Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extr...Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extracted from brown seaweeds by chemical sulfation.Alginate is composed of a linear backbone of polymannuronate(PM),polyguluronate(PG),and alternate residues of mannuronic acid and guluronic acid.It is unknown if heparin and sulfated PG(PGS)/PM(PMS) have the same or different anticoagulant molecular targets.In the current study,the anticoagulant activities of PGS,PMS,and their oligosaccharides were directly compared to that of heparin,Fondaparinux,and dermatan sulfate by the activated partial thrombinplastin time(aP TT) assay using normal,antithrombin III(ATIII)-deficient,heparin co-factor II(HCII)-deficient,and ATIII-and HCII-double deficient human plasmas.Our results showed that PGS,PMS,and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested.As expected,heparin was the best anticoagulant in normal plasma.Moreover,PGS,PGS6,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma.Most strikingly,PGS,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than that of heparin in ATIII-and HCII-double deficient human plasma.The results revealed for the first time that sulfated alginate had ATIII-and HCII-independent anticoagulant activities.Therefore,developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.展开更多
The fresh tissues were obtained from 64 colorectal adenocarcinoma (43 well-differentiated and moderately-differentiated adenocarcinoma, 12 poorly- differentiated adenocarcinoma and 9 mutinous cell carcinoma including ...The fresh tissues were obtained from 64 colorectal adenocarcinoma (43 well-differentiated and moderately-differentiated adenocarcinoma, 12 poorly- differentiated adenocarcinoma and 9 mutinous cell carcinoma including signet ring cell carcinoma) during surgical operation. The resected edge of each specimen was used for control group. The arylsulfatase B was studied by histochentical staining in different types of colorectal adenocarcinoma, among which 19 cases were investigated by electronhistochemical staining so as to observe the Ruthenium Red granules alteration which represented the extracellular proteoglycan changes and ultrastructure of cancer cells.The results showed that the mutinous cell carcinoma was of the most Intensive arylsulfatase B activity and has a lot of secretory granules with various electron densities in the cytoplasm. The Ruthenium Red granules close to the cancer cell disappeared, a part of remainders changed into the lowered electron density and indistinct shape. In contrast, the other types adenocarcinoma revealed less enzyme activity and a fewer secretory granules. The Ruthenium Red granules near the cancer nest showed that their electron density and size were identical with those of the control group. All of these mentioned above indicate that mucinouscell carcinoma may release hydrolase into pericancerous matrix to degrade the proteoglycans. In view of the network structure formed by proteoglycan in the connective tissue, network has ability to hinder the cancer cell spreading. Because the arylsulfatase B is able to degrade the dermatan sulfate proteoglycan which is component of proteoglycans in the extracellular matrix of human colon. We consider that the arylsulfatase B may lead to destruction of the network barriers in the connective tissue in favour of cancer cell invasion. So the mucinous cell carcinoma is more malignant than those of other colorectal adenocarcinoma.展开更多
基金supported by the National Natural Science Foundation of China(No.91129706)NSFCShandong Joint Fund(No.U1406402)Taishan Scholar Special Fund of Shandong Province in China(L.Z.)
文摘Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extracted from brown seaweeds by chemical sulfation.Alginate is composed of a linear backbone of polymannuronate(PM),polyguluronate(PG),and alternate residues of mannuronic acid and guluronic acid.It is unknown if heparin and sulfated PG(PGS)/PM(PMS) have the same or different anticoagulant molecular targets.In the current study,the anticoagulant activities of PGS,PMS,and their oligosaccharides were directly compared to that of heparin,Fondaparinux,and dermatan sulfate by the activated partial thrombinplastin time(aP TT) assay using normal,antithrombin III(ATIII)-deficient,heparin co-factor II(HCII)-deficient,and ATIII-and HCII-double deficient human plasmas.Our results showed that PGS,PMS,and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested.As expected,heparin was the best anticoagulant in normal plasma.Moreover,PGS,PGS6,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma.Most strikingly,PGS,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than that of heparin in ATIII-and HCII-double deficient human plasma.The results revealed for the first time that sulfated alginate had ATIII-and HCII-independent anticoagulant activities.Therefore,developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.
文摘The fresh tissues were obtained from 64 colorectal adenocarcinoma (43 well-differentiated and moderately-differentiated adenocarcinoma, 12 poorly- differentiated adenocarcinoma and 9 mutinous cell carcinoma including signet ring cell carcinoma) during surgical operation. The resected edge of each specimen was used for control group. The arylsulfatase B was studied by histochentical staining in different types of colorectal adenocarcinoma, among which 19 cases were investigated by electronhistochemical staining so as to observe the Ruthenium Red granules alteration which represented the extracellular proteoglycan changes and ultrastructure of cancer cells.The results showed that the mutinous cell carcinoma was of the most Intensive arylsulfatase B activity and has a lot of secretory granules with various electron densities in the cytoplasm. The Ruthenium Red granules close to the cancer cell disappeared, a part of remainders changed into the lowered electron density and indistinct shape. In contrast, the other types adenocarcinoma revealed less enzyme activity and a fewer secretory granules. The Ruthenium Red granules near the cancer nest showed that their electron density and size were identical with those of the control group. All of these mentioned above indicate that mucinouscell carcinoma may release hydrolase into pericancerous matrix to degrade the proteoglycans. In view of the network structure formed by proteoglycan in the connective tissue, network has ability to hinder the cancer cell spreading. Because the arylsulfatase B is able to degrade the dermatan sulfate proteoglycan which is component of proteoglycans in the extracellular matrix of human colon. We consider that the arylsulfatase B may lead to destruction of the network barriers in the connective tissue in favour of cancer cell invasion. So the mucinous cell carcinoma is more malignant than those of other colorectal adenocarcinoma.
