Wheat high-molecular-weight glutenin subunits(HMW-GS) determine dough elasticity and play an essential role in processing quality. HMW-GS are encoded by Glu-1 genes and controlled primarily at transcriptional level, i...Wheat high-molecular-weight glutenin subunits(HMW-GS) determine dough elasticity and play an essential role in processing quality. HMW-GS are encoded by Glu-1 genes and controlled primarily at transcriptional level, implemented through the interactions between cis-acting elements and trans-acting factors. However, transcriptional mechanism of Glu-1 genes remains elusive. Here we made a comprehensive analysis of cis-regulatory elements within 1-kb upstream of the Glu-1 start codon(-1000 to-1) and identified 30 conserved motifs. Based on motif distribution pattern, three conserved cis-regulatory modules(CCRMs), CCRM1(-300 to-101), CCRM2(-650 to-400), and CCRM3(-950 to-750), were defined, and their functions were characterized in wheat stable transgenic lines transformed with progressive 5′ deletion promoter::GUS fusion constructs. GUS staining, qP CR and enzyme activity assays indicated that CCRM2 and CCRM3 could enhance the expression level of Glu-1, whereas the 300-bp promoter(-300 to-1), spanning CCRM1 and core region(-100 to-1), was enough to ensure accurate Glu-1 initiation at 7 days after flowering(DAF) and shape its spatiotemporal expression pattern during seed development. Further transgenic assays demonstrated that CCRM1-2(-300 to-209) containing Complete HMW Enhancer(-246 to-209) was important for expression level but had no effect on expression specificity in the endosperm. In contrast, CCRM1-1(-208 to-101) was critical for both expression specificity and level of Glu-1. Our findings not only provide new insights to uncover Glu-1 transcription regulatory machinery but also lay foundations for modifying Glu-1 expression.展开更多
Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from t...Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.展开更多
Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153...Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153,and GSE66360 were downloaded from the Gene Expression Omnibus(GEO)database.We identified differentially expressed miRNAs(DE-miRNAs)and mRNAs(DE-mRNAs)in AMI samples compared with normal control samples.The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs.The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed,and a miRNA-mRNA network and a protein-protein interaction network were constructed,along with functional enrichment and pathway analyses.A total of 209 DE-miRNAs in the GSE31568 dataset,857 DE-miRNAs in the GSE148153 dataset,and 351 DE-mRNAs in the GSE66360 dataset were identified.Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets.Furthermore,miR-646,miR-127-5p,miR-509-5p,miR-509-3-5p,and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network.THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction(PPI)network,respectively.CDKN1A was important in both miRNA-mRNA network and PPI network.We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes,which might be used as biomarkers and potential therapeutic targets for patients with AMI.展开更多
Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant wo...Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.展开更多
Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study...Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study, we investigated the kinetics of Treg induction as well as their long-term homing in spleen and lungs correlating with reduced airway hyperresponsiveness (AHR) in a murine model of acute allergic asthma. We then evaluated the therapeutic implication of EFD BCG in a chronic asthma model. Methods: Tregs expressing Foxp3 were analyzed in various organs shortly and long-term after EFD BCG, live- and Heat Killed-(HK-) BCG treatments in an acute model of asthma. We further studied EFD BCG treatment on airway inflammation using a chronic model of asthma in mice. Results: Foxp3 expression peaked in the inguinal draining lymph-nodes (iDLNs) 2-4 days after EFD BCG treatment whereas it was long-term observed in spleen (days 7 to 90). This increase in Foxp3 expression was also found in lungs upon intranasal ovalbumin (OVA) challenge in OVA-sensitized mice. The loss of protection 4 months after EFD BCG treatment was correlated with the end of this phenomenon. Moreover, major lung inflammation hallmarks of severe asthma after multiple allergen challenges promoting chronic airway inflammation in OVA sensitized mice were reduced by EFD BCG treatment: AHR, eosinophils and neutrophils in bronchoalveolar lavage (BAL), mucus metaplasia, Th2 as well as Th17 cytokine levels in BAL and sera. EFD BCG treatment also enhances PPAR-γ expression and regulates NF-κBp65 translocation in lung extracts in this model of chronic asthma. Conclusions: EFD BCG treatment induced long-term protective effect associated to Foxp3 Tregs in the spleen and lungs in an acute model of asthma and inhibits AHR in a chronic model of asthma. EFD BCG could be a new and promising immuno-modulatory alternative treatment to corticoids in severe human asthma.展开更多
Improving plant resistance to Verticillium wilt(VW),which causes massive losses in Gossypium hirsutum,is a global challenge.Crop plants need to efficiently allocate their limited energy resources to maintain a balance...Improving plant resistance to Verticillium wilt(VW),which causes massive losses in Gossypium hirsutum,is a global challenge.Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense.However,few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton.In this study,we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V.dahliae infection relative to the other MYB types.One novel R2R3-MYB transcription factor(TF)that specifically responds to V.dahliae,GhMYB3D5,was identified.GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions,but it was dramatically induced by V.dahliae stress.We functionally characterized its positive role and underlying mechanism in VW resistance.Upon V.dahliae infection,the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1expression.In addition,GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1.Consequently,the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis(GhPAL,GhC4H,Gh4CL,and GhPOD/GhLAC)in cotton,thereby enhancing cotton VW resistance.Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation,which can be regarded as an effective way to orchestrate plant immunity and growth.展开更多
Carotenoid biosynthesis is closely associated with abscisic acid(ABA)during the ripening process of non-climacteric fruits,but the regulatory mechanism that links ABA signaling to carotenoid metabolism remains largely...Carotenoid biosynthesis is closely associated with abscisic acid(ABA)during the ripening process of non-climacteric fruits,but the regulatory mechanism that links ABA signaling to carotenoid metabolism remains largely unclear.Here,we identified two master regulators of ABA-mediated citrus fruit coloration,CsERF110 and CsERF53,which activate the expression of carotenoid metabolism genes(CsGGPPS,CsPSY,CsPDS,CsCRTISO,CsLCYB2,CsLCYE,CsHYD,CsZEP,and CsNCED2)to facilitate carotenoid accumulation.Further investigations showed that CsERF110 not only activates the expression of CsERF53 by binding to its promoter but also interacts with CsERF53 to form the transcriptional regulatory module CsERF110-CsERF53.We also discovered a positive feedback regulatory loop between the ABA signal and carotenoid metabolism regulated by the transcriptional regulatory module CsERF110-CsERF53.Our results reveal that the CsERF110-CsERF53 module responds to ABA signaling,thereby orchestrating citrus fruit coloration.Considering the importance of carotenoid content for citrus and many other carotenoid-rich crops,the revelation of molecular mechanisms that underlie ABA-mediated carotenoid biosynthesis in plants will facilitate the development of transgenic/gene-editing approaches,further contributing to improving the quality of citrus and other carotenoid-rich crops.展开更多
目的甘丙肽受体1(galanin receptor 1,GALR1)信号通路在痛觉调节中发挥重要作用,该研究利用坐骨神经慢性压迫(chronic constriction injury of the sciatic nerve,CCI)大鼠模型,探索慢病毒介导的DREAM沉默治疗在CCI模型大鼠疼痛中的作...目的甘丙肽受体1(galanin receptor 1,GALR1)信号通路在痛觉调节中发挥重要作用,该研究利用坐骨神经慢性压迫(chronic constriction injury of the sciatic nerve,CCI)大鼠模型,探索慢病毒介导的DREAM沉默治疗在CCI模型大鼠疼痛中的作用及其对GALR1的表达调控。方法选择健康雄性SD大鼠24只,随机分为4组(n=6):即RNA干扰组、空白载体组、单纯CCI组和正常对照组。鞘内置管前后分别测定基础痛阈,RNA干扰组和空白载体组于CCI后经微导管给予pKCSHR-Puro/GFP-DREAM慢病毒和空白载体,并测定腰段脊髓内下游调控元件拮抗分子(downstream regulatory element antagonist,DREAM)和GALR1的蛋白表达。结果大鼠痛阈的变化:手术同侧热痛阈和机械痛阈测定结果表明,CCI处理后,RNA干扰组、空白载体组及单纯CCI组在各个时间点热痛阈和机械痛阈较正常对照组均显著降低(P<0.01);RNA干扰组鞘内注射后较注射前痛阈显著升高,治疗后相同时间点RNA干扰组较空白载体组及单纯CCI组痛阈亦显著升高。Western blotting结果表明,与其他实验组对比,RNA干扰组的DREAM蛋白表达水平显著下调,而GALR1蛋白表达水平较空白载体组、单纯CCI组亦有显著下调。结论 DREAM可以调控GALR1的表达,提示甘丙肽受体1信号通路参与DREAM基因调节大鼠神经病理性疼痛。展开更多
目的:研究吉西他滨对人胰腺癌AsPC-1细胞体外生长的作用机制。方法:用脂质体转染法将含有p53正向凋亡调控因子(p53 upregulated modulator of apoptosis,PUMA)反义核酸的真核表达载体pcDNA3.1-PUMAAS和空载体pcDNA3.1导入AsPC-1细胞,G41...目的:研究吉西他滨对人胰腺癌AsPC-1细胞体外生长的作用机制。方法:用脂质体转染法将含有p53正向凋亡调控因子(p53 upregulated modulator of apoptosis,PUMA)反义核酸的真核表达载体pcDNA3.1-PUMAAS和空载体pcDNA3.1导入AsPC-1细胞,G418筛选阳性细胞,获得稳定转染的阳性克隆。将转染载体的AsPC-1阳性克隆细胞和未转染载体的AsPC-1细胞分别暴露于浓度为1、5、10和15μmol/L的吉西他滨溶液中作用72h。RT-PCR和Western印迹法检测不同组细胞经吉西他滨作用72h后的PUMA表达水平,MTT检测细胞生长抑制情况,FCM、Hoechst 33258荧光染色和TUNEL法检测细胞凋亡情况。结果:吉西他滨促进AsPC-1细胞凋亡,抑制细胞生长,并有明显的剂量依赖性,在细胞凋亡的同时伴有PUMA表达的上调;当细胞转染PUMA反义核酸抑制PUMA表达后,受吉西他滨作用的细胞中PUMA蛋白表达明显降低,同时伴有细胞凋亡的抑制及细胞增殖明显增加。结论:吉西他滨促进体外AsPC-1细胞凋亡,并抑制细胞生长,其诱导细胞凋亡与上调PUMA表达有关。展开更多
基金funded by the National Key Research and Development Program of China (2016YFD0100500)the National Natural Science Foundation of China (31571663, 31371623)Genetically Modified Organisms Breeding Major Project (2016ZX08009003-004)
文摘Wheat high-molecular-weight glutenin subunits(HMW-GS) determine dough elasticity and play an essential role in processing quality. HMW-GS are encoded by Glu-1 genes and controlled primarily at transcriptional level, implemented through the interactions between cis-acting elements and trans-acting factors. However, transcriptional mechanism of Glu-1 genes remains elusive. Here we made a comprehensive analysis of cis-regulatory elements within 1-kb upstream of the Glu-1 start codon(-1000 to-1) and identified 30 conserved motifs. Based on motif distribution pattern, three conserved cis-regulatory modules(CCRMs), CCRM1(-300 to-101), CCRM2(-650 to-400), and CCRM3(-950 to-750), were defined, and their functions were characterized in wheat stable transgenic lines transformed with progressive 5′ deletion promoter::GUS fusion constructs. GUS staining, qP CR and enzyme activity assays indicated that CCRM2 and CCRM3 could enhance the expression level of Glu-1, whereas the 300-bp promoter(-300 to-1), spanning CCRM1 and core region(-100 to-1), was enough to ensure accurate Glu-1 initiation at 7 days after flowering(DAF) and shape its spatiotemporal expression pattern during seed development. Further transgenic assays demonstrated that CCRM1-2(-300 to-209) containing Complete HMW Enhancer(-246 to-209) was important for expression level but had no effect on expression specificity in the endosperm. In contrast, CCRM1-1(-208 to-101) was critical for both expression specificity and level of Glu-1. Our findings not only provide new insights to uncover Glu-1 transcription regulatory machinery but also lay foundations for modifying Glu-1 expression.
文摘Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.
基金supported by the funds from the National Natural Science Foundation of China(Grant No.81871359 and No.81800445).
文摘Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153,and GSE66360 were downloaded from the Gene Expression Omnibus(GEO)database.We identified differentially expressed miRNAs(DE-miRNAs)and mRNAs(DE-mRNAs)in AMI samples compared with normal control samples.The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs.The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed,and a miRNA-mRNA network and a protein-protein interaction network were constructed,along with functional enrichment and pathway analyses.A total of 209 DE-miRNAs in the GSE31568 dataset,857 DE-miRNAs in the GSE148153 dataset,and 351 DE-mRNAs in the GSE66360 dataset were identified.Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets.Furthermore,miR-646,miR-127-5p,miR-509-5p,miR-509-3-5p,and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network.THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction(PPI)network,respectively.CDKN1A was important in both miRNA-mRNA network and PPI network.We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes,which might be used as biomarkers and potential therapeutic targets for patients with AMI.
基金supported by Science and Technology Project of Jiangxi Province(2009BSB10909)
文摘Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.
文摘Background: We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study, we investigated the kinetics of Treg induction as well as their long-term homing in spleen and lungs correlating with reduced airway hyperresponsiveness (AHR) in a murine model of acute allergic asthma. We then evaluated the therapeutic implication of EFD BCG in a chronic asthma model. Methods: Tregs expressing Foxp3 were analyzed in various organs shortly and long-term after EFD BCG, live- and Heat Killed-(HK-) BCG treatments in an acute model of asthma. We further studied EFD BCG treatment on airway inflammation using a chronic model of asthma in mice. Results: Foxp3 expression peaked in the inguinal draining lymph-nodes (iDLNs) 2-4 days after EFD BCG treatment whereas it was long-term observed in spleen (days 7 to 90). This increase in Foxp3 expression was also found in lungs upon intranasal ovalbumin (OVA) challenge in OVA-sensitized mice. The loss of protection 4 months after EFD BCG treatment was correlated with the end of this phenomenon. Moreover, major lung inflammation hallmarks of severe asthma after multiple allergen challenges promoting chronic airway inflammation in OVA sensitized mice were reduced by EFD BCG treatment: AHR, eosinophils and neutrophils in bronchoalveolar lavage (BAL), mucus metaplasia, Th2 as well as Th17 cytokine levels in BAL and sera. EFD BCG treatment also enhances PPAR-γ expression and regulates NF-κBp65 translocation in lung extracts in this model of chronic asthma. Conclusions: EFD BCG treatment induced long-term protective effect associated to Foxp3 Tregs in the spleen and lungs in an acute model of asthma and inhibits AHR in a chronic model of asthma. EFD BCG could be a new and promising immuno-modulatory alternative treatment to corticoids in severe human asthma.
基金supported by the National Key Research and Development Program of China(2022YFF1001403)the Natural Science Foundation of Hebei Province,China(C2022204205)+1 种基金the National Natural Science Foundation of China(32372194)the National Top Talent Project and Hebei Top Talent,China。
文摘Improving plant resistance to Verticillium wilt(VW),which causes massive losses in Gossypium hirsutum,is a global challenge.Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense.However,few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton.In this study,we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V.dahliae infection relative to the other MYB types.One novel R2R3-MYB transcription factor(TF)that specifically responds to V.dahliae,GhMYB3D5,was identified.GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions,but it was dramatically induced by V.dahliae stress.We functionally characterized its positive role and underlying mechanism in VW resistance.Upon V.dahliae infection,the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1expression.In addition,GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1.Consequently,the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis(GhPAL,GhC4H,Gh4CL,and GhPOD/GhLAC)in cotton,thereby enhancing cotton VW resistance.Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation,which can be regarded as an effective way to orchestrate plant immunity and growth.
基金National Key R&D Program of China(2023YFD2300600)National Natural Science Foundation of China(no.31930095)National Modern Agricultural(Citrus)Technology Systems of China(no.CARS-27).
文摘Carotenoid biosynthesis is closely associated with abscisic acid(ABA)during the ripening process of non-climacteric fruits,but the regulatory mechanism that links ABA signaling to carotenoid metabolism remains largely unclear.Here,we identified two master regulators of ABA-mediated citrus fruit coloration,CsERF110 and CsERF53,which activate the expression of carotenoid metabolism genes(CsGGPPS,CsPSY,CsPDS,CsCRTISO,CsLCYB2,CsLCYE,CsHYD,CsZEP,and CsNCED2)to facilitate carotenoid accumulation.Further investigations showed that CsERF110 not only activates the expression of CsERF53 by binding to its promoter but also interacts with CsERF53 to form the transcriptional regulatory module CsERF110-CsERF53.We also discovered a positive feedback regulatory loop between the ABA signal and carotenoid metabolism regulated by the transcriptional regulatory module CsERF110-CsERF53.Our results reveal that the CsERF110-CsERF53 module responds to ABA signaling,thereby orchestrating citrus fruit coloration.Considering the importance of carotenoid content for citrus and many other carotenoid-rich crops,the revelation of molecular mechanisms that underlie ABA-mediated carotenoid biosynthesis in plants will facilitate the development of transgenic/gene-editing approaches,further contributing to improving the quality of citrus and other carotenoid-rich crops.
文摘目的甘丙肽受体1(galanin receptor 1,GALR1)信号通路在痛觉调节中发挥重要作用,该研究利用坐骨神经慢性压迫(chronic constriction injury of the sciatic nerve,CCI)大鼠模型,探索慢病毒介导的DREAM沉默治疗在CCI模型大鼠疼痛中的作用及其对GALR1的表达调控。方法选择健康雄性SD大鼠24只,随机分为4组(n=6):即RNA干扰组、空白载体组、单纯CCI组和正常对照组。鞘内置管前后分别测定基础痛阈,RNA干扰组和空白载体组于CCI后经微导管给予pKCSHR-Puro/GFP-DREAM慢病毒和空白载体,并测定腰段脊髓内下游调控元件拮抗分子(downstream regulatory element antagonist,DREAM)和GALR1的蛋白表达。结果大鼠痛阈的变化:手术同侧热痛阈和机械痛阈测定结果表明,CCI处理后,RNA干扰组、空白载体组及单纯CCI组在各个时间点热痛阈和机械痛阈较正常对照组均显著降低(P<0.01);RNA干扰组鞘内注射后较注射前痛阈显著升高,治疗后相同时间点RNA干扰组较空白载体组及单纯CCI组痛阈亦显著升高。Western blotting结果表明,与其他实验组对比,RNA干扰组的DREAM蛋白表达水平显著下调,而GALR1蛋白表达水平较空白载体组、单纯CCI组亦有显著下调。结论 DREAM可以调控GALR1的表达,提示甘丙肽受体1信号通路参与DREAM基因调节大鼠神经病理性疼痛。
