• IMMUNE NETWORK
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• v.10 no.3
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• pp.99-103
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• 2010

Background: Glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) is a ubiquitous serine/threonine kinase that is regulated by serine phosphorylation at 9. Recent studies have reported the beneficial effects of a number of the pharmacological $GSK3{\beta}$ inhibitors in rodent models of septic shock. Since most of the $GSK3{\beta}$ inhibitors are targeted at the ATP-binding site, which is highly conserved among diverse protein kinases, the development of novel non-ATP competitive $GSK3{\beta}$ inhibitors is needed. Methods: Based on the unique phosphorylation motif of $GSK3{\beta}$, we designed and generated a novel class of $GSK3{\beta}$ inhibitor (GSK3i) peptides. In addition, we investigated the effects of a GSK3i peptide on lipopolysaccharide (LPS)-stimulated cytokine production and septic shock. Mice were intraperitoneally injected with GSK3i peptide and monitored over a 7-day period for survival. Results: We first demonstrate its effects on LPS-stimulated pro-inflammatory cytokine production including interleukin (IL)-6 and IL-12p40. LPS-induced IL-6 and IL-12p40 production in macrophages was suppressed when macrophages were treated with the GSKi peptide. Administration of the GSK3i peptide potently suppressed LPS-mediated endotoxin shock. Conclusion: Collectively, we present a rational strategy for the development of a therapeutic GSK3i peptide. This peptide may serve as a novel template for the design of non-ATP competitive GSK3 inhibitors.

• Journal of Acupuncture Research
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• v.22 no.5
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• pp.57-66
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• 2005

Objectives : We examined the effects of electroacupuncture on the cholecystokinin-octapeptide-induced acute pancreatitis in rats. Methods : Rats were administered with $75{\mu}g/kg$ cholecystokinin-octapeptide subcutaneously three times (1, 3 and 5h after shaving) for 5days. Three days after finishing cholecystokinin-octapeptide administration, high frequency electroacupuncture (100Hz) and low frequency electroacupuncture (2Hz) were applied to acupoint equivalent to ST36 (Zusanli) for 7 days. The author determined the pancreatic weight/body weight ratio, the levels of pancreatic heat shock protein HSP60 and HSP72. The author also assay the secretion of ${\beta}-amylase$, lipase and pro-inflammatory cytokines in serum. Repeated cholecysokinin-octapeptide treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. Results : Eelectroacupuncture significantly decreased the pancreatic weight/body weight ratio in cholecystokinin-octapeptide-induced acute pancreatitis, increased the pancreatic levels of HSP60 and HSP72, and decreased ${\beta}-amylase$ and lipase levels in cholecystokinin-octapeptide-induced acute pancreatitis. Additionally, the secretion of $Interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ was decreased in the animals treated with electroacupuncture. Conclusion : These results suggest that electroacupuncture may have protective effects against cholecystokinin-octapeptide-induced acute pancreatitis.

• Biomedical Science Letters
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• v.10 no.4
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• pp.459-465
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• 2004

The use of hemofiltration has been proposed to reduce excessive body fluid and inflammatory mediators produced during cardiac surgery with cardiopulmonary bypass (CPB) in infants and children. This study was undertaken to evaluate the efficacy of hemofiltration in adult cardiac surgery using (CPB). Twenty adult patients scheduled for elective cardiac surgery were randomly assigned to control group without hemofiltration (n=10) or hemofilter group with hemofiltration during CPB (n=lO). CBC and serum levels of interleukin-6 (IL-6), D-dimer, endothelin-l (ET-1), and cortisol were measured at before the initiation and immediately after the termination of CPB (Pre-CPB and End-CPB, respectively). Clinical data were assessed at postoperative period. In hemofilter group hematocrit was significantly higher (30.04±2.63％ vs 23.30±2.71％, P=0.0014) whereas total leukocyte count was lower than in control group (7.71±1.78×10³/㎣ vs 16.01 ±3.12x10³/㎣, P=0.021) at End-CPB. Increased rate of IL-6 (311.56±97.31％ vs 825.45±102.56％, P=0.012) and D-dimer levels (154.55±89.04％ vs 308.33±157.64％, P=0.026) at End-CPB were significantly less in hemofilter group than in control group. Postoperative blood transfusion in hemofilter group was low compared with that of control group (741.00±38.07 ml vs 1,137.50±169.82 ml, P=0.037). There were no significant differences between two groups in platelet count, ET -1, cortisol, pulmonary index, mechanical ventilation, postoperative blood loss, ICU-stay and hospitalization. Hemofiltration technique applied in the present study provided partly beneficial effect in adult cardiac surgery.

• Toxicological Research
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• v.20 no.3
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• pp.233-239
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• 2004

The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse kidney. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drink-ing water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity or renal toxicity as indicated by unaltered plasma alanine aminotransferase and aspartate aminotransferase levels, and terminal UTP nucleotide end-labeling assay from kidney, respectively. Mercury decreased kidney glutathione (GSH) and with LPS, it additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury inhibited LPS-induced activation of extra-cellular signal-regulated kinase (ERK) but had no effect alone. Mercury increased the gene expression of tumor necrosis factor $\alpha$ (TN F$\alpha$) and potentiated LPS-induced TNF$\alpha$ expression. Mercury did not affect LPS-induced interleukin-1$\beta$ (IL-1$\beta$) expression but decreased LPS-induced IL-6 expression. These results suggest that low levels of mercury might augment LPS-induced TNF$\alpha$ expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation, and downstream TNF$\alpha$ and IL-6 expression in kidney, respectively.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.237-244
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• 2006

Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

• Current Optics and Photonics
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• v.3 no.6
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• pp.485-495
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• 2019

Photobiomodulation (PBM) using organic light emitting diodes (OLEDs) surface light sources have recently been claimed to be the next generation of PBM light sources. However, the differences between light emitting diodes (LEDs) and OLED mechanisms in vitro and in vivo have not been well studied. In vivo mouse models were used to investigate the effects of OLED irradiation on cellular function and cutaneous wound healing compared to LED irradiation. Mice in the LED- and OLED-irradiated groups were subjected to irradiation with 6 J/㎠ LED and OLED (630 nm), respectively, for 14 days after wounding, and some mice were sacrificed for the experiments on days 3, 7, 10, and 14. To evaluate wound healing, we performed hematoxylin-eosin and Masson's trichrome staining and quantified collagen density by computerized image analysis. The results showed that the size of the wound, collagen density, neo-epidermis thickness, number of new blood vessels, and number of fibroblasts and neutrophils was significantly influenced by LED and OLED irradiation. The tissue levels of interleukin (IL)-β, IL-6 and tumor necrosis factor (TNF)-α were investigated by immunohistochemical staining. LED and OLED irradiation resulted in a significant increase in the tissue IL-β and IL-6 levels at the early stage of wound healing (P < 0.01), and a decrease in the tissue TNF-α level at all stages of wound healing (P < 0.05), compared to the no-treatment group. The expression levels of the genes encoding vascular endothelial growth factor and transforming growth factor-beta 1 were significantly increased in LED and OLED-irradiated wound tissue at the early stage of wound healing (P < 0.01) compared to the no-treatment group. Thus, OLED as well as LED irradiation accelerated wound healing by modulating the synthesis of anti-inflammatory cytokines and the expression levels of genes encoding growth factors, promoting collagen regeneration and reducing scarring. In conclusion, this suggests the possibility of OLED as a new light source to overcome the limitations of existing PBMs.

• Journal of Oriental Neuropsychiatry
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• v.15 no.2
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• pp.89-101
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• 2004

Objective : The present experiments were designed to study on the immune-enhancing effect of Mountain grown ginseng, Mountain cultivated ginseng, and Panax ginseng Method : In order to compare the immune-enhancing effect of moutain grown ginseng, moutain cultivated ginseng and Panax ginseng, the study was done through the forced swimming test (FST), measurement of T helper Th1, Th2 cytokines and fatigue related factors. Result : Moutain grown ginseng and panax ginseng decreased the immobility time in the FST compared to the control. Glucose, blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH) and Total-protein (T-protein) in serum were investigated. The serum achieved from ginseng administered mouse showed higher BUN, T-protein than the control. moutain grown ginseng administered group showed lower LDH than the control group. moutain grown ginseng administered mouse showed higher glucose than the control. Creatinine was same in either experimental or control group. Ginseng-induced cytokine production in human T-cell line, MOLT-4 cells and mouse peritoneal macrophages were compared. Moutain cultivated ginseng (10-4 dilution) and panax ginseng (10-3 dilution) were increased the interferon $IFN-{\gamma}$ production compared with media control (about 1.6-fold P<0.05) at 48 h. Moutain grown ginseng (10-4 dilution) was increased the $IFN-{\gamma}$ and interleukin IL-4 production compared with media control (about l.4-fold for $IFN-{\gamma}$ and 1.6-fold for IL-4 P<0.05) at 48 h. Moutain grown ginseng (10-3 dilution) and moutain cultivated ginseng (10-4 dilution) were increased the turmor necrosis factor $TNF-{\alpha}$ production compared with $rIFN-{\gamma}$ treated cells (about 1.9-fold for $TNF-{\alpha}$ P<0.05), respectively. Moutain cultivated ginseng (10-3 dilution) was increased the IL-12 production compared with $rIFN-{\gamma}$ treated cell (about 1.7-fold for IL-12 P<0.05). Conclusion : These data suggest that three different three kinds of ginseng act on immune responses in different aspects.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1378-1386
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• 2020

Objective: Chinese indigenous sheep breeds can be classified into the following three categories by their tail morphology: fat-tailed, fat-rumped and thin-tailed sheep. The typical sheep breeds corresponding to fat-tailed, fat-rumped, and thin-tailed sheep are large-tailed Han, Altay, and Tibetan sheep, respectively. Detection of copy number variation (CNV) and selection signatures provides information on the genetic mechanisms underlying the phenotypic differences of the different sheep types. Methods: In this study, PennCNV software and F-statistics (F_ST) were implemented to detect CNV and selection signatures, respectively, on the X chromosome in three Chinese indigenous sheep breeds using ovine high-density 600K single nucleotide polymorphism arrays. Results: In large-tailed Han, Altay, and Tibetan sheep, respectively, a total of six, four and 22 CNV regions (CNVRs) with lengths of 1.23, 0.93, and 7.02 Mb were identified on the X chromosome. In addition, 49, 34, and 55 candidate selection regions with respective lengths of 27.49, 16.47, and 25.42 Mb were identified in large-tailed Han, Altay, and Tibetan sheep, respectively. The bioinformatics analysis results indicated several genes in these regions were associated with fat, including dehydrogenase/reductase X-linked, calcium voltage-gated channel subunit alpha1 F, and patatin like phospholipase domain containing 4. In addition, three other genes were identified from this analysis: the family with sequence similarity 58 member A gene was associated with energy metabolism, the serine/arginine-rich protein specific kinase 3 gene was associated with skeletal muscle development, and the interleukin 2 receptor subunit gamma gene was associated with the immune system. Conclusion: The results of this study indicated CNVRs and selection regions on the X chromosome of Chinese indigenous sheep contained several genes associated with various heritable traits.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.175-184
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• 2011

Objectives: The purpose of this study was to investigate the effects of Angelicae pubescentis Radix water extract (ACE) on immune properties in macrophage cells. Methods: The cells were divided into two groups: As a control, the first was not treated with ACE, and the other was treated with ACE. Together with the cell viability, productions of nitric oxide (NO) and cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ by treating of ACE were monitored. Results: 1. There was no decrease of the cell viability after 24 hr incubation, but a significant decrease after 48 hr incubation with all four concentrations (25, 100, 200, and $400\;{\mu}g/m{\ell}$) of ACE. 2. A significant increase in the production of NO was observed in the concentrations above $50\;{\mu}g/m{\ell}$ of ACE after 24 hr incubation. 3. Further, after 48 hr incubation, the critical concentration of ACE for the increase was reduced to $25\;{\mu}g/m{\ell}$. 4. The production of (IL)-$1{\beta}$ significantly increased with the ACE concentrations of 100 and $200\;{\mu}g/m{\ell}$ after 24 hr incubation. 5. The production of IL-6 significantly increased with the ACE concentration of $200\;{\mu}g/m{\ell}$ after 24 hr incubation. 6. A significant increase in the production of (TNF)-${\alpha}$ was detected with ACE concentrations of 50, 100, and $200\;{\mu}g/m{\ell}$ after 24 hr incubation. Conclusions: These show that ACE increases mouse macrophage NO production at concentrations above $50\;{\mu}g/m{\ell}$, and the cytokines ((IL)-$1{\beta}$, IL-6, and (TNF)-${\alpha}$) at concentrations above $200\;{\mu}g/m{\ell}$. These results suggest that ACE improves macrophage immune property.

• The Journal of Pediatrics of Korean Medicine
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• v.34 no.3
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• pp.67-75
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• 2020

Objectives This study is conducted to evaluate Th2 skewed condition control through skin fat barrier formation from the treatment using Coptidis Rhizoma and Glycyrrhiza uralensis extract. Methods The 6-week-old NC/Nga mice were divided into 4 groups: Control group (Ctrl), lipid barrier eliminate treatment group (LBET), Coptidis Rhizoma and Glycyrrhiza uralensis feeding treatment after lipid barrier elimination group (CGFT), dexamethasone feeding treatment after lipid barrier elimination group (DxFT). After 3 days, differences in skin condition, improvement of skin fat barrier, and control of Th2 skewed condition of each group were observed. Results Pathologic skin damage and tissue changes were less in the CGFT group than in the LBET and DxFT groups, and Transepidermal water loss (TEWL) and pH were also significantly decreased (p < 0.05). The filaggrin intensity and positive response also increased significantly in the CGFT group (p < 0.05). Kallikrein-related peptidase (KLK) 7, Protease activated receptor (PAR)-2, Thymic stromal lymphopoietin (TSLP), Interleukin (IL)-4, and the products of the Th2 differentiation process also showed a significant decrease compared to the LBET and DxFT groups (all p < 0.05). Conclusions The Coptidis Rhizoma and Glycyrrhiza uralensis extract causes skin barrier recovery and function recovery through the formation of skin fat barrier. This leads to the conclusion that Coptidis Rhizoma and Glycyrrhiza uralensis extract can control Th2 differentiation through the formation of skin fat barrier.