| 1. |
- Liu, Huan, et al.
(author)
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The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway
- 2022
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In: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:1, s. 279-293
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing.METHODS: HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donors via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by real-time quantitative reverse transcription PCR (RT-qPCR).RESULTS: KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin, PPAR signaling pathway and cell adhesion molecules (CAMs) pathways were identified to be significantly altered in KBD.CONCLUSION: Differentiated chondrocytes deriving from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.
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| 2. |
- Ning, Yujie, et al.
(author)
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Nutrients other than selenium are important for promoting children's health in Kashin-Beck disease areas
- 2018
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In: Biological Trace Element Research. - : Springer. - 0163-4984 .- 1559-0720. ; 183:2, s. 233-244
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Journal article (peer-reviewed)abstract
- Overall nutritional status has been proved associated with people's health. The overall nutritional status of children in Kashin-Beck disease (KBD) areas has been overlooked for decades. Therefore, it is worth investigating in the current generation to gather evidence and make suggestions for improvement. A cross-sectional study with three 24-h dietary recalls was conducted to collect raw data on the daily food intake of children. Recorded food was converted into daily nutrient intakes using CDGSS 3.0 software. WHO AnthroPlus software was used to analyse the BMI-for-age z-score (BAZ) for estimating the overall nutrition status of children. All the comparisons and regression analyses were conducted with SPSS 18.0 software. Multiple nutrient intakes among children from the Se-supplemented KBD-endemic were under the estimated average requirement. The protein-to-carbohydrate ratio (P/C ratio) was significantly higher in children from the non-Se-supplemented KBD-endemic area than the other areas (P < 0.001). The children's BAZ was negatively associated with age (B = -0.095, P < 0.001) and the number of KBD relatives (B = -0.277, P = 0.04), and it was positively associated with better housing conditions, receiving colostrum, and daily intakes of niacin and zinc by multivariate regression analysis (F = 10.337, R = 0.609, P < 0.001).Compared to non-Se-supplemented KBD-endemic area and non-endemic areas, children in Se-supplemented KBD-endemic areas have an insufficient intake of multiple nutrients. School breakfast and lunch programmes are recommended, and strict implementation is the key to ensuring a positive effect.
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| 3. |
- Wang, Xi, et al.
(author)
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Gene expression signature in endemic osteoarthritis by microarray analysis
- 2015
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In: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI. - 1661-6596 .- 1422-0067. ; 16:5, s. 11465-11481
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Journal article (peer-reviewed)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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| 4. |
- Guo, Xiong, et al.
(author)
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Kashin-Beck Disease (KBD)
- 2017
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In: Endemic disease in China. - Beijing : People's Medical Publishing House. - 9787117247139 ; , s. 150-211
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Book chapter (peer-reviewed)
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| 5. |
- Ning, Yujie, et al.
(author)
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Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy
- 2022
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In: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 12
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Journal article (peer-reviewed)abstract
- The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
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| 6. |
- Ning, Yujie, et al.
(author)
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Imbalance of dietary nutrients and the associated differentially expressed genes and pathways may play important roles in juvenile Kashin-Beck disease
- 2018
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In: Journal of Trace Elements in Medicine and Biology. - : Elsevier. - 0946-672X .- 1878-3252. ; 50, s. 441-460
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Journal article (peer-reviewed)abstract
- BACKGROUND:Kashin-Beck disease (KBD) is a childhood-onset endemic osteoarthropathy in China. Nutrients including trace elements may play active roles in the development of KBD.OBJECTIVE:This study aimed to estimate the nutrient intakes of children in endemic areas and to identify the imbalanced nutrients associated differentially expressed genes in the juvenile patients with KBD.METHODS:In this cross-sectional study, a consecutive 3 day 24 h semi-quantitative dietary retrospect questionnaire was conducted to estimate the daily nutrient intakes of children using CDGSS 3.0 software. Gene profile analysis was employed to identify differentially expressed genes in peripheral blood mononuclear cells of children with KBD. GOC, CTD, KEGG, and REACTOME databases were used to establish the relationship between nutrients and nutrients-associated differentially expressed genes and pathways. Statistical analyses were accomplished by SPSS 18.0 software.RESULTS:Daily Se intakes without supplementation of children were significantly lower in Se-supplemented (Se + ) KBD areas (29.3 ∼ 29.6 mg/d) and non-endemic area (27.8 ± 7.9 mg/d) compared to non-Se-supplemented (Se-) KBD area (32.9 ± 7.9 mg/d, c2 = 20.24, P < .01). Children in Se+ KBD areas were suffering more serious insufficient intake of multiple nutrients, including vitamins-B2/-C/-E, Ca, Fe, Zn and I. Gene profile analysis combined with bioinformatics technique identified 34 nutrients associated differentially expressed genes and 10 significant pathways which are related to the pathological changes in juvenile KBD.CONCLUSIONS:Imbalance of dietary nutrients and nutrients-associated differentially expressed genes and pathways may play important roles in the development of juvenile KBD.
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