Downregulation of Salivary Proteins, Protective against Dental Caries, in Type 1 Diabetes

Proteomes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 33
Eftychia Pappa ◽  
Konstantinos Vougas ◽  
Jerome Zoidakis ◽  
William Papaioannou ◽  
Christos Rahiotis ◽  

Saliva, an essential oral secretion involved in protecting the oral cavity’s hard and soft tissues, is readily available and straightforward to collect. Recent studies have analyzed the salivary proteome in children and adolescents with extensive carious lesions to identify diagnostic and prognostic biomarkers. The current study aimed to investigate saliva’s diagnostic ability through proteomics to detect the potential differential expression of proteins specific for the occurrence of carious lesions. For this study, we performed bioinformatics and functional analysis of proteomic datasets, previously examined by our group, from samples of adolescents with regulated and unregulated type 1 diabetes, as they compare with healthy controls. Among the differentially expressed proteins relevant to caries pathology, alpha-amylase 2B, beta-defensin 4A, BPI fold containing family B member 2, protein S100-A7, mucin 5B, statherin, salivary proline-rich protein 2, and interleukin 36 gamma were significantly downregulated in poorly-controlled patients compared to healthy subjects. In addition, significant biological pathways (defense response to the bacterium, beta-defensin activity, proline-rich protein activity, oxygen binding, calcium binding, and glycosylation) were deregulated in this comparison, highlighting specific molecular characteristics in the cariogenic process. This analysis contributes to a better understanding of the mechanisms involved in caries vulnerability in adolescents with unregulated diabetes.

2009 ◽  
Vol 36 (1) ◽  
pp. 39-44 ◽  
F. JAVED ◽  

2014 ◽  
Vol 98 ◽  
pp. 905
P. Chhabra ◽  
R. Gehrau ◽  
J. Hansen ◽  
V. Mas ◽  
K. Brayman

2019 ◽  
Vol 20 (23) ◽  
pp. 5903 ◽  
Preethi Krishnan ◽  
Farooq Syed ◽  
Nicole Jiyun Kang ◽  
Raghavendra G. Mirmira ◽  
Carmella Evans-Molina

Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.

Diabetologia ◽  
2019 ◽  
Vol 63 (1) ◽  
pp. 124-136 ◽  
Giuliana Ventriglia ◽  
Francesca Mancarella ◽  
Guido Sebastiani ◽  
Dana P. Cook ◽  
Roberto Mallone ◽  

2014 ◽  
Carah A Figueroa-crisostomo ◽  
Ammira Sarah Akil ◽  
Andy Ho ◽  
Anand Hardikar ◽  
Ryan Farr ◽  

2021 ◽  
Humaira Amin ◽  
Syed Habib Bokhari ◽  
Khuram Shahzad

Abstract Preterm birth (PTB) is one of the major reasons of infant mortalities and morbidities worldwide. Exact mechanism of this disease has not been elucidated yet but studies have shown several factors which have been found associated with the disease. Through several studies, it has been discovered that different chronic diseases like obesity, type 1 diabetes and periodontitis are also associated with PTB but no omics studies have yet been performed to discover their association. In the current study, comparative transcriptome analysis of the preterm birth with type 1 diabetes, obesity and periodontitis using integrated bioinformatics approach was performed to validate their association with preterm birth. Four different datasets retrieved from Gene expression omnibus (GEO) were processed through Bioconductor packages in R. Pairwise comparison of preterm was performed with all three diseases. Several bioinformatics tools were used such as DAVID for Gene ontology (GO) terms and pathway analysis, DIA for impact and direction of KEGG pathways and Cytoscape along with its different plugins for construction of networks, identification of hub genes and modules. Significant number of common differentially expressed genes between datasets and their roles in different pathways were identified. Most of the significant genes and pathways found in these comparisons were involved in initiating different inflammatory processes, degradation of proteins leading to preterm premature rupture of membranes (PPROM), preeclampsia, and cancer which are the known risk factors of PTB. According to our results, all these three chronic diseases were found to have a strong association with PTB.

2020 ◽  
pp. 153537022096273
Ge Yang ◽  
Hui Yu ◽  
Yaoxi Liu ◽  
Weihua Ye ◽  
Guanghui Zhu ◽  

Treatment of congenital pseudarthrosis of the tibia (CPT) still is full of challenges in pediatric orthopedist. Serum-derived exosomes (SDEs) have been proven to be participated in bone remodeling. However, the molecular changes in SDEs of CPT children and their pathologies have not been elucidated. In this study, SDEs were isolated and purified from CPT patients (CPT-SDEs) associated with neurofibromatosis type 1 (NF1) and normal children (Norm-SDEs). Then we obtained the proteomics profile of SDEs by combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag label-based quantitation. In vitro, the efficacy of SDEs on osteoblastic differentiation of MC3T3-E1 cells and osteoclastogenesis ability of RAW264.7 cells were evaluated by quantitative real-time PCR (qRT-PCR) and cytochemical staining. In vivo, we used micro-CT to assess cortical bone mass and trabecular microstructures to reflect the influence of SDEs on bone remodeling after injection into the tail vein of rats. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. These proteins have multiple biological functions associated with cellular metabolic processes, catalytic activity, and protein binding, which are important for cell differentiation and proliferation. In vitro, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis of RAW264.7 cells. Injection of CPT-SDEs into the tail vein for two months resulted in bone loss in rats, as indicated by the decrease in trabecular and cortical bone mass. Our findings demonstrated the differences in proteins in SDEs between normal and CPT children with NF1. These differentially expressed proteins in CPT-SDEs contributed to deteriorating trabecular bone microstructures by inhibiting bone formation and stimulating bone resorption. Impact statement Congenital pseudarthrosis of the tibia (CPT) is an uncommon and puzzling disease associated with a high rate of disability. To date, the biological mechanisms related to this disease have largely not been elucidated. In this study, we determined the biological functions of serum-derived exosomes (SDEs) from children with neurofibromatosis type 1 (NF1) associated with CPT (CPT-SDEs) and compared their proteomic profiles with those of SDEs from normal children. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. In addition, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis ability of RAW264.7 cells. Moreover, injecting CPT-SDEs into the tail veins led to bone loss in rats, as detected by the reduction in trabecular and cortical bone mass. These findings indicate that CPT-SDEs impair bone quality, which may provide a reasonable explanation for the low bone quality and tibial nonunion in children with NF1 associated with congenital tibial pseudarthrosis.

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1005
A. Aneesh Kumar ◽  
G. S. Ajith Kumar ◽  
Gopika Satheesh ◽  
Arun Surendran ◽  
Mahesh Chandran ◽  

The variations in the protein profile of aortic-valvular (AVE) and endocardial endothelial (EE) cells are currently unknown. The current study’s objective is to identify differentially expressed proteins and associated pathways in both the endothelial cells. We used endothelial cells isolated from the porcine (Sus scrofa) aortic valve and endocardium for the profiling of proteins. Label-free proteomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our proteomics analysis revealed that 29 proteins were highly expressed, and 25 proteins were less expressed in the valve than the endocardial endothelium. The cell surface markers, such as CD63, ICAM1, PECAM1, PROCR, and TFRC, were highly expressed in EE. In contrast, CD44 was highly expressed in AVE. The pathway analysis showed that metabolic process-related proteins and extracellular matrix-related proteins were enriched in valves. Differential enrichment of signaling pathways was observed in the endocardium. The hemostasis function-related proteins were increased in both endothelial cells. The proteins and pathways enriched in aortic-valvular and endocardial endothelial cells revealed the distinct phenotype of these two closely related cells.

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