Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

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.

Current situation and influencing factors of novel coronavirus vaccine in college students of Hainan Province

Objective:To investigate the inoculation status of Novel Coronavirus vaccine among college students in Hainan province and its related influencing factors,and to provide scientific basis for improving the inoculation rate of this population.Methods:An electronic questionnaire survey was conducted among 7 colleges and universities in Hainan Province from April 16 to 19,2021.A total of 5896 valid questionnaires were collected with informed consent and voluntary filling.The questionnaire collected information including general demographic characteristics,knowledge attitude and behavioral problems related to COVID-19 vaccine.The difference in the vaccination rate of college students with different characteristics was compared.Multivariate Logistic regression analysis was used to screen the related factors affecting the vaccination rate of college students in Hainan.Results:There were 3,360(57%)female students,2,509(42.6%)medical students,2,380(40.4%)Hainan students,3,441(58.4%)undergraduates,3,281(57.3%)rural students,and 5,165(87.6%)Han students.The inoculation rate of COVID-19 vaccine among college students in Hainan province was 81.7%.The average score of knowledge about COVID-19 vaccine was 11.78±3.18,the total score was 17,and the relative attitude score was 47.77±6.10,the total score was 55.Univariate analysis found that difference gender,age,grade,stage of study,medical students,Hainanese origin,school organization vaccination,vaccine knowledge and attitude scores,the difference of inoculation rate was statistically significant(P<0.05).Multivariate analysis showed that women(OR=1.204),medical profession(OR=4.587),native place of Hainan(OR=1.541),rural area of origin(OR=1.311),school carrying out collective vaccine vaccination(OR=2.933),high scores of knowledge about COVID vaccine(OR=1.104)and attitude(OR=1.025)could increase the vaccination rate of college students(P<0.05).Conclusion:The vaccination rate of college students in Hainan Province still needs to be improved.It is necessary to strengthen the popularization of vaccine-related knowledge among male students and non-medical students,improve the mastery of the knowledge of the vaccine and enhance the confidence of the vaccine in China,which is conducive to the improvement of the vaccination rate of college students.

Epidemiological characteristics of 168 cases of COVID-19 in Hainan Island, tropical China: A descriptive study

Objective:To understand the epidemic characters of COVID-19 epidemic in Hainan province of tropical China and provid evidences for the prevention and control of the epidemic.Methods:Data on the COVID-19 epidemic collected from Health Commission of Hainan Province were analyzed by using the methods of retrospective descriptive epidemiology.Results:From January 22nd to February 21st,2020,COVID-19 was diagnosed in 168 confirmed cases(including 8 severe cases)in Hainan Province with the temporary fatality rate of 2.38%of 4 deaths,and 96 cases discharged from hospital,with the cure rate of 57.14%.The cases were distributed in altogether 15 cities and counties in Hainan Province,among which 121 cases were distributed in Sanya,Haikou,Danzhou and Wanning,accounting for 72.02%of the total number of cases.Cases in Sanya City were mainly found in Tianya district and Jiyang district,accounting for 69.81%of the total number of cases in Sanya.Cases in Haikou City were mainly found in Qiongshan district and Xiuying district,accounting for 72.5%of the total number of cases in Haikou.Among the patients,there were 81 males and 87 females,with a male-to-female ratio of 1.1;the youngest age was 3 months,the oldest was 79 years old,80%of the patients were in the age group of 30 to 69 years old,and the number of children and adolescents under 20 years old were relatively low.Conclusion:The daily number of new confirmed cases showed a gradual downward trend in Hainan province,and the epidemic situation was in transition from imported to local renewal,mainly in close contact between family members.With the increase of personnel mobility such as the resumption of work by enterprises and the return of migrant workers to the island,there is a risk of agglomeration epidemic.Prevention and control work in urban and rural areas should take a two-pronged approach.Amid preventing imported cases,more proactive measures should be taken to prevent and control the spread of local cases.

Gut microbiome,cognitive function and brain structure:a multi-omics integration analysis

Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.Methods:We included 1430 participants from the Guangzhou Nutrition and Health Study(GNHS)with both gut microbiome and cognitive assessment data available as a discovery cohort,of whom 272 individuals provided fecal samples twice before cognitive assessment.We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit.Fecal 16S rRNA and shotgun metagenomic sequencing,tar-geted serum metabolomics,and cytokine measurements were performed in the GNHS.The validation analyses were conducted in an Alzheimer’s disease case-control study(replication study 1,n=90)and another community-based cohort(replication study 2,n=1300)with cross-sectional dataset.Results:We found protective associations of specific gut microbial genera(Odoribacter,Butyricimonas,and Bac-teroides)with cognitive impairment in both the discovery cohort and the replication study 1.Result of Bacteroides was further validated in the replication study 2.Odoribacter was positively associated with hippocampal volume(β,0.16;95%CI 0.06-0.26,P=0.002),which might be mediated by acetic acids.Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment.We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Conclusions:Our findings reveal that specific gut microbial features are closely associated with cognitive impair-ment and decreased hippocampal volume,which may play an important role in dementia development.