Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the ...Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the development of organ failure is the major cause of death in AP,early identification of patients likely to develop organ failure is important.AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas.Destruction of the pancreatic parenchyma first induces an inflammatory reaction locally,but may lead to overwhelming systemic production of inflammatory mediators and early organ failure.Concomitantly,anti-inflammatory cytokines and specific cytokine inhibitors are produced.This anti-inflammatory reaction may overcompensate and inhibit the immune response,rendering the host at risk of systemic infection.At present,there is no specific treatment for AP.Increased understanding of the pathogenesis of systemic inflammation and development of organ dysfunction may provide us with drugs to ameliorate physiological disturbances.展开更多
Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidyli...Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.展开更多
文摘Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the development of organ failure is the major cause of death in AP,early identification of patients likely to develop organ failure is important.AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas.Destruction of the pancreatic parenchyma first induces an inflammatory reaction locally,but may lead to overwhelming systemic production of inflammatory mediators and early organ failure.Concomitantly,anti-inflammatory cytokines and specific cytokine inhibitors are produced.This anti-inflammatory reaction may overcompensate and inhibit the immune response,rendering the host at risk of systemic infection.At present,there is no specific treatment for AP.Increased understanding of the pathogenesis of systemic inflammation and development of organ dysfunction may provide us with drugs to ameliorate physiological disturbances.
基金supported by the National Natural Science Foundation of China(No.82003873)the Postdoctoral Science Foundation of China(No.2020M681899)the Zhejiang Provincial Natural Science Foundation of China(No.LR21H310001)。
文摘Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.
