• Tuberculosis and Respiratory Diseases
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• v.86 no.4
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• pp.304-318
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• 2023

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.207-215
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• 2003

Purpose: Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protin kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Materials and Methods: Murine hepatocarcinoma, HCa-I is known to be highly radioresistant with a TCD50 (radiation dose yield in $50\%$ cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case on radioresistant tumor. C3H/HeJ mice hearing $7.5\~8\;mm$ HCa-I, were treated with PD98059(intratumoral injection of $0.16\;\mug/50\;\mul$). Results: Downregulation on ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to Increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number on apoptotic nuclei in 1000 nuclei X100) was $1.2\%$ in the case of radiation treatment alone, $0.9\%$ in the case of drug treatment alone and $4.9\%,\;5.3\%$ in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed upregulation of p53, p$p21^{WAF1/CIP1}\;and\;Bcl-X_s$ in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as $Bcl-X_L4, Bax and Bcl-2 were changed to a lesser extent. Conclusion: The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.3
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• pp.347-355
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• 2006

A study was conducted to predict the rumen microbial protein production based on urinary excretion of purine derivatives in buffaloes fed a diet of wheat straw and concentrate (40:60) at four fixed levels of feed intake. (95, 80, 60 and 40% of preliminary voluntary feed intake) following experimental protocol of IAEA (Phase I). The buffaloes were allocated according to a $4{\times}4$ latin square design. The urinary allantoin, uric acid, total PD excretion (mmol/d) in treatments L-95, L-80, L-60 and L-40 was 20.13, 16.00, 12.96 and 9.17; 1.88, 2.12, 2.11 and 2.15; 22.01, 18.12, 15.07 and 11.32, respectively and were significantly (p<0.05) different among treatments except for uric acid. The rate of PD excretion (mmol/d) was positively correlated with the digestible organic matter intake. Variations were observed in PD and creatinine concentration in spot samples collected at 6-hour interval. However, daily PD:Creatinine ratio (PDC index) appears to be a reasonably good predictor of microbial-N supply. The contribution of basal purine excretion to total excretion of purine derivatives (PD) was determined in pre-fasting period followed by a fasting period of 6 d (Phase II). Daily PD and creatinine excretion (mmol/kg $W^{0.75}$) during fasting averaged 0.117 and 0.456 respectively for buffaloes. The excretion rates of PD decreased significantly (p<0.01) during fasting compare to pre-fasting period, the urinary creatinine excretion remained almost similar. Except for creatinine, plasma concentration of target parameters significantly (p<0.01) declined during fasting. Likewise, glomerular filtration rate (GFR) and renal clearance of allantoin and uric acid also decreased. Based on the PD excretion rates during fasting and at different levels of feed intake obtained in this study, a relationship between daily urinary PD excretion (Y-mmol) and microbial purine absorption (X-mmol) was developed for buffaloes as Y = 0.74X+0.117 kg $W^{0.75}$. The microbial N supply (g/kg DOMI) remained statistically similar irrespective of dietary treatment. The results showed that excretion of urinary purine derivatives is positively correlated with the levels of feed intake in Murrah buffaloes and thus, estimation of urinary purine derivatives and PDC index could be used to determine microbial nitrogen supply when there is large variation in level of feed intake.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.1
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• pp.23-30
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• 2021

This study is an experiment to evaluate the anti-atopy efficacy of five kinds of natural plant essential oils; Artemisia annua L. (AA), Citrus junos Sieb. ex TANAKA (CJ), Chrysanthemum boreale Makino (CB), Pinus koraiensis (PK), and Pinus densiflora for. erecta (PD). Through Agar diffusion test, five species of native plant essential oils were treated in a total of four strains, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. In order to invest the anti-inflammatory effect, five kinds of natural plant essential oils were treated in HaCaT cells-induced by TNF-α and IFN-γ (TI). AA, CJ, CB, PK and PD showed antibacterial effects on Candida albicans at a concentration of 10 mg/mL. We also found that the thymus and activation-regulated chemokine (TARC) expression was suppressed in 0.1 ㎍/mL of PK, 1 ㎍/mL of AA, CB, and PK. macrophage-derived chemokine (MDC) expression was suppressed in 1 ㎍/mL of AA and PK. IL-6 expression was suppressed in 0.1, 1 ㎍/mL of AA, PK in HaCaT cells. Hence it suggests that AA, CB, and PK have the anti-inflammatory effects, and it could contribute to atopic dermatitis relief by reducing the infiltration of immune cells to inflamed area.

• Food Science and Preservation
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• v.16 no.3
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• pp.348-354
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• 2009

We examined the quality characteristics of soybean paste prepared using Bacillus subtilisDH3, which expresses high levels of protease, and deep-sea water. The protease activity of Doenjang prepared with Bacillus subtilis DH3 was $278.83{\pm}1.68$ units/mL/min. Protease and angiotensin-converting enzyme (ACE) inhibition activities increased with aging, for up to 30 days. The electron-donating ability (EDA) of Doenjang PD(Doenjang fermented with protease prodncing B. Subtilis DH3) was $61.27{\pm}0.42%$, whereas Doenjang M (traditional Doenjang fermented with meju and salt) had a lower value of $14.47{\pm}0.41%$. The mineral content of Doenjang PD was higher than that of Doenjang M. The overall acceptability of Doenjang PD was better than that of Doenjang M.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.77-86
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• 2013

The neuroprotective effects of herbal ethanol extract (GP-EX) from Gynostemma pentaphyllum on dopamine neurons in animal model of Parkinson's disease (PD) were investigated. Rats and mice were administered with rotenone (2.5 mg/kg) for 28 days and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) for 5 days for the PD models, respectively and the animals were simultaneously treated with GP-EX (30 mg/kg, daily). After preparing the PD models, the animals were also administered with L-DOPA (10 mg/kg) for 14 days with or without GP-EX treatment. Treatment with GP-EX (30 mg/kg) inhibited the rotenone- and MPTP-induced neurotoxic effects in dopamine neurons of rats or mice, which was determined by the numbers of tyrosine hydroxylase-immunohistochemical staining survival cells, as well as the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. GP-EX (30 mg/kg) also showed the protective effects on neurotoxicity which was induced by long-term administration of L-DOPA (10 mg/kg) in rotenone- and MPTP-induced animal model of PD. The used doses of GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting, in rats and mice during the treatment periods. These results suggest that GP-EX has the protective functions against chronic L-DOPA-induced neurotoxic reactions in dopamine neurons of rotenone- and MPTP-induced animal model of PD. Therefore, the natural GP-EX may be beneficial in the prevention of PD progress and L-DOPA-induced neurotoxicity in PD patients.

• Food Science and Preservation
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• v.8 no.4
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• pp.367-373
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• 2001

In order to study the effect of modified atmosphere storage on extending shelf life of King Oyster mushroom was wrapped with PVC film and packed with 20$\mu\textrm{m}$polyolefin(PD941), and effects of temperature(0, 5, 10$^{\circ}C$) in packaging conditions on the respiration and keeping qualities were evaluated. Higher respiratory activity and weight loss were observed at higher temperature. The concentration of O$_2$and CO$_2$ of PVC wrap and polyolefin(PD941) packages for all showed 1∼2% and 10∼14%, respectively. Polyolefin(PD941) package wan superior to the PVC wrap packaging method in Hardness, Hunter L value, Hunter b value and sensory qualities, and reducing weight loss at 0$^{\circ}C$, 5$^{\circ}C$ and 10$^{\circ}C$ compared to PVC wrap. It was found that the optimum shelf-life period of King Oyster mushroom packaged by PVC wrap was estimated to be 50, 28 and 12 days at 0, 5 and 10$^{\circ}C$, respectively, and 50, 32 and 21 days in Polyolefin(PD941).

• Korean Journal of Clinical Pharmacy
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• v.24 no.3
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• pp.206-212
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• 2014

Objectives: This was to evaluate the current usage of three erythropoietin stimulating agents (ESA) and their efficacy for management of anemia in peritoneal dialysis (PD) patients with chronic kidney disease. Methods: It was a retrospective comparative study through review of electronic medical records of chronic kidney disease patients undergoing PD at a tertiary teaching hospital from January 1998 to June 2013. Results: Average administration frequency was 1.66 times/week in EPO group, 0.75 times/week in DA group, and 0.19 times/week in MPG-EPO group. At the first 4 weeks, there were significant differences in mean hemoglobin levels between EPO and DA groups ($9.25{\pm}1.28g/dL$, $10.02{\pm}0.95g/dL$ each, p = 0.018) and also in hemoglobin response rates (10.0%, 45.2% each, p = 0.008), but since after 4 week, there had been no significant differences. There also showed no significant differences in achievement of hemoglobin target between the two groups. When converted to MPG-EPO in EPO/DA groups, there showed a slight increase in hemoglobin levels of both groups. MPG-EPO was the highest compared with two other drugs by the average cost based on the average weekly dose. Conclusion: EPO, DA, and MPG-EPO showed similar effects in treatment of anemia of PD patients based on hemoglobin target range (11.0~12.0 g/dL) which NFK-K/DOQI guidelines suggest. Though the average cost of MPG-EPO was higher than the other two drugs, the number of PD patients using MPG-EPO has increased and it is thought that long half-life and low administration frequency of MPG-EPO have improved the compliance of PD patients who have to self-administrate.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.58-65
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• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.