BACKGROUND Cryptotanshinone(CPT)has wide biological functions,including anti-oxidative,antifibrosis,and anti-inflammatory properties.However,the effect of CPT on hepatic fibrosis is unknown.AIM To investigate the effe...BACKGROUND Cryptotanshinone(CPT)has wide biological functions,including anti-oxidative,antifibrosis,and anti-inflammatory properties.However,the effect of CPT on hepatic fibrosis is unknown.AIM To investigate the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action.METHODS Hepatic stellate cells(HSCs)and normal hepatocytes were treated with different concentrations of CPT and salubrinal.The CCK-8 assay was used to determine cell viability.Flow cytometry was used to measure apoptosis and cell cycle arrest.Reverse transcription polymerase chain reaction(RT-PCR)and Western blot analyses were used to measure mRNA levels and protein expression of endoplasmic reticulum stress(ERS)signaling pathway related molecules,respectively.Carbon tetrachloride(CCL4)was used to induce in vivo hepatic fibrosis in mice.Mice were treated with CPT and salubrinal,and blood and liver samples were collected for histopathological examination.RESULTS We found that CPT treatment significantly reduced fibrogenesis by modulating the synthesis and degradation of the extracellular matrix in vitro.CPT inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in cultured HSCs.Furthermore,we found that CPT promoted apoptosis of activated HSCs by upregulating expression of ERS markers(CHOP and GRP78)and activating ERS pathway molecules(PERK,IRE1α,and ATF4),which were inhibited by salubrinal.Inhibition of ERS by salubrinal partially eliminated the therapeutic effect of CPT in our CCL4-induced hepatic fibrosis mouse model.CONCLUSION CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway,which represents a promising strategy for treating hepatic fibrosis.展开更多
Ethylene is the main factor controlling fruit ripening of pear(Pyrus ussuriensis).Ethylene production rate is negatively correlated with fruit shelf life;therefore,it is important to decrease the ethylene levels for o...Ethylene is the main factor controlling fruit ripening of pear(Pyrus ussuriensis).Ethylene production rate is negatively correlated with fruit shelf life;therefore,it is important to decrease the ethylene levels for optimal fruit storage.Here,we observed that blue light treatment could inhibit ethylene production and promote the expression of ELONGATED HYPOCOTYL 5(PuHY5),a basic leucine zipper domain(bZIP)transcription factor.The following studies showed that PuHY5 could bind to the promoter of ACC synthase 1(PuACS1),a rate-limiting enzyme in ethylene biosynthesis,and inhibit its expression.For pears in which Pu HY5 was silenced,the ethylene production and PuACS1 expression were much higher than those in the control fruit.These results demonstrated that blue light inhibited ethylene production through the induction of Pu HY5 in pear.Our finding provides a new method for prolonging fruit shelf life.展开更多
基金Science and Technology Plan of Hainan Province(Clinical Research Center),No.LCYX202103 and No.LCYX202204Hainan Province Science and Technology Special Fund,No.ZDYF2022SHFZ067Hainan Province Clinical Medical Center.
文摘BACKGROUND Cryptotanshinone(CPT)has wide biological functions,including anti-oxidative,antifibrosis,and anti-inflammatory properties.However,the effect of CPT on hepatic fibrosis is unknown.AIM To investigate the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action.METHODS Hepatic stellate cells(HSCs)and normal hepatocytes were treated with different concentrations of CPT and salubrinal.The CCK-8 assay was used to determine cell viability.Flow cytometry was used to measure apoptosis and cell cycle arrest.Reverse transcription polymerase chain reaction(RT-PCR)and Western blot analyses were used to measure mRNA levels and protein expression of endoplasmic reticulum stress(ERS)signaling pathway related molecules,respectively.Carbon tetrachloride(CCL4)was used to induce in vivo hepatic fibrosis in mice.Mice were treated with CPT and salubrinal,and blood and liver samples were collected for histopathological examination.RESULTS We found that CPT treatment significantly reduced fibrogenesis by modulating the synthesis and degradation of the extracellular matrix in vitro.CPT inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in cultured HSCs.Furthermore,we found that CPT promoted apoptosis of activated HSCs by upregulating expression of ERS markers(CHOP and GRP78)and activating ERS pathway molecules(PERK,IRE1α,and ATF4),which were inhibited by salubrinal.Inhibition of ERS by salubrinal partially eliminated the therapeutic effect of CPT in our CCL4-induced hepatic fibrosis mouse model.CONCLUSION CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway,which represents a promising strategy for treating hepatic fibrosis.
基金supported by the National Natural Science Foundation of China(Grant Nos.32125034 and 31801834)。
文摘Ethylene is the main factor controlling fruit ripening of pear(Pyrus ussuriensis).Ethylene production rate is negatively correlated with fruit shelf life;therefore,it is important to decrease the ethylene levels for optimal fruit storage.Here,we observed that blue light treatment could inhibit ethylene production and promote the expression of ELONGATED HYPOCOTYL 5(PuHY5),a basic leucine zipper domain(bZIP)transcription factor.The following studies showed that PuHY5 could bind to the promoter of ACC synthase 1(PuACS1),a rate-limiting enzyme in ethylene biosynthesis,and inhibit its expression.For pears in which Pu HY5 was silenced,the ethylene production and PuACS1 expression were much higher than those in the control fruit.These results demonstrated that blue light inhibited ethylene production through the induction of Pu HY5 in pear.Our finding provides a new method for prolonging fruit shelf life.
