• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.83-88
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• 2005

Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half-life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.7
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• pp.920-929
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• 2017

Objective: The bursa of Fabricius (BF) is a central humoral immune organ belonging specifically to avians. Recent studies had suggested that miRNAs were active regulators involved in the immune processes. This study was to investigate the possible differences of the BF at miRNA level between two genetically disparate duck breeds. Methods: Using Illumina next-generation sequencing, the miRNAs libraries of ducks were established. Results: The results showed that there were 66 differentially expressed miRNAs and 28 novel miRNAs in bursa. A set of abundant miRNAs (i.e., let-7, miR-146a-5p, miR-21-5p, miR-17~92) which are involved in immunity and disease were detected and the predicted target genes of the novel miRNAs were associated with duck high anti-adversity ability. By gene ontology analysis and enriching KEGG pathway, the targets of differential expressed miRNAs were mainly involved in immunity and disease, supporting that there were differences in the BF immune functions between the two duck breeds. In addition, the metabolic pathway had the maximum enriched target genes and some enriched pathways that were related to cell cycle, protein synthesis, cell proliferation and apoptosis. It indicted that the difference of metabolism may be one of the reasons leading the immune difference between the BF of two duck breeds. Conclusion: This data lists the main differences in the BF at miRNAs level between two genetically disparate duck breeds and lays a foundation to carry out molecular assisted breeding of poultry in the future.

• Journal of Life Science
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• v.23 no.7
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• pp.926-932
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• 2013

Glutamine and serum are essential for cell survival and proliferation in vitro, yet the signaling pathways that sense glutamine and serum levels in endothelial cells remain uninvestigated. In this study, we examined the effects of glutamine deprivation and serum starvation on the fate of endothelial cells using a human umbilical vein endothelial cell (HUVEC) model. Our data indicated that glutamine deprivation and serum starvation trigger a progressive reduction in cell viability through apoptosis induction in HUVECs as determined by DAPI staining and flow cytometry analysis. Although the apoptotic effects were more predominant in the glutamine deprivation condition, both apoptotic actions were associated with an increase in the Bax/Bcl-2 (or Bcl-xL) ratio, down-regulation of the inhibitor of apoptosis protein (IAP) family proteins, activation of caspase activities, and concomitant degradation of poly (ADP-ribose) polymerases. Moreover, down-regulation of the expression of Bid or up-regulation of truncated Bid (tBid) were observed in cells grown under the same conditions, indicating that glutamine deprivation and serum starvation induce the apoptosis of HUVECs through a signaling cascade involving death-receptor-mediated extrinsic pathways, as well as mitochondria-mediated intrinsic caspase pathways. However, apoptosis was not induced in cells grown in glutamine- and serum-free media when compared with cells exposed to glutamine deprivation or serum starvation alone. Taken together, our data indicate that glutamine deprivation and serum starvation suppress cell viability without apoptosis induction in HUVECs.

• The Journal of the Korean dental association
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• v.53 no.7
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• pp.485-499
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• 2015

Purpose: Delayed intentional replantation was introduced as a new alternative to treat the teeth with severe periodontal involvement. The purpose of this study was to elucidate the possibility of delayed intentional replantation and establish theoretical backgrounds. Materials and Methods: Studies were performed into the following two subjects; (1)Clinical evaluation of patients who underwent delayed intentional replantation using clinical and radiographic data. Severe periodontitis involved teeth were carefully extracted and proper time for delayed replantation was evaluated by analyzing inflammation markers (IL-6, TNF-${\alpha}$). (2) Theoretical studies for efficacy of delayed intentional replantation using (-)-Epigallocatechin-3-gallate (EGCG) for preservation of periodontal ligament cells on root surface by minimizing inflammation and treatment of inflammatory extraction sockets. Results: Meaningful success ratio and survival rate were found in delayed intentional replantation showing reduced bone loss and maintained bone level. Additionally, viability of EGCG applied periodontal ligament cells was much higher than control group. Also, EGCG promoted healing of inflammatory extraction sockets by inhibiting inflammatory cell proliferation. Conclusion: Within the limitations of this study, 1-2 weeks after extraction is an appropriate time to do delayed intentional replantation. Also, EGCG provides helpful effects on viability of periodontal ligament cells and periodontium.

• Food Science and Preservation
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• v.13 no.5
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• pp.649-654
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• 2006

To enhance beneficial effects of citron fruits, anticancer and antioxidant activities of citron fruits extracts were assessed with or without ascorbic acid. Total phenolic acids and flavonoids of fruits peels and flesh extracts were determined. Fruits peels contained more phenolic acids and flavonoids than those detected in flesh extracts. Scavenging activities of 1,1-diphenyl-2-picrylhydrazyl radicals and reducing powers were increased depending on the concentration. The antioxidant activities on oxidation of linoleic acid emulsion incubated at $50^{\circ}C$ were increased but the effect was small to that of butylated hydroxy toluene and ascorbic acid. The anti-tumorigenic effect of these compounds were investigated. They were shown to inhibit the in vitro proliferation of four human tumorigenic cell lines, HT-29, MCF-7, DU-145 and HepG2, in a doso-dependent manner. This study demonstrated that the antioxidant and anticancer activities of citron fruits extracts were derived from their phenols and flavonoids.

• YAKHAK HOEJI
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• v.44 no.4
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• pp.340-346
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• 2000

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, named as Somatid, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Somatid inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, CaSki) and HaCaT keratinocytes in a dose response manner, In vitro binding assay and ELISA showed that Somatid inhibited the in vitro biding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Somatid inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by Somatid. Our data suggested that Somatid inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas caused by HPV.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1235-1242
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• 2006

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.179-204
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Angelicae Radix Pharmacopuncture(AR-P) at Joksamni(ST36) on collagen II induced arthritis in DBA/1J mice. The authors evaluated arthritis index, arthritis incidence and joint edema, and measured body weight, spleen size and stenosis rate, serum cytokine level, serum antibody level, immune cell populations In spleen, lymph node, and knee joint, and performed histological analysis of CIA mouse joint. Results : In the AR-P group, arthritis index, arthritis incidence and joint edema were decreased, and the enlargement, malformation and stenosis of spleen and the malformation of joint appeared milder than the control group. In AR-P group, the levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in serum were significantly decreased. And the level of anti-collagen II in serum was maintained lower in AR-P group than in the control group. In AR-P group, the level of $IFN-{\gamma}$ and IL-10, and $IFN-{\gamma}/IL-4$ ratio were significantly decreased, and the ratios of $CD3e^+$ cells to $CD45^+$ cells, $CD4^+$ cells to $CD8^+$ cells in spleen were similarly maintained as those of the normal group. In the AR-P group, the populations of $CD4^+/CD25^+$ cells in spleen and lymph nodes, $CD45R^+/CD69^+$ cells in lymph nodes, $CD3^+/CD69^+$ cells and $CD11b^+/Gr-1^+$ cells in knee joint were decreased. In the histological analysis, the cartilage destruction, synovial cell proliferation and the collagen fiber destruction were decreased in the AR-P group Conclusions : The results suggest that AR-P at right ST36 has a therapeutic effect on collagen-induced arthritis in mice.

• Journal of Life Science
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• v.26 no.8
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• pp.983-989
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• 2016

All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

• Journal of Life Science
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• v.27 no.12
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• pp.1470-1478
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• 2017

The aim of this study was to investigate biological activity and biochemical properties of extracts from Bacillus subtilis-fermented silkworm (Bombyx mori L., SP) powder of different origin (Buan, Namwon, and Boeun). An additional aim was to determine the inhibition of cancer cell (B16-F10, HT-29, LNcaP, and MCF-7) proliferation and nitric oxide (NO) production from lipopolysaccharide (LPS)-induced RAW264.7 cells. Biological activities (${\alpha},{\alpha}^{\prime}$-diphenyl-${\beta}$-picrylhydrazyl [DPPH], free radical scavenging activity, fibrinolytic activity, antiproliferation activity, and anti-inflammatory activity) and biochemical properties (compositional amino acid contents, and mineral contents) were examined in water extracts from silkworm powder and B. subtilis-fermented silkworm powder. The highest amino acid contents were detected in Buan silkworm powder (BU). After fermented, the highest contents were found in B. subtilis-fermented Buan silkworm powder (BBO). The major minerals detected were K, Ca, and Mg. Rates of these minerals, especially those of Na increased after fermented. DPPH radical scavenging activity and fibrinolytic activity were stronger in the fermented group than non-fermented group. DPPH radical scavenging activity and fibrinolytic activity were highest in the extract from BBO. The inhibition activities of LNcaP and MCF-7 cells viability were significantly decreased in the BBO, and there was no inhibition activity in other cancer cells (B16-F10 and HT-29). An SRB assay of the cell viability of RAW 264.7 cells exposed to extracts of silkworm powder and B. subtilis-fermented silkworm powder revealed no toxicity in any of the groups. Compared with the LPS-treated group, the biggest reduction in NO production was detected in the BBO group. Based on these results, extracts from Boeun silkworm powder fermented with B. subtilis could be a candidate material as a dietary supplement for use in healthy functional foods.