Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosi...Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.展开更多
The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Cen...The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.展开更多
Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease...Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.展开更多
Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to partici...Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.展开更多
目的:探讨输卵管上皮内N-乙酰葡萄糖胺-6-转磺酶(CHST2)和岩藻糖基转移酶7(Fuc T-VII)表达与输卵管妊娠发生的关系。方法:采用免疫组织化学和实时荧光定量PCR(RTPCR)的方法,检测输卵管妊娠患者的输卵管胚囊着床部位组织(EP-2组,n=23),...目的:探讨输卵管上皮内N-乙酰葡萄糖胺-6-转磺酶(CHST2)和岩藻糖基转移酶7(Fuc T-VII)表达与输卵管妊娠发生的关系。方法:采用免疫组织化学和实时荧光定量PCR(RTPCR)的方法,检测输卵管妊娠患者的输卵管胚囊着床部位组织(EP-2组,n=23),输卵管胚囊着床旁部位组织(EP-1组,n=23),正常输卵管组织(CT组,n=16)的CHST2和Fuc T-VII的表达情况。结果:免疫组织化学法检测到输卵管妊娠胚囊着床部位CHST2和Fuc T-VII表达明显上调,与正常组相比差异有显著统计学意义(P<0.05)。RT-PCR方法检测CHST2 m RNA和Fuc T-VII m RNA在输卵管妊娠胚囊着床部表达水平高于正常组,差异有显著统计学意义(P<0.05)。结论:L-选择素与其配体相结合的机制可能参与了输卵管妊娠的发生。展开更多
Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, signi...Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII(fV II) is produced in the liver and secreted into the blood stream. Tissue factor(TF), the cellular receptor for fV II, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fV II complex may be formed in the absence of injury, because f VII potentially exists in the tissue fluid within cancer tissues. The active form of this complex(TF-fV IIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fV II pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mecha-nisms by which TF-fV II signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fV II synthesis and regulation in breast cancer cells. Our current understanding of the TF-fV II pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81873576)Wenzhou Municipal Science and Technology Bureau,China(Grant No.:Y20220023).
文摘Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.
文摘The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.
文摘Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.
基金supported by the National Natural Science Foundation of China(No.81473485)the Natural Science Foundation of Shandong Province(No.2014ZRE27321)
文摘Cancerous inhibitor of protein phosphatase 2A(CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer(NSCLC). CIP2A plays an ’oncogenic nexus’ to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and m TORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/m TOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I(PPI) and polyphyllin VII(PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin(DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/m TOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of m TOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
文摘目的:探讨输卵管上皮内N-乙酰葡萄糖胺-6-转磺酶(CHST2)和岩藻糖基转移酶7(Fuc T-VII)表达与输卵管妊娠发生的关系。方法:采用免疫组织化学和实时荧光定量PCR(RTPCR)的方法,检测输卵管妊娠患者的输卵管胚囊着床部位组织(EP-2组,n=23),输卵管胚囊着床旁部位组织(EP-1组,n=23),正常输卵管组织(CT组,n=16)的CHST2和Fuc T-VII的表达情况。结果:免疫组织化学法检测到输卵管妊娠胚囊着床部位CHST2和Fuc T-VII表达明显上调,与正常组相比差异有显著统计学意义(P<0.05)。RT-PCR方法检测CHST2 m RNA和Fuc T-VII m RNA在输卵管妊娠胚囊着床部表达水平高于正常组,差异有显著统计学意义(P<0.05)。结论:L-选择素与其配体相结合的机制可能参与了输卵管妊娠的发生。
文摘Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII(fV II) is produced in the liver and secreted into the blood stream. Tissue factor(TF), the cellular receptor for fV II, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fV II complex may be formed in the absence of injury, because f VII potentially exists in the tissue fluid within cancer tissues. The active form of this complex(TF-fV IIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fV II pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mecha-nisms by which TF-fV II signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fV II synthesis and regulation in breast cancer cells. Our current understanding of the TF-fV II pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies.
