scholarly journals Screening of differentially expressed proteins from syncytiotrophoblast for severe early-onset preeclampsia in women with gestational diabetes mellitus using tandem mass tag quantitative proteomics

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaotong Sun ◽  
Tao Qu ◽  
Xiyan He ◽  
Xueping Yang ◽  
Nan Guo ◽  
...  
Author(s):  
Sun X ◽  
◽  
Qu T ◽  
Yang X ◽  
He X ◽  
...  

Gestational Diabetes Mellitus (GDM) is one of the diseases occurring in pregnancy. Although normal postpartum glycometabolism can be restored in most patients with GDM, they have a significantly increased risk of developing complications in the future. In recent years, many studies on the screening of differentially expressed proteins have been performed in patients with GDM by means of proteomics, but the pathogenesis of GDM in the placenta was still unclear. Thus, using the Tandem Mass Tag (TMT) quantitative technology, we aimed to identify candidate biomarkers that could predict GDM occurrence early and provide targets for future therapy. Placenta samples were obtained from pregnant women immediately after delivery. Quantitative proteomics was performed using TMT isobaric tags and liquid chromatography-tandem mass spectrometry. Bioinformatic analysis was performed to elucidate the biological processes that these differentially expressed proteins were involved in. Thirtyfive differentially expressed proteins were identified between patients with GDM and normal pregnant women. Therein, 7 and 28 proteins were upregulated and downregulated, respectively. Differentially expressed proteins were mainly enriched in African trypanosomiasis pathway, hematopoietic cell lineage, gap junction, glucagon signaling pathway, and retinol metabolism. Insulin resistance induced by the excessively activated glucagon signaling pathway in the placenta may be one of the reasons for GDM onset. Among the 35 differentially expressed proteins, excluding 12 unknown proteins or antibodies, 17 of the remaining 23 proteins converged to the same protein-protein interaction network, indicating that a highly linked protein interaction network in the placenta of patients with GDM affected the occurrence of disease.


2020 ◽  
Vol 8 (1) ◽  
pp. e001234
Author(s):  
Sayuri Nakanishi ◽  
Shigeru Aoki ◽  
Junko Kasai ◽  
Ryosuke Shindo ◽  
Soichiro Obata ◽  
...  

IntroductionThis study aimed to assess the validity of applying the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) at any time during pregnancy.Research design and methodsThis multicenter cohort study was conducted at five Japanese facilities from January 2018 to April 2019. The study cohort included women at a high risk of GDM who met one or more of the following IADPSG criteria during early pregnancy: fasting plasma glucose (FPG) ≥92 mg/dL and 75 g oral glucose tolerance test (OGTT) value of ≥180 mg/dL at 1 hour, or ≥153 mg/dL at 2 hour (hereafter early-onset GDM). Women diagnosed with early-onset GDM were followed up without therapeutic intervention and underwent the 75 g OGTT again during 24–28 weeks of gestation. Those exhibiting the GDM patterns on the second 75 g OGTT were diagnosed with true GDM and treated, whereas those exhibiting the normal patterns were diagnosed with false positive early GDM and received no therapeutic intervention.ResultsOf the 146 women diagnosed with early-onset GDM, 69 (47%) had normal 75 g OGTT values at 24–28 weeks of gestation, indicating a false-positive result. FPG levels were significantly higher in the first 75 g-OGTT test than in the second 75 g-OGTT test (93 mg/dL and 87.5 mg/dL, respectively; p<0.001). FPG levels were high in 86 (59%) women with early-onset GDM during early pregnancy but in only 39 (27%) women during mid-pregnancy. Compared with false positive early GDM, true GDM was more frequently associated with adverse pregnancy outcomes.ConclusionsAlthough women with early-onset GDM were followed up without treatment, the results of repeated 75 g OGTT during mid-pregnancy were normal in about 50%. Our data did not support the adoption of IADPSG thresholds for the diagnosis of GDM prior to 20 weeks of gestation.


2021 ◽  
Vol 14 ◽  
Author(s):  
Changci Tong ◽  
Peifang Cong ◽  
Ying Liu ◽  
Xiuyun Shi ◽  
Lin Shi ◽  
...  

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.


2021 ◽  
Author(s):  
Basavaraj Mallikarjunayya Vastrad ◽  
Chanabasayya Mallikarjunayya Vastrad

Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.


Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 166 ◽  
Author(s):  
Qianqian He ◽  
Xinmei Fang ◽  
Tianhui Zhu ◽  
Shan Han ◽  
Hanmingyue Zhu ◽  
...  

Bambusa pervariabilis McClure × Dendrocalamopsis grandis (Q.H.Dai & X.l.Tao ex Keng f.) Ohrnb. blight is a widespread and dangerous forest fungus disease, and has been listed as a supplementary object of forest phytosanitary measures. In order to study the control of B. pervariabilis × D. grandis blight, this experiment was carried out. In this work, a toxin purified from the pathogen Arthrinium phaeospermum (Corda) Elli, which causes blight in B. pervariabilis × D. grandis, with homologous heterogeneity, was used as an inducer to increase resistance to B. pervariabilis × D. grandis. A functional analysis of the differentially expressed proteins after induction using a tandem mass tag labeling technique was combined with mass spectrometry and liquid chromatography mass spectrometry in order to effectively screen for the proteins related to the resistance of B. pervariabilis × D. grandis to blight. After peptide labeling, a total of 3320 unique peptides and 1791 quantitative proteins were obtained by liquid chromatography mass spectrometry analysis. Annotation and enrichment analysis of these peptides and proteins using the Gene ontology and Kyoto Encyclopedia of Genes and Genomes databases with bioinformatics software show that the differentially expressed protein functional annotation items are mainly concentrated on biological processes and cell components. Several pathways that are prominent in the Kyoto Encyclopedia of Genes and Genomes annotation and enrichment include metabolic pathways, the citrate cycle, and phenylpropanoid biosynthesis. In the Protein-protein interaction networks four differentially expressed proteins-sucrose synthase, adenosine triphosphate-citrate synthase beta chain protein 1, peroxidase, and phenylalanine ammonia-lyase significantly interact with multiple proteins and significantly enrich metabolic pathways. To verify the results of tandem mass tag, the candidate proteins were further verified by parallel reaction monitoring, and the results were consistent with the tandem mass tag data analysis results. It is confirmed that the data obtained by tandem mass tag technology are reliable. Therefore, the differentially expressed proteins and signaling pathways discovered here is the primary concern for subsequent disease resistance studies.


2019 ◽  
Vol 17 ◽  
Author(s):  
Shuang Tian ◽  
Dongjun Yang ◽  
Qian Long ◽  
Min Ling

: Mycobacterium tuberculosis (MTB) and Mycobacterium avium (MA) belong to the intracellular parasitic bacteria. To better understand how MTB survives in macrophages and the different pathogenic mechanisms of MTB and MA, the tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used for analysis of the differentially expressed proteins in MTB-infected macrophages and MA-infected macrophages. A total of 682 proteins were found to be differentially expressed in MTB-infected cells in comparison with MA-infected cells. Gene Ontology annotation revealed the involvement of 682 differentially expressed proteins in cellular components, biological processes and molecular functions including binding, catalytic activity, metabolic processes, cellular processes, cell part, cell proliferation and apoptosis, etc. Among these, 10 proteins (O60812, P06576, O43660-2, E9PL10, O00442, M0R050, Q9H8H0, Q9BSJ8, P41240 and Q8TD57-3) were down-regulated in MTB-infected cells. We found that M0R050, O00442, Q9H8H0, O60812 and O43660 are interactive proteins which participate in a multitude of cellular RNA processing, suggesting that these five down-regulated proteins might repress the synthesis of some resistant proteins in MTB-infected cells to promote MTB survival in macrophages.


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