Salmonella alters heparanase expression and reduces tumor metastasis.

Salmonella causes salmonellosis, is a facultative anaerobe and is one of the common Gram-negative bacteria. Salmonella has anti-tumor potential and tumor-targeting activity. The heparin sulfate on cell surfaces can be cleaved by heparanase that is an endo-ß-D-glucuronidase. Heparanase can destroy the extracellular matrix and is involved in tumor metastasis and angiogenic activity. Previously, Salmonella was demonstrated to inhibit tumor metastasis. It remains unclear whether Salmonella inhibits metastasis by regulating heparanase. The expression of heparanase in Salmonella-treated tumor cells was found to be decreased. Transwell and wound-healing assays demonstrated the inhibition of cell migration after Salmonella treatment. Salmonella was found to influence the levels of phosphate-protein kinase B (P-AKT) and phosphate-extracellular regulated protein kinases (P-ERK), which are involved in heparanase expression. Salmonella reduced the heparanase expression induced upregulating PERK and PAKT signaling pathways. The mice bearing an experimental metastasis tumor model was used to evaluate the anti-tumor metastatic effects of Salmonella. Compared with the control group, Salmonella significantly reduced the number of metastatic nodules and enhanced survival. The results of our study indicate that Salmonella plays a vital role in the inhibition of tumor metastasis through the downregulation of heparanase.

Hyperpnea-induced production of TBHP-initiated chemiluminescence in guinea pigs.

Antioxidants attenuate hyperpnea-induced airway constriction. It was hypothesized that this type of airway constriction is closely related to reactive oxygen species (ROS). However, there is no direct evidence of an increase in ROS during or right after the course of hyperpnea. To detect ROS production induced by hyperpnea, forty one guinea pigs were divided into four groups: control; control with 95% O2-5% CO2; hyperpnea with 95% air-5% CO2; and hyperpnea with 95% O2-5% CO2. Three minutes following hyperpnea or at the equivalent time, we obtained bronchoalveolar lavage (BAL) and measured its chemiluminescence (CL) counts. In addition, hyperpnea with 95% O2-5% CO2 gas mixture was carried out and BAL was collected 3 minutes after the hyperpnea in an additional forty animals. We measured CL counts in BAL samples before and after the treatments of the following ROS scavenger(s) or saline in vitro: control (saline); superoxide dismutase (SOD); catalase; dimethylthiourea (DMTU); and SOD+catalase+DMTU. Hyperpnea with 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced significant increase in t-butyl hydroperoxide-initiated CL counts, which were inhibited by DMTU, catalase, or SOD in vitro. Our data suggest that hyperpnea with a 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced an increase in ROS production.