Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evalu...Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evaluate the effects of apigenin.Liver function was assessed using biochemical tests,and inflammation-associated markers,including interleukin-1 beta(IL-1β),IL-6,IL-10,and tumor necrosis factor-alpha(TNF-α),were determined by enzyme-linked immunosorbent assay(ELISA).H&E staining,Sirius Red staining,and collagen immunohistochemistry were also conducted.In addition,antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.Results:CCl_(4)administration induced hepatic stellate cell activation and liver fibrogenesis in mice.Apigenin treatment markedly decreased liver injury markers,inflammation,oxidative stress,and collagen deposition,mitigating CCl_(4)-induced liver fibrosis.Furthermore,it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta(PI3K/AKT/GSK3β)pathway by reducing the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3βin liver tissue.Conclusions:Apigenin ameliorates CCl_(4)-induced liver fibrosis in mice,likely through the inhibition of the PI3K/AKT/GSK3βsignaling pathway.These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.展开更多
Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can p...Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.展开更多
基金supported by the grant from Henan Province Science and Technology Research Project(Project No:242102310250,222102310373)Key Research Project Program of Higher Education Institutions in Henan Province(NO 24A32006,22B360003)Medical Science and Technology Tackling Program of Henan Province(NO LHGJ20230677).
文摘Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evaluate the effects of apigenin.Liver function was assessed using biochemical tests,and inflammation-associated markers,including interleukin-1 beta(IL-1β),IL-6,IL-10,and tumor necrosis factor-alpha(TNF-α),were determined by enzyme-linked immunosorbent assay(ELISA).H&E staining,Sirius Red staining,and collagen immunohistochemistry were also conducted.In addition,antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.Results:CCl_(4)administration induced hepatic stellate cell activation and liver fibrogenesis in mice.Apigenin treatment markedly decreased liver injury markers,inflammation,oxidative stress,and collagen deposition,mitigating CCl_(4)-induced liver fibrosis.Furthermore,it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta(PI3K/AKT/GSK3β)pathway by reducing the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3βin liver tissue.Conclusions:Apigenin ameliorates CCl_(4)-induced liver fibrosis in mice,likely through the inhibition of the PI3K/AKT/GSK3βsignaling pathway.These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.
基金supported by grants from the National Natural Science Foundation of China(Nos.82072664,81974374,82173125,82103677).
文摘Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.
