Objective:Patients with colon adenocarcinoma(COAD)who undergo radiation therapy develop radiation enteritis(RE).The predictive value of RE in COAD is yet to be established.Berberine,an active compound derived from the...Objective:Patients with colon adenocarcinoma(COAD)who undergo radiation therapy develop radiation enteritis(RE).The predictive value of RE in COAD is yet to be established.Berberine,an active compound derived from the traditional Chinese medicinal plant,Coptis chinensis,has notable anti-inflammatory properties and offers protection to the intestinal mucosa.This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE(COAD&RE).Methods:Relevant genetic features of diverse COAD&RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model.The therapeutic targets of berberine were predicted using network pharmacology and molecular docking.In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking.Results:RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&RE.In addition,we identified five core therapeutic targets of berberine by network pharmacology and molecular docking:CCND1,MYC,AR,LEP,and CYP19A1.In vivo experiments showed that berberine increased short-term survival rate,body weight,and intestinal epithelial cell recovery in mice after radiation.In an in vitro study,berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation,and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects.Conclusions:This study predicted the potential therapeutic effects of berberine on COAD&RE and verified the relevant mechanisms,which may provide insights and suggestions for the clinical treatment of COAD&RE.展开更多
Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and ...Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and quality of life.The protective effects and underlying mechanisms of action of isofraxidin(IF)against IR-induced testicular injury were investigated.Methods:A mouse testis injury model was established using 5 Gy irradiation.Hematoxylin and eosin(H&E)staining,immunofluorescence staining,and enzyme-linked immunosorbent assay were used to measure DNA damage,apoptosis,inflammatory reactions,and oxidative stress in the testes of mice after irradiation.The effectiveness of IF irradiation on testicular injury was evaluated,and the mechanisms of the related oxidative stress and inflammatory response pathways were discussed.Results:IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage,apoptosis rate,oxidative stress,and inflammatory factors.The radioprotective effects of IF on testicular injury are mediated by the stimulation of nuclear factor E2-related factor 2(Nrf2)/heme oxidase-1(HO-1)or suppression of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome signaling pathways.In addition,crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated,in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure.Conclusion:IF can be a potent radioprotective agent to mitigate testicular damage,and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.展开更多
文摘Objective:Patients with colon adenocarcinoma(COAD)who undergo radiation therapy develop radiation enteritis(RE).The predictive value of RE in COAD is yet to be established.Berberine,an active compound derived from the traditional Chinese medicinal plant,Coptis chinensis,has notable anti-inflammatory properties and offers protection to the intestinal mucosa.This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE(COAD&RE).Methods:Relevant genetic features of diverse COAD&RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model.The therapeutic targets of berberine were predicted using network pharmacology and molecular docking.In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking.Results:RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&RE.In addition,we identified five core therapeutic targets of berberine by network pharmacology and molecular docking:CCND1,MYC,AR,LEP,and CYP19A1.In vivo experiments showed that berberine increased short-term survival rate,body weight,and intestinal epithelial cell recovery in mice after radiation.In an in vitro study,berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation,and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects.Conclusions:This study predicted the potential therapeutic effects of berberine on COAD&RE and verified the relevant mechanisms,which may provide insights and suggestions for the clinical treatment of COAD&RE.
基金National Natural Science Foundation of China(82192911,82103776)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207).
文摘Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and quality of life.The protective effects and underlying mechanisms of action of isofraxidin(IF)against IR-induced testicular injury were investigated.Methods:A mouse testis injury model was established using 5 Gy irradiation.Hematoxylin and eosin(H&E)staining,immunofluorescence staining,and enzyme-linked immunosorbent assay were used to measure DNA damage,apoptosis,inflammatory reactions,and oxidative stress in the testes of mice after irradiation.The effectiveness of IF irradiation on testicular injury was evaluated,and the mechanisms of the related oxidative stress and inflammatory response pathways were discussed.Results:IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage,apoptosis rate,oxidative stress,and inflammatory factors.The radioprotective effects of IF on testicular injury are mediated by the stimulation of nuclear factor E2-related factor 2(Nrf2)/heme oxidase-1(HO-1)or suppression of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome signaling pathways.In addition,crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated,in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure.Conclusion:IF can be a potent radioprotective agent to mitigate testicular damage,and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.
基金supported by the National Natural Science Foundation of China(82103776,Zebin Liao,82192911,Yue Gao)innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207,Yue Gao).
