BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby ne...BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby necessitating the pursuit of more efficacious treatment strategies.Within traditional Chinese medicine,spleen deficiency is regarded as a central pathogenic mechanism in CRC,persisting throughout the entire disease course.AIM To elucidate the mechanism by which modified Yigong San confers therapeutic efficacy against CRC,potentially exerting its effects through apoptosis regulation mediated by the enhancer of zeste homolog 2(EZH2)/methyltransferase-like 3(METTL3)/SRY-box transcription factor 4(SOX4)axis.METHODS In the clinical study,CRC tissues and corresponding adjacent normal samples that fulfilled inclusion criteria were procured.Quantitative reverse transcription polymerase chain reaction was employed to determine the transcriptional expression of EZH2 and METTL3 mRNA.For in vitro experimentation,SW-480 cells were allocated into five experimental conditions:Control,control+serum,control+negative control,control+overexpressing-EZH2,and control+overexpressing-EZH2+serum.The mRNA expression levels of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax across groups were quantified via quantitative reverse transcription polymerase chain reaction,while protein levels were assessed using western blot analysis.The presence of EZH2 binding sites within the METTL3 promoter region was verified through chromatin immunoprecipitation polymerase chain reaction.The optimal concentration of drug-containing serum(5%,10%,15%)was determined using the Cell Counting Kit-8 assay.Cell migratory ability was evaluated via scratch assays,and apoptotic activity was quantified by flow cytometry.RESULTS The clinical findings demonstrated significantly elevated transcriptional levels of METTL3 and EZH2 mRNA in tumor tissues compared to their adjacent normal counterparts(P<0.05).In vitro,cells treated with modified Yigong San exhibited a substantial downregulation of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax mRNA and protein levels(P<0.05),relative to the control group.Apoptotic rates were markedly increased,while migratory capacity was significantly attenuated.Furthermore,in EZH2-overexpressing cells treated with modified Yigong San,similar reductions in both mRNA and protein levels of the aforementioned targets were observed(P<0.05),concomitant with enhanced apoptosis and reduced migration.Chromatin immunoprecipitation polymerase chain reaction analysis confirmed EZH2 occupancy at specific loci within the METTL3 promoter.CONCLUSION Modified Yigong San exhibits both preventive and therapeutic potential against CRC,likely mediated through the regulation of apoptosis via the EZH2/METTL3/SOX4 signaling pathway.展开更多
BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate ...BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.展开更多
目的观察胃苓汤合异功散加减治疗小儿过敏性紫癜性肾炎(HSPN)脾虚湿热证的临床疗效。方法选取2022年1月至2023年6月于淳安县中医院中医儿科就诊的82例HSPN脾虚湿热证患儿,按照随机数字表法分为对照组40例和治疗组42例。对照组予强的松...目的观察胃苓汤合异功散加减治疗小儿过敏性紫癜性肾炎(HSPN)脾虚湿热证的临床疗效。方法选取2022年1月至2023年6月于淳安县中医院中医儿科就诊的82例HSPN脾虚湿热证患儿,按照随机数字表法分为对照组40例和治疗组42例。对照组予强的松、贝那普利片口服,治疗组在对照组治疗方法的基础上口服胃苓汤合异功散加减。2组均以4周为1个疗程,连续治疗2个疗程后统计疗效。结果治疗组的总有效率为95.24%(40/42),显著高于对照组的80.00%(32/40),2组比较,差异有统计学意义(P<0.05)。治疗组的蛋白尿、血尿、紫癜消失时间均显著短于对照组,2组比较,差异均有统计学意义(P<0.05)。治疗前2组的24 h尿蛋白定量(24 h UPE)、尿转铁蛋白(Tf)、血肌酐(Scr)、血尿素氮(BUN)水平比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的上述指标水平均显著降低,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低更显著(P<0.05)。治疗前2组的免疫调节指标辅助性T细胞17(Th17)、调节性T细胞(Treg)、Th17/Treg比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的Th17、Th17/Treg均显著降低,Treg显著升高,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低或升高更显著(P<0.05)。治疗前2组的肾脏损伤相关因子中期因子(MK)、可溶性fms-样酪氨酸激酶受体l(sFlt-1)、高迁移率族蛋白B1(HMGB1)水平比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的上述指标水平均显著降低,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低更显著(P<0.05)。2组均未见肝肾功能损伤、消化性溃疡、糖尿病等严重不良反应。结论胃苓汤合异功散加减治疗HSPN脾虚湿热证患儿,可明显缩短病程,促进症状消退,通过纠正Th17/Treg免疫失衡,抑制MK、sFlt-1、HMGB1表达以发挥更好的肾保护效果,且不良反应少,值得临床推广应用。展开更多
基金Supported by Liaoning Provincial Science and Technology Department Project,No.2023JH2/101700149Open Fund Project of Liaoning University of Traditional Chinese Medicine,No.zyzx2205.
文摘BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby necessitating the pursuit of more efficacious treatment strategies.Within traditional Chinese medicine,spleen deficiency is regarded as a central pathogenic mechanism in CRC,persisting throughout the entire disease course.AIM To elucidate the mechanism by which modified Yigong San confers therapeutic efficacy against CRC,potentially exerting its effects through apoptosis regulation mediated by the enhancer of zeste homolog 2(EZH2)/methyltransferase-like 3(METTL3)/SRY-box transcription factor 4(SOX4)axis.METHODS In the clinical study,CRC tissues and corresponding adjacent normal samples that fulfilled inclusion criteria were procured.Quantitative reverse transcription polymerase chain reaction was employed to determine the transcriptional expression of EZH2 and METTL3 mRNA.For in vitro experimentation,SW-480 cells were allocated into five experimental conditions:Control,control+serum,control+negative control,control+overexpressing-EZH2,and control+overexpressing-EZH2+serum.The mRNA expression levels of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax across groups were quantified via quantitative reverse transcription polymerase chain reaction,while protein levels were assessed using western blot analysis.The presence of EZH2 binding sites within the METTL3 promoter region was verified through chromatin immunoprecipitation polymerase chain reaction.The optimal concentration of drug-containing serum(5%,10%,15%)was determined using the Cell Counting Kit-8 assay.Cell migratory ability was evaluated via scratch assays,and apoptotic activity was quantified by flow cytometry.RESULTS The clinical findings demonstrated significantly elevated transcriptional levels of METTL3 and EZH2 mRNA in tumor tissues compared to their adjacent normal counterparts(P<0.05).In vitro,cells treated with modified Yigong San exhibited a substantial downregulation of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax mRNA and protein levels(P<0.05),relative to the control group.Apoptotic rates were markedly increased,while migratory capacity was significantly attenuated.Furthermore,in EZH2-overexpressing cells treated with modified Yigong San,similar reductions in both mRNA and protein levels of the aforementioned targets were observed(P<0.05),concomitant with enhanced apoptosis and reduced migration.Chromatin immunoprecipitation polymerase chain reaction analysis confirmed EZH2 occupancy at specific loci within the METTL3 promoter.CONCLUSION Modified Yigong San exhibits both preventive and therapeutic potential against CRC,likely mediated through the regulation of apoptosis via the EZH2/METTL3/SOX4 signaling pathway.
基金Supported by Ningxia Key Research and Development Program,No.2023BEG02015Ningxia Science and Technology Benefiting People Program,No.2022CMG03064+1 种基金Ningxia Natural Science Foundation,No.2022AAC02039National Natural Science Foundation of China,No.82260879 and No.82374261.
文摘BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.
文摘目的观察胃苓汤合异功散加减治疗小儿过敏性紫癜性肾炎(HSPN)脾虚湿热证的临床疗效。方法选取2022年1月至2023年6月于淳安县中医院中医儿科就诊的82例HSPN脾虚湿热证患儿,按照随机数字表法分为对照组40例和治疗组42例。对照组予强的松、贝那普利片口服,治疗组在对照组治疗方法的基础上口服胃苓汤合异功散加减。2组均以4周为1个疗程,连续治疗2个疗程后统计疗效。结果治疗组的总有效率为95.24%(40/42),显著高于对照组的80.00%(32/40),2组比较,差异有统计学意义(P<0.05)。治疗组的蛋白尿、血尿、紫癜消失时间均显著短于对照组,2组比较,差异均有统计学意义(P<0.05)。治疗前2组的24 h尿蛋白定量(24 h UPE)、尿转铁蛋白(Tf)、血肌酐(Scr)、血尿素氮(BUN)水平比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的上述指标水平均显著降低,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低更显著(P<0.05)。治疗前2组的免疫调节指标辅助性T细胞17(Th17)、调节性T细胞(Treg)、Th17/Treg比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的Th17、Th17/Treg均显著降低,Treg显著升高,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低或升高更显著(P<0.05)。治疗前2组的肾脏损伤相关因子中期因子(MK)、可溶性fms-样酪氨酸激酶受体l(sFlt-1)、高迁移率族蛋白B1(HMGB1)水平比较,差异均无统计学意义(P>0.05),具有可比性;治疗后2组的上述指标水平均显著降低,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组降低更显著(P<0.05)。2组均未见肝肾功能损伤、消化性溃疡、糖尿病等严重不良反应。结论胃苓汤合异功散加减治疗HSPN脾虚湿热证患儿,可明显缩短病程,促进症状消退,通过纠正Th17/Treg免疫失衡,抑制MK、sFlt-1、HMGB1表达以发挥更好的肾保护效果,且不良反应少,值得临床推广应用。
