Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manife...Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.展开更多
1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[...1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[J].Br J Cancer,2021,124(4):744−753.doi:10.1038/s41416-020-01180-1.2研究背景N端赖氨酸残基的组蛋白乙酰化是一种常见的翻译后修饰,在转录调控中起重要作用。被称为溴结构域(bromodomains,BRD)的蛋白质相互作用结构域能够识别并结合赖氨酸乙酰化基序,从而允许含BRD的蛋白质影响转录。BRD和超末端结构域(BRD and extra-terminal,BET)蛋白通过BRD模块中的疏水口袋与乙酰化染色质结合,随后募集并稳定调节转录效应因子。展开更多
1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-0107...1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-01077-z.2证据水平2a。3研究背景溴结构域和超末端结构域(bromodomain and extra-terminal,BET)家族(BRD2、BRD3、BRD4和BRDT)包含两个串联的异染色质蛋白域,这些域可结合乙酰化赖氨酸残基,促进转录蛋白招募到染色质上。BRD4定位于染色质的启动子和增强子区域,并通过与中介复合体和pTEFb的相互作用来调节RNA聚合酶Ⅱ介导的延伸和转录。展开更多
Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,establis...Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.展开更多
Introduction:This study aimed to assess the clinical efficacy of Pidan Jianqing decoction in the treatment of type 2 diabetes.Methods:A total of 72 patients with type 2 diabetes differentiated as spleen deficiency wit...Introduction:This study aimed to assess the clinical efficacy of Pidan Jianqing decoction in the treatment of type 2 diabetes.Methods:A total of 72 patients with type 2 diabetes differentiated as spleen deficiency with damp-heat syndrome were randomly assigned to a treatment group(n=35)or control group(n=32).Patients in the control group received diet and exercise guidance and medication in the form of 0.5 g metformin hydrochloride tablets,while patients in the treatment group received Pidan Jianqing decoction in addition to the treatment given to the control group.Efficacy was evaluated after 8 weeks of treatment.Results:Efficacy was 91.4%in the treatment group versus 68.8%in the control group,which was a statistically significant difference(P<0.05).Significant group differences were also noted in the number of patients with improvement in symptoms such as dry mouth and polydipsia,frequency of urination and polyuria,abdominal distention and loss of appetite,fatigue and weakness,and sticky stools(all P<0.05),with greater improvement in the treatment group compared to the control group.The fasting blood glucose(FBG)and 2 h postprandial blood glucose levels significantly improved in both groups after treatment(P<0.05);however,there was no significant difference in glycated hemoglobin levels before and after treatment in both groups.Conclusion:Pidan Jianqing decoction can lower blood glucose levels and improve symptoms in patients with type 2 diabetes.展开更多
Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simult...Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.展开更多
[Objectives] To explore the clinical effect of Modified Gegen Qinlian Decoction combined with western medicine on children with rotavirus enteritis with damp-heat syndrome and its influence on myocardial enzymes.
Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great pote...Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.展开更多
1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30...1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30):3007−3014.doi:10.1200/JCO.2018.78.2292.2证据水平1b。3研究背景伴睾丸核蛋白(nuclear protein in testis,NUT)基因重排的中线癌又称NUT癌,是一种罕见的具有高度侵袭性的鳞状癌。它的发病与位于15号染色体长臂的NUT中线癌家族成员1基因(NUT midline carcinoma family member 1,NUTM1)重排有关。展开更多
基金supported by a grant from Hubei Key Laboratory of Diabetes and Angiopathy Program of Hubei University of Science and Technology(2020XZ10)Project of Education Commission of Hubei Province(B2022192).
文摘Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.
文摘1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[J].Br J Cancer,2021,124(4):744−753.doi:10.1038/s41416-020-01180-1.2研究背景N端赖氨酸残基的组蛋白乙酰化是一种常见的翻译后修饰,在转录调控中起重要作用。被称为溴结构域(bromodomains,BRD)的蛋白质相互作用结构域能够识别并结合赖氨酸乙酰化基序,从而允许含BRD的蛋白质影响转录。BRD和超末端结构域(BRD and extra-terminal,BET)蛋白通过BRD模块中的疏水口袋与乙酰化染色质结合,随后募集并稳定调节转录效应因子。
文摘1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-01077-z.2证据水平2a。3研究背景溴结构域和超末端结构域(bromodomain and extra-terminal,BET)家族(BRD2、BRD3、BRD4和BRDT)包含两个串联的异染色质蛋白域,这些域可结合乙酰化赖氨酸残基,促进转录蛋白招募到染色质上。BRD4定位于染色质的启动子和增强子区域,并通过与中介复合体和pTEFb的相互作用来调节RNA聚合酶Ⅱ介导的延伸和转录。
基金This project was supported by the Fundamental Research Funds for the Central Universities(2017-JYB-JS-075)National Key Project for Drug Discovery(2017ZX09304019).
文摘Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.
基金This work was supported by Science and Technology Projects of Yunnan Province(No.202101AT070246).
文摘Introduction:This study aimed to assess the clinical efficacy of Pidan Jianqing decoction in the treatment of type 2 diabetes.Methods:A total of 72 patients with type 2 diabetes differentiated as spleen deficiency with damp-heat syndrome were randomly assigned to a treatment group(n=35)or control group(n=32).Patients in the control group received diet and exercise guidance and medication in the form of 0.5 g metformin hydrochloride tablets,while patients in the treatment group received Pidan Jianqing decoction in addition to the treatment given to the control group.Efficacy was evaluated after 8 weeks of treatment.Results:Efficacy was 91.4%in the treatment group versus 68.8%in the control group,which was a statistically significant difference(P<0.05).Significant group differences were also noted in the number of patients with improvement in symptoms such as dry mouth and polydipsia,frequency of urination and polyuria,abdominal distention and loss of appetite,fatigue and weakness,and sticky stools(all P<0.05),with greater improvement in the treatment group compared to the control group.The fasting blood glucose(FBG)and 2 h postprandial blood glucose levels significantly improved in both groups after treatment(P<0.05);however,there was no significant difference in glycated hemoglobin levels before and after treatment in both groups.Conclusion:Pidan Jianqing decoction can lower blood glucose levels and improve symptoms in patients with type 2 diabetes.
基金supported by the National Natural Science Foundation of China(82273223 to F.L.,32270798 to P.L.)the National Key Research and Development Program of China(2022YFA1103900 to F.L.).
文摘Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.
文摘[Objectives] To explore the clinical effect of Modified Gegen Qinlian Decoction combined with western medicine on children with rotavirus enteritis with damp-heat syndrome and its influence on myocardial enzymes.
基金This work was supported by grants from the National Natural Science Foundation of China(82103183,82102803,82272849)the Natural Science Foundation of Hunan Province(2022JJ40767,2021JJ40976)+1 种基金the Natural Science Fund for Outstanding Youths in Hunan Province(2023JJ20093)the National Key Research and Development Program(2022YFC2504700).
文摘Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.
文摘1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30):3007−3014.doi:10.1200/JCO.2018.78.2292.2证据水平1b。3研究背景伴睾丸核蛋白(nuclear protein in testis,NUT)基因重排的中线癌又称NUT癌,是一种罕见的具有高度侵袭性的鳞状癌。它的发病与位于15号染色体长臂的NUT中线癌家族成员1基因(NUT midline carcinoma family member 1,NUTM1)重排有关。
