• Journal of Life Science
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• v.27 no.5
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• pp.509-516
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• 2017

Perilla frutescens (L.) Britton var. sprouts (PFS) is a plant of the labiatae family. The purpose of this work was to assess the preventive effects of PFS ethanolic extracts (PFSEs) on cytokine-induced ${\beta}$-cell damage. Cytokines, which are released by the infiltration of inflammatory cells around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. The combination of interleukin-$1{\beta}$ (IL-1), interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) induced formation of reactive oxygen species (ROS). Accumulation of intracellular ROS led to ${\beta}$-cell dysfunction and apoptosis. PFSEs possess antioxidant activity and thus lead to downregulation of ROS generation. Cytokines decrease cell viability, stimulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and induce the production of nitric oxide (NO). PFSEs prevented cytokine-induced cell viability in a dose-dependent manner. Incubation with PFSE resulted in significant reduction in cytokine-induced NO production that correlated with reduced levels of the iNOS and COX-2 protein expression. Furthermore, PFSE significantly decreased the activation of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) by inhibition of $I{\kappa}B{\alpha}$ phosphorylation in RINm5F cells. In summary, our results suggest that the protective effects of PFSE might serve to counteract cytokine-induced ${\beta}$-cell destruction. Findings indicate that consumption of Perilla frutescens (L.) Britton var. sprouts alleviates hyperglycemia-mediated oxidative stress and pro-inflammatory cytokine-induced ${\beta}$-cell damage and thus has beneficial anti-diabetic effects.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.542-550
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• 2003

Background : Synthetic glucocorticoids are widely used in many chronic inflammatory diseases because of their excellent anti-inflammatory activity. Enhancing the transcription of $I{\kappa}B$ and preventing activated NF-${\kappa}B$ from binding to ${\kappa}B$ sites are thought to be the underlying mechanisms. But these data are largely derived from in vitro studies using cell lines. In this study, after administrating a steroid to volunteers, we evaluated the effect on the NF-${\kappa}B$ system. Methods : Prednisolone(0.5mg/kg/d) was orally administered to 5 healthy volunteers for 7 days. Before and after the administration, we sampled their peripheral blood monocytes, and performed western blot analysis both with stimulation, using IL-$1{\beta}$, LPS, TNF, and without stimulation(baseline). We also performed EMSA after stimulation with LPS. Results : After ingestion of the steroid, baseline expressions of $I{\kappa}B{\alpha}$ were increased in two of the subjects, while suppressed degradations of $I{\kappa}B{\alpha}$ to stimulations were observed in all five. In addition, the binding capacity of NF-${\kappa}B$ after the administration was decreased. Conclusion : Steroid plays such roles as enhancing the transcription of $I{\kappa}B{\alpha}$, suppressing the DNA binding capacity of NF-${\kappa}B$, and suppressing the degradation of $I{\kappa}B{\alpha}$.

• Journal of Applied Biological Chemistry
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• v.64 no.2
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• pp.185-192
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• 2021

Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1116-1124
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• 2007

Purpose : Juvenile dermatomyositis (JDM) is the most common of the idiopathic inflammatory myopathies in children. The purpose of this study is to observe demographic, initial presentations, duration of time between disease onset and diagnosis, clinical manifestations and laboratory findings at diagnosis of patients with JDM. Methods : Forty seven patients identified at Seoul National University Children's Hospital from January 1986 to May 2007. Medical records were reviewed retrospectively focusing on initial presentations, clinical manifestations and laboratory findings at the time of diagnosis of patients with JDM. Results : Male and female patients were 25 and 22, respectively and sex ratio was 1.14:1. The average age at the time of diagnosis was 6.51 years. Skin rash (94%) was the most common symptom, followed by the proximal muscle weakness (89%). The disease activity score was 10.8. The duration between the onset of the skin rash and the muscle weakness and diagnosis was 7.18 and 4.70 months, respectively. The serum muscle enzymes, LDH, AST, CK and aldolase, were elevated in the patient with JDM. Autoimmune antibodies, antinuclear antibody, anti SSA antibody and anti SSB antibody, were negative findings. Electromyography findings were consistent with JDM in 88% of the patients, the muscle biopsy was in 91% and all MRI findings were compatible with those of patients with JDM. The most common symptom besides musculocutaneous lesions was the calcinosis (62.5%). The most common site of calcinosis was the pelvic area and buttocks. Conclusion : This study shows that the major symptoms are proximal muscle weakness and cutaneous lesion, and they are important to diagnose JDM.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• KSBB Journal
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• v.19 no.6 s.89
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• pp.471-477
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• 2004

Oldenlandia diffusa is a Chinese medicinal herb with antitumor activity capable of suppressing the growth of some cancer cell lines. Oleanolic acid and ursolic acid are triterpenoid compounds that exist in Oldenlandia diffusa. Recently, these have been noted for anti-inflammatory, anti-cancer, and hepato-protective effects. Application of both plant growth regulators, 2,4-D and kinetin, was found to be essential for the initiation of callus and suspension cells. Leaf blades of Oldenlandia diffusa was transformed into callus on Schenk and Hildebrandt medium supplemented with 0.5 mg/L 2,4-D and 0.1 mg/L kinetin, while optimum initiation condition for suspension cells of Oldenlandia diffusa was determined to be 0.75 mg/L 2,4-D and 0.1 mg/L kinetin. Chromatographic separation of oleanolic acid from its derivatives was achieved using Rexchrom S5-100-ODS column. Analytical conditions for oleanolic acid were determined as follows: flow rate at 1.0 mL/min, UV length at 200 nm and mobile phase of $80\%$ acetonitrile and $20\%$ water. Production of secondary metabolites was found to be increased by the treatment with elicitors or signal transducers. The maximum production of oleanolic acid was 99.6 mg/L in cultures with 0.5 mM salicylic acid. It is 1.74 times higher than that of control.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.5
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• pp.682-689
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• 2013

This study determined the effects of cabbage juice and cabbage-mixed juices on the growth of AGS human gastric cancer cells and their anti-gastritic effects on HCl-ethanol induced gastritis in SD rats. Cabbage juice showed the highest growth inhibition on AGS gastric cancer cells in vitro (42%), compared with chlorella (20%) and kale juice (21%). However, cabbage-chlorella and cabbage-kale juice mixtures (at a 7:3 ratio) showed synergistic effects (57% and 65% inhibitory effects, respectively) on the gastric cancer cells. Inflammatory genes (iNOS, COX-2, TNF-${\alpha}$ and IL-$1{\beta}$) were significantly down-regulated in the mixed juices. Tests of DPPH radical scavenging activity and acid-neutralizing capacity with the mixed juices also showed this trend, as cabbage-chlorella and cabbage-kale mixed juices showed synergistic effects compared to cabbage juice alone. The inhibition rate of acute gastritis induced by HCl-ethanol in rats was 46% with high amounts of cabbage (CH; 800 mg/kg), 71% with high amounts of cabbage and chlorella (CChH; 800 mg/kg), 74% with high amounts of cabbage and kale (CKH; 800 mg/kg), and 75% with cimetidine (positive control) compared with the control. In addition, rates with CChH and CKH showed decreasing gastric secretions with increasing pH. These results show that cabbage juice and cabbage-mixed juices, especially with chlorella or kale, exhibit remarkable anti-gastritic effects and can be administered for a long period for the prevention and treatment of gastric cancer and gastritis.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.695-701
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• 2003

Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

• The Journal of Korean Obstetrics and Gynecology
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• v.15 no.4
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• pp.45-60
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• 2002

Mouse calvarial osteoblast cells were isolated and cultured. To examine whether the cells produce active gelatinases in culture medium or not,the cells were analyzed using by zymograsphic analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). We show that mouse calvarial osteoblasts in culture constitutively synthesize progelatinase- A. Then, mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agent's, showed increased collagenolysis by producing the active gelatinase. However, treatment of indomethacin and dexamethasone significantly decreased those effects of collagenolysis in mouse osteoblastic cells. On the other hand, IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, when it was examined the effects of indomethacin and dexamethasone on the dose dependent responses of $IL-1{\alpha}$, indomethacin and dexametasone produced a rightward shift in the IL-1 dose response curve. The results of in vitro cytotoxicities showed that Taeyoungjon-Jahage water extracts(T.Y.J-J.H.G extracts) have no any cytotoxicities in concentrations of $1-200\;{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $300\;{\mu}g/ml$ on mouse calvarial bone cells. T.Y.J.-J.H.G. extracts had protective activity against PTH (2 units/mI), or MCM (5%, v/v), or $rhIL-1{\alpha}$ (1 ng/mI) or $1,25(OH)_2D3$ (10 ng/ml) , $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the T.Y.J.-J.H.G.extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore. the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resortion agents of PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ and $IL-1{\alpha}$, with strong protective effect in pretreatment with the extracts. T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. The inhibition extent and phenomena of IL-1 stimulated bone resorption by nonsteroidal anti-inflammatory agents of indomethacin and dexamethasone were similar to those obtained by T.Y.J.-J.H.G. extracts treatment in the mouse calvarial tissue culture system. These results indicated that the T.Y.J.-J.H.G.-water extracts are highly stable and applicable to clinical uses in osteoporosis.

• Journal of Dairy Science and Biotechnology
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• v.33 no.2
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• pp.111-118
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• 2015

Probiotic, prebiotic, and synbiotic substances as well as microorganisms were added to infant formula in an attempt to influence the intestinal microflora with an aim to stimulate the growth of lactic acid bacteria, especially bifidobacteria and lactobacilli. Over the last 10 years, new synbiotic infant formulas containing probiotics and prebiotics have been proposed in order to simulate the effect of breast-feeding on the intestinal microflora. Owing to their synergistic effect, the new synbiotics are expected to be more helpful than using probiotics and prebiotics individually. Maintenance of the viability of the probiotics during food processing and the passage through the gastrointestinal tract should be the most important consideration, since a sufficient number of bacteria ($10^8cfu/g$) should reach the intended location to have a positive effect on the host. Storage conditions and the processing technology used for the manufacture of products such as infant formula adversely affect the viability of the probiotics. When an appropriate and cost-effective microencapsulation methodology using the generally recognized as safe (GRAS) status and substances with high biological value are developed, the quality of infant formulas would improve. The effect of probiotics may be called a double-effect, where one is an immunomodulatory effect, induced by live probiotics that advantageously alter the gastrointestinal microflora, and the other comprises anti-inflammatory responses elicited by dead cells. At present, a new terminology is required to define the dead microorganisms or crude microbial fractions that positively affect health. The term "paraprobiotics" (or ghost probiotics) has been proposed to define dead microbial cells (not damaged or broken) or crude cell extracts (i.e., cell extracts with complex chemical composition) that are beneficial to humans and animals when a sufficient amount is orally or topically administered. The fecal microflora of bottle-fed infants is altered when the milk-based infant formula is supplemented with probiotics or prebiotics. Thus, by increasing the proportion of beneficial bacteria such as bifidobacteria and lactobacilli, prebiotics modify the fecal microbial composition and accordingly regulate the activity of the immune system. Therefore, considerable attention has been focused on the improvement of infant formula quality such that its beneficial effects are comparable to those of human milk, using prebiotics such as inulin and oligosaccharides and potential specific probiotics such as bifidobacteria, which selectively stimulate the proliferation of beneficial bacteria in the microflora and the indigenous intestinal metabolic activity of the microflora.