Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins

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Loss of core fucosylation suppressed the humoral immune response in Salmonella typhimurium infected mice

BackgroundThe humoral immune response is pivotal to protect the host from Salmonella typhimurium (S. typhimurium) infection. Previously, we found that core fucosylation catalyzed by core fucosyltransferase (Fut8) could regulate the immune responses. However, the role of core fucosylation during S. typhimurium infection remains unclear.MethodsTo demonstrate the role of Fut8 in S. typhimurium infection, we infected Fut8^+/+ and Fut8^−/− mice using S. typhimurium. The production of antiserum against the S. typhimurium was detected. The expression of T and B cell activation-related genes during S. typhimurium infection was analyzed. The role of core fucosylation on CD4⁺ T-B cell interaction and B cell generation was investigated during S. typhimurium infection. The production of sIgA was compared between Fut8^+/+ and Fut8^−/− mice.ResultsCompared to Fut8^+/+ mice, the number of S. typhimurium colonized in the cecum was markedly increased in Fut8^−/− mice. The production of the IgG and sIgA specific for S. typhimurium was significantly decreased in Fut8^−/− mice. Moreover, loss of Fut8 decreased the induction of Th2-type cytokines from splenic cells of Fut8^−/− mice during S. typhimurium infection. In addition, we found that the core fucosylation regulated the interaction between B and T cells in the lipid raft formation.ConclusionCore fucosylation plays important roles in host defence against S. typhimurium infection.     

Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein

Background and Aim: Fucosylated alpha‐fetoprotein (AFP‐L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP‐L3 under low AFP (≤ 20 ng/mL). The aim of this study was to elucidate the role of AFP‐L3 in HCC patients with low AFP conditions. Methods: One hundred and ninety six consecutive newly developed HCC patients with low AFP (≤ 20 ng/mL) were examined for serum AFP‐L3 expression by a newly‐developed micro‐total analysis system that could stably measure AFP‐L3 in low AFP circumstances, and its clinical importance was analyzed. Results: Positivity of AFP‐L3 in HCC patients was 13.3% at a cut‐off level of 10%. Five‐year survivals of HCC patients with AFP‐L3 (< 10%) and AFP‐L3 (≥ 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des‐gamma carboxy prothrombin were observed in the high AFP‐L3 (≥ 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR] = 3.24, 95% confidence interval [CI] = 1.27–8.26), the presence of ascites (RR = 3.44, 95% CI = 1.22–9.34), multiple tumor number (RR = 3.06, 95% CI = 1.33–7.17), and high AFP‐L3 (RR = 8.36, 95% CI = 2.79–25.5) were risk factors for survival. High AFP‐L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048). Conclusions: AFP‐L3 is a strong prognostic factor for survival even in HCC patients with low AFP (≤ 20 ng/mL).     

Local administration of 2% trimecaine affects the content of fucosylated glycoconjugates in goblet cells in rabbit tracheal epithelium

The proportion of fucosylated glycoconjugate-containing rabbit tracheal goblet cells after intratracheal application of trimecaine was studied to evaluate its possible unfavourable effects. This lapine model is comparable with diagnostic findings in humans because airway epithelia in humans and rabbits are similar; tracheal epithelium is also practically identical to bronchial epithelium in both species. Local trimecaine anaesthesia caused a proportional decrease in percentage of the tracheal goblet cells containing both alpha(1-2)- and alpha(1-6)-, alpha(1-3)- and alpha(1-4)-fucosylated glycoconjugates as revealed 10 min postexposure using lectin histochemistry. In previous studies, only mild ultrastructural damage to the airway's epithelium was revealed, but a conspicuous decrease in sialylated glycoconjugate-containing tracheal goblet cells and the dominance of acidic sulphated glycoconjugates were observed as after-effects of the same treatment. Glycoconjugate changes can influence the inner environment of airways (e.g. viscoelastic properties of the airways' mucus and mucosal barrier functions) and thus the patient's defence barriers in airways may be weakened. Concurrently, the histochemical properties of goblet cells can be altered in bronchoscopic specimens. Since trimecaine is widely used as local anaesthesia in airways in bronchoscopy, it is necessary to heed these aforementioned effects.     

Challenges in the Application of Glyco-Technology to Hepatitis B Virus Therapy and Diagnosis

Hepatitis B virus (HBV) is a major pathogen that causes acute/chronic hepatitis. Continuous HBV infection can lead to the development of hepatocellular carcinoma (HCC). Although several different anti-HBV treatments are available for chronic hepatitis B patients, discontinuing these medications is difficult. Patients with chronic hepatitis B at high risk for HCC therefore require close observation. However, no suitable biomarkers for detecting high-risk groups for HCC exist, except for serum HBV-DNA, but a number of HCC biomarkers are used clinically, such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II). Glycosylation is an important post-translational protein modification involved in many human pathologic conditions. HBV surface proteins contain various oligosaccharides, and several reports have described their biological functions. Inhibition of HBV glycosylation represents a potential novel anti-HBV therapy. It is thought that glycosylation of hepatocytes/hepatoma cells is also important for HBV infection, as it prevents HBV from infecting cells other than hepatocytes, even if the cells express the HBV receptor. In this review, we summarize considerable research regarding the relationship between HBV and glycosylation as it relates to the development of novel diagnostic tests and therapies for HBV.     

Application of glycoscience to the early detection of pancreatic cancer

The prognosis of pancreatic cancer is extremely poor compared to other cancers. One of the reasons for this is the difficulty of early diagnosis. Surveillance using cancer biomarkers and image diagnosis can enable early detection and has improved the prognosis of hepatocellular carcinoma in Japan. However, it is very difficult to detect pancreatic cancer at an early stage using cancer biomarkers and image diagnosis alone. Fucosylation is one of the most important types of glycosylation involved in cancer and inflammation. We have developed a novel glycocancer biomarker, fucosylated haptoglobin (Fuc‐Hpt), and have investigated its usefulness for the diagnosis of pancreatic cancer over approximately 10 years. Recently, we also found that most pancreatic tissues surrounding pancreatic cancer exhibit chronic pancreatitis with fibrosis and/or fatty degeneration. Certain forms of chronic pancreatitis might indicate high risk for the development of pancreatic cancer. In this review, we provide a historical summary of our research on Fuc‐Hpt as a cancer biomarker, and discuss a potential early detection system for pancreatic cancer.