AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon te...AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride(CCl_4) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation(CCK8 assay),motility(scratch test and Transwell assay), contraction(collagen gel contraction assay), extracellular matrix(ECM) secretion(Western blot), and angiogenesis(ELISA and tube formation assay) was investigated. We also analyzed the possible signaling pathways involved by Western blot analysis.RESULTS Mice developed marked liver fibrosis after intraperitoneal injection with CCl_4 for 6 wk. Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl_4-treated mice. Platelet-derived growth factor(PDGF) promoted the fibrogenic response of HSCs in vitro, while metformin inhibited the activation, proliferation, migration, and contraction of HSCs, and reduced the secretion of ECM. Metformin decreased the expression of vascular endothelial growth factor(VEGF) in HSCs through inhibition of hypoxia inducible factor(HIF)-1α in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro. The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin(m TOR) and extracellular signal-regulated kinase(ERK) pathways via the activation of adenosine monophosphate-activated protein kinase(AMPK).CONCLUSION Metformin attenuates the fibrogenic response of HSCs in vivo and in vitro, and may therefore be useful for the treatment of chronic liver diseases.展开更多
Objective:To study the correlation of large conductance Ca2+ activated K+ channel (BKCa)α andβ subunit expression in uterine smooth muscle with the postpartum hemorrhage induced by uterine inertia.Methods: The puerp...Objective:To study the correlation of large conductance Ca2+ activated K+ channel (BKCa)α andβ subunit expression in uterine smooth muscle with the postpartum hemorrhage induced by uterine inertia.Methods: The puerperae who underwent cesarean section and had postpartum hemorrhage induced by uterine inertia in Panzhihua Women and Children Health Hospital between March 2015 and May 2017 were selected as the hemorrhage group of the study, and the puerperae who underwent cesarean section and were without postpartum hemorrhage in Panzhihua Women and Children Health Hospital during the same period were selected as the control group. Proper amount of uterine muscle tissue was collected during the cesarean section to measure the expression of BKCaα andβ subunits and the levels of contraction-related proteins in uterine muscle as well as the contraction characteristic parameters of the uterine muscle.Results: The mRNA expression and protein expression of BKCaα andβ subunits in uterine muscle tissue of hemorrhage group were significantly higher than those of control group;the contraction amplitude, contraction frequency and contraction activity of uterine muscle tissue as well as the OTR, COX2, CX43 and HSP27 levels in uterine muscle tissue of hemorrhage group were significantly lower than those of control group;the BKCaα andβ subunit expression in uterine muscle tissue of hemorrhage group were negatively correlated with the contraction amplitude, contraction frequency and contraction activity as well as the OTR, COX2, CX43 and HSP27 levels.Conclusion: The high expression of BKCa in uterine smooth muscle can reduce the uterine muscle contractility and decrease the levels of contraction-related proteins, and it is closely related to the occurrence of postpartum hemorrhage induced by uterine inertia.展开更多
Background The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused b...Background The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases （MAPK） in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown. Methods Sprague-Dawley rats were randomly divided into three groups： Sham group, coronary microembolization （CME） group and SB203580 group （n=-10 per group）. CME rats were produced by injection of 42 pm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction （LVEF） was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor （TNF）-a was assessed by the technique of semi-quantitative polymerase chain reaction amplification. Results LVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-a mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function. Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-a expression and preserve cardiac contractile function.展开更多
Adhesive hydrogel has drawn great attention for wide applications in wound healing owing to its excellent biocompatibility and lasting adhesiveness.However,traditional adhesive hydrogels only keep the wound moist to p...Adhesive hydrogel has drawn great attention for wide applications in wound healing owing to its excellent biocompatibility and lasting adhesiveness.However,traditional adhesive hydrogels only keep the wound moist to promote wound healing.It is still imperative to fabricate adhesive hydrogels that exhibit efficient antibacterial ability,active driving dynamic wound closure,and reactive oxygen species(ROS)scavenging together with excellent mechanical properties.Here,a novel hydrogel based on poly(N-isopropyl acrylamide)(PNIPAAm),a thermoresponsive polymer,and tannic acid(TA)-Ag nanoparticles(TA-Ag NPs)exhibiting active contraction,tissue adhesion,anti-inflammatory and antibacterial functions was developed.TA-Ag dispersed in the hydrogel not only functioned as the catalyst to polymerize the reaction but also provided additional anti-inflammatory and antibacterial properties.Besides,tannic acid containing catechol groups endowed the hydrogel with adhesive ability.More interestingly,the obtained hydrogel exhibited the thermoresponsive shrinkage ability,which could mechanically drive wound closure due to the presence of PNIPAAm network.In vivo mouse full-thickness skin defect model demonstrated that this actively contractible and antibacterial hydrogel is a promising dressing to improve wound healing process by accelerating tissue regeneration and preventing bacterial infection.Therefore,this multi-functional adhesive hydrogel developed here may provide a new possibility for wound healing.展开更多
基金Supported by National Natural Science Foundation of China,No.81370590
文摘AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride(CCl_4) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation(CCK8 assay),motility(scratch test and Transwell assay), contraction(collagen gel contraction assay), extracellular matrix(ECM) secretion(Western blot), and angiogenesis(ELISA and tube formation assay) was investigated. We also analyzed the possible signaling pathways involved by Western blot analysis.RESULTS Mice developed marked liver fibrosis after intraperitoneal injection with CCl_4 for 6 wk. Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl_4-treated mice. Platelet-derived growth factor(PDGF) promoted the fibrogenic response of HSCs in vitro, while metformin inhibited the activation, proliferation, migration, and contraction of HSCs, and reduced the secretion of ECM. Metformin decreased the expression of vascular endothelial growth factor(VEGF) in HSCs through inhibition of hypoxia inducible factor(HIF)-1α in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro. The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin(m TOR) and extracellular signal-regulated kinase(ERK) pathways via the activation of adenosine monophosphate-activated protein kinase(AMPK).CONCLUSION Metformin attenuates the fibrogenic response of HSCs in vivo and in vitro, and may therefore be useful for the treatment of chronic liver diseases.
文摘Objective:To study the correlation of large conductance Ca2+ activated K+ channel (BKCa)α andβ subunit expression in uterine smooth muscle with the postpartum hemorrhage induced by uterine inertia.Methods: The puerperae who underwent cesarean section and had postpartum hemorrhage induced by uterine inertia in Panzhihua Women and Children Health Hospital between March 2015 and May 2017 were selected as the hemorrhage group of the study, and the puerperae who underwent cesarean section and were without postpartum hemorrhage in Panzhihua Women and Children Health Hospital during the same period were selected as the control group. Proper amount of uterine muscle tissue was collected during the cesarean section to measure the expression of BKCaα andβ subunits and the levels of contraction-related proteins in uterine muscle as well as the contraction characteristic parameters of the uterine muscle.Results: The mRNA expression and protein expression of BKCaα andβ subunits in uterine muscle tissue of hemorrhage group were significantly higher than those of control group;the contraction amplitude, contraction frequency and contraction activity of uterine muscle tissue as well as the OTR, COX2, CX43 and HSP27 levels in uterine muscle tissue of hemorrhage group were significantly lower than those of control group;the BKCaα andβ subunit expression in uterine muscle tissue of hemorrhage group were negatively correlated with the contraction amplitude, contraction frequency and contraction activity as well as the OTR, COX2, CX43 and HSP27 levels.Conclusion: The high expression of BKCa in uterine smooth muscle can reduce the uterine muscle contractility and decrease the levels of contraction-related proteins, and it is closely related to the occurrence of postpartum hemorrhage induced by uterine inertia.
文摘Background The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases （MAPK） in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown. Methods Sprague-Dawley rats were randomly divided into three groups： Sham group, coronary microembolization （CME） group and SB203580 group （n=-10 per group）. CME rats were produced by injection of 42 pm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction （LVEF） was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor （TNF）-a was assessed by the technique of semi-quantitative polymerase chain reaction amplification. Results LVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-a mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function. Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-a expression and preserve cardiac contractile function.
基金supported by the National Research Programs of China(Nos.2020YFA0211100,and 2022YFA1206500)the National Natural Science Foundation of China(Nos.52250002,and 52325106)Suzhou Key Laboratory of Nanotechnology and Biomedicine,Collaborative Innovation Center of Suzhou Nano Science and Technology,and the 111 Program from the Ministry of Education of China.
文摘Adhesive hydrogel has drawn great attention for wide applications in wound healing owing to its excellent biocompatibility and lasting adhesiveness.However,traditional adhesive hydrogels only keep the wound moist to promote wound healing.It is still imperative to fabricate adhesive hydrogels that exhibit efficient antibacterial ability,active driving dynamic wound closure,and reactive oxygen species(ROS)scavenging together with excellent mechanical properties.Here,a novel hydrogel based on poly(N-isopropyl acrylamide)(PNIPAAm),a thermoresponsive polymer,and tannic acid(TA)-Ag nanoparticles(TA-Ag NPs)exhibiting active contraction,tissue adhesion,anti-inflammatory and antibacterial functions was developed.TA-Ag dispersed in the hydrogel not only functioned as the catalyst to polymerize the reaction but also provided additional anti-inflammatory and antibacterial properties.Besides,tannic acid containing catechol groups endowed the hydrogel with adhesive ability.More interestingly,the obtained hydrogel exhibited the thermoresponsive shrinkage ability,which could mechanically drive wound closure due to the presence of PNIPAAm network.In vivo mouse full-thickness skin defect model demonstrated that this actively contractible and antibacterial hydrogel is a promising dressing to improve wound healing process by accelerating tissue regeneration and preventing bacterial infection.Therefore,this multi-functional adhesive hydrogel developed here may provide a new possibility for wound healing.
