Myeon-Sik Yang

Therapeutic effects of zerumbone in an alkali-burned corneal wound healing model

Abstract Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis, leading to vision loss. The purpose of this study was to examine the effects of Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was induced by alkali‐burn injury in BALB/C female mice. Topical ZER (three times per day, 3 &mgr;l each time, at concentrations of 5, 15, and 30 &mgr;M) was applied to treat alkali‐burned mouse corneas for 14 consecutive days. Histopathologically, ZER treatment suppressed alkali burn‐induced CNV and decreased corneal epithelial defects induced by alkali burns. Corneal tissue treated with ZER showed reduced mRNA levels of pro‐angiogenic genes, including vascular endothelial growth factor, matrix metalloproteinase‐2 and 9, and pro‐fibrotic factors such as alpha smooth muscle actin and transforming growth factor‐1 and 2. Immunohistochemical analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells was significantly decreased in ZER‐treated corneas. ZER markedly inhibited the mRNA and protein levels of monocyte chemoattractant protein‐1 (MCP‐1) in human corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis revealed that ZER decreased the activation of signal transducer and activator of transcription 3 (STAT3), with consequent reduction of MCP‐1 production by these cells. In conclusion, topical administration of ZER accelerated corneal wound healing by inhibition of STAT3 and MCP‐1 production. HighlightsZerumbone treatment ameliorates alkali‐burned corneal wounds.Zerumbone treatment inhibits neovascularization and fibrosis in injured corneas.Zerumbone treatment down‐regulates the production of MCP‐1 and the activation of STAT3.

Vaccination of goats with a combination Salmonella vector expressing four Brucella antigens (BLS, PrpA, Omp19, and SOD) confers protection against Brucella abortus infection

Salmonella is an intracellular pathogen with a cellular infection mechanism similar to that of Brucella, making it a suitable choice for use in an anti-Brucella immune boost system. This study explores the efficacy of a Salmonella Typhimurium delivery-based combination vaccine for four heterologous Brucella antigens (Brucella lumazine synthase, proline racemase subunit A, outer-membrane protein 19, and Cu/Zn superoxide dismutase) targeting brucellosis in goats. We inoculated the attenuated Salmonella delivery-based vaccine combination subcutaneously at two different inoculation levels; 5 × 109 colony-forming unit (CFU)/mL (Group B) and 5 × 1010 CFU/mL (Group C) and challenged the inoculations with virulent Brucella abortus at 6 weeks post-immunization. Serum immunoglobulin G titers against individual antigens in Salmonella immunized goats (Group C) were significantly higher than those of the non-immunized goats (Group A) at 3 and 6 weeks after vaccination. Upon antigenic stimulation, interferon-γ from peripheral blood mononuclear cells was significantly elevated in Groups B and C compared to that in Group A. The immunized goats had a significantly higher level of protection as demonstrated by the low bacterial loads in most tissues from the goats challenged with B. abortus. Relative real-time polymerase chain reaction results revealed that the expression of Brucella antigens was lower in spleen, kidney, and lung of immunized goats than of non-immunized animals. Also, treatment with our combination vaccine ameliorated histopathological lesions induced by the Brucella infection. Overall, the Salmonella Typhimurium delivery-based combination vaccine was effective in delivering immunogenic Brucella proteins, making it potentially useful in protecting livestock from brucellosis.

Effects of high molecular weight poly-γ-glutamic acid on PIGS with porcine preproductive and respiratory syndrome virus (PRRSV) infection

Abstract Bacillus subtilis sups. chungkookjang produces a higher molecular mass poly-γ-glutamic acid (γ-PGA). Recently, previous studies have demonstrated immune stimulation and an antitumor effect of the high molecular mass γ-PGA using various mouse models although these effects have not been shown in other species of animals. Therefore, the current study was conducted to determine the effect of γ-PGA in pigs with and without PRRSV infection. PRRS-negative pigs were intramuscularly injected with 1, 3, or 5 ml of 20 mg/mll γ-PGA, and one group of pigs served as a non-treatment (NT) group. All groups treated with γ-PGA had significantly higher weight gains, and pigs treated with 5 ml of γ-PGA exhibited higher tumor necrosis factor (TNF)-α, interferon (IFN)-α and IFN-β expression levels compared with the NT group. According to the preliminary results, an animal challenge study was conducted with a highly virulent PRRSV strain, MN184, along with γ-PGA treatment at different time points. Pigs treated with γ-PGA had lower levels of viral loads in the sera and in lungs and gained significantly more weight (p<0.05) compared with the NT group after being challenged with MN184. Moreover, γ-PGA-treatment groups had higher levels of neutralizing antibodies and cytokines related to proinflammatory, humoral and cell-mediated responses than the control group after the PRRSV challenge. Therefore, it was concluded that γ-PGA induces higher levels of immune responses and increases resistance to PRRSV infection in pigs.