We previously demonstrated that endogenous phosphatidic acid(PA)promotes liver regeneration after acetaminophen(APAP)hepatotoxicity.Here,we hypothesized that exogenous PA is also beneficial.To test that,we treated mic...We previously demonstrated that endogenous phosphatidic acid(PA)promotes liver regeneration after acetaminophen(APAP)hepatotoxicity.Here,we hypothesized that exogenous PA is also beneficial.To test that,we treated mice with a toxic APAP dose at 0 h,followed by PA or vehicle(Veh)posttreatment.We then collected blood and liver at 6,24,and 52 h.Post-treatment with PA 2 h after APAP protected against liver injury at 6 h,and the combination of PA and N-acetyl-L-cysteine(NAC)reduced injury more than NAC alone.Interestingly,PA did not affect canonical mechanisms of APAP toxicity.Instead,transcriptomics revealed that PA activated interleukin-6(IL-6)signaling in the liver.Consistent with that,serum IL-6 and hepatic signal transducer and activator of transcription 3(Stat3)phosphorylation increased in PA-treated mice.Furthermore,PA failed to protect against APAP in IL-6-deficient animals.Interestingly,IL-6 expression increased 18-fold in adipose tissue after PA,indicating that adipose is a source of PA-induced circulating IL-6.Surprisingly,however,exogenous PA did not alter regeneration,despite the importance of endogenous PA in liver repair,possibly due to its short half-life.These data demonstrate that exogenous PA is also beneficial in APAP toxicity and reinforce the protective effects of IL-6 in this model.展开更多
We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary b...We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy.This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition.Clinical vigilance,especially in atypical clinical presentations,can result in early accurate diagnosis and prompt treatment.展开更多
基金funded in part by a 2018 Pinnacle Research Award from the AASLD Foundation,USA(Mitchell R.McGill)the Arkansas Biosciences Institute(Mitchell R.McGill),which is the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000,USAthe National Institutes of Health grants(USA)T32 GM106999(Mitchell R.Mc Gill and Joel H.Vazquez),R01 DK104735(Brian N.Finck),R01 DK117657(Brian N.Finck),R42 DK121652(Brian N.Finck),R56 DK111735(Brian N.Finck),R42 DK079387(Laura P.James),UL1 TR003107(Laura P.James and Stefanie Kennon-Mc Gill),and TR003108(Laura P.James and Stefanie Kennon-McGill)。
文摘We previously demonstrated that endogenous phosphatidic acid(PA)promotes liver regeneration after acetaminophen(APAP)hepatotoxicity.Here,we hypothesized that exogenous PA is also beneficial.To test that,we treated mice with a toxic APAP dose at 0 h,followed by PA or vehicle(Veh)posttreatment.We then collected blood and liver at 6,24,and 52 h.Post-treatment with PA 2 h after APAP protected against liver injury at 6 h,and the combination of PA and N-acetyl-L-cysteine(NAC)reduced injury more than NAC alone.Interestingly,PA did not affect canonical mechanisms of APAP toxicity.Instead,transcriptomics revealed that PA activated interleukin-6(IL-6)signaling in the liver.Consistent with that,serum IL-6 and hepatic signal transducer and activator of transcription 3(Stat3)phosphorylation increased in PA-treated mice.Furthermore,PA failed to protect against APAP in IL-6-deficient animals.Interestingly,IL-6 expression increased 18-fold in adipose tissue after PA,indicating that adipose is a source of PA-induced circulating IL-6.Surprisingly,however,exogenous PA did not alter regeneration,despite the importance of endogenous PA in liver repair,possibly due to its short half-life.These data demonstrate that exogenous PA is also beneficial in APAP toxicity and reinforce the protective effects of IL-6 in this model.
文摘We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy.This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition.Clinical vigilance,especially in atypical clinical presentations,can result in early accurate diagnosis and prompt treatment.
