Melanoma ◽

Enrichment Analysis ◽

Gene Interaction ◽

Underlying Mechanism ◽

Bioinformatic Analysis ◽

Pathway Enrichment Analysis ◽

Melanoma Metastasis ◽

Ppi Network ◽

Hub Genes

Abstract Background: Melanoma has the highest mortality rate of all skin tumors, and metastases are the major cause of death from it. The molecular mechanism leading to melanoma metastasis is currently unclear. Methods: With the goal of revealing the underlying mechanism, three data sets with accession numbers GSE8401, GSE46517 and GSE7956 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed gene (DEG) of primary melanoma and metastatic melanoma, three kinds of analyses were performed, namely functional annotation, protein‐protein interaction (PPI) network and module construction, and co-expression and drug-gene interaction prediction analysis. Results: A total of 41 up-regulated genes and 79 down-regulated genes was selected for subsequent analyses. Results of pathway enrichment analysis showed that extracellular matrix organization and proteoglycans in cancer are closely related to melanoma metastasis. In addition, seven pivotal genes were identified from PPI network, including CXCL8, THBS1, COL3A1, TIMP3, KIT, DCN, and IGFBP5, which have all been verified in the TCGA database and clinical specimens, but only CXCL8, THBS1 and KIT had significant differences in expression. Conclusions: To conclude, CXCL8, THBS1 and KIT may be the hub genes in the metastasis of melanoma and thus may be regarded as therapeutic targets in the future.

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Bioinformatic analysis reveals hub genes and pathways that promote melanoma metastasis

BMC Cancer ◽

10.1186/s12885-020-07372-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Wenxing Su ◽

Yi Guan ◽

Biao Huang ◽

Juanjuan Wang ◽

Yuqian Wei ◽

...

Keyword(s):

Differentially Expressed Gene ◽

Primary Melanoma ◽

Enrichment Analysis ◽

Gene Interaction ◽

Underlying Mechanism ◽

Bioinformatic Analysis ◽

Pathway Enrichment Analysis ◽

Melanoma Metastasis ◽

Ppi Network ◽

Hub Genes

Abstract Background Melanoma has the highest mortality rate of all skin tumors, and metastases are the major cause of death from it. The molecular mechanism leading to melanoma metastasis is currently unclear. Methods With the goal of revealing the underlying mechanism, three data sets with accession numbers GSE8401, GSE46517 and GSE7956 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed gene (DEG) of primary melanoma and metastatic melanoma, three kinds of analyses were performed, namely functional annotation, protein-protein interaction (PPI) network and module construction, and co-expression and drug-gene interaction prediction analysis. Results A total of 41 up-regulated genes and 79 down-regulated genes was selected for subsequent analyses. Results of pathway enrichment analysis showed that extracellular matrix organization and proteoglycans in cancer are closely related to melanoma metastasis. In addition, seven pivotal genes were identified from PPI network, including CXCL8, THBS1, COL3A1, TIMP3, KIT, DCN, and IGFBP5, which have all been verified in the TCGA database and clinical specimens, but only CXCL8, THBS1 and KIT had significant differences in expression. Conclusions To conclude, CXCL8, THBS1 and KIT may be the hub genes in the metastasis of melanoma and thus may be regarded as therapeutic targets in the future.

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Fucoidan–Fucoxanthin Ameliorated Cardiac Function via IRS1/GRB2/ SOS1, GSK3β/CREB Pathways and Metabolic Pathways in Senescent Mice

Marine Drugs ◽

10.3390/md17010069 ◽

2019 ◽

Vol 17 (1) ◽

pp. 69 ◽

Cited By ~ 8

Author(s):

Po-Ming Chang ◽

Kuan-Lun Li ◽

Yen-Chang Lin

Keyword(s):

Cardiac Function ◽

Metabolic Pathways ◽

High Performance ◽

Cardiac Tissue ◽

Enrichment Analysis ◽

Tca Cycle ◽

Pathway Enrichment Analysis ◽

Whole Cell Patch Clamp ◽

The Tca Cycle ◽

Hormone Biosynthesis

The effects of low molecular weight fucoidan (LMWF) in combination with high-stability fucoxanthin (HSFUCO) on cardiac function and the metabolic pathways of aging mice (Mus musculus) were investigated. We demonstrated that LMWF and HSFUCO could improve cardiac function in aging mice. Aging mice were treated with LMWF and HSFUCO, either on their own or in combination, on 28 consecutive days. Electrocardiography and whole-cell patch-clamp were used to measure QT interval and action potential duration (APD) of the subjects. Cardiac tissue morphology, reactive oxygen species, and Western blot were also applied. Ultra-high-performance liquid chromatography–quadrupole time-of-flight (UPLC-QTOF) mass spectrometry was used for investigating metabolic alterations. The use of LMWF and HSFUCO resulted in improvements in both ventricular rhythms (QT and APD). Treatment with fucoidan and fucoxanthin reduced the expression levels of SOS1 and GRB2 while increasing GSK3β, CREB and IRS1 proteins expression in the aging process. Three main metabolic pathways, namely the TCA cycle, glycolysis, and steroid hormone biosynthesis, were highly enriched in the pathway enrichment analysis. When taken together, the LMWF and HSFUCO treatment improved both the ventricular rhythm and the muscular function of aging subjects by interfering with the metabolism and gene function.

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Identification of tRNA-derived small RNAs and their potential roles in the hippocampus of nicotine exposure rats

10.21203/rs.3.rs-152478/v2 ◽

2021 ◽

Author(s):

Jiali Shao ◽

Yanxia Fei ◽

Chen Su ◽

Wangyuan Zou ◽

Jinfeng Yang

Keyword(s):

Small Rnas ◽

Health Care Systems ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Rat Hippocampus ◽

Differentially Expressed ◽

Exposure Model ◽

Pathway Enrichment Analysis ◽

Nicotine Exposure ◽

Care Systems

Abstract Nicotine use is highly prevalent and brings a huge burden on individuals, society, health-care systems and economic development. The existing mechanisms underlying nicotine’ actions can’t illuminate all basic and clinical problems thoroughly. Transfer RNA-derived small RNAs (tsRNAs) is a novel class of small non-coding RNAs (sncRNAs), possessing potential regulatory functions in various diseases. However, the roles of tsRNAs in nicotine exposure have not been determined yet. In this study, firstly we established nicotine exposure model by subcutaneously injecting (sc.) with 0.5mg/kg of nicotine twice daily for 14 consecutive days, and conducted some behavioral observations (the pain threshold and body weight gains). Secondly, we identified the differentially expressed profiles of tsRNAs in rat hippocampus on saline or nicotine delivery conditions by using ncRNA-Seq, and then predicted the promising functions of the putative genes of the tsRNAs by bioinformatic method. The results shown that there were 26 differentially expressed tsRNAs (7 up-regulated and 19 down-regulated tsRNAs) (Fold change > 1.5; P < 0.05), of which the tRF-5 was the most common type. Eight tsRNAs were selected to validate the sequencing result by RT-qPCR. Then, based on the sequencing and RT-qPCR data, five candidate tsRNAs (tRF-1-T28-His-GTG-1, tRF-5c-Glu-CTC-1, tRF-5c-Glu-CTC-3, tRF-5c-Gly-GCC-2-M2, tRF-5c-Glu-TTC-4) were finally selected for further bioinformatic analysis. The GO and KEGG pathway enrichment analysis suggested that the five candidate tsRNAs might play regulatory roles through the cholinergic synapse pathways, dopaminergic synapse pathways, etc. In conclusion, our results indicated that tsRNAs were dysregulated in the rat hippocampus after nicotine exposure, and among them, tRF-5c-Glu-CTC-1 was the most promising one, which might lay a novel foundation for further research into nicotine’ actions.

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Network Pharmacology Reveals That Resveratrol Can Alleviate COVID-19-Related Hyperinflammation

Disease Markers ◽

10.1155/2021/4129993 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zijian Xiao ◽

Qing Ye ◽

Xiaomei Duan ◽

Tao Xiang

Keyword(s):

Signaling Pathway ◽

Antiviral Agent ◽

Interaction Network ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Gene Expression Omnibus ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Kegg Pathways ◽

Go Terms

Hyperinflammation is related to the development of COVID-19. Resveratrol is considered an anti-inflammatory and antiviral agent. Herein, we used a network pharmacological approach and bioinformatic gene analysis to explore the pharmacological mechanism of Resveratrol in COVID-19 therapy. Potential targets of Resveratrol were obtained from public databases. SARS-CoV-2 differentially expressed genes (DEGs) were screened out via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE147507, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; then, protein-protein interaction network was constructed. The common targets, GO terms, and KEGG pathways of Resveratrol targets and SARS-CoV-2 DEGs were confirmed. KEGG Mapper queried the location of common targets in the key pathways. A notable overlap of the GO terms and KEGG pathways between Resveratrol targets and SARS-CoV-2 DEGs was revealed. The shared targets between Resveratrol targets and SARS-CoV-2 mainly involved the IL-17 signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Our study uncovered that Resveratrol is a promising therapeutic candidate for COVID-19 and we also revealed the probable key targets and pathways involved. Ultimately, we bring forward new insights and encourage more studies on Resveratol to benefit COVID-19 patients.

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