It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated...It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.展开更多
Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.Howeve...Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after er展开更多
Xyloglucans in the non-lignified primary cell walls of different species of monocotyledons have diverse struc- tures, with widely varying proportions of oligosaccharide units that contain fucosylated side chains （F s...Xyloglucans in the non-lignified primary cell walls of different species of monocotyledons have diverse struc- tures, with widely varying proportions of oligosaccharide units that contain fucosylated side chains （F side chains）. To determine whether fucosylated xyloglucans occur in all non-lignified walls in a range of monocotyledon species, we used immunofluorescence microscopy with the monoclonal antibody CCRC-M1. The epitope of this antibody, α-L-FUCp-（1 →2）- β-D-Galp, occurs in F side chains. In most non-commelinid monocotyledons, the epitope was found in all non-lignified walls. A similar distribution was found in the palm Phoenix canariensis, which is a member of the basal commelinid order Arecales. However, in the other commelinid orders Zingiberales, Commelinales, and Poales, the occurrence of the epitope was restricted, sometimes occurring in only the phloem walls, but often also in walls of other cell types including stomatal guard and subsidiary cells and raphide idioblasts. No epitope was found in the walls of the commelinids Tradescantia virginiana （Commelinaceae, Commelinales） and Zea mays （Poaceae, Poales）, but it occurred in the phloem walls of two other Poaceae species, Lolium multiflorum and L. perenne. The distribution of the epitope is discussed in relation to xyloglucan structures in the different taxa. However, the functional significance of the restricted distributions is unknown.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sen...BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sensitivity and high variability characteristics limit clinical efficacy.Thus,the establishment of better biomarkers is expected.Fucosylation is one of the most important glycosylation modifications of proteins.Fucosylated haptoglobin(Fuc-Hpt)is used as a biomarker for several cancers and inflammation-related diseases.We recently established a novel glycan monoclonal antibody(mAb),designated 10-7G,which recognizes Fuc-Hpt.We developed an enzyme-linked immunosorbent assay(ELISA)to measure serum levels of Fuc-Hpt(10-7G values).AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.METHODS This was a case control study.Intestinal tissues of IBD patients(n=10)were examined immunohistochemically using the 10-7G mAb.We determined 10-7G values using serum from patients with ulcerative colitis(UC,n=110),Crohn’s disease(n=45),acute enteritis(AE,n=11),and healthy volunteers(HVs)who exhibited normal(n=20)or high(n=79)C-reactive protein(CRP)levels at medical check-up.We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.RESULTS In the immunohistochemical analysis,positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles.The 10-7G values were significantly higher in patients with IBD(P<0.001)and AE(P<0.05)compared with HVs.In addition,10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC,particularly the CRP level(rs=0.525,P=0.003展开更多
目的研究海地瓜岩藻糖基化海参硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Acaudina molpadioides,Am-CHS)对Ⅱ型糖尿病小鼠胰岛素抵抗的改善作用。方法以高脂高糖饲料饲喂法建立Ⅱ型糖尿病小鼠模型。雄性C57B...目的研究海地瓜岩藻糖基化海参硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Acaudina molpadioides,Am-CHS)对Ⅱ型糖尿病小鼠胰岛素抵抗的改善作用。方法以高脂高糖饲料饲喂法建立Ⅱ型糖尿病小鼠模型。雄性C57BL/6小鼠随机分为正常对照组、模型对照组、阳性对照组、实验A、B、C组。正常对照组饲喂标准饲料,其它组饲喂高脂饲料。阳性对照组、实验A、B、C组分别在饲料中添加罗格列酮(rosiglitazone,RSG,1mg·kg-1·d-1)、高剂量Am-CHS(80mg·kg-1·d-1)、低剂量Am-CHS+RSG(20+1mg·kg-1·d-1)、高剂量Am-CHS+RSG(80+1mg·kg-1·d-1)。各组小鼠自由摄食摄水19周。实验结束后,称重小鼠白色脂肪重量,检测空腹血糖、空腹血清胰岛素及血清脂联素、抵抗素、瘦素、肿瘤坏死因子-α(TNF-α)水平。结果 Am-CHS可显著降低Ⅱ型糖尿病小鼠的脂肪积累,降低血糖和胰岛素水平,改善胰岛素抵抗,提高血清脂联素含量,降低抵抗素、瘦素和TNF-α含量。Am-CHS与RSG复配使用,效果更显著。结论 Am-CHS能显著改善Ⅱ型糖尿病小鼠的胰岛素抵抗程度,其作用机制可能与改善肥胖引起的脂肪细胞因子的分泌紊乱有关。展开更多
以高脂高糖饲料(high-fat high-sucrose,HFSD)饲喂法建立胰岛素抵抗小鼠模型。研究了冰岛刺参岩藻糖基化硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Cucumaria frondosa,Cf-CHS)对胰岛素抵抗小鼠的降血糖及改...以高脂高糖饲料(high-fat high-sucrose,HFSD)饲喂法建立胰岛素抵抗小鼠模型。研究了冰岛刺参岩藻糖基化硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Cucumaria frondosa,Cf-CHS)对胰岛素抵抗小鼠的降血糖及改善胰岛素抵抗作用。雄性C57BL/6J小鼠随机分为正常对照(标准饲料)、模型对照(HFSD)、阳性对照(HFSD+rosiglitazone(RSG),1mg·(kg·d)-1)、Cf-CHS组(HFSD+Cf-CHS,80mg·(kg·d)-1)及Cf-CHS+RSG组(HFSD+Cf-CHS+RSG,80+1mg·(kg·d)-1)。各组小鼠自由摄食摄水19周。实验结束后,称重小鼠白色脂肪质量,检测空腹血糖、血清胰岛素及血清脂联素、抵抗素、瘦素、肿瘤坏死因子-α(TNF-α)水平。实验结果表明:Cf-CHS可显著降低胰岛素抵抗小鼠的脂肪积累(p<0.01),降低血糖(p<0.01)和胰岛素(p<0.05)水平,改善胰岛素抵抗(p<0.05),提高血清脂联素含量(p<0.05),降低抵抗素(p<0.01)、瘦素(p<0.01)和TNF-α(p<0.05)含量。Cf-CHS与RSG复配使用,效果更显著(p<0.05,p<0.01)。Cf-CHS能显著改善胰岛素抵抗小鼠的高血糖症状及胰岛素抵抗程度,其作用机制可能与改善肥胖引起的脂肪细胞因子的分泌紊乱有关。展开更多
基金supported by the National Nature Science Foundation of China(No.30070183,No.30470398)Key Subject Foundation of Shanghai Municipal Education Committee(No.B9808010).
文摘It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.
基金Supported by the Russian Science Foundation,No.20-65-47026。
文摘Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after er
文摘Xyloglucans in the non-lignified primary cell walls of different species of monocotyledons have diverse struc- tures, with widely varying proportions of oligosaccharide units that contain fucosylated side chains （F side chains）. To determine whether fucosylated xyloglucans occur in all non-lignified walls in a range of monocotyledon species, we used immunofluorescence microscopy with the monoclonal antibody CCRC-M1. The epitope of this antibody, α-L-FUCp-（1 →2）- β-D-Galp, occurs in F side chains. In most non-commelinid monocotyledons, the epitope was found in all non-lignified walls. A similar distribution was found in the palm Phoenix canariensis, which is a member of the basal commelinid order Arecales. However, in the other commelinid orders Zingiberales, Commelinales, and Poales, the occurrence of the epitope was restricted, sometimes occurring in only the phloem walls, but often also in walls of other cell types including stomatal guard and subsidiary cells and raphide idioblasts. No epitope was found in the walls of the commelinids Tradescantia virginiana （Commelinaceae, Commelinales） and Zea mays （Poaceae, Poales）, but it occurred in the phloem walls of two other Poaceae species, Lolium multiflorum and L. perenne. The distribution of the epitope is discussed in relation to xyloglucan structures in the different taxa. However, the functional significance of the restricted distributions is unknown.
基金Ministry of Education,Culture,Sports,Science and Technology of Japan,No.19H03562FUJIFILM Wako Pure Chemical Corporation,No.J770701626.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sensitivity and high variability characteristics limit clinical efficacy.Thus,the establishment of better biomarkers is expected.Fucosylation is one of the most important glycosylation modifications of proteins.Fucosylated haptoglobin(Fuc-Hpt)is used as a biomarker for several cancers and inflammation-related diseases.We recently established a novel glycan monoclonal antibody(mAb),designated 10-7G,which recognizes Fuc-Hpt.We developed an enzyme-linked immunosorbent assay(ELISA)to measure serum levels of Fuc-Hpt(10-7G values).AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.METHODS This was a case control study.Intestinal tissues of IBD patients(n=10)were examined immunohistochemically using the 10-7G mAb.We determined 10-7G values using serum from patients with ulcerative colitis(UC,n=110),Crohn’s disease(n=45),acute enteritis(AE,n=11),and healthy volunteers(HVs)who exhibited normal(n=20)or high(n=79)C-reactive protein(CRP)levels at medical check-up.We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.RESULTS In the immunohistochemical analysis,positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles.The 10-7G values were significantly higher in patients with IBD(P<0.001)and AE(P<0.05)compared with HVs.In addition,10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC,particularly the CRP level(rs=0.525,P=0.003
文摘以高脂高糖饲料(high-fat high-sucrose,HFSD)饲喂法建立胰岛素抵抗小鼠模型。研究了冰岛刺参岩藻糖基化硫酸软骨素(fucosylated chondroitin sulfate from the sea cucumber Cucumaria frondosa,Cf-CHS)对胰岛素抵抗小鼠的降血糖及改善胰岛素抵抗作用。雄性C57BL/6J小鼠随机分为正常对照(标准饲料)、模型对照(HFSD)、阳性对照(HFSD+rosiglitazone(RSG),1mg·(kg·d)-1)、Cf-CHS组(HFSD+Cf-CHS,80mg·(kg·d)-1)及Cf-CHS+RSG组(HFSD+Cf-CHS+RSG,80+1mg·(kg·d)-1)。各组小鼠自由摄食摄水19周。实验结束后,称重小鼠白色脂肪质量,检测空腹血糖、血清胰岛素及血清脂联素、抵抗素、瘦素、肿瘤坏死因子-α(TNF-α)水平。实验结果表明:Cf-CHS可显著降低胰岛素抵抗小鼠的脂肪积累(p<0.01),降低血糖(p<0.01)和胰岛素(p<0.05)水平,改善胰岛素抵抗(p<0.05),提高血清脂联素含量(p<0.05),降低抵抗素(p<0.01)、瘦素(p<0.01)和TNF-α(p<0.05)含量。Cf-CHS与RSG复配使用,效果更显著(p<0.05,p<0.01)。Cf-CHS能显著改善胰岛素抵抗小鼠的高血糖症状及胰岛素抵抗程度,其作用机制可能与改善肥胖引起的脂肪细胞因子的分泌紊乱有关。
