Effects of oral deoxynivalenol exposure on immune-related parameters in lymphoid organs and serum of mice vaccinated with porcine parvovirus vaccine

Mice were exposed to deoxynivalenol (DON) via drinking water at a concentration of 2 mg/L for 36 days. On day 8 of treatment, inactivated porcine parvovirus vaccine (PPV) was injected intraperitoneally. The relative and absolute weight of the spleen was significantly decreased in the DON-treated group (DON). Antibody titers to parvovirus in serum were 47.9?±?2.4 in the vaccination group (Vac), but 15.2?±?6.5 in the group treated with DON and vaccine (DON?+?Vac). The IgA and IgG was not different in the DON, Vac an,d DON?+?Vac groups. IgM was significantly lower only in the DON?+?Vac group. However IgE was significantly increased in the Vac and DON?+?Vac group, but no change was observed between the Vac and DON?+?Vac groups. The concentrations of IL-2, IL-4, GM-CSF, MCP-1 and Rantes in serum, and IL-1α in mesenteric lymph node and MIP-1β in spleen were significantly increased by DON treatment compared to control. The concentrations of IL-2, IL-5, IL-6, IL-9, IL-12, IL-13 and Rantes in thymus, of IL-2 in spleen, and of IL-1α, IL-1β, IL-3, IL-5, IL-10, IL-17, G-CSF, GM-CSF and MCP-1 in mesenteric lymph nodes were significantly decreased in mice compared to those in the Vac group, while concentrations of IL-1α, IL-2, IL-9, IL-13,G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1α and TNF-α were significantly increased in serum compared to the Vac group. In conclusion, the results presented here indicate that exposure to DON at 2.0 mg/L via drinking water can disrupt the immune response in vaccinated mice by modulating cytokines and chemokines involved in their immune response to infectious disease.     

Marine algal fucoxanthin inhibits the metastatic potential of cancer cells

Metastasis is major cause of malignant cancer-associated mortality. Fucoxanthin has effect on various pharmacological activities including anti-cancer activity. However, the inhibitory effect of fucoxanthin on cancer metastasis remains unclear. Here, we show that fucoxanthin isolated from brown alga Saccharina japonica has anti-metastatic activity. To check anti-metastatic properties of fucoxanthin, in vitro models including assays for invasion, migration, actin fiber organization and cancer cell–endothelial cell interaction were used. Fucoxanthin inhibited the expression and secretion of MMP-9 which plays a critical role in tumor invasion and migration, and also suppressed invasion of highly metastatic B16-F10 melanoma cells as evidenced by transwell invasion assay. In addition, fucoxanthin diminished the expressions of the cell surface glycoprotein CD44 and CXC chemokine receptor-4 (CXCR4) which play roles in migration, invasion and cancer–endothelial cell adhesion. Fucoxanthin markedly suppressed cell migration in wound healing assay and inhibited actin fiber formation. The adhesion of B16-F10 melanoma cells to the endothelial cells was significantly inhibited by fucoxanthin. Moreover, in experimental lung metastasis in vivo assay, fucoxanthin resulted in significant reduction of tumor nodules. Taken together, we demonstrate, for the first time, that fucoxanthin suppresses metastasis of highly metastatic B16-F10 melanoma cells in vitro and in vivo.     

FERM domain promotes resveratrol-induced apoptosis in endothelial cells via inhibition of NO production

Focal adhesion kinase (FAK) consists of an N-terminal band 4.1; ezrin, radixin, moesin (FERM) domain; tyrosine kinase domain; and C-terminal FA targeting domain. Here we show that ectopically expressed FERM is largely located in the cytosolic fraction under quiescent conditions. We further found that this ectopically expressed FERM domain aggravates endothelial cell apoptosis triggered by 100 μM resveratrol, whereas FERM had no effect on apoptosis induced by TNF-α. We determined that resveratrol at low doses (<20 μM) promotes phosphorylation (S1177) of eNOS via an AMPK-dependent pathway. The presence of the FERM domain blocked this resveratrol-stimulated eNOS phosphorylation and NO production. Thus, the pro-apoptotic activity of cytosolic FERM domain is at least partially mediated by down-regulation of NO, a critical cell survival factor. Consistently, we found that the apoptosis induced by cytosolic FERM in the presence of resveratrol was reversed by an NO donor, SNAP. In conclusion, FERM located in the cytosolic fraction plays a pivotal role in aggravating cell apoptosis through diminishing NO production.     

Candidate target genes for the Saccharomyces cerevisiae transcription factor, Yap2

In Saccharomyces cerevisiae, the Yap family of basic leucine zipper (bZip) proteins contains eight members. The Yap family proteins are implicated in a variety of stress responses; among these proteins, Yap1 acts as a major regulator of oxidative stress responses. However, the functional roles of the remaining Yap family members are poorly understood. To elucidate the function of Yap2, we mined candidate target genes of Yap2 by proteomic analysis. Among the identified genes, FRM2 was previously identified as a target gene of Yap2, which confirmed the validity of our screening method. YNL134C and YDL124W were also identified as candidate Yap2 target genes. These genes were upregulated in strains overexpressing Yap2 and possess Yap2 target sequences in their promoter regions. Furthermore, chromatin immunoprecipitation assays showed that YNL134C and YDL124W have Yap2 binding motif. These data will help to elucidate the functional role of Yap2.     

Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum

Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D₂ (2), butyl lucidenate E₂ (3) and butyl lucidenate Q (4) along with 11 known compounds (5–15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC₅₀ values of 7.4, 6.4, 4.3, 9.4, 9.2 and 4.5 μM, respectively. Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions. Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein.     

Non hemolytic short peptidomimetics as a new class of potent and broad-spectrum antimicrobial agents

Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics.     

Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

In Parkinson’s disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson’s disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson’s disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure–activity relationship study revealed that the piperidino group was the best choice for the R¹ amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC₅₀ values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound 1n with the thiazolopyridine core structure showed the most potent activity with the IC₅₀ value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives.