scholarly journals iTRAQ-Based Comparative Proteomics Analysis of Urolithiasis Rats Induced by Ethylene Glycol

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yanan Cao ◽  
Bin Duan ◽  
Xiaowei Gao ◽  
E. Wang ◽  
Zhitao Dong

Nephrolithiasis is a frequent chronic urological condition with a high prevalence and recurrence rate. Proteomics studies on urolithiasis rat models are highly important in characterizing the pathophysiology of kidney stones and identifying potential approaches for preventing and treating kidney stones. The isobaric tags for relative and absolute quantification (iTRAQ) were performed to identify differentially expressed proteins (DEPs) in the kidney between urolithiasis rats and control rats. The results showed that 127 DEPs (85 upregulated and 42 downregulated) were identified in urolithiasis and control rats. The functions of DEPs were predicted by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) network analysis. The expression of four upregulated proteins (Tagln, Akr1c9, Spp1, and Fbn1) and four downregulated proteins (Hbb, Epb42, Hmgcs2, and Ca1) were validated by parallel reaction monitoring (PRM). Proteomics studies of ethylene glycol-induced urolithiasis rat models using iTRAQ and PRM helped to elucidate the molecular mechanism governing nephrolithiasis and to identify candidate proteins for the treatment of kidney stones.

2019 ◽  
Vol 47 (8) ◽  
pp. 3580-3589 ◽  
Author(s):  
Yingyuan Li ◽  
Wulin Tan ◽  
Fang Ye ◽  
Faling Xue ◽  
Shaowei Gao ◽  
...  

Objective We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF). Methods Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed. Results Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3. Conclusion The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.


2020 ◽  
Vol 19 ◽  
pp. 153303382097748
Author(s):  
Shao-wei Zhang ◽  
Nan Zhang ◽  
Na Wang

Background: Esophageal cancer (EC) is a primary malignant tumor originating from the esophageal of the epithelium. Surgical resection is a potential treatment for EC, but this is only appropriate for patients who have locally resectable lesions suitable for surgery. However, most patients with EC are at a late stage when diagnosed. Therefore, there is an urgent need to further explore the pathogenesis of EC to enable early diagnosis and treatment. Methods: Our study downloaded 2 expression spectrum datasets (GSE92396 and GSE100942) in the Gene Expression Omnibus (GEO) database. GEO2 R was used to identify the Differentially expressed genes (DEGs) between the samples of EC and control. Using the DAVID tool to make the Functional enrichment analysis. Constructing A protein–protein interaction (PPI) network. Identifying the Hub genes. The impact of hub gene expression on overall survival and their expression based on immunohistochemistry were analyzed. Associated microRNAs were also predicted. Results: There were 36 common DEGs identified. The analysis of GO and KEGG results shown that the variations were predominantly concentrated in the extracellular matrix (ECM), ECM organization, DNA binding, platelet activation, and ECM-receptor interactions. COL3A1 and POSTN had high expression in EC tissues which was compared with their expression in healthy tissues. Analysis of pathologic stages showed that when COL3A1 and POSTN were highly expressed, the stage of the pathologic of EC patients was relatively high (P < 0.005). Conclusions: COL3A1 and POSTN may play an important role in the advancement and occurrence of EC. These genes could provide some novel ideas and basis for the diagnosis and targeted treatment of EC.


2020 ◽  
Author(s):  
Jinjing Guo ◽  
Xiaoxi Liu ◽  
Yuanjie Li ◽  
Hongyan Ji ◽  
Cheng Liu ◽  
...  

Abstract Background: Hispidin (HIP) and its derivatives, a class of natural fungal metabolites, possess extremely complex and interesting chemical structures with extensive pharmacological activities. Phellinus igniarius, which is the most common sources of HIP, can be used as both medicine and food. The biosynthetic pasthway of HIP in P. igniarius is not yet clear and hence effective regulatory mechanism of HIP is absent.The purpose of this paper was to illustrate a biosynthesis system for hispidin and its derivatives at the protein level. Results: We found that tricetolatone (TL) is a key biosynthetic precursor in the biosynthetic pathway of hispidin and that its addition led to increased production of hispidin and various hispidin derivatives. Based on the changes in the concentrations of precursors and intermediates, key timepoints in the biosynthetic process were identified. We used isobaric tags for relative and absolute quantification (iTRAQ) to study dynamic changes of related proteins in vitro. The 270 differentially expressed proteins were determined by GO enrichment analysis to be primarily related to energy metabolism, oxidative phosphorylation, and environmental stress responses after TL supplementation. The differentially expressed proteins were related to ATP synthase, NAD binding protein, oxidoreductase, and other elements associated with electron transfer and dehydrogenation reactions during the biosynthesis of hispidin and its derivatives. Multiple reaction monitoring (MRM) technology was used to selectively verify the iTRAQ results, leading us to screen 11 proteins that were predicted to be related to the biosynthesis pathways.Conclution: These findings help to clarify the molecular mechanism of biosynthesis of hispidin and its derivatives and may serve as a foundation for future strategies to identify new hispidin derivatives.


2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.


2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Chibuzor M. Nsofor ◽  
Mirabeau Y. Tattfeng ◽  
Chijioke A. Nsofor

Abstract Background This study was aimed to determine the prevalence of qnr genes among fluoroquinolone-resistant Escherichia coli (FREC) isolates from Nigeria. Antimicrobial susceptibility testing was performed by disc diffusion technique. Polymerase chain reaction was used to identify Escherichia coli (E. coli) and for the detection of qnr genes. Results A total of 206 non-duplicate E. coli were isolated from 300 clinical specimens analyzed. In all, 30 (14.6%) of these isolates were FREC; the resistance to fluoroquinolones among these 30 FREC showed 80% (24), 86.7% (26), 86.7% (26), 100% (30), 86.7% (26), 93.3% (28) and 86.7% (26) were resistant to pefloxacin, ciprofloxacin, sparfloxacin, levofloxacin, nalidixic acid, ofloxacin and moxifloxacin, respectively. The distribution of FREC among the various sample sources analyzed showed that 14%, 10%, 13.3%, 16.7% and 20% of the isolates came from urine, stool, high vaginal swab, endo cervical swab and wound swab specimens, respectively. More FREC were isolated from female samples 73.3% (22) compared to male samples 26.7% (8) and were more prevalent among the age group 26–35 years (40%). Twenty eight out of the 30 (93.3%) FREC isolates possessed at least one fluoroquinolone resistance gene in the form of qnrA 10 (33.3%) and qnrB 18 (60%), respectively; qnrS was not detected among the FREC isolates analyzed and 13.5% of the isolates possessed both the qnrA and qnrB genes. Phylogenetic analysis showed that these isolates were genetically diverse. Conclusions These findings suggest a possible resistance to fluoroquinolone is of high interest for better management of patients and control of antimicrobial resistance in Nigeria.


2021 ◽  
Vol 22 (12) ◽  
pp. 6505
Author(s):  
Jishizhan Chen ◽  
Jia Hua ◽  
Wenhui Song

Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Baoyu Jia ◽  
Jiachong Liang ◽  
Chunrong Lv ◽  
Sameeullah Memon ◽  
Yi Fang ◽  
...  

AbstractSperm motility is an index tightly associated with male fertility. A close relationship between seminal plasma and sperm motility has been confirmed. This study was to assess the protein and metabolite profiles of seminal plasma obtained from adult goats with high or low sperm motility using the proteomic and metabolomic strategies. In total, 2098 proteins were found. 449 differentially abundant proteins (DAPs) were identified, and 175 DAPs were enriched in the high motility group. The obtained DAPs primarily exist in cytoplasma and extra-cellular portion. The Gene Ontology enrichment analysis demonstrated the main functional roles of these DAPs in regulating biological process, metabolic process of organic substances, cellular-metabolic process, primary-metabolic process, metabolic process of nitrogen compounds, etc. Additionally, the Kyoto-Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DAPs were primarily involved in phosphatidylinositol signaling system, salivary secretion, proteasome, apoptosis, mitophagy-animal, etc. Aided by the parallel reaction monitoring technology, the abundance changing pattern of 19 selected DAPs was consistent with that of the corresponding proteins obtained by TMT. A total of 4603 metabolites were identified in seminal plasma. 1857 differential metabolites were found between the high motility group and the low motility group, and 999 metabolites were up-regulated in the high motility group. The KEGG analysis demonstrated the primary involvement of the differential metabolites in metabolic and synthetic activities. In conclusion, we first established the proteome and metabolome databank of goat seminal plasma, detecting some proteins and metabolites which may affect sperm motility. This study will be valuable for understanding mechanisms leading to poor sperm motility.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110162
Author(s):  
Yangming Hou ◽  
Xin Wang ◽  
Junwei Wang ◽  
Xuemei Sun ◽  
Xinbo Liu ◽  
...  

Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.


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