Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of...Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.展开更多
Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and...Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and palpitations,whereas neuroglycopenenic symptoms include confusion,behavioural changes,personality changes,visual disturbances,seizure,and coma.Diagnosis of suspected cases is based on standard endocrine tests,especially the prolonged fasting test.Non-invasive imaging procedures,such as computed tomography and magnetic resonance imaging,are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion.Invasive modalities,such as endoscopic ultrasonography and arterial stimulation venous sampling,are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to noninvasive localization techniques.The range of techniques available for the localization of insulinomas means thatblind resection can be avoided.Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas.A high proportion of patients with insulinomas can be cured with surgery.In patients with malignant insulinomas,an aggressive medical approach,including extended pancreatic resection,liver resection,liver transplantation,chemoembolization,or radiofrequency ablation,is recommended to improve both survival and quality of life.In patients with unresectable or uncontrollable insulinomas,such as malignant insulinoma of the pancreas,several techniques should be considered,including administration of ocreotide and/or continuous glucose monitoring,to prevent hypoglycemic episodes and to improve quality of life.展开更多
Pedpheral neuropathy, and specifically distal peripheral neuropathy （DPN）, is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diab...Pedpheral neuropathy, and specifically distal peripheral neuropathy （DPN）, is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.展开更多
基金supported by the Natural Science Foundation of Shanghai of China,No.17ZR1425800(to KYL)the Shanghai Pudong District Health Bureau of China,No.PDZX2017-25(to KYL)
文摘Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
基金Supported by Kochi Organization for Medical Reformation and Renewal Fundthe support of SatoshiIto and Kazuhiro Hanazaki(Kochi Medical School)
文摘Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and palpitations,whereas neuroglycopenenic symptoms include confusion,behavioural changes,personality changes,visual disturbances,seizure,and coma.Diagnosis of suspected cases is based on standard endocrine tests,especially the prolonged fasting test.Non-invasive imaging procedures,such as computed tomography and magnetic resonance imaging,are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion.Invasive modalities,such as endoscopic ultrasonography and arterial stimulation venous sampling,are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to noninvasive localization techniques.The range of techniques available for the localization of insulinomas means thatblind resection can be avoided.Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas.A high proportion of patients with insulinomas can be cured with surgery.In patients with malignant insulinomas,an aggressive medical approach,including extended pancreatic resection,liver resection,liver transplantation,chemoembolization,or radiofrequency ablation,is recommended to improve both survival and quality of life.In patients with unresectable or uncontrollable insulinomas,such as malignant insulinoma of the pancreas,several techniques should be considered,including administration of ocreotide and/or continuous glucose monitoring,to prevent hypoglycemic episodes and to improve quality of life.
基金Supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases, No. DK067248
文摘Pedpheral neuropathy, and specifically distal peripheral neuropathy （DPN）, is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.
