Anti-tumor Activity of Saussurea laniceps against Pancreas Adenocarcinoma

The purpose of this study was to confirm the anti-tumor activity of an ethanol extract of Saussurea laniceps against pancreatic tumor and to isolate the active compound from S.laniceps extract. Treatment with S.laniceps extract and hispidulin inhibited proliferation of pancreatic cell lines, such as Capan-1, Capan-2, Panc-1 and S2-013 in a dose-dependent manner using the hollow fiber assay. Hispidulin showed typical hallmarks of apoptotic cell death a significant anti-tumor activity on Capan-2 cells at a dose of 100 mg/kg and 200 mg/kg. S.laniceps has potential cytotoxic and apoptotic effects on human pancreatic carcinoma cells. Its mechanism of action might be associated with the apoptotic cell death through DNA fragmentation.

Anti-inflammatory Effect of Quercetin on Picryl Chloride-induced Contact Dermatitis in BALB/c Mice / 한국실험동물학회지

In this study, we investigated that anti-inflammatory effect of quercetin on picryl chloride(PCL)-induced contact dermatitis in BALB/c Mice. Experimental animals were divided into three groups and comprising five animals. All groups of oral administration was begun on the first day of PCL treatment and ceased on day 5. For the induction of contact dermatitis, BALB/c mice were sensitized with 40 microliter of 1.5% picryl choloride (PCL) to the left and right ear, respectively. Ear swelling responses were much weaker in high-dose group (100 mg/kg) than control group (0 mg/kg). Total serum IgE levels and histamine levels were measured by sandwich ELISA method using mouse IgE, histamine measuring Kit. Both total serum IgE and histamine levels were significantly decreased in high-dose group (100 mg/kg) than other groups. Degranulation of mast cells were also confirmed by Toluidine Blue (TB) staining method. In high-dose group (100 mg/kg), the number of mast cells were significantly decreased and there are many mast cells were shown degranulation in control group (0 mg/kg). All of these results demonstrate that the pharmacological actions of quercetin indicate their potential activity for allergic inflammatory diseases through the down-regulation of mast cell activation.

Cordycepin inhibits UVB-induced matrix metalloproteinase expression by suppressing the NF-kappa B pathway in human dermal fibroblasts

Cordycepin (3'-deoxyadenosine) has been shown to exhibit many pharmacological activities, including anti-cancer, anti-inflammatory, and anti-infection activities. However, the anti-skin photoaging effects of cordycepin have not yet been reported. In the present study, we investigated the inhibitory effects of cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated NF-kappa B activity, which was determined by I kappa B alpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappa B binding activity. However, UVB-induced NF-kappa B activation and MMP expression were completely blocked by cordycepin pretreatment. These findings suggest that cordycepin could prevent UVB-induced MMPs expressions through inhibition of NF-kappa B activation. In conclusion, cordycepin might be used as a potential agent for the prevention and treatment of skin photoaging.

Low-density lipoprotein protects Vibrio vulnificus-induced lethality through blocking lipopolysaccharide action

Lipoprotein plays a role in the host defense against bacterial infection, and its serum level has been demonstrated to be an important prognosis factor of survival. We have previously demonstrated that LDL directly inactivates the hemolytic activity of Vibrio vulnificus cytolysin (VVC) in vitro. The object of this study was therefore to examine whether the LDL-mediated inactivation of VVC leads to protection against lethal infection of V. vulnificus in vivo, using wild and VVC-deficient V. vulnificus strains. Unexpectedly, we found that LDL protects mouse lethality induced by VVC-deficient as well as wild V. vulnificus strain. We also demonstrated that LDL blocks V. vulnificus LPS-induced lethality in mice. These results suggest that LDL preferentially act on endotoxin rather than exotoxin in the protection against V. vulnificus-induced mice lethality.

Reverse Chevron Transmalleolar Osteotomy for Exposure of the Medial Talar Dome Lesions: Operative Technique / 대한족부족관절학회지

For the adequate intraarticular exposure in medial talar dome lesions, medial malleolar osteotomy is necessary in some cases. Many operative techniques including transverse, oblique, inverted V-shape, crescentic and step-cut osteotomies of the medial malleolus have been described previously. But their techniques have several problems such as nonunion, rotation and limited access to lesions. So we introduce the new reverse chevron medial malleolar osteotomy which provides excellent access to lesions, good stability and a broad cancellous surface for rapid healing.

Protease-activated Receptor 2 is Associated with Activation of Human Macrophage Cell Line THP-1

BACKGROUND: Protease-activated receptor 2 (PAR2) belongs to a family of G protein- coupled receptors activated by proteolytic cleavage. Trypsin-like serine proteases interact with PAR2 expressed by a variety of tissues and immune cells. The aim of our study was to investigate whether PAR2 stimulation can lead to the activation of human macrophages. METHODS: PAR2-mediated proliferation of human macrophage cell line THP-1 was measured with MTT assay. We also examined the extracellular regulated kinase (ERK) phosphorylation and cytokine production induced by trypsin and PAR2-agonist using western blot and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Treatment of trypsin or PAR2-activating peptide increased cell proliferation in a dose-dependent manner, and induced the activation of ERK1/2 in THP-1 cells. In addition, trypsin-induced cell proliferation was inhibited by pretreatment of an ERK inhibitor (PD98059) or trypsin inhibitor (SBTI). Moreover, PAR2 activation by trypsin increased the secretion of TNF-alpha in THP-1 cells. CONCLUSION: There results suggest that PAR2 activation by trypsin-like serine proteases can induce cell proliferation through the activation of ERK in human macrophage and that PAR2 may play a crucial role in the cell proliferation and cytokine secretion induced by trypsin-like serine proteases.

Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically

Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.

Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin

Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to calcium ions in pulmonary endothelial cells, and has been suggested as an important virulence factor that sequestrate neutrophils primarily in the lung. To elucidate the mechanism we investigated whether the cytolysin affect the expression of endothelial P-selectin and adhesiveness of pulmonary endothelial cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a pulmonary endothelial cell line, for neutrophils in a concentrationand time-dependent manner. The increase of adhesiveness occurred within several minutes after the cytolysin exposure, persisted up to 90 min, and was not affected by cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin enhanced the level of P-selectin on CPAE cell surface. Therefore, these results suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial cells for neutrophils is mediated by the mobilization of endothelial P-selectin to the cell surface.

Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin

Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to calcium ions in pulmonary endothelial cells, and has been suggested as an important virulence factor that sequestrate neutrophils primarily in the lung. To elucidate the mechanism we investigated whether the cytolysin affect the expression of endothelial P-selectin and adhesiveness of pulmonary endothelial cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a pulmonary endothelial cell line, for neutrophils in a concentrationand time-dependent manner. The increase of adhesiveness occurred within several minutes after the cytolysin exposure, persisted up to 90 min, and was not affected by cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin enhanced the level of P-selectin on CPAE cell surface. Therefore, these results suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial cells for neutrophils is mediated by the mobilization of endothelial P-selectin to the cell surface.

Persistent infection with Strongyloides venezuelensis in the Mongolian gerbil (Meriones unguiculatus)

To examine the fate of Strongyloides venezuelensis. Mongolian gerbils (Meriones unguicalatus) were orally infected with 1,000 L3 larvae per animal. Altogether, 50 gerbils divided into 5 groups of 10 each were monitored for a period of 570 days to document the kinetics of faecal egg output, adults worm population, morphological development, fecundity, and hematological changes including peripheral blood eosinophilia. This study chronicled a life long parasitism of S. venezuelensis in the gerbil host, and showed that S. venezuelensis infection was quite stable throughout the course of infection and the worms maintained their normal development as evidenced by their body dimension. A progressive loss of body condition of the infected gerbils was observed as the level of infection advanced. However, no detectable pathological changes were observed in the gastrointestinal tract. The present findings indicate that an immunocompetent host, such as the Mongolian gerbil, can serve as a life long carrier model of S. venezuelensis if the worms are not expelled within 570 days after infection.

Immunogenicity and protective efficacy of solubilized merozoite-enriched Theileria sergenti immmunogens III. Characterization of immunodominant peptides

Immunoblot analysis utilizing bovine sera from naturally or experimentally infected with Theileria sergenti were used to determine the immunodominant polypeptides of T. sergenti (Korea isolate).The previously recognized major bands, 18 kDa, 29 kDa, 34 kDa, and 45 kDa, were excised after electrophoresis and trasferred to PVDF membrane. The individual bands were sequenced. The 34 kDa polypeptide which was the most antigenic and immunogenic peptide was observed in the Western blot. However, Chou-Fasman prediction sites (antiginic site) for antigen determinants of the 45 kDa,34 kDa, 29 kDa and 18 kDa polypeptide were 6, 4, 2 and 0, respectively. However, the 45 kDa polypeptide showed no reaction with anti-T. sergenti hyperimmune serum.