D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the imp...D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.展开更多
BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factor...BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.展开更多
Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens...Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient(2 mg kg-1feed), iron-sufficient(35 mg kg-1feed), or iron-enriched diet(350 mg kg-1feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice.Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.展开更多
Mucin 2 and occludin play a crucial role in preserving the intestinal mucosal integrity. However, the role for leucine mediating intestinal mucin 2 and occludin expression has little been investigated. The current stu...Mucin 2 and occludin play a crucial role in preserving the intestinal mucosal integrity. However, the role for leucine mediating intestinal mucin 2 and occludin expression has little been investigated. The current study was conducted to test the hypothesis that leucine treatment could increase mucin 2 and occludin levels in LS174 T cells. The LS174 T cells were incubated in the Dulbecco's Modified Eagle Medium(DMEM)supplementing 0, 0.5 and 5 mmol/L L-leucine for the various durations. Two hours after the leucine treatment, the inhibitor of mammalian target of rapamycin(mTOR) and protein kinase B(Akt) phosphorylation in LS174 T cells were significantly increased(P < 0.05), and the mucin 2 and occludin levels were also significantly enhanced(P < 0.05). However, the pretreatment of 10 nmol/L rapamycin, which was an mTOR inhibitor, or 1 μmol/L wortmanin, which was an inhibitor of phosphatidylinositol 3-kinase(PI3 K), completely inhibited leucine-induced mTOR or Akt phosphorylation(P < 0.05), and significantly reduced leucine-stimulated mucin 2 and occludin levels(P < 0.05). These results suggest that leucine treatment promotes the mucin 2 and occludin levels in LS174 T cells partially through the PI3 K-Akt-mTOR signaling pathway.展开更多
Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibil...Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.展开更多
基金funded by the National Natural Science Foundation of China(No.32030083)。
文摘D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.
基金Supported by National Natural Science Foundation of China,No.81501539the Natural Science Foundation of Guangdong Province,China,No.2016A030312008+2 种基金Science and Technology Planning Project of Shantou,China,No.200617105260368Medical Scientific Research Foundation of Guangdong,China,No.A2020627“Dengfeng Project”for the Construction of High-level Hospital in Guangdong Province-The First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.
基金supported by Outstanding Youth Fund of Hunan Natural Science Foundation (2021JJ20045)the National Natural Science Foundation of China (32130099)+4 种基金the Science and Technology Program of Hunan Province (2020NK2013, 2020GK4095)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022370)the key R&D Program of Guangxi Province (2021AB20063)the China Agriculture Research System of MOF and MARAthe National Center of Technology Innovation for Pigs。
文摘Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient(2 mg kg-1feed), iron-sufficient(35 mg kg-1feed), or iron-enriched diet(350 mg kg-1feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice.Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.
基金financially supported by the grant from the National Natural Science Foundation of China (31201812)the earmarked fund for the China Agriculture Research System(CARS-36)the grant from the Science and Technology Support Program of Sichuan Province(13ZC2237)
文摘Mucin 2 and occludin play a crucial role in preserving the intestinal mucosal integrity. However, the role for leucine mediating intestinal mucin 2 and occludin expression has little been investigated. The current study was conducted to test the hypothesis that leucine treatment could increase mucin 2 and occludin levels in LS174 T cells. The LS174 T cells were incubated in the Dulbecco's Modified Eagle Medium(DMEM)supplementing 0, 0.5 and 5 mmol/L L-leucine for the various durations. Two hours after the leucine treatment, the inhibitor of mammalian target of rapamycin(mTOR) and protein kinase B(Akt) phosphorylation in LS174 T cells were significantly increased(P < 0.05), and the mucin 2 and occludin levels were also significantly enhanced(P < 0.05). However, the pretreatment of 10 nmol/L rapamycin, which was an mTOR inhibitor, or 1 μmol/L wortmanin, which was an inhibitor of phosphatidylinositol 3-kinase(PI3 K), completely inhibited leucine-induced mTOR or Akt phosphorylation(P < 0.05), and significantly reduced leucine-stimulated mucin 2 and occludin levels(P < 0.05). These results suggest that leucine treatment promotes the mucin 2 and occludin levels in LS174 T cells partially through the PI3 K-Akt-mTOR signaling pathway.
基金This research was supported by grants from the National Science and Technology Major Project(2018ZX10711-001)the National Natural Science Foundation of China(NSFC)(No.81601813).
文摘Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.
