Insights into the history and tendency of glycosylation and digestive system tumor:A bibliometric-based visual analysis

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.

Cut-off value of glycated hemoglobin A1c for detecting diabetic retinopathy in the Chinese population

BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience.However,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean populations in Jilin,China,remains inconclusive.AIM To determine the best cut-off of HbA1c for diagnosing DR among the Chinese.METHODS This cross-sectional study included 1933 participants from the Yanbian area of Jilin Province,China.Trained investigators employed a questionnaire-based survey,physical examination,laboratory tests,and fundus photography for the investigation.The best cut-off value for HbA1c was established via the receiver operating characteristic curve.The factors associated with HbA1c-associated risk factors were determined via linear regression.RESULTS The analysis included 887 eligible Chinese Han and Korean participants,591 of whom were assigned randomly to the training set and 296 to the validation set.The prevalence of DR was 3.27% in the total population.HbA1c of 6.2% was the best cut-off value in the training set,while it was 5.9% in the validation set.In both Chinese Han and Korean populations,an HbA1c level of 6.2% was the best cut-off value.The optimal cut-off values of fasting blood glucose(FBG)≥7 mmol/L and<7 mmol/L were 8.1% and 6.2% respectively in Han populations,while those in Korean populations were 6.9%and 5.3%,respectively.Age,body mass index,and FBG were determined as the risk factors impacting HbA1c levels.CONCLUSION HbA1c may serve as a useful diagnostic indicator for DR.An HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.

Effect of Glycosylation on the Physicochemical Properties,Structure and Iron Bioavailability of Ferritin Extracted from Tegillarca granosa

Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.

Description of a Putative Oligosaccharyl:S-Layer Protein Transferase from the Tyrosine <i>O</i>-Glycosylation System of <i>Paenibacillus alvei</i>CCM 2051^T

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.

Inhibition of KL-6/MUC1 glycosylation limits aggressive progression of pancreatic cancer

AIM: To evaluate the significance of KL-6/MUC1 (a type of MUC1) glycosylation in pancreatic cancer progression.

Aberrant glycosylation of the anti-Thomsen-Friedenreich glycotope immunoglobulin G in gastric cancer patients

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.

Glycated hemoglobin A1C and diabetes mellitus in critically ill patients

BACKGROUND:Hyperglycemia has been detected in many critically ill patients in the department of emergency medicine.But its mechanism and prognosis have not been well elucidated.In this study,we measured the serum level of glycated hemoglobin A1C(HbA1c) in critically ill patients to evaluate the effects of hyperglycemia on the prognosis of the patients.METHODS:A total of 826 critically ill patients,who had been treated at the Department of Emergency Medicine of Chaoyang Hospital during October 2006 and November 2007,were divided into a diabetes mellitus group(n=184) and a non-diabetes mellitus group(642) according to whether they had diabetes mellitus.Fasting glucose and HbA1 c were measured in all patients.Those in the diabetes mellitus group were further assigned to a drug therapy subgroup and a non-drug therapy subgroup;the serum level of HbA1 c and its relationship with short-term outcome were evaluated.RESULTS:Fasting glucose increased in 78.8% of the patients(88.6%in the diabetes mellitus group,and 75.9%in the non-diabetes mellitus group,P<0.05),and HbA1 c was elevated in 45.5% of the patients(78.3% in the diabetes mellitus group,and 36.1%in the non-diabetes mellitus group,P<0.01).Fasting glucose,HbA1 c and 28-day mortality were improved more significantly(P<0.01) in the drug therapy subgroup than in the non-drug therapy subgroup.The 28-day mortality was more significantly different in patients with fasting blood glucose >8.33 mmol/L than in those with fasting blood glucose <8.33 mmol/L.CONCLUSIONS:Hyperglycemia of critically ill patients could not totally attribute to stress response,especially in those who have no history of diabetes mellitus.Prognosis of hyperglycemia may vary among critically ill patients.

Deglycosylation altered the gating properties of rNav1.3:glycosylation/deglycosylation homeostasis probably complicates the functional regulation of voltage-gated sodium channel

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.

Glycosylation of the hemagglutinin protein of H9N2 subtype avian influenza virus influences its replication and virulence in mice

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.

Serum Mac-2 binding protein glycosylation isomer level predicts hepatocellular carcinoma development in E-negative chronic hepatitis B patients

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.

RELATIONSHIP BETWEEN HEMOGLOBIN A1C AND BLOOD GLUCOSE THROUGHOUT THE DAY IN WELL-GLYCEMIC-CONTROLLED MEDICAL NUTRITION THERAPY ALONE TYPE 2 DIABETIC PATIENTS

Objective To investigate the relationship between glycosylated hemoglobin A1 c （HbA1 c） and blood glucose levels of eight different points throughout the day in well-glycemic-controlled medical nutrition therapy （MNT） alone type 2 diabetic pafients. Methods Data were collected as＂ capillary blood glucose value of eight different sample points among sixteen observing days in thirty MNT alone type 2 diabetic patients. The correlation between HbAI c and capillary blood glucose value was evaluated by Pearson＇s correlation method. Results The r-values between HbA1c and capillary blood glucose of 3：00, 6：00, and bedtime （22：00-23：00） were 0. 81,0. 79, and 0. 78, respectively（P 〈0. 001 ）. The best correlation was found between the mean value of 8- point blood glucose value throughout the day and HbA1c （ r=0. 84, P 〈0. 001 ）. Conclustion Fasting blood glucose and postabsorptive blood glucose have better correlations with HbAlc compared with other points in this group of well-glycemic-controlled MNT alone type 2 diabetic patients.

H_2SO_4-SiO_2:Highly efficient and novel catalyst for the Ferrier-type glycosylation

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）.

EXPRESSION AND GLYCOSYLATION OF ROTAVIRUS STRAIN SA11 VP4 PROTEIN IN A RECOMBINANT ADENOVIRUS

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.

O-linked N-acetylglucosamine transferase(OGT) is overexpressed and promotes O-linked protein glycosylation in esophageal squamous cell carcinoma

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.

EFFECT OF GLYCOSYLATION AT ASN302 OF PRO-UROKINASE ON ITS STABILITY IN CULTURE SUPERNATANT

Objective To investigate the effect of glycosylation at Asn302 of pro-urokinase （pro-UK） on the stability in culture supematant. Methods Nonglycosylated pro-UK was constructed by site-directed mutagenesis of Asn302 to Ala302. The pro-UK mutant and native pro-UK were transfected into dhfr-CHO cells, and serum-free culture supematant was harvested and incubated at 4℃ and 37℃, respectively. The pro-UK activity in culture supematant was measured by the optical density （OD） increase with time （ 12 hours） at 405 nm. Without thermolysin activation, the percentage of single chain pro-UK was measured. Rcsults After 48 hours of incubation at 4℃, the activities of pro-UK mutant and native pro-UK decreased 3.7% and 2.9% respectively, and at 37℃ decreased 37.9% and 23.5%, respectively. The total activity of native pro-UK was significantly higher than that of nonglycosylated mutant at 37℃. The single-chain percentage of native pro-UK was higher than that of nonglycosylated mutant at both 4℃ and 37℃. Conclusion Higher temperature increases the proteolysis of pro-UK. The glycosylation site on Asn302 is beneficial to pro-UK stability in culture supematant.

Full-length core sequence dependent complex-type glycosylation of hepatitis C virus E2 glycoprotein

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.

Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma

AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.

Usefulness of Mac-2 binding protein glycosylation isomer in noninvasive probing liver disease in the Vietnamese population

BACKGROUND Early diagnosis is critical for successful intervention before liver disease progresses to cirrhosis and hepatocellular carcinoma.AIM To examine a novel biomarker for probing early liver disease quickly using an automated immunology system.METHODS This was a cross-sectional study.140 patients at various stages of liver disease were randomly selected.The cohort consisted of patients who were treatment naïve and currently undergoing therapy.We included patients with diverse liver disease etiologies.Mac-2 binding protein glycosylation isomer(M2BPGi)levels in addition to different clinical parameters,co-morbidities and transient elastography results were collected and compared.RESULTS M2BPGi levels were significantly correlated with transient elastography for liver fibrosis staging across all disease etiologies.Statistically significant differences were observed in patients with F0-1;F2 and>F3 liver fibrosis.Further examination showed that M2BPGi levels were two-fold higher in F4 than F3 hepatitis C(HCV)patients.M2BPGi was observed to be etiology-specific and HCV patients had higher mean M2BPGi levels.We also observed significant correlations with aspartate aminotransferase to platelet ratio index and fibrosis-4 index as well as HBV DNA levels.Mean M2BPGi levels for HBV patients with a viral load lower than 2000 IU/mL was 1.75-fold lower than those with a viral load greater than 2000 IU/mL.CONCLUSION M2BPGi was observed to be a good indicator of early liver disease in patients with different etiologies.Our results provide reference cut-offs for different causes of liver disease and demonstrated the utility of this marker for early disease monitoring.This is useful for remote regions in developing countries.

The role of intracellular protein O-glycosylation in cell adhesion and disease

Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine （O-G1cNAc） to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.

Biological transformation,kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...