BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported ...BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.展开更多
Background:As a congenital malformation that results in infertility and an inability to have vaginal intercourse,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome places a considerable psychological burden on patients...Background:As a congenital malformation that results in infertility and an inability to have vaginal intercourse,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome places a considerable psychological burden on patients,which results in anxiety symptoms.However,only single case studies or a few small to medium-sized cross-sectional studies were identified to focus on anxiety symptoms in MRKH patients.Thus,the aim of this study was to explore the status of anxiety symptoms and the related factors in patients with MRKH syndrome.Methods:This cross-sectional study involving 141 patients with MRKH syndrome and 178 healthy women was conducted from January 2018 to December 2018.All participants were required to complete a demographic questionnaire and the Generalized Anxiety Disorder 7-item scale(GAD-7),Patient Health Questionnaire-9,Eysenck Personality Questionnaire-Revised,Short Scale for Chinese,and Chinese Version of the Female Sexual Function Index.The main outcome was the anxiety symptoms measured by the GAD-7.Main outcome was compared between the MRKH syndrome group and the healthy control group.Then,we explored the related factors by comparing patients with and without anxiety symptoms.Results:Of the respondents,24.1%experienced moderate to severe anxiety symptoms.Patients with MRKH syndrome manifested more severe anxiety symptoms than healthy women.Negative self-evaluation of femininity(odds ratio[OR]2.706,95%confidence interval[CI]1.010-7.247),neurotic personality traits(OR 1.100,95%CI 1.029-1.175),and coexisting depressive symptoms(OR 4.422,95%CI 1.498-13.049)were more prevalent in anxious patients.Conclusion:The findings stress the importance of anxiety symptom screening in MRKH patients and identify patients at risk of anxiety symptoms,providing a possible basis for future intervention.展开更多
基金the Natural Science Foundation of Hainan Province,No.823MS046the Talent Program of Hainan Medical University,No.XRC2022007.
文摘BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
文摘Background:As a congenital malformation that results in infertility and an inability to have vaginal intercourse,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome places a considerable psychological burden on patients,which results in anxiety symptoms.However,only single case studies or a few small to medium-sized cross-sectional studies were identified to focus on anxiety symptoms in MRKH patients.Thus,the aim of this study was to explore the status of anxiety symptoms and the related factors in patients with MRKH syndrome.Methods:This cross-sectional study involving 141 patients with MRKH syndrome and 178 healthy women was conducted from January 2018 to December 2018.All participants were required to complete a demographic questionnaire and the Generalized Anxiety Disorder 7-item scale(GAD-7),Patient Health Questionnaire-9,Eysenck Personality Questionnaire-Revised,Short Scale for Chinese,and Chinese Version of the Female Sexual Function Index.The main outcome was the anxiety symptoms measured by the GAD-7.Main outcome was compared between the MRKH syndrome group and the healthy control group.Then,we explored the related factors by comparing patients with and without anxiety symptoms.Results:Of the respondents,24.1%experienced moderate to severe anxiety symptoms.Patients with MRKH syndrome manifested more severe anxiety symptoms than healthy women.Negative self-evaluation of femininity(odds ratio[OR]2.706,95%confidence interval[CI]1.010-7.247),neurotic personality traits(OR 1.100,95%CI 1.029-1.175),and coexisting depressive symptoms(OR 4.422,95%CI 1.498-13.049)were more prevalent in anxious patients.Conclusion:The findings stress the importance of anxiety symptom screening in MRKH patients and identify patients at risk of anxiety symptoms,providing a possible basis for future intervention.
