Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promot...Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.展开更多
Chronic obstructive pulmonary disease(COPD), lung cancer(LC) and tuberculosis(TB) are common chronic lung diseases that generate a large disease burden and significant health care resource use in China. The aim of thi...Chronic obstructive pulmonary disease(COPD), lung cancer(LC) and tuberculosis(TB) are common chronic lung diseases that generate a large disease burden and significant health care resource use in China. The aim of this study was to quantify spatial patterns and effects of air pollution and meteorological factors on hospitalization of COPD, LC and TB in Beijing. Daily counts of hospitalization for 2010 were obtained from the Beijing Urban Employees Basic Medical Insurance(UEBMI) system.Bayesian hierarchical Poisson regression models were applied to identify spatial patterns of hospitalization for COPD, LC and TB at the district level and explore associations with inhalable particulate matter(aerodynamic diameter <10 μm, PM10), sulfur dioxide(SO2), nitrogen dioxide(NO2), mean temperature and relative humidity. There were 18,882, 14,295 and 2,940 counts of hospitalizations for COPD, LC and TB respectively, in Beijing in 2010. Clusters of high relative risk were in different locations for the three diseases. The effect of relative humidity on COPD hospitalization was most significant with a relative risk(RR) of 1.070(95%CI: 1.054, 1.086) per one percent increase. For lung cancer hospitalization, exposure to ambient SO2 was associated with a RR of 1.034(95%CI: 1.011, 1.058) per μg m–3 increase. For tuberculosis, the effect of mean temperature was significant with a RR of 1.107(95%CI: 1.038, 1.180) per °C increase. Risk factors and spatial patterns were different for hospitalization of non-infectious and infectious chronic lung disease in Beijing. Even over a short time period(one year), associations were apparent with air pollution and meteorological factors.展开更多
基金supported by the National Natural Science Foundation of China(81960851)Jiangxi Natural Science Foundation(20202BABL206132)Key Research Office of Traditional Chinese Medicine Syndrome Foundation of Jiangxi Administration of Traditional Chinese Medicine(8-4),and Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22016).
文摘Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.
文摘Chronic obstructive pulmonary disease(COPD), lung cancer(LC) and tuberculosis(TB) are common chronic lung diseases that generate a large disease burden and significant health care resource use in China. The aim of this study was to quantify spatial patterns and effects of air pollution and meteorological factors on hospitalization of COPD, LC and TB in Beijing. Daily counts of hospitalization for 2010 were obtained from the Beijing Urban Employees Basic Medical Insurance(UEBMI) system.Bayesian hierarchical Poisson regression models were applied to identify spatial patterns of hospitalization for COPD, LC and TB at the district level and explore associations with inhalable particulate matter(aerodynamic diameter <10 μm, PM10), sulfur dioxide(SO2), nitrogen dioxide(NO2), mean temperature and relative humidity. There were 18,882, 14,295 and 2,940 counts of hospitalizations for COPD, LC and TB respectively, in Beijing in 2010. Clusters of high relative risk were in different locations for the three diseases. The effect of relative humidity on COPD hospitalization was most significant with a relative risk(RR) of 1.070(95%CI: 1.054, 1.086) per one percent increase. For lung cancer hospitalization, exposure to ambient SO2 was associated with a RR of 1.034(95%CI: 1.011, 1.058) per μg m–3 increase. For tuberculosis, the effect of mean temperature was significant with a RR of 1.107(95%CI: 1.038, 1.180) per °C increase. Risk factors and spatial patterns were different for hospitalization of non-infectious and infectious chronic lung disease in Beijing. Even over a short time period(one year), associations were apparent with air pollution and meteorological factors.
