Chemical Structure and Anticoagulant Property of a Novel Sulfated Polysaccharide from the Green Alga Cladophora oligoclada.

Marine macroalgae are efficient producers of sulfated polysaccharides. The algal sulfated polysaccharides possess diverse bioactivities and peculiar chemical structures, and represent a great potential source to be explored. In the present study, a heparinoid-active sulfated polysaccharide was isolated from the green alga Cladophora oligoclada. Results of chemical and spectroscopic analyses indicated that the sulfated polysaccharide was composed of →6)-ß-d-Galp-(1→, ß-d-Galp-(1→, →6)-α-d-Glcp-(1→ and →3)-ß-d-Galp-(1→ units with sulfate esters at C-2/C-4 of →6)-ß-d-Galp-(1→, C-6 of →3)-ß-d-Galp-(1→ and C-3 of →6)-α-d-Glcp-(1→ units. The branches consisting of ß-d-Galp-(1→ and →6)-ß-d-Galp-(1→ units were located in C-3 of →6)-ß-d-Galp-(1→ units. The sulfated polysaccharide exhibited potent anticoagulant activity in vitro and in vivo as evaluated by activated partial thromboplastin time (APTT), thrombin time, and the fibrinogen level. For the APTT, the signal for clotting time was more than 200 s at 100 µg/mL in vitro and at 15 mg/kg in vivo. The obvious thrombolytic activity of the sulfated polysaccharide in vitro was also found. The mechanism analysis of anticoagulant action demonstrated that the sulfated polysaccharide significantly inhibited the activities of all intrinsic coagulation factors, which were less than 1.0% at 50 µg/mL, but selectively inhibited common coagulation factors. Furthermore, the sulfated polysaccharide strongly stimulated the inhibition of thrombin by potentiating antithrombin-III (AT-III) or heparin cofactor-II, and it also largely promoted the inhibition of factor Xa mediated by AT-III. These results revealed that the sulfated polysaccharide from C. oligoclada had potential to become an anticoagulant agent for prevention and therapy of thrombotic diseases.

Anti-diabetic activity of a sulfated galactoarabinan with unique structural characteristics from Cladophora oligoclada (Chlorophyta).

The polysaccharide from green alga Cladophora oligoclada, OHSS2, was a sulfated galactoarabinan which was constituted by a backbone of (1 â†’ 4)-ß-l-arabinopyranose units with partial sulfate at C-3 of (1 â†’ 4)-ß-l-arabinopyranose units. The side chains containing (1 â†’ 4)-ß-l-arabinopyranose, (1 â†’ 4)-ß-d-galactopyranose and/or (1 â†’ 4,6)-ß-d-galactopyranose units were in C-2/C-3 of (1 â†’ 4)-ß-l-arabinopyranose units. OHSS2 had strong anti-diabetic activity in vitro assessed by inhibition of human islet amyloid polypeptide (hIAPP) aggregation. The mechanism analysis of anti-diabetic activity showed that OHSS2 diminished the production of intracellular reactive oxygen species and alleviated hIAPP aggregation-induced oxidative stress in NIT-1 cells. OHSS2 stabilized mitochondrial membrane potential, and enhanced the mitochondrial complex I, II or III activity and ATP level. Thus, OHSS2 effectively protected mitochondria from hIAPP aggregation-induced damage. Furthermore, OHSS2 was co-localized with mitochondria and could have a direct influence on mitochondrial function. These results revealed that OHSS2 had potential as a novel anti-diabetic agent.

[Clinical discussion on the pathological diagnosis of high-grade intraepithelial neoplasia in gastric biopsy].

OBJECTIVE: To evaluate the value and inadequacy in clinical practice of the concept of gastric high-grade intraepithelial neoplasia (HIN). METHODS: Forty-five cases with gastric HIN diagnosed by the esophagogastroduodenoscopy (EGD) biopsy were treated from 2003 to 2009. The clinical and histopathological data were analyzed retrospectively. RESULTS: Radical surgeries were successfully performed on all the patients, among whom 33 underwent distal subtotal gastrectomy, 3 proximal partial gastrectomy, 7 total gastrectomy, and 2 endoscopic mucosal resection. In postoperative pathological examination, only 15 cases (33.3%) were HIN, while 14 cases (31.1%) were found to be early gastric cancers, and 16 (35.6%) were advanced cancers. Twelve(40.0%) out of 30 cancers had regional lymph nodes metastasis. When the maximum diameter of the HIN lesion was greater than 3.0 cm, or when ulcer or the features of poorly-differentiated carcinoma or signet-ring cell carcinoma were present in preoperative biopsy, the likelihood of cancer in postoperative pathological examination was higher (P<0.05), and when malignancy was confirmed, the presence of the features above was associated with lymph nodes metastasis and advanced cancer. CONCLUSIONS: Carcinoma is identified in a large proportion of patients with gastric HIN by the EGD biopsy. Lymph nodes metastasis or advanced cancer may be detected in these cases. Cautions must be taken when the new concept of HIN is widely used for diagnosing gastric lesion. Radical resection should be considered when the maximum diameter of the HIN lesion is greater than 3.0 cm, or when ulcer, or the feature of poorly-differentiated carcinoma or signet-ring cell carcinoma are present in the EGD biopsy.

The combination of docetaxel and cisplatin plus fluorouracil as neoadjuvant chemotherapy in the treatment of T4 stage gastric cancer.

The prognosis of local advanced gastric carcinoma is very poor. We evaluated the impact on survival and the effects induced by the triple combination docetaxel-cisplatin-fluorouracil (DCF) as neoadjuvant chemotherapy in 24 T4 stage gastric tumor patients. They received 2-3 cycles DCF chemotherapy, followed by radical gastric resection. Tumor downstaging detected by CT was obtained in 17 out of 24 patients. The overall 3-year survival rate was 68.2%. Patients who received R0 resection (19/22) showed a 3-year survival rate of 78.9%. T downstaged patients (17/22) showed a higher 3-year survival rate of 82.4%. Those who responded to the triple combination of docetaxel-cisplatin-fluorouracil, exhibited T downstaging and subsequently received an R0 resection had a definitely better chance of a cure as compared to surgery alone, according to a complete 3-year follow-up.