Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B (NF-kappaB) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B (IkappaB)-alpha in the cytoplasm, and suppressed the translocation of NF-kappaB p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of NF-kappaB in LPS-stimulated RAW264.7 and BV2 cells.
Cytokines ; Cytoplasm ; Dinoprostone ; Fungi ; Interleukin-1beta ; Interleukin-6 ; NF-kappa B* ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Penicillium* ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Streptococcus mutans (S. mutans) is a facultative anaerobic bacterium mainly found in the oral cavity and is known to contribute to tooth decay and gingivitis. Recent studies on intestinal microbiota have revealed that microorganisms forming a biofilm play important roles in maintaining tissue homeostasis through their own metabolism. However, the physiological roles of oral microorganisms such as S. mutans are still unclear. In our current study, we identified that constituents released from S. mutans (CR) reduce arecoline-mediated cytotoxicity without producing toxic effects themselves. Arecoline, as a major alkaloid of areca nut, is known to mediate cytotoxicity on oral epithelial cells and induces a sustained intracellular Ca2+ ([Ca2+]i) increase that is cytotoxic. The exposure of human gingival fibroblast (HGF) cells to CR not only inhibited the sustained [Ca2+]i increase but also the initial [Ca2+]i elevation. In contrast, CR had no effects on the gene regulation mediated by arecoline. These results demonstrate that S. mutans has physiological role in reducing cytotoxicity in HGF cells and may be considered a novel pharmaceutical candidate.
Areca ; Arecoline ; Biofilms ; Epithelial Cells ; Fibroblasts ; Gingivitis ; Homeostasis ; Humans ; Metabolism ; Microbiota ; Mouth ; Nuts ; Streptococcus mutans* ; Tooth

BACKGROUND: It has been well known that the degree of HLA matching in renal transplantation is important in graft and patient survival. Because HLA-identical living-related donor grafts are free from immunological attacks, they have benefits of one immunosuppressants or early withdrawal of steroids. However, there is acute rejection due to early withdrawal of immunosuppressants and graft loss due to recurrent glomerulonephritis following HLA- identical living-related renal transplantation. The purpose of this study is to determine the graft survival and the impact of recurrent glomerulonephritis on graft survival in HLA-identical living-related donor grafts. METHODS: From December 1984 to March 2004, 44 HLA-identical and 80 HLA-haploidentical living- related renal transplants in Bongsaeng Memorial Hospital were included in this study. We evaluated graft survivals, immunosuppressants and causes of graft failure. RESULTS: The mean graft survival for HLA-identical transplants is 198 months (16.5 years) and for HLA-haploidentical transplants is 166 months (13.8 years), respectively (p=NS). Acute rejection episodes occurred in 2 of the 44 (5%) identical transplants and 17 of the 80 (21%) haploidentical transplants, respectively (p=0.013). 6 grafts were lost in HLA- identical transplants and the causes are 4 recurrent glomerulonephritis (66.7%), 2 chronic rejections (33.4 %). 11 grafts were lost in HLA-haploidentical transplants and the causes are 6 chronic rejections (54.5 %), 1 acute rejection (9.1%), 1 drug toxicity (9.1%), 3 patient deaths (27.3%). Recurrent glomerulonephritis in HLA-identical transplants are three, but in HLA-haploidentical transplants are none. CONCLUSION: Our data revealed that there was no difference in graft survival between the two groups, but lower acute rejection rate in HLA-identical groups. Recurrent glomerulonephritis was the main cause of graft failure in HLA-identical groups and the impact of recurrent disease on graft survival needs to be investigated.
Drug-Related Side Effects and Adverse Reactions ; Glomerulonephritis ; Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Steroids ; Tissue Donors* ; Transplants

Objective: To investigate the effects of Gastrodiae rhizoma, a dried root of Gastrodia elata Blume, on proliferation and differentiation of human NSCs derived from embryonic stem cells. Methods: A 70% ethanol extract of Gastrodiae rhizoma (EEGR) was estimated with 4-hydroxybenzyl alcohol as a representative constituent by HPLC. Results: MTT assay showed that the treatment with EEGR increased the viability of NSCs in growth media. Compared to control, EEGR increased the number of dendrites and denritic spines extended from a differentiated NSC. Whereas EEGR decreased the mRNA expression of Nestin, it increased that of Tuj1 and MAP2 in NSCs grown in differentiation media. Immunocytochemical analysis using confocal microscopy also revealed the increased expression of MAP2 in dendrites of EEGR-treated NSCs. Furthermore, EEGR decreased mRNA expression of Sox2 in NSCs grown even in growth media. Conclusions: In conclusion, our study demonstrates for the first time that EEGR induced proliferation and neuronal differentiation of NSCs, suggesting its potential benefits on NSC-based therapies and neuroregeneration in various neurodegenerative diseases and brain injuries.