Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidativ...Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.展开更多
Tropomyosin(TM)is the predominant allergenic protein in shrimp,which has induced IgE-mediated food allergy reactions.In this study,Lit v 1 was purified from Penaeus vannamei muscles,which were glyco sylated by pectic ...Tropomyosin(TM)is the predominant allergenic protein in shrimp,which has induced IgE-mediated food allergy reactions.In this study,Lit v 1 was purified from Penaeus vannamei muscles,which were glyco sylated by pectic oligosaccharides.The results showed that di-galacturonic acid(DGA)and galacturonic acid(GA)induced the unfolding of the primary protein structure of TM,and changedα-helical structure,and IgE binding capacity.In addition,compared with TM-sensitized BALB/c mice,GA-modified TM(GA-TM)and DGA-modified TM(DGA-TM)were insufficient to stimulate sensitization,and significantly reduced the hypersecretion of IgE,IgG1,HIS,and IL-4,up-regulated IgG2a and IFN-y levels to improve imbalanced Th1/Th2,Treg/Th17 immunity,and promoted mRNA expression of tight junction proteins.Together,this study confirmed that glycosylation modification alleviated sensitization by altering TM structure,reducing IgE binding allergic inflammatory response,and regulating cytokine immune balance.Overall,these results indicated that glycosylation modification was a promising method for decreasing the allergenic reactivity of allergic proteins.展开更多
BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibr...BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibrosis in patients with chronic hepatitis B(CHB),and its changes during treatment.METHODS This was a prospective,longitudinal study.A total of 348 eligible patients were recruited from the Hepatology Department,Medic Medical Center between March 2020 and December 2023.Liver enzyme tests,platelet counts,M2BPGi levels,and FibroScan were conducted at baseline and at 3-month intervals until six months post-treatment.Correlation plots of M2BPGi,FibroScan,and the other parameters were generated.Receiver operating characteristic curves were constructed for M2BPGi and the other parameters to evaluate their performance.RESULTS M2BPGi levels correlated well with FibroScan results and increased as the fibrosis stage advanced.The median M2BPGi levels at the different stages of fibrosis showed statistically significant differences.The cut-off values of M2BPGi for diagnosing significant fibrosis(F≥2),advanced fibrosis(F3),and cirrhosis(F4)were determined to be 1.08,1.4,and 1.52,respectively.In the context of fibrosis regression in CHB patients during the first 6-month of treatment,M2BPGi levels appeared to decrease before this pattern occurred in the FibroScan results.CONCLUSION M2BPGi levels were strongly correlated with FibroScan.M2BPGi can be used to assess liver fibrosis,and to serve as a tool for monitoring fibrosis regression in CHB patients undergoing treatment.展开更多
BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-assoc...BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-associated steatotic liver disease(MASLD)is rising in prevalence and there is an urgent need for better clinical management,particularly in early detection methods that will improve overall prognosis.AIM To examine M2BPGi cut-off values for staging liver fibrosis in patients with MASLD and risk factors associated with disease progression.METHODS A total of 301 individuals with ultrasound-confirmed or FibroScan-confirmed diagnosis of fatty liver were enrolled in the study.The participants were stratified according to fibrosis stage,measured via magnetic resonance elastography.M2-BPGi,Fibrosis-4(FIB-4)Index score,and routine parameters of liver function were assessed to statistically investigate the correlation of M2BPGi levels in various fibrosis stages and to identify risk factors associated with fibrosis severity.RESULTS M2BPGi levels positively correlated with fibrosis stages,with cut-off indexes of 0.57 for F0-1,0.68 for F2-3,and 0.78 for F4.M2BPGi levels in the F0-1 group were significantly different from those in both the F2-3 group(P=0.038)and the F4 group(P=0.0051);the F2-3 and F4 groups did not show a significant difference(P=0.39).Females exhibited significantly higher M2BPGi levels than males for all fibrosis stages,particularly in the F2-3 group(P=0.01)and F4 group(P=0.0006).In the F4(cirrhosis)group,individuals with diabetes had significantly higher M2BPGi levels than those without.M2BPGi,hemoglobin A1c,and FIB-4 score were identified as independent risk factors for greater fibrosis and cirrhosis.CONCLUSION M2BPGi levels varied significantly throughout fibrosis progression,from early MASLD to cirrhosis,with sex correlation.M2BPGi holds promise as an early biomarker for fibrosis characterization in MASLD adult patient populations.展开更多
Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride ...Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride which is easily prepared,stable and user-friendly.The resulting donors exhibit exceptional shelf stability while can be readily activated to achieve high-yielding glycosylation,encompassing comprehensively aldosyl,ketosyl and ulosonyl donors,and both O-and N-glycosylation acceptors.Notably,the reactivity gradient across different generations of imidates,coupled with the accessible imidate acceptor from selective reaction of imidoyl fluoride at the anomeric hydroxyl group,enables a fully catalytic one-pot synthesis of oligosaccharides.展开更多
Glycosyl radicals,produced under mild photoredox conditions,show unique utility in the preparation of C-linked glycoconjugates.We herein report the construction of C-glycosidic bonds on α,β-dehydroalanine(DHA)of pep...Glycosyl radicals,produced under mild photoredox conditions,show unique utility in the preparation of C-linked glycoconjugates.We herein report the construction of C-glycosidic bonds on α,β-dehydroalanine(DHA)of peptides with easily available glycosyl bromides as glycosyl radical precursors under highly anomeric control,leading to C-glycosylation modifications of peptides.This method not only has outstanding functional group compatibility,but also is feasible in near-physiological conditions(pH~7 and temperature T≤37℃ in aqueous media).展开更多
Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development ...Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.展开更多
BACKGROUND Glycosylation,a commonly occurring post-translational modification,is highly expressed in several tumors,specifically in those of the digestive system,and plays a role in various cellular pathophysiological...BACKGROUND Glycosylation,a commonly occurring post-translational modification,is highly expressed in several tumors,specifically in those of the digestive system,and plays a role in various cellular pathophysiological mechanisms.Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years,bibliometric analysis of this field remains scarce.The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors.AIM To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors.METHODS We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace(version 6.1.R6)to perform bibliometric analysis.RESULTS A total of 2042 documents spanning from 1978 to the present were analyzed,with the research process divided into three phases:the period of obscurity(1978-1990),continuous development period(1991-2006),and the rapid outbreak period(2007-2023).These documents were authored by researchers from 66 countries or regions,with the United States and China leading in terms of publication output.Reis Celso A had the highest number of publications,while Pinho SS was the most cited author.Co-occurrence analysis revealed the most popular keywords in this field are glycosylation,expression,cancer,colorectal cancer,and pancreatic cancer.Furthermore,the Journal of Proteome Research was the most prolific journal in terms of publications,while the Journal of Biological Chemistry had the most citations.CONCLUSION The bibliometric analysis shows current research focus is primarily on basic research in this field.However,future research should aim to utilize glycosylation as a target for treating tumor patients.展开更多
Surface (S)-layer proteins are model systems for studying protein glycosylation in bacteria and simultaneously hold promises for the design of novel, glyco-functionalized modules for nanobiotechnology due to their 2D ...Surface (S)-layer proteins are model systems for studying protein glycosylation in bacteria and simultaneously hold promises for the design of novel, glyco-functionalized modules for nanobiotechnology due to their 2D self-assembly capability. Understanding the mechanism governing S-layer glycan biosynthesis in the Gram-positive bacterium Paenibacillus alvei CCM 2051T is necessary for the tailored glyco-functionalization of its S-layer. Here, the putative oligosaccharyl:S-layer protein transferase WsfB from the P. alvei S-layer glycosylation gene locus is characterized. The enzyme is proposed to catalyze the final step of the glycosylation pathway, transferring the elongated S-layer glycan onto distinct tyrosine O-glycosylation sites. Genetic knock-out of WsfB is shown to abolish glycosylation of the S-layer protein SpaA but not that of other glycoproteins present in P. alvei CCM 2051T, confining its role to the S-layer glycosylation pathway. A transmembrane topology model of the 781-amino acid WsfB protein is inferred from activity measurements of green fluorescent protein and phosphatase A fused to defined truncations of WsfB. This model shows an overall number of 13 membrane spanning helices with the Wzy_C domain characteristic of O-oligosaccharyl:protein transferases (O-OTases) located in a central extra-cytoplasmic loop, which both compares well to the topology of OTases from Gram-negative bacteria. Mutations in the Wzy C motif resulted in loss of WsfB function evidenced in reconstitution experiments in P. alvei ΔWsfB cells. Attempts to use WsfB for transferring heterologous oligosaccharides to its native S-layer target protein in Escherichia coli CWG702 and Salmonella enterica SL3749, which should provide lipid-linked oligosaccharide substrates mimicking to some extent those of the natural host, were not successful, possibly due to the stringent function of WsfB. Concluding, WsfB has all features of a bacterial O-OTase, making it the most probable candidate for the oligosaccharyl:S-layer protein transferase of P. alvei, and a promising candidate for the first O-OTase reported in Gram-positives.展开更多
Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was ...Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control. Results Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV. Conclusion Glycosylation altered the gating properties of rNav 1.3 and contributed to the functional diversity.展开更多
AIM: To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV. The purpose of this study is to investigate the affection of context se...AIM: To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV. The purpose of this study is to investigate the affection of context sequences on hepatitis C virus (HCV) E2 processing. METHODS: HCV genes of different lengths were expressed and compared in vaccinia virus/T7 system with homologous patient serum S94 and mouse anti-serum M( E2116) raised against E.coli -derived E2 peptide, respectively.Deglycosylation analysis and GNA ( Galanthus nivalus ) lectin binding assay were performed to study the post-translational processing of the expressed products. RESULTS: E2 glycoproteins with different molecular weights (-75 kDa and -60 kDa) were detected using S94 and M( E2116), respectively. Deglycosylation analysis showed that this difference was mainly due to different glycosylation. Endo H resistance and its failure to bind to GNA lectin demonstrated that the higher molecular weight form (75 kDa) of E2 was complex-type glycosylated, which was readily recognized by homologous patient serum S94. Expression of complex-type glycosylated E2 could not be detected in all of the core-truncated constructs tested, but readily detected in constructs encoding full-length core sequences. CONCLUSION: The upstream conserved full-length core coding sequence was required for the production of E2 glycoproteins carrying complex-type N-glycans which reacted strongly with homologous patient serum and therefore possibly represented more mature forms of E2. As complex-type N-glycans indicated modification by Golgi enzymes, the results suggest that the presence of full-length core might be critical for E1/E2 complex to leave ER. Our data may contribute to a better understanding of the processing of HCV structural proteins as well as HCV morphogenesis.展开更多
AIM: To study whether alterations in the glycosylation of immunoglobulin G (IgG) specific to the ThomsenFriedenreich glycotope (TF) have diagnostic and prognostic potential in gastric cancer. METHODS: Serum samples we...AIM: To study whether alterations in the glycosylation of immunoglobulin G (IgG) specific to the ThomsenFriedenreich glycotope (TF) have diagnostic and prognostic potential in gastric cancer. METHODS: Serum samples were obtained from patients with histologically verified gastric carcinoma (n = 89), healthy blood donors (n = 40), and patients with benign stomach diseases (n = 22). The lectin-enzymelinked immunosorbent assay-based glycoprofiling of TF-specific IgG (anti-TF IgG) was performed using synthetic TF-polyacrylamide conjugate as antigen, total IgG purified by affinity chromatography on protein G sepharose, and lectins of various sugar specificities: mannose-specific concanavalin A (ConA), fucose-specificAleuria aurantia lectin (AAL) and sialic acid-specific Sambucus nigra agglutinin (SNA). The sensitivity and specificity of the differences between cancer patients and controls were evaluated by receiver operator characteristic (ROC) curve analysis. Overall survival was analyzed by the Kaplan-Meier method. Time-dependent ROC curve statistics were applied to determine cut-off values for survival analysis. All calculations and comparisons were performed using the GraphPad Prism 5 and SPSS 15.0 software.RESULTS: The level of TF-specific IgG was significantly increased in cancer patients compared with non-cancer controls (P < 0.001). This increase was pronounced mostly in stage 1 of the disease. Cancer patients showed a higher level of ConA binding to antiTF-IgG (P < 0.05) and a very low level of SNA lectin binding (P = 0.0001). No appreciable stage-dependency of the binding of any lectin to anti-TF IgG was found. A strong positive correlation between the binding of AAL and SNA was found in all groups studied (r = 0.71-0.72; P < 0.0001). The changes in ConA reactivity were not related to those of the fucoseor sialic acid-specific lectin. Changes in the SNA binding index and the ConA/SNA binding ratio demonstrated good sensitivity and specificity for stomach cancer: sensitivity 78.79% (95%CI: 61.09-91.02) and 72.73% (95%CI: 57.21-85.04); specificity 79.17 (95%CI: 65.01-89.53) and 88.64% (95%CI: 71.8-96.6), for the SNA binding index and the ConA/SNA binding ratio, respectively. The other combinations of lectins did not improve the accuracy of the assay. The low level of ConA-positive anti-TF IgG was associated with a survival benefit in cancer patients (HR = 1.56; 95%CI: 0.78-3.09; P = 0.19), especially in stages 3-4 of the disease (HR = 2.17; 95%CI: 0.98-4.79; P = 0.048). A significantly better survival rate was found in all cancer patients with a low reactivity of anti-TF IgG to the fucose-specific AAL lectin (HR = 2.39; 95%CI: 1.0-5.7;P = 0.038).CONCLUSION: The changes in the TF-specific IgG glycosylation pattern can be used as a biomarker for stomach cancer detection, and to predict patient survival.展开更多
OBJECTIVE： To study the effects of Xixin decoction （XXD） on O-linked N-acetylglucosamine （O-GIcNAc） glycosylation of tau proteins in rat brain with spo- radic Alzheimer disease （SAD）, and discuss its possi- ble...OBJECTIVE： To study the effects of Xixin decoction （XXD） on O-linked N-acetylglucosamine （O-GIcNAc） glycosylation of tau proteins in rat brain with spo- radic Alzheimer disease （SAD）, and discuss its possi- ble mechanism on prevention and treatment of SAD. METHODS： The rat model of SAD was established by intracerebroventricular injection of streptozoto- cin. The specific pathogen free male Sprague-Daw- ley rats were randomly divided into sham-opera- tion group （S）, model group （M）, donepezil group （D）, XXD at a low dose group （XL）, XXD at a medium dose group （XM） and XXD at a high dose group （XH）. After treatment and praxiology test, immuno- histochemistry and western blotting were used to detect O-GIcNAc glycosylation level of tau proteins in rat brain with SAD. O-GIcNAc glycosylation and expression of tau proteins were detected by O-GIcNAc-specific antibodies RL2 and CTD110.6. RESULTS： O-GIcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significant- ly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups （P〈0.05, P〈0.01）, while no obvious dif- ferences were observed between D group and M group （P〉0.05）. CONCLUSION： XXD can significantly improve O-GIcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hy- perphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological pro- cess of SAD.展开更多
N-Linked glycosylation of hemagglutinin(HA) has been demonstrated to regulate the virulence and receptor-binding specificity of avian influenza virus(AIV).In this study,we characterized the variation trend of naturall...N-Linked glycosylation of hemagglutinin(HA) has been demonstrated to regulate the virulence and receptor-binding specificity of avian influenza virus(AIV).In this study,we characterized the variation trend of naturally isolated H9 N2 viruses for the potential N-linked glycosylation sites in HA proteins,and explored any important role of some glycosylation sites.HA genes of 19 H9 N2 subtype AIV strains since 2001 were sequenced and analyzed for the potential glycosylation sites.The results showed that the viruses varied by losing one potential glycosylation site at residues 200 to 202,and having an additional one at residues 295 to 297 over the past few years.Further molecular and single mutation analysis revealed that the N200 Q mutation lost an N-linked glycosylation at positions 200 to 202 of the HA protein and affected the human-derived receptor affinity.We further found that this N-linked glycosylation increased viral productivity in the lung of the infected mice.These findings provide a novel insight on understanding the determinants of host adaption and virulence of H9 N2 viruses in mammals.展开更多
BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for f...BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.展开更多
The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the ad...The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.展开更多
Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain. Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terminal. The chimera...Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain. Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terminal. The chimera gene was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co- transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation. Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed product in recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence assay. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosylation of VP4 protein. Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicity and immunogenicity of expressed protein.展开更多
The present study was designed to explore the substrate scope and biocatalytic capability of Gliocladium deliquescens NRRL 1086 on phenolic natural products. Emodin was subjected to the fermentation culture of Gliocla...The present study was designed to explore the substrate scope and biocatalytic capability of Gliocladium deliquescens NRRL 1086 on phenolic natural products. Emodin was subjected to the fermentation culture of Gliocladium deliquescens NRRL 1086 according to the standard two-stage protocol. The biotransformation process was monitored by HPLC-DAD-MS, the main product was isolated by column chromatography, and the structure was elucidated on the basis of NMR spectroscopy. Emodin could be fully metabolized by Gliocladium deliquescens NRRL 1086, resulting in high yield of emodin 6-O-β-D-glucopyranoside and small amount of sulfated product. In conclusion, our results may provide a convenient method to prepare emodin 6-O-β-D-glucopyranoside and the microbe catalyzed glucosylation/sulfation will give an inspiration to pharmacokinetic model studies in vitro.展开更多
Sulfuric acid immobilized on silica gel is designed as a very useful catalyst for synthesis of 2,3-unsaturated glycopyranosides. This handy,metal-free,environment friendly transformation provides high yields andα-ste...Sulfuric acid immobilized on silica gel is designed as a very useful catalyst for synthesis of 2,3-unsaturated glycopyranosides. This handy,metal-free,environment friendly transformation provides high yields andα-stereoselectivities in a very few amount （0.02 eq.） of catalyst and in short reaction times（10 min）.展开更多
基金supported by the Open Project of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202201)Tianjin Food Processing Control and Safety Engineering Technology Center(GCZX202303)。
文摘Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.
基金supported by the National Natural Science Fund(31601395)Central Guidance on Local Science and Technology Development Fund of Guizhou Province([2023]016)+1 种基金China National Center for Food Safety Risk Assessment(2018K01-20171211)Lueyang Black-Bone Chicken Industry Development Research Institute(WJYJY-2021-9)。
文摘Tropomyosin(TM)is the predominant allergenic protein in shrimp,which has induced IgE-mediated food allergy reactions.In this study,Lit v 1 was purified from Penaeus vannamei muscles,which were glyco sylated by pectic oligosaccharides.The results showed that di-galacturonic acid(DGA)and galacturonic acid(GA)induced the unfolding of the primary protein structure of TM,and changedα-helical structure,and IgE binding capacity.In addition,compared with TM-sensitized BALB/c mice,GA-modified TM(GA-TM)and DGA-modified TM(DGA-TM)were insufficient to stimulate sensitization,and significantly reduced the hypersecretion of IgE,IgG1,HIS,and IL-4,up-regulated IgG2a and IFN-y levels to improve imbalanced Th1/Th2,Treg/Th17 immunity,and promoted mRNA expression of tight junction proteins.Together,this study confirmed that glycosylation modification alleviated sensitization by altering TM structure,reducing IgE binding allergic inflammatory response,and regulating cytokine immune balance.Overall,these results indicated that glycosylation modification was a promising method for decreasing the allergenic reactivity of allergic proteins.
文摘BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibrosis in patients with chronic hepatitis B(CHB),and its changes during treatment.METHODS This was a prospective,longitudinal study.A total of 348 eligible patients were recruited from the Hepatology Department,Medic Medical Center between March 2020 and December 2023.Liver enzyme tests,platelet counts,M2BPGi levels,and FibroScan were conducted at baseline and at 3-month intervals until six months post-treatment.Correlation plots of M2BPGi,FibroScan,and the other parameters were generated.Receiver operating characteristic curves were constructed for M2BPGi and the other parameters to evaluate their performance.RESULTS M2BPGi levels correlated well with FibroScan results and increased as the fibrosis stage advanced.The median M2BPGi levels at the different stages of fibrosis showed statistically significant differences.The cut-off values of M2BPGi for diagnosing significant fibrosis(F≥2),advanced fibrosis(F3),and cirrhosis(F4)were determined to be 1.08,1.4,and 1.52,respectively.In the context of fibrosis regression in CHB patients during the first 6-month of treatment,M2BPGi levels appeared to decrease before this pattern occurred in the FibroScan results.CONCLUSION M2BPGi levels were strongly correlated with FibroScan.M2BPGi can be used to assess liver fibrosis,and to serve as a tool for monitoring fibrosis regression in CHB patients undergoing treatment.
文摘BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-associated steatotic liver disease(MASLD)is rising in prevalence and there is an urgent need for better clinical management,particularly in early detection methods that will improve overall prognosis.AIM To examine M2BPGi cut-off values for staging liver fibrosis in patients with MASLD and risk factors associated with disease progression.METHODS A total of 301 individuals with ultrasound-confirmed or FibroScan-confirmed diagnosis of fatty liver were enrolled in the study.The participants were stratified according to fibrosis stage,measured via magnetic resonance elastography.M2-BPGi,Fibrosis-4(FIB-4)Index score,and routine parameters of liver function were assessed to statistically investigate the correlation of M2BPGi levels in various fibrosis stages and to identify risk factors associated with fibrosis severity.RESULTS M2BPGi levels positively correlated with fibrosis stages,with cut-off indexes of 0.57 for F0-1,0.68 for F2-3,and 0.78 for F4.M2BPGi levels in the F0-1 group were significantly different from those in both the F2-3 group(P=0.038)and the F4 group(P=0.0051);the F2-3 and F4 groups did not show a significant difference(P=0.39).Females exhibited significantly higher M2BPGi levels than males for all fibrosis stages,particularly in the F2-3 group(P=0.01)and F4 group(P=0.0006).In the F4(cirrhosis)group,individuals with diabetes had significantly higher M2BPGi levels than those without.M2BPGi,hemoglobin A1c,and FIB-4 score were identified as independent risk factors for greater fibrosis and cirrhosis.CONCLUSION M2BPGi levels varied significantly throughout fibrosis progression,from early MASLD to cirrhosis,with sex correlation.M2BPGi holds promise as an early biomarker for fibrosis characterization in MASLD adult patient populations.
基金the National Natural Science Foundation of China(No.21672147)Shanghai University of Traditional Chinese Medicine for financial support。
文摘Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride which is easily prepared,stable and user-friendly.The resulting donors exhibit exceptional shelf stability while can be readily activated to achieve high-yielding glycosylation,encompassing comprehensively aldosyl,ketosyl and ulosonyl donors,and both O-and N-glycosylation acceptors.Notably,the reactivity gradient across different generations of imidates,coupled with the accessible imidate acceptor from selective reaction of imidoyl fluoride at the anomeric hydroxyl group,enables a fully catalytic one-pot synthesis of oligosaccharides.
基金supported by National Natural Science Foundation of China(No.22171133)State Key Laboratory of Analytical Chemistry for Life Science(No.5431ZZXM2308)。
文摘Glycosyl radicals,produced under mild photoredox conditions,show unique utility in the preparation of C-linked glycoconjugates.We herein report the construction of C-glycosidic bonds on α,β-dehydroalanine(DHA)of peptides with easily available glycosyl bromides as glycosyl radical precursors under highly anomeric control,leading to C-glycosylation modifications of peptides.This method not only has outstanding functional group compatibility,but also is feasible in near-physiological conditions(pH~7 and temperature T≤37℃ in aqueous media).
基金approved by the Research Ethics Committees of Zhejiang Provincial People’s Hospital(No.QT2022387).
文摘Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
基金the National Natural Science Foundation of China,No.82072662Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support,No.2019142+1 种基金Shanghai Three-year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,No.SHDC2020CR4022the 2021 Shanghai“Rising Stars of Medical Talent”Youth Development Program:Outstanding Youth Medical Talents.
文摘BACKGROUND Glycosylation,a commonly occurring post-translational modification,is highly expressed in several tumors,specifically in those of the digestive system,and plays a role in various cellular pathophysiological mechanisms.Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years,bibliometric analysis of this field remains scarce.The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors.AIM To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors.METHODS We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace(version 6.1.R6)to perform bibliometric analysis.RESULTS A total of 2042 documents spanning from 1978 to the present were analyzed,with the research process divided into three phases:the period of obscurity(1978-1990),continuous development period(1991-2006),and the rapid outbreak period(2007-2023).These documents were authored by researchers from 66 countries or regions,with the United States and China leading in terms of publication output.Reis Celso A had the highest number of publications,while Pinho SS was the most cited author.Co-occurrence analysis revealed the most popular keywords in this field are glycosylation,expression,cancer,colorectal cancer,and pancreatic cancer.Furthermore,the Journal of Proteome Research was the most prolific journal in terms of publications,while the Journal of Biological Chemistry had the most citations.CONCLUSION The bibliometric analysis shows current research focus is primarily on basic research in this field.However,future research should aim to utilize glycosylation as a target for treating tumor patients.
文摘Surface (S)-layer proteins are model systems for studying protein glycosylation in bacteria and simultaneously hold promises for the design of novel, glyco-functionalized modules for nanobiotechnology due to their 2D self-assembly capability. Understanding the mechanism governing S-layer glycan biosynthesis in the Gram-positive bacterium Paenibacillus alvei CCM 2051T is necessary for the tailored glyco-functionalization of its S-layer. Here, the putative oligosaccharyl:S-layer protein transferase WsfB from the P. alvei S-layer glycosylation gene locus is characterized. The enzyme is proposed to catalyze the final step of the glycosylation pathway, transferring the elongated S-layer glycan onto distinct tyrosine O-glycosylation sites. Genetic knock-out of WsfB is shown to abolish glycosylation of the S-layer protein SpaA but not that of other glycoproteins present in P. alvei CCM 2051T, confining its role to the S-layer glycosylation pathway. A transmembrane topology model of the 781-amino acid WsfB protein is inferred from activity measurements of green fluorescent protein and phosphatase A fused to defined truncations of WsfB. This model shows an overall number of 13 membrane spanning helices with the Wzy_C domain characteristic of O-oligosaccharyl:protein transferases (O-OTases) located in a central extra-cytoplasmic loop, which both compares well to the topology of OTases from Gram-negative bacteria. Mutations in the Wzy C motif resulted in loss of WsfB function evidenced in reconstitution experiments in P. alvei ΔWsfB cells. Attempts to use WsfB for transferring heterologous oligosaccharides to its native S-layer target protein in Escherichia coli CWG702 and Salmonella enterica SL3749, which should provide lipid-linked oligosaccharide substrates mimicking to some extent those of the natural host, were not successful, possibly due to the stringent function of WsfB. Concluding, WsfB has all features of a bacterial O-OTase, making it the most probable candidate for the oligosaccharyl:S-layer protein transferase of P. alvei, and a promising candidate for the first O-OTase reported in Gram-positives.
基金the National Basic Research Development Program of China (No. 2006CB500801).
文摘Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control. Results Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV. Conclusion Glycosylation altered the gating properties of rNav 1.3 and contributed to the functional diversity.
基金the National 863 High Technology Foundation of China,No.863-102-07-02-02,No.2001AA215171the project CHN 98/112 (WTZ-Internationales Buro des BMBF).
文摘AIM: To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV. The purpose of this study is to investigate the affection of context sequences on hepatitis C virus (HCV) E2 processing. METHODS: HCV genes of different lengths were expressed and compared in vaccinia virus/T7 system with homologous patient serum S94 and mouse anti-serum M( E2116) raised against E.coli -derived E2 peptide, respectively.Deglycosylation analysis and GNA ( Galanthus nivalus ) lectin binding assay were performed to study the post-translational processing of the expressed products. RESULTS: E2 glycoproteins with different molecular weights (-75 kDa and -60 kDa) were detected using S94 and M( E2116), respectively. Deglycosylation analysis showed that this difference was mainly due to different glycosylation. Endo H resistance and its failure to bind to GNA lectin demonstrated that the higher molecular weight form (75 kDa) of E2 was complex-type glycosylated, which was readily recognized by homologous patient serum S94. Expression of complex-type glycosylated E2 could not be detected in all of the core-truncated constructs tested, but readily detected in constructs encoding full-length core sequences. CONCLUSION: The upstream conserved full-length core coding sequence was required for the production of E2 glycoproteins carrying complex-type N-glycans which reacted strongly with homologous patient serum and therefore possibly represented more mature forms of E2. As complex-type N-glycans indicated modification by Golgi enzymes, the results suggest that the presence of full-length core might be critical for E1/E2 complex to leave ER. Our data may contribute to a better understanding of the processing of HCV structural proteins as well as HCV morphogenesis.
基金Supported by Grants from the National Natural Science Foundation of China,No.81302906Beijing Natural Science Foundation,No.7144190New Teacher Fund for Doctor Stations of Ministry of Education of China,No.20131107120019
文摘AIM: To evaluate the significance of KL-6/MUC1 (a type of MUC1) glycosylation in pancreatic cancer progression.
基金Supported by The Estonian Science foundation, No. 7317 and 8399
文摘AIM: To study whether alterations in the glycosylation of immunoglobulin G (IgG) specific to the ThomsenFriedenreich glycotope (TF) have diagnostic and prognostic potential in gastric cancer. METHODS: Serum samples were obtained from patients with histologically verified gastric carcinoma (n = 89), healthy blood donors (n = 40), and patients with benign stomach diseases (n = 22). The lectin-enzymelinked immunosorbent assay-based glycoprofiling of TF-specific IgG (anti-TF IgG) was performed using synthetic TF-polyacrylamide conjugate as antigen, total IgG purified by affinity chromatography on protein G sepharose, and lectins of various sugar specificities: mannose-specific concanavalin A (ConA), fucose-specificAleuria aurantia lectin (AAL) and sialic acid-specific Sambucus nigra agglutinin (SNA). The sensitivity and specificity of the differences between cancer patients and controls were evaluated by receiver operator characteristic (ROC) curve analysis. Overall survival was analyzed by the Kaplan-Meier method. Time-dependent ROC curve statistics were applied to determine cut-off values for survival analysis. All calculations and comparisons were performed using the GraphPad Prism 5 and SPSS 15.0 software.RESULTS: The level of TF-specific IgG was significantly increased in cancer patients compared with non-cancer controls (P < 0.001). This increase was pronounced mostly in stage 1 of the disease. Cancer patients showed a higher level of ConA binding to antiTF-IgG (P < 0.05) and a very low level of SNA lectin binding (P = 0.0001). No appreciable stage-dependency of the binding of any lectin to anti-TF IgG was found. A strong positive correlation between the binding of AAL and SNA was found in all groups studied (r = 0.71-0.72; P < 0.0001). The changes in ConA reactivity were not related to those of the fucoseor sialic acid-specific lectin. Changes in the SNA binding index and the ConA/SNA binding ratio demonstrated good sensitivity and specificity for stomach cancer: sensitivity 78.79% (95%CI: 61.09-91.02) and 72.73% (95%CI: 57.21-85.04); specificity 79.17 (95%CI: 65.01-89.53) and 88.64% (95%CI: 71.8-96.6), for the SNA binding index and the ConA/SNA binding ratio, respectively. The other combinations of lectins did not improve the accuracy of the assay. The low level of ConA-positive anti-TF IgG was associated with a survival benefit in cancer patients (HR = 1.56; 95%CI: 0.78-3.09; P = 0.19), especially in stages 3-4 of the disease (HR = 2.17; 95%CI: 0.98-4.79; P = 0.048). A significantly better survival rate was found in all cancer patients with a low reactivity of anti-TF IgG to the fucose-specific AAL lectin (HR = 2.39; 95%CI: 1.0-5.7;P = 0.038).CONCLUSION: The changes in the TF-specific IgG glycosylation pattern can be used as a biomarker for stomach cancer detection, and to predict patient survival.
基金Supported by National Nature Science Foundation(No.30973738)
文摘OBJECTIVE： To study the effects of Xixin decoction （XXD） on O-linked N-acetylglucosamine （O-GIcNAc） glycosylation of tau proteins in rat brain with spo- radic Alzheimer disease （SAD）, and discuss its possi- ble mechanism on prevention and treatment of SAD. METHODS： The rat model of SAD was established by intracerebroventricular injection of streptozoto- cin. The specific pathogen free male Sprague-Daw- ley rats were randomly divided into sham-opera- tion group （S）, model group （M）, donepezil group （D）, XXD at a low dose group （XL）, XXD at a medium dose group （XM） and XXD at a high dose group （XH）. After treatment and praxiology test, immuno- histochemistry and western blotting were used to detect O-GIcNAc glycosylation level of tau proteins in rat brain with SAD. O-GIcNAc glycosylation and expression of tau proteins were detected by O-GIcNAc-specific antibodies RL2 and CTD110.6. RESULTS： O-GIcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significant- ly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups （P〈0.05, P〈0.01）, while no obvious dif- ferences were observed between D group and M group （P〉0.05）. CONCLUSION： XXD can significantly improve O-GIcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hy- perphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological pro- cess of SAD.
基金supported by the National Key R&D Program of China(2016YFD0500201)the Natural Science Foundation of Shandong Province,China(ZR2017BC094)+1 种基金the earmarked fund for China Agriculture Research System(CARS-41-Z10)the High-Level Talents and Innovative Team Recruitment Program of the Shandong Academy of Agricultural Sciences,China
文摘N-Linked glycosylation of hemagglutinin(HA) has been demonstrated to regulate the virulence and receptor-binding specificity of avian influenza virus(AIV).In this study,we characterized the variation trend of naturally isolated H9 N2 viruses for the potential N-linked glycosylation sites in HA proteins,and explored any important role of some glycosylation sites.HA genes of 19 H9 N2 subtype AIV strains since 2001 were sequenced and analyzed for the potential glycosylation sites.The results showed that the viruses varied by losing one potential glycosylation site at residues 200 to 202,and having an additional one at residues 295 to 297 over the past few years.Further molecular and single mutation analysis revealed that the N200 Q mutation lost an N-linked glycosylation at positions 200 to 202 of the HA protein and affected the human-derived receptor affinity.We further found that this N-linked glycosylation increased viral productivity in the lung of the infected mice.These findings provide a novel insight on understanding the determinants of host adaption and virulence of H9 N2 viruses in mammals.
文摘BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.
文摘The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.
文摘Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain. Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terminal. The chimera gene was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co- transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation. Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed product in recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence assay. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosylation of VP4 protein. Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicity and immunogenicity of expressed protein.
基金supported by the National Nature Science Foundation of China(No.21302052)"Program for New Century Excellent Talents in University"awarded to Prof.Jian Zhang"111 Project"from the Ministry of Education of China+1 种基金Fundamental Research Funds for the Central Universities(No.JKZ2011017)Scientific and Innovation Research of College Graduates in Jangsu Province(No.CXLX11_0788)
文摘The present study was designed to explore the substrate scope and biocatalytic capability of Gliocladium deliquescens NRRL 1086 on phenolic natural products. Emodin was subjected to the fermentation culture of Gliocladium deliquescens NRRL 1086 according to the standard two-stage protocol. The biotransformation process was monitored by HPLC-DAD-MS, the main product was isolated by column chromatography, and the structure was elucidated on the basis of NMR spectroscopy. Emodin could be fully metabolized by Gliocladium deliquescens NRRL 1086, resulting in high yield of emodin 6-O-β-D-glucopyranoside and small amount of sulfated product. In conclusion, our results may provide a convenient method to prepare emodin 6-O-β-D-glucopyranoside and the microbe catalyzed glucosylation/sulfation will give an inspiration to pharmacokinetic model studies in vitro.
基金The project was supported by Shanghai Rising-Star Program(No.06QA14018)University Students Innovative Activities Project of Shanghai Municipal Education Commission(No.KY2008-09S)
文摘Sulfuric acid immobilized on silica gel is designed as a very useful catalyst for synthesis of 2,3-unsaturated glycopyranosides. This handy,metal-free,environment friendly transformation provides high yields andα-stereoselectivities in a very few amount （0.02 eq.） of catalyst and in short reaction times（10 min）.
