• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.103-112
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• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• Toxicological Research
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• v.9 no.2
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• pp.225-232
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• 1993

SCi-B-Vac, the 3rd hepatitis B vaccine , was selected for clinical evaluation on the basis of toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, organs which are mainly affected, and to estimate its lethality in mice and rats given Sci-B-Vac through two routes of administratin. In male and female rats given a single intragastrical dose of Sci-B-Vac, we estimated that $LD_{50}$ values were over 2.00 ml/100g B.W. (10ng/ml), respectively.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.385-400
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• 2008

Objectives : This study was carried out to investigate the effects of Soyumjungjang-tang(SJT) on the experimental ulcerative colitis induced by dextran sulfate sodium(DSS) in mice. Methods : Ulcerative colitis was induced through supplying 4% DSS solution as the drinking water for 7 days in 6-week-old male ICR mice. The colitic mice were divided into three groups: the sample groups were orally administered SJT in doses of 25mg/kg(S25 group) or 100mg/kg(S100 group) once a day for 10 days, from 3 days before starting drinking the DSS solution, and the control(C) group was administered normal saline instead of SJT. The DSS solution or SJT was not administered to the normal(N) group. The length of colon, histologic finding, the activities of myeloperoxidase(MPO) and alkaline phosphatase(AP), and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$, and $I{\kappa}B$ in colonic mucosa was checked using immunoblot, ELISA, etc. The activities of chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$ in stool were also measured. Results : The length of colon shortened, histologic finding deteriorated, the activities of MPO, AP, chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$, and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$ increased, and the expression of $I{\kappa}B$ decreased in the C group. All measures, except $NF-{\kappa}B$, were restored in S25 group, but some measures deteriorated more in the S100 group than in the C group. Conclusions : According to the above results, it is supposed that SJT has a potential therapeutic effect on ulcerative colitis.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.78-88
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• 2005

Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.

• Korean Journal of Veterinary Research
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• v.27 no.1
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• pp.53-60
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• 1987

This experiment was performed on mice to investigate the effects of an immunopotentiator, picibanil(PC), on the immune responses such as phagocytic activity of reticuloen-dothelial(RE) system, E rosette formation rate of splenic lmphocytes and morphological changes of lymph node tissue. Groups of mice were treated with a single(1KE/kg BW) or sequential(0.1, 0.25 and 0.5KE/kg BW for successive 3 days) intravenous injections of PC. PC treated and untreated control mice were sensitized with 50% sheep erythrocyte suspension(0.2ml/mouse) at 1, 3, 5, 7 and 10 days after PC treatment. Functional and morphological examinations were carried out 5 days after sensitization. The following results were obtained: The phagocytic activity of RE system and the weight of liver and spleen were increased significantly at 3rd, 5th and 7th day. The peripheral polymorphonuclear leukocyte and percent of lymphocyte and monocyte were slightly increased. The rates of E rosette formation of splenic lymphotytes, sequential PC treated groups were more increased at 3rd and 5th day in sequential PC treated groups than in single treated groups. Thereafter it returned gradually to the control level by the time of 10th day. Microscopically primary lymph follicles with indistinct germinal center (GC) were partially disrupted and the parafollicular areas were consisted of the pyroninophilic cells in control group. In PC treated group, the parafollicular areas were markedly proliferated and developments of secondary lymph follicles with enlarged and prominent GC were more pronounced in the sequential injected groups compared to single injected groups. These results indicate that PC affected not only parafollicular area of the T-cell area, but also GC of the B-cell area. It suggests that PC may potentiate both cell mediated immunity and humoral immunity.

• Progress in Medical Physics
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• v.21 no.2
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• pp.209-217
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• 2010

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Since retinal prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. Therefore, in this paper, we focused on retinal ganglion cell (RGC) responses to different voltage stimulation parameters and compared threshold charge densities in normal and rd1 mice. For this purpose, we used in vitro preparation for the retina of normal and rd1 mice on micro-electrode arrays. When the neural network of rd1 mouse retinas is stimulated with voltage-controlled pulses, RGCs in degenerated retina also respond to voltage amplitude or voltage duration modulation as well in wild-type RGCs. But the temporal pattern of RGCs response is very different; in wild-type RGCs, single peak within 100 ms appears while in RGCs in degenerated retina multiple peaks (~4 peaks) with ~10 Hz rhythm within 400 ms appear. The thresholds for electrical activation of RGCs are overall more elevated in rd1 mouse retinas compared to wild-type mouse retinas: The thresholds for activation of RGCs in rd1 mouse retinas were on average two times higher ($70.50{\sim}99.87\;{\mu}C/cm^2$ vs. $37.23{\sim}61.65\;{\mu}C/cm^2$) in the experiment of voltage amplitude modulation and five times higher ($120.5{\sim}170.6\;{\mu}C/cm^2$ vs. $22.69{\sim}37.57\;{\mu}C/cm^2$) in the experiment of voltage duration modulation than those in wild-type mouse retinas. This is compatible with the findings from human studies that the currents required for evoking visual percepts in RP patients is much higher than those needed in healthy individuals. These results will be used as a guideline for optimal stimulation parameters for upcoming Korean-type retinal prosthesis.

• Korean Journal of Plant Resources
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• v.34 no.5
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• pp.433-442
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• 2021

The fermented red ginseng by microorganism is known to increase pharmacological activity in vivo. To evaluate the bioavailablity of red ginseng fermented by probiotics, we conducted the pharmacokinetic study of ginsenoside Rb1, Rd and total ginsenosides (TG, ginsenosides Rb1 + Rd + Rg1 + F2 + Rg3 + compound K) in BALB/C mice. The AUC value of ginsenoside Rb1 in mice serum administered with 600mg/kg drugs showed 21.93 ± 14.68 ng·h/mL (RGw, water extract), 275.211 ± 110.04 ng·h/mL (RGe, 50% ethanol extract) and 404.91 ± 162.57 ng·h/mL (fRGe, fermented red ginseng extract). Analysis of ginsenoside Rd also showed a higher ACU value in fRGe than in RGw or RGe. And the AUC value of total ginsenosides in mice serum treated with 600 mg/kg were observed 42.12 ± 23.44 ng·h/mL (RGw), 321.44 ± 133.5 ng·h/mL (RGe) and 537.33 ± 229.01 ng·h/mL (fRGe), respectively. C_max value of ginsenoside Rb1 in mice administered with 600mg/kg were observed 3.67 ± 3.34 ng/mL (RGw), 23.27 ± 8.81 ng/mL (RGe) and 25.52 ± 7.29 ng/mL (fRGe). These results can be considered that the fermented red ginseng has more bioavailability than that of unfermented red ginseng. In quantitative analysis of the inflammation-related cytokines IL-1β and TNF, no significant difference was found between the fermented red ginseng (fRGe) and the red ginseng (RGe).

• Journal of Ginseng Research
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• v.46 no.1
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• pp.115-125
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• 2022

Background: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. Methods: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Results: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. Conclusion: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

• The Journal of Internal Korean Medicine
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• v.23 no.1
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• pp.123-131
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• 2002

Objective : It is well known that modern chemotherapy against cancer has side effects to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effective ways to reduce them. Recently, traditional Korean herb medicine has been reported to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medical Center. Methods : We injected 200mg/kg of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2mg, SAKT 10mg, SAKT 50mg, SAKT 2mg, CPX, SAKT 10mg+CPX, SAKT 50mg+CPX. We injected Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice. The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, lymphocyte proliferation activity and lymphocyte subsets for immunological toxcity. Results : We have found that Soamgudamikgitang has inhibitory effects on the formation of Cyclophosphamide's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50mg of Soamgudamikgitang respectively were observed. Platelets(2mg of Soamgudamikgitang, p<0.05 ;10mg, p<0.01 ;50mg, p<0.001), liver weight(50mg, p<0.01), spleen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2mg, p<0.01 ;10mg, p<0.05 ;50mg, p<0.01), BUN(2mg, p<0.01 ;50mg, p<0.05). Although immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgitang has a strong effect on T cell activities. Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer patients.

• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1585-1591
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• 2010

A comprehensive study on the production of inflammatory mediators in the lungs of BALB/c mice following infection with Stenotrophomonas maltophilia was conducted. The levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-${\alpha}$), and interleukin-1${\beta}$ (IL-1${\beta}$) were raised in the lungs of infected mice compared with control. The production of anti-inflammatory cytokine IL-10 was slightly delayed. Its peak level was on the $2^{nd}$ day, whereas the peak of pro-inflammatory cytokines was observed on day 1 after intranasal challenge. This was accompanied by a rise in myeloperoxidase (MPO) and malondialdehyde (MDA) on day 1. The increase in MPO levels matched with histopathological observations, as neutrophils infiltration was detected on the first day. Alveolar macrophages (AMs) obtained from infected animals showed a higher rate of uptake and killing when exposed to bacteria in vitro, compared with similar experiments conducted with AMs from normal mice (control). This suggests that AMs were more efficient in cleaning the bacteria. The nitric oxide (NO) production however started early during infection but reached its maximum on the $3^{rd}$ day. No mortality was observed among the infected animals, and infection was resolved by the $5^{th}$ day post infection. No drastic changes in the lung tissue were observed on histopathological examination.