Immunogenicity of Lactobacillus-expressing VP2 and VP3 of the infectious pancreatic necrosis virus (IPNV) in rainbow trout.

Infectious pancreatic necrosis virus (IPNV) infects salmonid fish with high mortality and causes serious economic losses to salmonid aquaculture. Lactobacillus strains have a number of properties that make them attractive candidates as delivery vehicles for the presentation to the mucosa of compounds with pharmaceutical interest, in particular vaccines. Here, Lactobacilli/Escherichia coli shuttle vector pPG1 (surface-displayed) or pPG2 (secretory) with the capsid VP2 gene inserted was transformed into Lactobacillus casei to yield two recombinant strains: Lc:PG1-VP2 and Lc:PG2-VP2, respectively. Rainbow trout immunized respectively with Lc:PG1-VP2, Lc:PG2-VP2, Lc:PG1-VP3 and Lc:PG2-VP3 elicited anti-IPNV immune responses (serum IgM) via oral route. Statistical results of serum IgM titer with neutralizing activity showed that immunogenicity of Lc:PG2-VP2 was more powerful than that of Lc:PG1-VP2 (P < 0.001), Lc:PG1-VP3 (P < 0.001) and Lc:PG2-VP3 (P < 0.001), which was confirmed by viral loads reduction analyzed by real-time RT-PCR in orally immunized rainbow trout after virus challenge. Comparing with negative control, rainbow trout orally dosed with Lc:PG2-VP2 resulted in ∼46-fold reduction in virus load on days 10 post viral challenge as well as Lc:PG1-VP2(∼20-fold), Lc:PG2-VP3(∼6-fold) and Lc:PG1-VP3(∼3-fold). Taken together, Lc:PG2-VP2 exhibited a more appropriate candidate as live bacteria vaccine against IPNV infection in rainbow trout.

System design and experimental research of lower esophageal sphincter stimulator for treatment of gastroesophageal reflux disease.

Electrical stimulation therapy (EST) of lower esophageal sphincters (LES) is a new technique for the treatment of gastroesophageal reflux disease (GERD). In this paper, an implantable LES stimulator with wireless power transmission is proposed for the treatment of GERD. The LES stimulator is composed of an implantable pulse generator (IPG), an external controller, and a wireless power transmission module. The IPG, whose area is 31×21 mm2, is designed to generate voltage-regulated constant-current stimulation pulses. The external controller allows for wireless programming of the IPG via a Bluetooth Low Energy (BLE) module. The wireless power transmission module provides power for the IPG. According to the measurement of output stimulus waveforms, the proposed LES stimulator is capable of delivering electrical stimulations with a current ranging between 0 and 8 mA. To evaluate the safety and efficacy of the proposed LES stimulator, experiments were performed on 12 male New Zealand white rabbits. Esophageal manometry was performed before and after the procedure and the LES pressure (LESP) has been recorded. The mean LESP is increased significantly in the stimulation group than the sham group (stimulation group: 9.25±1.24 mmHg vs 13.99 ±1.28 mmHg, p<;0.05; sham group: 9.00±1.22 mmHg vs 9.23±1.27 mmHg, p=0.267). The results show that the electrical stimulation delivered by the LES stimulator can safely and effectively increase resting LES pressure in acute animal models, suggesting that the implantable LES stimulator is a perspective approach for treating GERD in clinics.

Overexpression of caveolin-1 in cancer-associated fibroblasts predicts good outcome in breast cancer.

BACKGROUND: The aim of this study was to investigate the expression of caveolin-1 (Cav-1) in cancer-associated fibroblasts (CAFs) and to explore its correlation with clinicopathologic parameters and prognosis. MATERIALS AND METHODS: Cav-1 expression was detected in the stroma of 143 patients with breast cancer, 10 patients with ductal carcinoma in situ (DCIS), and 10 normal breast tissue samples. RESULTS: Overexpression of stromal Cav-1 in breast cancer was associated with histological type, low histological grade, estrogen receptor (ER) negativity, and molecular subtypes. The expression rate of stromal Cav-1 in breast cancer (65.7%, 94/143) was significantly higher than that of DCIS (0%, 0/10) and normal breast tissue (0%, 0/10) (p = 0.000). A positive correlation was found between stromal Cav-1 and ER (p = 0.046, rs = 0.218). Stromal Cav-1 expression in luminal B was significantly higher than in basal-like type (p = 0.048). Furthermore, stromal expression of Cav-1 was significantly correlated with the 5-year survival rate (p = 0.029), and it was an independent prognostic factor (p = 0.009). CONCLUSION: Cav-1 expression in CAFs was correlated with histological type, histological grade, ER status, and molecular subtypes in breast cancer. Stromal Cav-1 expression was an independent prognostic factor, and the absence or reduction of Cav-1 expression in stromal CAFs of invasive breast cancer predicts poor prognostic outcome.