BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular compone...BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components,maintain intracellular homeostasis,and promote apoptosis by upregulating the activity of caspases.Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases,the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.AIM To investigate the effect of Alox15 expression in cerulein-induced AP in rats.METHODS Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP.The expression of Alox15 was then assessed at the mRNA and protein levels.RESULTS Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats.Further,the mRNA expression levels of tumor necrosis factor alpha,interleukin(IL)-1β,IL-6,and monocyte chemoattractant protein-1,as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced.Additionally,we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells.The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.CONCLUSION Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy,making it a potential therapeutic target for AP.展开更多
BACKGROUND Sarcopenia is a nutrition-related disease and has a profound effect on the longterm overall survival(OS)of patients with gastric cancer.Its diagnostic criterion is critical to clinical diagnosis and treatme...BACKGROUND Sarcopenia is a nutrition-related disease and has a profound effect on the longterm overall survival(OS)of patients with gastric cancer.Its diagnostic criterion is critical to clinical diagnosis and treatment.However,previous research reported widely differing sarcopenia prevalence due to different criteria.AWGS2019 and EWGSOP2 are the two latest and widely adopted criteria.AIM To compare the effects of AWGS2019 and EWGSOP2 on the long-term OS of Chinese gastric cancer patient after radical gastrectomy.METHODS An observational study was conducted from July 2014 to January 2017,which included 648 consecutive gastric cancer patients who underwent radical gastrectomy.The sarcopenia elements(skeletal muscle index,handgrip strength,and gait speed)were measured within 1 mo or 7 d before surgery.The patients were followed at fixed intervals to gain the outcomes.Multivariate Cox regression analysis was performed to determine the association between sarcopenia and the long-term OS of these patients according to the two criteria separately.The predictive performance of the models with AWGS2019 and EWGSOP2 were evaluated by the concordance index(C-index)and area under the time-dependent receiver operating characteristic curve(AUC).The Akaike information criterion(AIC)was applied to compare model fits.RESULTS The prevalence of sarcopenia was 20.5%and 11.3%according to AWGS2019 and EWGSOP2,respectively.Sarcopenia was an independent risk factor for the longterm OS no matter based on AWGS2019 or EWGSOP2,but AWGS2019-sarcopenia in multivariate model had a higher hazard ratio(HR)[2.150(1.547-2.988)]than EWGSOP2-sarcopenia[HR 1.599(1.092-2.339)].Meanwhile,the model with AWGS2019-sarcopenia[C-index 0.773(0.742-0.804);AIC 2193.7;time-dependent AUC 0.812(0.756-0.867)for 1-year OS,0.815(0.778-0.852)for 3-year OS,and 0.809(0.759-0.859)for 5-year OS]had better predictive power and model fits than the model with EWGSOP2-sarcopenia[C-index 0.762(0.729-0.795);AIC 2215.2;timedependent AUC 0.797(0.741-0.854)for 1-year OS,0.804(0.767-0.842)for 3-year OS,and 0.799(0.748-0.850)for 5-year OS].CONCLUSION Sarcopenia is an independent risk factor for the long-term OS in Chinese gastric cancer patients undergoing radical gastrectomy.The prediction model with AWGS2019-sarcopenia has better predictive power and model fits than the prediction model with EWGSOP2-sarcopenia.AWGS2019 may be more appropriate for diagnosing sarcopenia in these Chinese patients than EWGSOP2.展开更多
基金National Health Commission Research Fund,No.WKJ-ZJ-2342National Natural Science Foundation of China,No.81900583Science and Technology Plan Project of Wenzhou,No.Y20180103.
文摘BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components,maintain intracellular homeostasis,and promote apoptosis by upregulating the activity of caspases.Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases,the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.AIM To investigate the effect of Alox15 expression in cerulein-induced AP in rats.METHODS Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP.The expression of Alox15 was then assessed at the mRNA and protein levels.RESULTS Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats.Further,the mRNA expression levels of tumor necrosis factor alpha,interleukin(IL)-1β,IL-6,and monocyte chemoattractant protein-1,as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced.Additionally,we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells.The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.CONCLUSION Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy,making it a potential therapeutic target for AP.
基金Supported by Zhejiang Provincial Health Department Medical Support Discipline-Nutrition,No.11-ZC24Wenzhou Municipal Science and Bureau,No.Y2020732.
文摘BACKGROUND Sarcopenia is a nutrition-related disease and has a profound effect on the longterm overall survival(OS)of patients with gastric cancer.Its diagnostic criterion is critical to clinical diagnosis and treatment.However,previous research reported widely differing sarcopenia prevalence due to different criteria.AWGS2019 and EWGSOP2 are the two latest and widely adopted criteria.AIM To compare the effects of AWGS2019 and EWGSOP2 on the long-term OS of Chinese gastric cancer patient after radical gastrectomy.METHODS An observational study was conducted from July 2014 to January 2017,which included 648 consecutive gastric cancer patients who underwent radical gastrectomy.The sarcopenia elements(skeletal muscle index,handgrip strength,and gait speed)were measured within 1 mo or 7 d before surgery.The patients were followed at fixed intervals to gain the outcomes.Multivariate Cox regression analysis was performed to determine the association between sarcopenia and the long-term OS of these patients according to the two criteria separately.The predictive performance of the models with AWGS2019 and EWGSOP2 were evaluated by the concordance index(C-index)and area under the time-dependent receiver operating characteristic curve(AUC).The Akaike information criterion(AIC)was applied to compare model fits.RESULTS The prevalence of sarcopenia was 20.5%and 11.3%according to AWGS2019 and EWGSOP2,respectively.Sarcopenia was an independent risk factor for the longterm OS no matter based on AWGS2019 or EWGSOP2,but AWGS2019-sarcopenia in multivariate model had a higher hazard ratio(HR)[2.150(1.547-2.988)]than EWGSOP2-sarcopenia[HR 1.599(1.092-2.339)].Meanwhile,the model with AWGS2019-sarcopenia[C-index 0.773(0.742-0.804);AIC 2193.7;time-dependent AUC 0.812(0.756-0.867)for 1-year OS,0.815(0.778-0.852)for 3-year OS,and 0.809(0.759-0.859)for 5-year OS]had better predictive power and model fits than the model with EWGSOP2-sarcopenia[C-index 0.762(0.729-0.795);AIC 2215.2;timedependent AUC 0.797(0.741-0.854)for 1-year OS,0.804(0.767-0.842)for 3-year OS,and 0.799(0.748-0.850)for 5-year OS].CONCLUSION Sarcopenia is an independent risk factor for the long-term OS in Chinese gastric cancer patients undergoing radical gastrectomy.The prediction model with AWGS2019-sarcopenia has better predictive power and model fits than the prediction model with EWGSOP2-sarcopenia.AWGS2019 may be more appropriate for diagnosing sarcopenia in these Chinese patients than EWGSOP2.
