BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is impor...BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.展开更多
The electronic, elastic, vibrational, and thermodynamic properties of Sr_（10）（PO_4）_6F_2（Sr-FAP） and Ca_（10）（PO_4）_6F_2（CaFAP） are systematically investigated by the first-principles calculations. The calc...The electronic, elastic, vibrational, and thermodynamic properties of Sr_（10）（PO_4）_6F_2（Sr-FAP） and Ca_（10）（PO_4）_6F_2（CaFAP） are systematically investigated by the first-principles calculations. The calculated electronic band structure indicates that the Sr-FAP and Ca-FAP are insulator materials with the indirect band gap of 5.273 eV and 5.592 eV, respectively. The elastic constants are obtained by the “stress–strain” method, and elastic modulus are further evaluated and discussed. The vibrational properties, including the phonon dispersion curves, the phonon density of states, the Born effective charge, and associated longitudinal optical and transverse optical（LO–TO） splitting of optical modes, as well as the phonon frequencies at zone-center are obtained within the linear-response approach. Substitution of Ca by Sr causes phonon frequencies to shift to lower values as expected due to the mass effect. Additionally, some phonon-related thermodynamic properties, such as Helmholtz free energy F, internal energy E, entropy S, and specific heat C_V of Sr-FAP and Ca-FAP are predicted with the harmonic approximation. The present calculated results of two apatites are consistent with the reported experimental and theoretical results.展开更多
目的采用活性导向分离法分离蓝萼香茶菜中具有TDO(色氨酸2,3双加氧酶)抑制作用的成分。方法蓝萼香茶菜经水提醇沉后得粗多糖XPS,XPS经活性跟踪测定、DEAE Sepharose Fast Flow阴离子交换树脂分离和Superdex-75系列凝胶纯化后得XPS5-1,并...目的采用活性导向分离法分离蓝萼香茶菜中具有TDO(色氨酸2,3双加氧酶)抑制作用的成分。方法蓝萼香茶菜经水提醇沉后得粗多糖XPS,XPS经活性跟踪测定、DEAE Sepharose Fast Flow阴离子交换树脂分离和Superdex-75系列凝胶纯化后得XPS5-1,并对XPS5-1进行HPGPC法分析、单糖组成测定、氨基酸组成分析和TDO抑制活性检测。结果采用活性跟踪方法,从蓝萼香茶菜中得到一种具有TDO抑制作用的均一糖蛋白成分XPS5-1,相对分子量为3170 Da,糖类部分主要由鼠李糖、葡萄糖和阿拉伯糖组成,三种单糖的摩尔比为:10.0:3.5:0.9,氨基酸主要谷氨酸、丝氨酸和甘氨酸组成,摩尔比为:30.2:21.6:48.2,XPS5-1表现出较强的TDO抑制活性,其IC50为14.02±0.8 mg/L。结论从蓝萼香茶菜中成功分离到具有TDO抑制作用的糖蛋白,为蓝萼香茶菜的化学物质基础研究提供了依据。展开更多
文摘BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.
基金supported by the National High Technology Research and Development Program of China(Grant No.2015AA034202)the National Natural Science Foundation of China(Grant No.11305147)
文摘The electronic, elastic, vibrational, and thermodynamic properties of Sr_（10）（PO_4）_6F_2（Sr-FAP） and Ca_（10）（PO_4）_6F_2（CaFAP） are systematically investigated by the first-principles calculations. The calculated electronic band structure indicates that the Sr-FAP and Ca-FAP are insulator materials with the indirect band gap of 5.273 eV and 5.592 eV, respectively. The elastic constants are obtained by the “stress–strain” method, and elastic modulus are further evaluated and discussed. The vibrational properties, including the phonon dispersion curves, the phonon density of states, the Born effective charge, and associated longitudinal optical and transverse optical（LO–TO） splitting of optical modes, as well as the phonon frequencies at zone-center are obtained within the linear-response approach. Substitution of Ca by Sr causes phonon frequencies to shift to lower values as expected due to the mass effect. Additionally, some phonon-related thermodynamic properties, such as Helmholtz free energy F, internal energy E, entropy S, and specific heat C_V of Sr-FAP and Ca-FAP are predicted with the harmonic approximation. The present calculated results of two apatites are consistent with the reported experimental and theoretical results.
