Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disea...Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.展开更多
Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammat...Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to man...Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to many other diseases.Current research shows that patients with hypopituitarism have a high risk of developing NAFLD.After the adenohypophysis is dominated by hypothalamic hormones,hormones are secreted to act on the corresponding tissues or organs.It is characterized by a decrease in the thyroid hormone,cortisol,and growth hormone levels.In this review,we analyzed the mechanisms related to NAFLD through thyroid secretion,growth hormone secretion,sex hormone,and prolactin axes in patients with hypopituitarism,which will provide information and a theoretical basis for clinical diagnosis and treatment.展开更多
In recent years,humanity has been confronted with a global pandemic due to coronavirus disease 2019(COVID-19),which has caused an unprecedented health and economic crisis worldwide.Apart from the respiratory symptoms,...In recent years,humanity has been confronted with a global pandemic due to coronavirus disease 2019(COVID-19),which has caused an unprecedented health and economic crisis worldwide.Apart from the respiratory symptoms,which are considered the principal manifestations of COVID-19,it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems.Across the spectrum of organ involvement in COVID-19,acute liver injury(ALI)has been gradually gaining increasing attention by the international scientific community.COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course.Indeed,COVID-19 patients hospitalized in the intensive care unit(ICU)run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure.The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature.Several theories have been proposed to explain the occurrence of ALI in the ICU setting,such as hypoperfusion and ischemia due to hemodynamic instability,passive liver congestion as a result of congestive heart failure,ischemia-reperfusion injury,hypoxia due to respiratory failure,mechanical ventilation itself,sepsis and septic shock,cytokine storm,endotheliitis with concomitant coagulopathy,druginduced liver injury,parenteral nutrition and direct cytopathic viral effect.It should be noted that no specific therapy for COVID-19 induced ALI exists.Therefore,the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues.The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients,explore its clinical implications,shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches.Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues,in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.展开更多
文摘Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.
基金This work has been supported by the Liaoning Province Natural Science Foundation(Grant Nos.:2020-ZLLH-47,2020-MS-065,2021-YGJC-02,and 2017225054).Figures in the paper were drawn using Figdraw,and we sincerely thank the free drawing support provided by the Figdraw platform(www.fgdraw.com).We also would like to thank Editage(www.editage.cn)for English language editing.
文摘Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
文摘Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to many other diseases.Current research shows that patients with hypopituitarism have a high risk of developing NAFLD.After the adenohypophysis is dominated by hypothalamic hormones,hormones are secreted to act on the corresponding tissues or organs.It is characterized by a decrease in the thyroid hormone,cortisol,and growth hormone levels.In this review,we analyzed the mechanisms related to NAFLD through thyroid secretion,growth hormone secretion,sex hormone,and prolactin axes in patients with hypopituitarism,which will provide information and a theoretical basis for clinical diagnosis and treatment.
文摘In recent years,humanity has been confronted with a global pandemic due to coronavirus disease 2019(COVID-19),which has caused an unprecedented health and economic crisis worldwide.Apart from the respiratory symptoms,which are considered the principal manifestations of COVID-19,it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems.Across the spectrum of organ involvement in COVID-19,acute liver injury(ALI)has been gradually gaining increasing attention by the international scientific community.COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course.Indeed,COVID-19 patients hospitalized in the intensive care unit(ICU)run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure.The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature.Several theories have been proposed to explain the occurrence of ALI in the ICU setting,such as hypoperfusion and ischemia due to hemodynamic instability,passive liver congestion as a result of congestive heart failure,ischemia-reperfusion injury,hypoxia due to respiratory failure,mechanical ventilation itself,sepsis and septic shock,cytokine storm,endotheliitis with concomitant coagulopathy,druginduced liver injury,parenteral nutrition and direct cytopathic viral effect.It should be noted that no specific therapy for COVID-19 induced ALI exists.Therefore,the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues.The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients,explore its clinical implications,shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches.Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues,in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.
