| 1. |
- Han, Jing, et al.
(författare)
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The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).METHODS: The changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.RESULTS: It was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.CONCLUSION: These findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.
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| 2. |
- Wang, Pan, et al.
(författare)
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Genome-wide study identifies the regulatory glycosyltransferase genes networks and signaling pathways from Keshan disease
- 2014
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Ingår i: Journal of Health Science. - : David Publishing Company. ; 2:4, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- KD (Keshan disease) is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC (peripheral blood mononuclear cell) derived respectively from KD patients and healthy in KD areas were compared. Total RNA was isolated, amplified, labeled and hybridized to Agilent 4 × 44 K Whole Human Genome Oligonucleotide Microarray. Significant canonical pathways were analyzed by IPA (ingenuity pathway analysis) to identify differently expressed genes and pathways involved in the cardiovascular system development and function. Quantitative RT-PCR was applied tofurther validate our microarray results. Eighty-three up-regulated (ratios ≥ 2.0) and nine down-regulated glycosyltransferase genes (ratios ≤ 0.5) in PBMC in KD patients were detected by significance analysis of microarrays. Two significant canonical pathways from glycosyltransferase gene expression profiles were screened by IPA. The results of qRT-PCR show that four up-regulated (BMP1/7/10 and FGF18) and one down-regulated (BMP2) genes are consistent with those in microarray experiment, confirming the validity of the microarray data. Based on the results of the study, it is suggested that bone morphogenetic proteins and fibroblast growth factors might play an important role in the pathogenesis of KD. This further helps us to understand the pathogenesis of KD, as well as dilated cardiomyopathy
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| 3. |
- Wang, Sen, et al.
(författare)
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Network analysis of Se-and Zn-related proteins in the serum proteomics expression profile of the endemic dilated cardiomyopathy Keshan disease
- 2018
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Ingår i: Biological Trace Element Research. - : Springer. - 0163-4984 .- 1559-0720. ; 183:1, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.
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| 4. |
- Wang, Sen, et al.
(författare)
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Prediction of co-expression genes and integrative analysis of gene microarray and proteomics profile of Keshan disease
- 2018
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Keshan disease (KD) is a kind of endemic cardiomyopathy which has a high mortality. However, molecular mechanism in the pathogenesis of KD remains poorly understood. Serum samples were collected from 112 KD patients and 112 normal controls. Gene microarray was used to screen differently expressed genes. Genevestigator was applied to forecast co-expression genes of significant gene. iTRAQ proteomics analysis was used to verify significant genes and their co-expression genes. GO, COG, IPA and STRING were applied to undertake function categorization, pathway and network analysis separately. We identified 32 differentially expressed genes; IDH2, FEM1A, SSPB1 and their respective 30 co-expression genes; 68 differential proteins in KD. Significant proteins were categorized into 23 biological processes, 16 molecular functions, 16 cellular components, 15 function classes, 13 KD pathways and 1 network. IDH2, FEM1A, SSBP1, CALR, NDUFS2, IDH3A, GAPDH, TCA Cycle II (Eukaryotic) pathway and NADP repair pathway may play important roles in the pathogenesis of KD.
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| 5. |
- Wang, Sen, et al.
(författare)
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Roles of glycoproteins in the diagnosis and differential diagnosis of chronic and latent Keshan disease
- 2017
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 CKD, 50 LKD patients and 54 normal individuals. Saliva and serum lectin microarrays and saliva and serum microarrays were used to screen and verify the differences in the levels of lectin among the three groups. In the male saliva lectin microarray, Solanum tuberosum (potato) lectin (STL) and other 9 lectins showed differences between CKD and normal; STL and other 9 lectins showed differences between LKD and normal; Aleuria aurantia lectin (AAL) and other 15 lectins showed differences between CKD and LKD. In the female saliva microarray, Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) and other 9 lectins showed differences between CKD and normal; STL and other 7 lectins showed differences between LKD and normal; Maackia amurensis lectin I (MAL-I) and Triticum vulgaris (WGA) showed difference between CKD and LKD. In the male serum lectin microarray, Psophocarpus tetragonolobus lectin I (PTL-I) and other 16 lectins showed differences between CKD and normal; Ulexeuropaeus agglutinin I (UEA-I) and other 9 lectins showed differences between LKD and normal; AAL and other 13 lectins showed differences between CKD and LKD. In the female serum lectin microarray, WGA and other 13 lectins showed differences between CKD and normal; Euonymus europaeus lectin (EEL) and other 6 lectins showed differences between LKD and normal; MAL-I and other 14 lectins showed differences between CKD and LKD. Carbohydrate chain GlcNAc and α-Gal may play crucial roles in the pathogenesis of KD. STL may be considered the diagnostic biomarker for male CKD and LKD, while WGA may be useful in distinguishing between the two stages. STL may be considered the diagnostic biomarker for female LKD.
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| 6. |
- Wang, Xi, et al.
(författare)
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Gene expression signature in endemic osteoarthritis by microarray analysis
- 2015
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Ingår i: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI. - 1661-6596 .- 1422-0067. ; 16:5, s. 11465-11481
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based gene signature for the detection of KBD. Previously published gene expression profile data on cartilage and peripheral blood mononuclear cells (PBMCs) from adults with KBD were compared to select potential target genes. Microarray analysis was conducted to evaluate the expression of the target genes in a cohort of 100 KBD patients and 100 healthy controls. A gene expression signature was identified using a training set, which was subsequently validated using an independent test set with a minimum redundancy maximum relevance (mRMR) algorithm and support vector machine (SVM) algorithm. Fifty unique genes were differentially expressed between KBD patients and healthy controls. A 20-gene signature was identified that distinguished between KBD patients and controls with 90% accuracy, 85% sensitivity, and 95% specificity. This study identified a 20-gene signature that accurately distinguishes between patients with KBD and controls using peripheral blood samples. These results promote the further development of blood-based genetic biomarkers for detection of KBD.
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