• Molecules and Cells
• /
• v.44 no.1
• /
• pp.38-49
• /
• 2021

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.

• Korean Journal of Radiology
• /
• v.20 no.5
• /
• pp.830-843
• /
• 2019

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2^*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D^*), perfusion fraction (f) were calculated. Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D^* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2^* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2^* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.22 no.3
• /
• pp.63-70
• /
• 2009

Objectives : The present study was examined to evaluate the anti-inflammatory effects of the Gentianae Macrophyllae Radix MeOH extracts (GMR) in vivo. Methods : The effects of GMR on anti-inflammation were measured by production of NO, TNF-$\alpha$ (Tumor Necrosis Factor-alpha) and IL-$1{\beta}$ (Interleukin-$1{\beta}$), IL-6 in Raw 264.7 macrophage cells stimulated with LPS. Results : 1. All concentrations of GMR(0.10 mg/ml) had no significant cytotoxicity in Raw 264.7 cell during the entire experimental period. 2. The level of NO and iNOS in culture medium was dramatically increased by LPS application. However, these increases were dose-dependently(0.03 and 0.10 mg/ml) attenuated by treatment with GMR. 3. All concentrations of GMR significantly inhibited the production of IL-$1{\beta}$ in Raw 264.7 macrophage cells stimulated with LPS. Conclusions : These results provide evidences that therapeutic effect of GMR on heat syndrome, especially due to the acute inflammation, are partly due to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of $p-I{\kappa}B{\alpha}$. Moreover, it suggests that the mechanism of action of GMR comes from the suppression of inflammatory mediators, such as NO, PGE2 and pro-inflammatory cytokines.

• Korean Journal of Community Nutrition
• /
• v.17 no.5
• /
• pp.623-636
• /
• 2012

Health Belief Model is a socio-psychological theory of decision making to individual health-related behaviors. This study was aimed to develop an effective education program for hypertension based on health belief model. The main factors of health belief model were investigated by focus group interview (FGI) with 23 hypertensive or prehypertensive subjects aged over fifty years. 'Perceived susceptibility' to hypertension was family history, neglect of health care, preference for salty food, broth of soup and stew. Lifelong medication, complications, and medical costs were reported as 'perceived severity' of hypertension. 'Perceived benefits' of hypertension management were decrease of medicinal dose, reduction of medical costs, and healthy eating habits of the family, while 'perceived barriers' were lack of palatability of low salt diet, convenience-oriented dietary habits, and limited choice of foods when eating out. Subjects mentioned TV health programs, public health center programs, and advice from doctors and family as 'cues to action' of hypertension management. These qualitative information provided basis for developing a nutrition education program for hypertension which could be implemented in the public health center. Eight week program was composed of understanding hypertension, risk factor management (eating habits, weight), low salt diet (principles, cooking), advanced management for healthy diet in 2 sessions, and summary. Each session was designed to alert the susceptibility and severity, to emphasize the benefits, and to reduce the barriers by providing dietary monitoring, practical advice, and action tips.

• Preventive Nutrition and Food Science
• /
• v.8 no.3
• /
• pp.253-259
• /
• 2003

Conjugated linoleic acid (CLA) is a class of positional, geometric conjugated dienoic isomers of linoleic acid (LA). CLA activates the immune system, protects against tumorigenesis, and reduces the incidence of atherosclerosis. Trans-10, cis-12 CLA has specific effects on lipid metabolism, it has been shown to reduce body fat gain and regulates some adipocyte secreted proteins in vivo and in vitro. Here we report that a CLA mixture affects cytokine secretion from rat primary adipocytes. Rat primary adipocytes were treated with 1 mM, 100 $\mu$M, 1 $\mu$M or 100 nM CLA mixture doses; and leptin, tumor necrosis factor alpha (TNF a ), interleukin-6 (IL-6) and glycerol levels in the medium were measured. Leptin secretion was lower, TNF $\alpha$ secretion higher and IL-6 secretion did not change in response to the CLA mixture. Leptin and TNF $\alpha$ secretions did not change with CLA mixture treatment in a dose-dependent manner. In addition, the CLA mixture did not appear to enhance lipolysis in rat primary adipocytes. In conclusion, our study demonstrates that the decrease in leptin and increase in TNF $\alpha$ secretion in adipocytes treated with CLA mixture may be due to the apoptotic effect and to a reduction in peroxisome proliferator-activated receptor gamma (PPAR ${\gamma}$ ) ligands.

• Journal of Korean Neurosurgical Society
• /
• v.50 no.3
• /
• pp.179-184
• /
• 2011

Objective : The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods : We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results : The overall median survival after GKRS was $9.1{\pm}1.7$ months. Among various factors, primary tumor control was a significant prognostic factor ($11.1{\pm}$1.3 months vs. $3.3{\pm}2.4$ months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion : According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase.

• Korean Journal of Veterinary Research
• /
• v.51 no.3
• /
• pp.177-183
• /
• 2011

The radioprotective efficacy of a methanol extract of the red algae Polyopes lancifolia (Harvey) kawaguchi et wang (mPL) was evaluated in mice subjected to total-body gamma irradiation. mPL protection against radiation-induced oxidative stress was examined by histological evaluation of intestinal crypt-cell survival and liver activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). mPL (100 mg/kg body weight) administered intraperitoneally at 24 h and 1 h prior to irradiation protected jejunal crypt cells from radiation-induced apoptosis (p < 0.01). The pretreatment of mPL attenuated a radiation-induced decrease in villous height (p < 0.05), and improved jejunal crypt survival (p < 0.05). The dose reduction factor was 1.14 at 3.5 days after irradiation. Treatment with mPL prior to irradiation resulted in significantly higher (p < 0.01) levels of SOD and CAT activities, compared to those levels of irradiated control mice with vehicle treatment. These results suggest that mPL is a useful radioprotective agent capable of defending intestinal progenitor cells against total-body irradiation, at least in part through mPL antioxidative activity.

• Korean Journal of Pharmacognosy
• /
• v.46 no.4
• /
• pp.334-341
• /
• 2015

HAE series (HAE 01 - 06), are the mixtures of medicinal plants; Lonicerae Folium et Caulis (Lonicera japonica), Scutellariae Radix (Scutellaria baicalensis), Adenophorae Radix (Adenophora triphylla var. japonica), Polygonati Oddorati Rhizoma (Polygonatum odoratum var. pluriflorum), Platycodi Radix (Platycodon grandiflorum), Liriopis seu Ophiopogonis Tuber (Liriope platyphylla). HAE 06 showed the significant antitussive effect in HAE series. HAE 04, 05, and 06 increased the effect of expectorant measured by secretion of phenol red in rats. All tested HAE series were observed to have the anti-oxidant activity determined by the scavenging activity. HAE 01, 03 and 06 were significantly reduced the production of nitric oxide (NO) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) increased by LPS. HAE 06 was selected based on the results and done further experiments. HAE 06 inhibited the number of coughing induced by citric acid in dose dependent manner. HAE 06 effectively increased the effect of expectorant. HAE 06 exhibited anti-inflammatory effects by inhibiting the production of NO and TNF-${\alpha}$. In addition, HAE 06 significantly suppressed inducible Cyclooxygenase-2 (COX-2). Especially HAE 06 has the highest effect in alleviating the respiratory symptoms. Moreover, the enhancement antioxidant activity and reduction inflammation partly were attributed to it. HAE 06 may become the promising candidate for the treatment of respiratory symptom in the future.

• Korean Journal of Food Science and Technology
• /
• v.28 no.2
• /
• pp.366-370
• /
• 1996

Gamma irradiation was applied to red ginseng powder for improving its hygienic quality 7.5 kGy of gamma irradiation completely eliminated the microorganisms contaminated in red ginseng powder. And there was no growth of microorganisms after six months of storage at room temperature. The molds isolated from red ginseng powder were identified as Pen. commune, Asp. niger, Asp. versicolor and Asp. Unguis, the conidia of which showed the decimal reduction dose ($D_{10}$ value) of 0.37-0.50 kGy, 0.24-0.31 kGy, 0.25-0.36 kGy and 0.28-0.41 kGy and inactivation factor of 5.0-6.5, 7.4-9.3, 6.5-9.1 and 6.1-8.4, respectively The radiosensitivity of identified molds' conidia decreased in medium containing red ginseng extract.

• Journal of Society of Preventive Korean Medicine
• /
• v.14 no.1
• /
• pp.97-110
• /
• 2010

The wound healing process can be categorized as follows : inflammation, fibroplasia, neovascularization, collagen deposition, epithelialization, and wound contraction. During the healing process, various growth factors are secreted to accelerate wound healing. Previous studies have demonstrated that endogenous growth factors, such as vascular endothelial growth factor(VEGF) are the important regulatory polypeptides for coordinating the healing process. They are released from macrophages, fibroblasts, and keratinocytes at the site of injury and participate in the regulation of reepithelization, granulation tissue formation, collagen synthesis and neovascularization. Onchung-Um has been used clinically to treat various skin diseases. In addition, Onchung-Um has been also used for congestive inflammations. In the present study, we evaluated the effects of Onchung-Um on wound healing process and wound size reduction in rats. Full-thickness skin wounds ($15mm\;{\times}\;15mm$) were created on the back of rats. Rats were then divided into 2 groups : The Onchung-Um treated group that was orally administered with a dose of 193.9mg/100g of Onchung-Um extract per day for 15 days and Control group without Onchung-Um administration. Moreover, the histological changes and VEGF immunoexpressions of two groups were estimated. In results, wound closures were significantly accelerated by oral administration of Onchung-Um extract. Furthermore, in Onchung-Um treated group, there were significant increases in fibroblast migration, epithelialization compared with the Control group. VEGF expressions were also increased in Onchung-Um treated group. This study has therefore demonstrated the Onchung-Um can significantly improve the quality of wound healing and scar formation and the oral administration of Onchung-Um extract may increase early tissue angiogenesis in the incisional wound of an experimental animal model.