BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cyt...BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cytokines,such asβ2-microglobulin(β2-MG),glycosylated hemoglobin(HbA1c),and vascular endothelial growth factor(VEGF),in the pathogenesis of this disease.In this study,we identified novel therapeutic options for this disease.AIM To analyze the guiding significance ofβ2-MG,HbA1c,and VEGF levels in patients with DN.METHODS A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study.Additionally,107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups.Changes inβ2-MG,HbA1c,and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.RESULTS Changes inβ2-MG,HbA1c,and VEGF levels in the disease,healthy,and simple diabetes groups were significantly different(P<0.05).The expression of these factors from high to low were evaluated in different groups by pairwise comparison.In the disease group,high to low changes inβ2-MG,HbA1c,and VEGF levels were noted in the massive proteinuria,microproteinuria,and normal urinary protein groups,respectively.Changes in these factors were positively correlated with disease progression.CONCLUSION The expression of serumβ2-MG,HbA1c,and VEGF was closely correlated with DN progression,and disease progression could be evaluated by these factors.展开更多
A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl glucoside.Concanavalin A (Con A),a glucose recognizing lectin,c...A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl glucoside.Concanavalin A (Con A),a glucose recognizing lectin,could be specifically adsorbed to the membrane surface.On the other hand,the membrane surface showed no recognition ability to another lectin peanut agglutinin.Moreover,the recognition complex between the glycosylated membrane surface and Con A could be inhibited by glucose and mannose solutio...展开更多
Background: Diabetes mellitus is a common disease and it is a major cause of morbidity;several studies indicate that diabetes is a likely under reported cause of death. Chromium’s is important trace element to contro...Background: Diabetes mellitus is a common disease and it is a major cause of morbidity;several studies indicate that diabetes is a likely under reported cause of death. Chromium’s is important trace element to control diabetes mellitus and metabolism of carbohydrate, lipid and protein. Objective: The purpose of this study was to understand the relationship between serum chromium, with HbA1c, Total cholesterol and Triglycerides among type 2 diabetes patients among diabetic patients. Methodology: This is cross-sectional study done in Jabber Abu Ezz Centre for treatment and care of diabetics in Khartoum—Sudan. Four hundred subjects were enrolled in this study;one hundred subjects were normal healthy as control group, and three hundred subjects diabetic patient type 2 as test group;demographic and biochemical data were collected;serum chromium, Glycosylated Haemoglobin (HbA1c), Total cholesterol Triglycerides, were determined by using NYCOCARD READER II, spectrophotometer (Biosystem 310) and spectrophotometer 210-VGP. Result: In this study there is significant parameters level means of FBS HbA1c, Total Cholesterol, Triglycerides and Chromium of the test groups when compared with healthy control groups subjects (P = 0.001, 0.018, 0.01, 0.011, 0.004), respectively. Significant negative correlation is between FBS, HbA1c, Total Cholesterol, Triglycerides and Chromium (r = ?0.555, P value = 0.003), (r = ?0.668, P value = 0.002), (r = ?0.335, P value = 0.004) and (r = ?0.774, P value = 0.002) respectively. Conclusion: There was significant correlation between serum Chromium level with fasting blood sugaer, Glycosylated Haemoglobin (HbA1c), Total cholesterol and Triglycerides among type 2 diabetes patients.展开更多
Ovalbumin(OVA),the main protein in egg white,affects most of the functional properties of egg white protein in food processing.The aim of this study was to investigate the effects of spray drying(SD)and microwave free...Ovalbumin(OVA),the main protein in egg white,affects most of the functional properties of egg white protein in food processing.The aim of this study was to investigate the effects of spray drying(SD)and microwave freeze drying(MFD)on the preparation of hydrolyzed/glycosylated ovalbumin(HGOVA)and provide useful information on the applications of egg protein powders in the food industry.Results demonstrated that the structure of HGOVA was considerably changed,and its functional properties were improved compared with those of native OVA.SD and MFD processing did not lead to dissociation of HGOVA subunits.SD-HGOVA exhibited higher protein solubility,emulsifying activity,foaming capacities,and gel hardness than MFD-HGOVA.However,MFD-HGOVA was better than the SD-HGOVA in terms of color,emulsion stability,foam stability,water/oil absorption capacity,and thermal stability.Selection of an appropriate drying method could enhance the potential applications of HGOVA in the food industry.展开更多
The Hantzsch synthesis has been used for the preparation of the 1,4-Dihydropyridines compounds with different pharmacophore groups. The use of a designed glycosylated compound in Hantzsch synthesis would lead to a nov...The Hantzsch synthesis has been used for the preparation of the 1,4-Dihydropyridines compounds with different pharmacophore groups. The use of a designed glycosylated compound in Hantzsch synthesis would lead to a novel Dihydropyridines C-Glycosylated compound. We used the 6-methoxy-2, 2-dimethyltetrahydrofuro [3, 4-d] [1, 3] dioxole-4-carbaldehyde as a glycosylated-based aldehydes. The 4-(3,4-Dihydroxy-5-methoxy-tetrahydro-furan-2-yl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxy-lic acid 3-ethyl ester 5-methyl ester was synthesized. The structure of compounds was determined by NMR spectroscopy, FTIR and mass spectroscopy methods. We synthesized this 1,4-Dihydropyridines compound by ionic liquid under ultrasound irradiation as a green chemistry synthesis.展开更多
Glucose transporter(GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines.However,the transcytosis process remains elusive....Glucose transporter(GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines.However,the transcytosis process remains elusive.Glycopeptide-modified nanodisks(Gly-A7R-NDs),which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports,were utilized to better understand the whole transcytosis process.Gly-A7R-NDs internalized brain capillary endothelial cells mainly via GLUT-mediated/clathrin dependent endocytosis and macropinocytosis.The intracellular Gly-A7R-NDs remained intact,and the main excretion route of Gly-A7R-NDs was lysosomal exocytosis.Glycosylation of nanomedicine was crucial in GLUT-mediated transcytosis,while morphology did not affect the efficiency.This study highlights the pivotal roles of lysosomal exocytosis in the process of GLUT-mediated transcytosis,providing a new impetus to development of brain targeting drug delivery by accelerating lysosomal exocytosis.展开更多
Antibody-directed enzyme prodrug therapy(ADEPT) is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drug...Antibody-directed enzyme prodrug therapy(ADEPT) is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol(glycosyl donors) to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.展开更多
Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles ...Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles in cancer cell survival and spreading. HIF regulates several genes such as genes of glucose transporters that enhance anaerobic glycolysis, angiogenesis, erythropoiesis and carbonic anhydrase IX (CA-IX). CA-IX is a cell-surface glycoprotein that catalyzes the hydration of CO2 to protons and bicarbonate ions (respiratory acidification). This process is involved in adaptation to acidosis and implicated in cancer progression. Therefore, CA-IX inhibitors (such as sulfonamide-based compounds) showed hoping results in reduction malignancy progression. The article aims to reversal the malignant hypoxic environment in solid tumors to create a condition of weakness within the cancer for further focused cisplatin potency. This article suggests the use of modified synthesized HIF as a drug delivery molecule for both carbonic anhydrase IX inhibitor and glycosylated cisplatin that damages the DNA of malignant cell. HIF molecule has high affinity to bind with CA IX-expressing malignant cells, which is followed by cell entrance via endocytosis. Once the HIF-Cisplatin-CA-inhibitor complex enters the cell, the carbonic anhydrase inhibitor will improve the cellular pH that makes the environment unsuitable for HIF 1α function and it may be ubiquitinated. So, the raise in target genes transcription will be arrested. On the other hand, once the synthetized HIF is degraded, the cisplatin molecules will be released inside the malignant cell and start to damage its DNA. This approach may be a good solution for many solid tumors.展开更多
Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reacti...Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.展开更多
BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor ...BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor markers in T2DM are important.AIM To evaluate the expression of serum tumor markers[CA199,CA242,and carcinoembryonic antigen(CEA)]and the clinical implications of the expression in T2DM.METHODS For this observational study conducted at Hefei BOE Hospital,China,we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020.Levels of fasting blood glucose(FBG),tumor markers(CA199,CEA,and CA242),glycosylated hemoglobin(HbA1c),etc.were measured and group index levels were compared.Moreover,FBG and HbA1c levels were correlated with tumor marker levels.Tumor markers were tested for diagnostic accuracy in patients with>9%HbA1c using the receiver operating curve(ROC)curve.RESULTS The T2DM group had high serum FBG,HbA1c,CA199,and CEA levels(P<0.05).A comparative analysis of the two groups based on HbA1c levels(Group A:HbA1c≤9%;Group B:HbA1c>9%)revealed significant differences in CEA and CA199 levels(P<0.05).The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809,respectively.CA199,CEA,and CA242 levels positively correlated with HbA1c(r=0.308,0.426,and 0.551,respectively)and FBG levels(r=0.236,0.231,and 0.298,respectively).CONCLUSION As compared to controls,serum CEA and CA199 levels were higher in patients with T2DM.HbA1c and FBG levels correlated with CA199,CEA,and CA242 levels.Patients with poorly controlled blood sugar must be screened for tumor markers.展开更多
目的:开发基于大豆分离蛋白(soybean protein isolate,SPI)的新型乳化剂。方法:采用限制性酶解结合糖基化处理对SPI进行结构修饰,研究协同改性对SPI乳化特性的影响。结果:SPI水解物(soybean protein isolate hydrolysate,SPIH)中的相对...目的:开发基于大豆分离蛋白(soybean protein isolate,SPI)的新型乳化剂。方法:采用限制性酶解结合糖基化处理对SPI进行结构修饰,研究协同改性对SPI乳化特性的影响。结果:SPI水解物(soybean protein isolate hydrolysate,SPIH)中的相对分子质量较大组分(F30)的乳化性最佳,且糖基化反应4 h的F30-葡聚糖轭合物乳化稳定性相对最好。相较于SPI,SPIH与F30,F30-葡聚糖轭合物稳定的乳液表现出最低的初始平均粒径,并且具有最佳的贮藏稳定性。当pH接近SPI等电点或体系处于高盐浓度时,所有乳液均出现不稳定聚集现象。与SPI相比,SPIH和F30稳定乳液的聚集程度更高,而F30-葡聚糖轭合物由于共价结合的葡聚糖提供了额外的空间位阻和亲水性,使得轭合物稳定的乳液能够耐受离子强度和温度的变化,在不利环境条件下表现出更高的抵抗力。结论:限制性酶解结合糖基化改性是开发SPI基乳化配料的潜在可靠途径。展开更多
UDP-Glycosyltransferases(UGTs)catalyze the transfer of nucleotide-activated sugars to specific acceptors,among which the GT1 family enzymes are well-known for their function in biosynthesis of natural product glycosid...UDP-Glycosyltransferases(UGTs)catalyze the transfer of nucleotide-activated sugars to specific acceptors,among which the GT1 family enzymes are well-known for their function in biosynthesis of natural product glycosides.Elucidating GT function represents necessary step in metabolic engineering of aglycone glycosylation to produce drug leads,cosmetics,nutrients and sweeteners.In this review,we systematically summarize the phylogenetic distribution and catalytic diversity of plant GTs.We also discuss recent progress in the identifi-cation of novel GT candidates for synthesis of plant natural products(PNPs)using multi-omics technology and deep learning predicted models.We also highlight recent advances in rational design and directed evolution engineering strategies for new or improved GT functions.Finally,we cover recent breakthroughs in the appli-cation of GTs for microbial biosynthesis of some representative glycosylated PNPs,including flavonoid glycosides(fisetin 3-O-glycosides,astragalin,scutellarein 7-O-glucoside),terpenoid glycosides(rebaudioside A,ginseno-sides)and polyketide glycosides(salidroside,polydatin).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
文摘BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cytokines,such asβ2-microglobulin(β2-MG),glycosylated hemoglobin(HbA1c),and vascular endothelial growth factor(VEGF),in the pathogenesis of this disease.In this study,we identified novel therapeutic options for this disease.AIM To analyze the guiding significance ofβ2-MG,HbA1c,and VEGF levels in patients with DN.METHODS A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study.Additionally,107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups.Changes inβ2-MG,HbA1c,and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.RESULTS Changes inβ2-MG,HbA1c,and VEGF levels in the disease,healthy,and simple diabetes groups were significantly different(P<0.05).The expression of these factors from high to low were evaluated in different groups by pairwise comparison.In the disease group,high to low changes inβ2-MG,HbA1c,and VEGF levels were noted in the massive proteinuria,microproteinuria,and normal urinary protein groups,respectively.Changes in these factors were positively correlated with disease progression.CONCLUSION The expression of serumβ2-MG,HbA1c,and VEGF was closely correlated with DN progression,and disease progression could be evaluated by these factors.
基金the National Natural Science Foundation of China (No.20474054)the National Natural Science Foundation of China for Distinguished Young Scholars (No.50625309).
文摘A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl glucoside.Concanavalin A (Con A),a glucose recognizing lectin,could be specifically adsorbed to the membrane surface.On the other hand,the membrane surface showed no recognition ability to another lectin peanut agglutinin.Moreover,the recognition complex between the glycosylated membrane surface and Con A could be inhibited by glucose and mannose solutio...
文摘Background: Diabetes mellitus is a common disease and it is a major cause of morbidity;several studies indicate that diabetes is a likely under reported cause of death. Chromium’s is important trace element to control diabetes mellitus and metabolism of carbohydrate, lipid and protein. Objective: The purpose of this study was to understand the relationship between serum chromium, with HbA1c, Total cholesterol and Triglycerides among type 2 diabetes patients among diabetic patients. Methodology: This is cross-sectional study done in Jabber Abu Ezz Centre for treatment and care of diabetics in Khartoum—Sudan. Four hundred subjects were enrolled in this study;one hundred subjects were normal healthy as control group, and three hundred subjects diabetic patient type 2 as test group;demographic and biochemical data were collected;serum chromium, Glycosylated Haemoglobin (HbA1c), Total cholesterol Triglycerides, were determined by using NYCOCARD READER II, spectrophotometer (Biosystem 310) and spectrophotometer 210-VGP. Result: In this study there is significant parameters level means of FBS HbA1c, Total Cholesterol, Triglycerides and Chromium of the test groups when compared with healthy control groups subjects (P = 0.001, 0.018, 0.01, 0.011, 0.004), respectively. Significant negative correlation is between FBS, HbA1c, Total Cholesterol, Triglycerides and Chromium (r = ?0.555, P value = 0.003), (r = ?0.668, P value = 0.002), (r = ?0.335, P value = 0.004) and (r = ?0.774, P value = 0.002) respectively. Conclusion: There was significant correlation between serum Chromium level with fasting blood sugaer, Glycosylated Haemoglobin (HbA1c), Total cholesterol and Triglycerides among type 2 diabetes patients.
基金Natural Science Foundation of China(No.U1704114)Key Scientific Research Program of Henan Province(No.182102110346,161100110900).
文摘Ovalbumin(OVA),the main protein in egg white,affects most of the functional properties of egg white protein in food processing.The aim of this study was to investigate the effects of spray drying(SD)and microwave freeze drying(MFD)on the preparation of hydrolyzed/glycosylated ovalbumin(HGOVA)and provide useful information on the applications of egg protein powders in the food industry.Results demonstrated that the structure of HGOVA was considerably changed,and its functional properties were improved compared with those of native OVA.SD and MFD processing did not lead to dissociation of HGOVA subunits.SD-HGOVA exhibited higher protein solubility,emulsifying activity,foaming capacities,and gel hardness than MFD-HGOVA.However,MFD-HGOVA was better than the SD-HGOVA in terms of color,emulsion stability,foam stability,water/oil absorption capacity,and thermal stability.Selection of an appropriate drying method could enhance the potential applications of HGOVA in the food industry.
文摘The Hantzsch synthesis has been used for the preparation of the 1,4-Dihydropyridines compounds with different pharmacophore groups. The use of a designed glycosylated compound in Hantzsch synthesis would lead to a novel Dihydropyridines C-Glycosylated compound. We used the 6-methoxy-2, 2-dimethyltetrahydrofuro [3, 4-d] [1, 3] dioxole-4-carbaldehyde as a glycosylated-based aldehydes. The 4-(3,4-Dihydroxy-5-methoxy-tetrahydro-furan-2-yl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxy-lic acid 3-ethyl ester 5-methyl ester was synthesized. The structure of compounds was determined by NMR spectroscopy, FTIR and mass spectroscopy methods. We synthesized this 1,4-Dihydropyridines compound by ionic liquid under ultrasound irradiation as a green chemistry synthesis.
基金financially supported by the National Natural Science Foundation of China(81973245,81773657,81673361,81690263 and 81673370)China Postdoctoral Science Foundation(2019M651385)+3 种基金National Postdoctoral Program for Innovative Talent(BX20190086)Shanghai Municipal Commission of Health and Family Planning(2018BR04)Shanghai Natural Science Foundation(19431900300 and18ZR1404800)Pudong New Area Commission of Science&Technology(PKJ2016-Y46).
文摘Glucose transporter(GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines.However,the transcytosis process remains elusive.Glycopeptide-modified nanodisks(Gly-A7R-NDs),which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports,were utilized to better understand the whole transcytosis process.Gly-A7R-NDs internalized brain capillary endothelial cells mainly via GLUT-mediated/clathrin dependent endocytosis and macropinocytosis.The intracellular Gly-A7R-NDs remained intact,and the main excretion route of Gly-A7R-NDs was lysosomal exocytosis.Glycosylation of nanomedicine was crucial in GLUT-mediated transcytosis,while morphology did not affect the efficiency.This study highlights the pivotal roles of lysosomal exocytosis in the process of GLUT-mediated transcytosis,providing a new impetus to development of brain targeting drug delivery by accelerating lysosomal exocytosis.
基金Supported by the National Natural Science Foundation of China(No20030708)the Natural Science Foundation of JinlinProrince, P R China(No20050702-4)
文摘Antibody-directed enzyme prodrug therapy(ADEPT) is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol(glycosyl donors) to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.
文摘Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles in cancer cell survival and spreading. HIF regulates several genes such as genes of glucose transporters that enhance anaerobic glycolysis, angiogenesis, erythropoiesis and carbonic anhydrase IX (CA-IX). CA-IX is a cell-surface glycoprotein that catalyzes the hydration of CO2 to protons and bicarbonate ions (respiratory acidification). This process is involved in adaptation to acidosis and implicated in cancer progression. Therefore, CA-IX inhibitors (such as sulfonamide-based compounds) showed hoping results in reduction malignancy progression. The article aims to reversal the malignant hypoxic environment in solid tumors to create a condition of weakness within the cancer for further focused cisplatin potency. This article suggests the use of modified synthesized HIF as a drug delivery molecule for both carbonic anhydrase IX inhibitor and glycosylated cisplatin that damages the DNA of malignant cell. HIF molecule has high affinity to bind with CA IX-expressing malignant cells, which is followed by cell entrance via endocytosis. Once the HIF-Cisplatin-CA-inhibitor complex enters the cell, the carbonic anhydrase inhibitor will improve the cellular pH that makes the environment unsuitable for HIF 1α function and it may be ubiquitinated. So, the raise in target genes transcription will be arrested. On the other hand, once the synthetized HIF is degraded, the cisplatin molecules will be released inside the malignant cell and start to damage its DNA. This approach may be a good solution for many solid tumors.
基金supported by the National Natural Science Foundation of China(32101883)Fellowship China Postdoctoral Science Foundation(2021M693902)National Agricultural Science and Technology Innovation Project(CAAS-ASTIP-2022)。
文摘Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.
文摘BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor markers in T2DM are important.AIM To evaluate the expression of serum tumor markers[CA199,CA242,and carcinoembryonic antigen(CEA)]and the clinical implications of the expression in T2DM.METHODS For this observational study conducted at Hefei BOE Hospital,China,we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020.Levels of fasting blood glucose(FBG),tumor markers(CA199,CEA,and CA242),glycosylated hemoglobin(HbA1c),etc.were measured and group index levels were compared.Moreover,FBG and HbA1c levels were correlated with tumor marker levels.Tumor markers were tested for diagnostic accuracy in patients with>9%HbA1c using the receiver operating curve(ROC)curve.RESULTS The T2DM group had high serum FBG,HbA1c,CA199,and CEA levels(P<0.05).A comparative analysis of the two groups based on HbA1c levels(Group A:HbA1c≤9%;Group B:HbA1c>9%)revealed significant differences in CEA and CA199 levels(P<0.05).The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809,respectively.CA199,CEA,and CA242 levels positively correlated with HbA1c(r=0.308,0.426,and 0.551,respectively)and FBG levels(r=0.236,0.231,and 0.298,respectively).CONCLUSION As compared to controls,serum CEA and CA199 levels were higher in patients with T2DM.HbA1c and FBG levels correlated with CA199,CEA,and CA242 levels.Patients with poorly controlled blood sugar must be screened for tumor markers.
文摘目的:开发基于大豆分离蛋白(soybean protein isolate,SPI)的新型乳化剂。方法:采用限制性酶解结合糖基化处理对SPI进行结构修饰,研究协同改性对SPI乳化特性的影响。结果:SPI水解物(soybean protein isolate hydrolysate,SPIH)中的相对分子质量较大组分(F30)的乳化性最佳,且糖基化反应4 h的F30-葡聚糖轭合物乳化稳定性相对最好。相较于SPI,SPIH与F30,F30-葡聚糖轭合物稳定的乳液表现出最低的初始平均粒径,并且具有最佳的贮藏稳定性。当pH接近SPI等电点或体系处于高盐浓度时,所有乳液均出现不稳定聚集现象。与SPI相比,SPIH和F30稳定乳液的聚集程度更高,而F30-葡聚糖轭合物由于共价结合的葡聚糖提供了额外的空间位阻和亲水性,使得轭合物稳定的乳液能够耐受离子强度和温度的变化,在不利环境条件下表现出更高的抵抗力。结论:限制性酶解结合糖基化改性是开发SPI基乳化配料的潜在可靠途径。
文摘目的:探讨胎盘生长因子(placental growth factor,PLGF)、可溶性fms样酪氨酸激酶-1(soluble fms-like tyrosine kinase-1,SFLT-1)和糖基化纤连蛋白(glycosylated fibronectin,GLYFN)检测对子痫前期的预测价值。方法:选择在无锡市妇幼保健院就诊的188例孕妇,分154例正常孕妇(对照组)和34例子痫前期患者(子痫组),应用免疫荧光法分别检测其在孕16~18周血清中PLGF、SFLT-1和GLYFN的浓度,比较子痫前期组和对照组各标志物的水平,并使用受试者操作特征曲线(receiver operating characteristic,ROC)对3种标志物的预测价值进行效能评估。结果:在妊娠中期,子痫前期组血清PLGF浓度低于对照组,SFLT-1及GLYFN浓度均高于对照组,3种标志物的差异均有统计学意义(3指标P=0.000)。95%置信区间的ROC曲线下面积(areas under the ROC curve,AUC)为,PLGF为0.941(0.907~0.974),SFLT-1为0.881(0.800~0.962),GLYFN为0.951(0.918~0.985),联合指标SFLT-1和GLYFN、3项指标联合检测在ROC曲线下面积(areas under the ROC curve,AUC)分别为0.968、0.986。结论:PLGF、SFLT-1、GLYFN 3种标志物水平在对照组和子痫前期组均存在明显差异,对子痫前期的发病具有一定的预测价值,SFLT-1联合PLGF、SFLT-1联合GLYFN、3项指标联合检测对子痫前期的预测价值高于任一单项指标。
基金the National Key R&D Program of China(2020YFA0907900,2018YFE0200501)the National Natural Science Foundation of China(Grant number 32030063).
文摘UDP-Glycosyltransferases(UGTs)catalyze the transfer of nucleotide-activated sugars to specific acceptors,among which the GT1 family enzymes are well-known for their function in biosynthesis of natural product glycosides.Elucidating GT function represents necessary step in metabolic engineering of aglycone glycosylation to produce drug leads,cosmetics,nutrients and sweeteners.In this review,we systematically summarize the phylogenetic distribution and catalytic diversity of plant GTs.We also discuss recent progress in the identifi-cation of novel GT candidates for synthesis of plant natural products(PNPs)using multi-omics technology and deep learning predicted models.We also highlight recent advances in rational design and directed evolution engineering strategies for new or improved GT functions.Finally,we cover recent breakthroughs in the appli-cation of GTs for microbial biosynthesis of some representative glycosylated PNPs,including flavonoid glycosides(fisetin 3-O-glycosides,astragalin,scutellarein 7-O-glucoside),terpenoid glycosides(rebaudioside A,ginseno-sides)and polyketide glycosides(salidroside,polydatin).
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.
