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NRF2 nuclear translocation and interaction with DUSP1 regulate the osteogenic differentiation of murine mandibular osteoblasts stimulated with Porphyromonas gingivalis lipopolysaccharide 认领 引用
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作者 Xufei YU Jiaqi BAO +4 位作者 Yingming WEI Yuting YANG Wenlin YUAN Lili CHEN Zhongxiu WANG 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2025年第9期881-896,共16页
Background:Periodontitis is characterized by alveolar bone resorption,aggravated by osteoblast dysfunction,and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2(N... Background:Periodontitis is characterized by alveolar bone resorption,aggravated by osteoblast dysfunction,and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2(NRF2)level.We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation.Methods:Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide(Pg-LPS)or other stimuli.Reactive oxygen species(ROS)and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide(JC-1)staining were used to detect intracellular oxidative stress.Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts.Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase(MAPK)pathway and related molecule activities.Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1(DUSP1)in cells.Results:Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples.Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation,whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate.NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression,thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts.The interaction between NRF2 and DUSP1 was observed.Conclusions:NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway.These findings form the basis of periodontitis treatment. 展开更多
关键词 Periodontitis Nuclear factor erythroid 2-related factor 2(NRF2) Dual-specific phosphatase 1(DUSP1) Mitogen-activated protein kinase(MAPK) Oxidative stress Osteogenesis
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Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing impairment in a Chinese family 认领 引用 被引量：6
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作者 Ping Liu Hu Li +8 位作者 Xiang Ren Haiyan Mao Qihui Zhu Zhengfeng Zhu Rong Yang Wenlin Yuan Jingyu Liu Qing Wang Mugen Liu 《Journal of Genetics and Genomics》 SCIE CAS 北大核心 2008年第9期553-558,共6页
γ -actin （ACTG1） gene is a cytoplasmic nonmuscle actin gene, which encodes a major cytoskeletal protein in the sensory hair cells of the cochlea. Mutations in ACTG1 were found to cause autosomal dominant, progressi... γ -actin （ACTG1） gene is a cytoplasmic nonmuscle actin gene, which encodes a major cytoskeletal protein in the sensory hair cells of the cochlea. Mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing loss linked to the DFNA 20/26 locus on chromosome 17q25.3 in European and American families, respectively. In this study, a novel missense mutation （c.364A〉G; p.I122V） co-segregated with the affected individuals in the family and did not exist in the unaffected family members and 150 unrelated normal controls. The alteration of residue Ile122 was predicted to damage its interaction with actin-binding proteins, which may cause disruption of hair cell organization and function. These findings strongly suggested that the I122V mutation in ACTG1 caused autosomal dominant non-syndromic hearing impairment in a Chinese family and expanded the spectrum of ACTG1 mutations causing hearing loss. 展开更多
关键词 non-syndromic heating impairment （NSHI） ACTG1 linkage sequence analysis restriction fragment length polymorphism （RFLP） analysis
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Serum protein profile of yang-deficiency constitution in traditional Chinese medicine revealed by protein microarray analyses 认领 引用 被引量：4
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作者 Shuxian Sun Xiuping Zhang +7 位作者 Jiayi Ma Cheng Ni Xiao Ying Ji Wang Lingru Li Wenlin Yuan Xujun Heng Jing Xia 《Journal of Traditional Chinese Medical Sciences》 CAS 2019年第1期67-74,共8页
Background:Based on the theory of traditional Chinese medicine (TCM) and preepidemiological investigation,Professor Qi Wang classified the entire human population into nine constitutions and put forward the theory of ... Background:Based on the theory of traditional Chinese medicine (TCM) and preepidemiological investigation,Professor Qi Wang classified the entire human population into nine constitutions and put forward the theory of 'Nine-Constitution Medicine.' Among these constitutions,the main feature of the yang-deficiency constitution (YADC) is intolerance of the cold,which has been proven to reduce quality of life and confer susceptibility to specific diseases.Previous studies explored the genetic and transcriptional bases of YADC.In this experiment,we explored the potential mechanism of YADC using protein microarray,to deepen our understanding of its biological mechanism.Methods:Subjects identified with a YADC (n =12) or a balance constitution (BC;n =12) in accordance with the Classification and Determination Standards of Constitutions in Traditional Chinese Medicine were selected.Blood was collected to separate serum and protein microarray technology was used to analyze serum protein expression.Results:The clustering of subjects' constitutions based on protein expression profiling largely coincided with the TCM classification.Based on false discovery rate correction (P <.01) and fold change ≥ 5 or ≤ 0.2,a total of 85 proteins differentially expressed in YADC compared with their status in BC were selected,including 64 upregulated and 21 downregulated ones.Enrichment analysis suggested that subjects with YADC are susceptible to endocrine and energy metabolism disorders,as well as decline in immune function.Conclusion:This study revealed that YADC exhibits systematic differences in its protein expression profile.Moreover,we can potentially explain the characteristics of YADC partly via differentially expressed proteins. 展开更多
关键词 Yang-deficiency constitution Protein microarray PI3K-Akt Endocrine Energy metabolism
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A Dynamic Early Warning Model for Flash Floods Based on Rainfall Pattern Identification 认领 引用 被引量：4
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作者 Wenlin Yuan Bohui Jing +2 位作者 Hongshi Xu Yanjie Tang Shuaihu Zhang 《International Journal of Disaster Risk Science》 SCIE CSCD 2024年第5期769-788,共20页
Flash floods are one of the most devastating natural hazards in mountainous and hilly areas.In this study,a dynamic warning model was proposed to improve the warning accuracy by addressing the problem of ignoring the ... Flash floods are one of the most devastating natural hazards in mountainous and hilly areas.In this study,a dynamic warning model was proposed to improve the warning accuracy by addressing the problem of ignoring the randomness and uncertainty of rainfall patterns in flash flood warning.A dynamic identification method for rainfall patterns was proposed based on the similarity theory and characteristic rainfall patterns database.The characteristic rainfall patterns were constructed by k-means clustering of historical rainfall data.Subsequently,the dynamic flood early warning model was proposed based on the real-time correction of rainfall patterns and flooding simulation by the HEC-HMS(Hydrologic Engineering Center's Hydrologic Modeling System)model.To verify the proposed model,three small watersheds in China were selected as case studies.The results show that the rainfall patterns identified by the proposed approach exhibit a high correlation with the observed rainfall.With the increase of measured rainfall information,the dynamic correction of the identified rainfall patterns results in corresponding flood forecasts with Nash-Sutcliffe efficiency(NSE)exceeding 0.8 at t=4,t=5,and t=6,thereby improving the accuracy of flash flood warnings.Simultaneously,the proposed model extends the forecast lead time with high accuracy.For rainfall with a duration of six hours in the Xinxian watershed and eight hours in the Tengzhou watershed,the proposed model issues early warnings two hours and three hours before the end of the rainfall,respectively,with a warning accuracy of more than 0.90.The proposed model can provide technical support for flash flood management in mountainous and hilly watersheds. 展开更多
关键词 China Dynamic early warning model Flash floods HEC-HMS model Rainfall pattern identification
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