Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of...Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.展开更多
BACKGROUND S-adenosylmethionine(AdoMet)is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis(IHC)and chronic liver diseases.While the efficacy of AdoMet has been demonstrated previously,it has...BACKGROUND S-adenosylmethionine(AdoMet)is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis(IHC)and chronic liver diseases.While the efficacy of AdoMet has been demonstrated previously,it has not been systematically investigated within the early weeks of treatment.AIM To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.METHODS Studies reporting the efficacy of intravenous,intramuscular,or oral forms of AdoMet within 8 wk of treatment initiation were considered;three randomized and six non-randomized studies were eligible for inclusion(PROSPERO registration number CRD42018090936).Of the three randomized studies,two were double-blind and placebo-controlled,and one was comparator-controlled with unclear blinding and a relatively high risk of bias.Mean serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and gamma-glutamyl transferase(γGT)following AdoMet treatment vs placebo,comparator,or baseline were summarized to determine differences in liver enzymes.Changes in patient-reported clinical symptoms of cholestasis were also summarized.RESULTS Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet vs placebo within 2 wk.One of these also reported significant ALP reductions,and the other reported significant AST andγGT reductions within 2 wk.The comparator-controlled randomized study,which had a number of notable limitations,reported significant reductions in serum ALT and AST levels with AdoMet vs potassium magnesium aspartate within 4 wk,but not within2 wk.All of the non-randomized studies(4/4)that investigated ALT,AST,ALP and/orγGT reported significant reductions in at least two of these parameters within 2 wk.Of the five studies that evaluated fatigue,reductions were observed within 2 wk in one randomized and two nonrandomized studies.The remaining two non-randomized studies reported improvements in fatigue within 6 and 8 wk.Of the four studies r展开更多
Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting,especially with the automatization of testing in this technological era.These tests include aminotran...Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting,especially with the automatization of testing in this technological era.These tests include aminotransferases,alkaline phosphatase,gamma-glutamyl transferase,bilirubin,albumin,prothrombin time and international normalized ratio(INR).Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation.Generally,abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild[<5×upper limit of normal(ULN)],moderate(>5-<15×ULN)and severe(>15×ULN).Hepatocellular pattern causes include but are not limited to;non-alcoholic fatty liver disease/non-alcoholic steatohepatitis,alcohol use,chronic viral hepatitis,liver cirrhosis(variable),autoimmune hepatitis,hemochromatosis,Wilson’s disease,alpha-1 antitrypsin deficiency,celiac disease,medication-induced and ischemic hepatitis.Cholestatic pattern causes include but is not limited to;biliary pathology(obstruction,autoimmune),other conditions with hyperbilirubinemia(conjugated and unconjugated).It is crucial to interpret these commonly ordered tests accurately as appropriate further workup,treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.展开更多
基金This review was supported by the National Natural Science Foundation of China(grant no.81930028,91749206,81625007 and 31921003).
文摘Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.
文摘BACKGROUND S-adenosylmethionine(AdoMet)is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis(IHC)and chronic liver diseases.While the efficacy of AdoMet has been demonstrated previously,it has not been systematically investigated within the early weeks of treatment.AIM To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.METHODS Studies reporting the efficacy of intravenous,intramuscular,or oral forms of AdoMet within 8 wk of treatment initiation were considered;three randomized and six non-randomized studies were eligible for inclusion(PROSPERO registration number CRD42018090936).Of the three randomized studies,two were double-blind and placebo-controlled,and one was comparator-controlled with unclear blinding and a relatively high risk of bias.Mean serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and gamma-glutamyl transferase(γGT)following AdoMet treatment vs placebo,comparator,or baseline were summarized to determine differences in liver enzymes.Changes in patient-reported clinical symptoms of cholestasis were also summarized.RESULTS Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet vs placebo within 2 wk.One of these also reported significant ALP reductions,and the other reported significant AST andγGT reductions within 2 wk.The comparator-controlled randomized study,which had a number of notable limitations,reported significant reductions in serum ALT and AST levels with AdoMet vs potassium magnesium aspartate within 4 wk,but not within2 wk.All of the non-randomized studies(4/4)that investigated ALT,AST,ALP and/orγGT reported significant reductions in at least two of these parameters within 2 wk.Of the five studies that evaluated fatigue,reductions were observed within 2 wk in one randomized and two nonrandomized studies.The remaining two non-randomized studies reported improvements in fatigue within 6 and 8 wk.Of the four studies r
文摘Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting,especially with the automatization of testing in this technological era.These tests include aminotransferases,alkaline phosphatase,gamma-glutamyl transferase,bilirubin,albumin,prothrombin time and international normalized ratio(INR).Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation.Generally,abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild[<5×upper limit of normal(ULN)],moderate(>5-<15×ULN)and severe(>15×ULN).Hepatocellular pattern causes include but are not limited to;non-alcoholic fatty liver disease/non-alcoholic steatohepatitis,alcohol use,chronic viral hepatitis,liver cirrhosis(variable),autoimmune hepatitis,hemochromatosis,Wilson’s disease,alpha-1 antitrypsin deficiency,celiac disease,medication-induced and ischemic hepatitis.Cholestatic pattern causes include but is not limited to;biliary pathology(obstruction,autoimmune),other conditions with hyperbilirubinemia(conjugated and unconjugated).It is crucial to interpret these commonly ordered tests accurately as appropriate further workup,treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.
