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Antiinflammatory and Antiallergic Activity of Fermented Turmeric by Lactobacillus johnsonii IDCC 9203 (Lactobacillus johnsonii IDCC 9203으로 발효한 울금의 소염 및 항알레르기 효과)

  • Kim, Seong-Beom;Kang, Byung-Hwa;Kwon, Hyuk-Sang;Kang, Jae-Hoon
    • Microbiology and Biotechnology Letters
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    • v.39 no.3
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    • pp.266-273
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    • 2011
  • Although turmeric has numerous pharmacological effects, the poor water-solubility of curcuminoids, active components of turmeric, restricts their systemic availability in orally administered formulations and limits their therapeutic potential. In this study we attempted turmeric fermentation using several probiotic bacteria to improve its solubility, and also investigated the effects of turmeric and fermented turmeric on anti-inflammatory activity. Fermented turmeric, by L. johnsonii IDCC 9203, more strongly inhibited LPS-induced expression of the pro-inflammatory cytokines than non-fermented turmeric and fermented turmeric by other probiotic strains. We used an NC/Nga mouse model for mite antigen-induced atopic dermatitis to examine the efficacy of the fermented turmeric. Fermented turmeric-fed mice exhibited a significantly reduced serum IgE level and mitigated acute inflammation. When the fermented turmeric was pre-treated by oral administration, it had more preventive activity against acute anaphylactic reaction than the non-fermented group. In addition, we observed that fermentation of turmeric leads to increased water-solubility of curcumin and a change in the active components ratios for bisdemethoxycurcumin, demethoxycrucumin and curcumin. Taken together, these results strongly suggest that fermented turmeric by L. johnsonii IDCC 9203 could be used as a functional food ingredient for improving treatments for atopic dermatitis.

Performance of Homologous and Heterologous Prime-Boost Immunization Regimens of Recombinant Adenovirus and Modified Vaccinia Virus Ankara Expressing an Ag85B-TB10.4 Fusion Protein against Mycobacterium tuberculosis

  • Kou, Yiming;Wan, Mingming;Shi, Wei;Liu, Jie;Zhao, Zhilei;Xu, Yongqing;Wei, Wei;Sun, Bo;Gao, Feng;Cai, Linjun;Jiang, Chunlai
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.1022-1029
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    • 2018
  • Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. In the present study, we constructed recombinant Ad and MVA expressing an Ag85B-TB10.4 fusion protein (AdH4 and MVAH4) and evaluated the impact of their different immunization regimens on the humoral and cellular immune responses. We found that the viral vector-based vaccines could generate significantly higher levels of antigen-specific antibodies, $IFN-{\gamma}$-producing splenocytes, $CD69^+CD8^+$ T cells, and $IFN-{\gamma}$ secretion when compared with bacillus Calmette-$Gu{\acute{e}}rin$ (BCG) in a mouse model. AdH4-containing immunization regimens (AdH4-AdH4, AdH4-MVAH4, and MVAH4-AdH4) induced significantly stronger antibody responses, much more $IFN-{\gamma}$-producing splenocytes and $CD69^+CD8^+$ T cells, and higher levels of $IFN-{\gamma}$ secretion when compared with the MVAH4-MVAH4 immunization regimen. The number of $IFN-{\gamma}$-producing splenocytes sensitive to $CD8^+$ T-cell restricted peptides of Ag85B (9-1p and 9-2p) and Th1-related cytokines ($IFN-{\gamma}$ and $TNF-{\alpha}$) in the AdH4-MVAH4 heterologous prime-boost regimen immunization group was significantly higher than that in the other viral vector-based vaccine- and BCG-immunized groups, respectively. These results indicate that an immunization regimen involving AdH4 may have a higher capacity to induce humoral and cellular immune responses against TB in mice than that by regimens containing BCG or MVAH4 alone, and the AdH4-MVAH4 prime-boost regimen may generate an ideal protective effect.

THE EFFECT OF PERIODONTAL REGENERATION AND ANTI-RESTORATION OF DEXAMETHASONE AND OP-1 FOLLOWING DELAYED REPLANTATION IN RAT MODEL (흰 쥐 모델에서 지연재식 시 dexamethasone과 OP-1의 표면처리가 치주조직 재생 및 항흡수 작용에 미치는 효과)

  • Kwon, O-Taek;Kum, Kee-Yeon;Lee, Seung-Jong
    • Restorative Dentistry and Endodontics
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    • v.26 no.4
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    • pp.296-306
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    • 2001
  • The purpose of this study was to observe the effect of dexamethasone and osteogenic protein-1(BMP-7) on bone, cementum and periodontal tissue regeneration. A total of 60 Sprague-Dawley white female mice were selected and beta-APN was used for five days to extract the maxillary first molar a traumatically. After the extraction of the teeth, the mesiobuccal root canal was filled with Caviton$^{\circledR}$. The teeth were etched with citric acid for 1 min and coated with one of four different experimental solutions : DEX(500nM/ml), DEX(1000nM/ml), OP-1(100$\mu\textrm{g}$/ml) and OP-1(500$\mu\textrm{g}$/ml) for three minutes depending on the group. All teeth were then replanted under microscope. All replantation procedures were done within 30 minutes. Teeth that were replanted after 30 minutes of bench dry only was used as positive control. All animals were sacrificed at 3 weeks following replantation and histologic observtion was done. The results were as follows ; 1. Active root resorption rate was decreased by the order of OP-1(500$\mu\textrm{g}$/ml), DEX(1000nM/ml), OP-1(100$\mu\textrm{g}$/ml), and DEX(500nM/ml). There was statistically less root resorption in OP-1 (500$\mu\textrm{g}$/ml) and DEX(1000nM/ml) group(P<0.05). 2. The group with higher concentration of dexamethasone(1000nM/ml) had statistically more bone union compared to positive control group(P<0.05),but there were no significant differences among four experimental groups. 3. OP-1(500$\mu\textrm{g}$/ml) and DEX(1000nM/ml) groups showed less degree of inflammation compared to the OP-1(100$\mu\textrm{g}$/ml). DEX(500nM/ml), and positive control group (P<0.05). In conclusion, the group with higher concentration of OP-1 had the best results on root resorption, bone ankylosis and anti-inflammatory effects compared to the other experimental groups, but a long-term study is also necessary to evaluate the exact pharmacological effects of the drugs in the future.

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Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation

  • Jeong, Dahye;Irfan, Muhammad;Kim, Sung-Dae;Kim, Suk;Oh, Jun-Hwan;Park, Chae-Kyu;Kim, Hyun-Kyoung;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.548-555
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    • 2017
  • Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Skin UVB Photo Aging Effect from Extract of Fermented Reynoutria elliptica (호장근(Reynoutria elliptica) 발효 추출물의 UVB에 의한 피부 광노화 억제효과)

  • Lim, Ae-Kyung;Jung, Yu-Jung;Kim, Kil-Soo;Kim, Yong-Hae;Kwak, Jung-Hoon;Hong, Joo-Heon;Kim, Hak-Yoon;Kim, Dae-Ik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.3
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    • pp.369-375
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    • 2010
  • To evaluate the skin aging inhibition effect of fermented Reynoutria elliptica, skin aging model was produced by the irradiation of UVB to hairless mice for 5 weeks. The skin erythema index for the positive control (PC), not fermented Reynoutria elliptica extract (NFR), and fermented Reynoutria elliptica extract (FR-500, 1000, 2000) groups were lower than that of the control group. However, both lipid and water capacity for the PC and FR groups were higher than those of the control group. Collagen fibers in dermis of the FR groups were almost intact with a regular arrangement which were similar to the normal (NO) group. Also, relatively much less number of mast cells and inflammatory cells were found in FR groups. The skin TBARS contents and XO activity in the FR group were significantly lower than the control group. The activities of GSH, SOD and CAT for the FR groups were significant higher than the control group. Therefore, fermented Reynoutria elliptica extract can be practically useful for the prevention or improvement of skin aging in terms of health promotion and beauty for the people.

The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model

  • Ahn, Ji-Su;Seo, Yoojin;Oh, Su-Jeong;Yang, Ji Won;Shin, Ye Young;Lee, Byung-Chul;Kang, Kyung-Sun;Sung, Eui-Suk;Lee, Byung-Joo;Mohammadpour, Hemn;Hur, Jin;Shin, Tae-Hoon;Kim, Hyung-Sik
    • BMB Reports
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    • v.53 no.6
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    • pp.329-334
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    • 2020
  • Inflammasomes are cytosolic, multiprotein complexes that act at the frontline of the immune responses by recognizing pathogen- or danger-associated molecular patterns or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects. In this study, we investigated the expression and functional regulation of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). hUCB-MSCs expressed inflammasome components that are necessary for its complex assembly. Interestingly, NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs.

A Study on the Effects of Bee Venom Aqua-Acupuncture on Pain related Neuronal activity in the Spinal Cord (봉독약침(蜂毒藥鍼)이 척수내(脊髓內) 통증관련(痛症關聯) 신경세포(神經細胞)의 활성(活性)에 미치는 영향(影響))

  • Jeong, Sun-Hee;Lee, Jae-Dong;Koh, Hyung-Kyun;Ahn, Byoung-Choul;Choi, Do-Young;Park, Dong-Suk
    • Journal of Acupuncture Research
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    • v.17 no.2
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    • pp.153-168
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    • 2000
  • Introduction : In spite of the use of Bee Venom aqua-acupuncture in the clinics, the scientific evaluation on effects is not enough. Bee Venom aqua-acupuncture is used according to the stimulation of acupuncture point and the chemical effects of Bee Venom. The aims of this study is to investigate the analgegic effects of the Bee Venom aqua-acupuncture, through the change of writhing reflex and the change of c-fos in secondary neurons in the spinal cord. Materials and Methods : Pain animal model was used acetic acid method. The changes of writhing reflex of the mice which were derived pain by injecting acetic acid into the abdomen, after stimulating Bee Venom aqua-acupuncture on Chungwan(CV12) were measured. We used Fos immunohistochemical technique to study the neuronal activity in the spinal cord. Results : 1. Expression of c-fos in superficial dorsal horn(SDH), nucleus proprius(NP) and neck of dorsal hom(N) on 6~9th thoracic spine decreased significantly at $2.5{\times}10-4$g/kg Bee Venom aqua-acupuncture, compared with saline-acetic acid group. 2. The numeral change of Fos-LI neurons on the NP, N, and ventral gray(V) on 6-9th thoracic spine, SDH on 9-11th thoracic spine, and SDH and V on 11~13th thoracic spine decreased significantly at Chungwan(CV12) Bee Venom aqua-acupuncture, compared with saline-acetic acid group. 3. The correlation between the numbers of writhing refleax and Fos-LI neurons in T6-13 segment was statistically statistically significant at Chungwan(CV12) Bee Venom aqua-acupuncture. Conclusion : This study shows that the Bee Venom aqua-acupuncture on Chungwan(CV12) decreases the numbers of Fos-LI neurons. As the analgegic effects of Bee Venom aqua-acupuncture is recognized. Bee Venom aqua-acupuncture treatment is expected for pain modulation. In order to use it in many ways, more researches are needed for the dose and stability of Bee Venom aqua-acupuncture.

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Osteogenic effects of polyethyleneimine-condensed BMP-2 genes in vitro and in vivo (Polyethyleneimine-응축 BMP-2 발현 유전자를 이용한 골형성 효과)

  • Cheong, Hee-Sun;Kim, Kyoung-Hwa;Park, Yoon-Jeong;Kim, Tae-Il;Lee, Yong-Moo;Ku, Young;Rhyu, In-Chul;Lee, Dong-Soo;Lee, Seung-Jin;Chung, Chong-Pyoung;Han, Soo-Boo;Seol, Yang-Jo
    • Journal of Periodontal and Implant Science
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    • v.37 no.4
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    • pp.859-869
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    • 2007
  • Naked DNA and standard vectors have been previously used for gene delivery. Among these, PEI can efficiently condense DNA and has high intrinsic endosomal activities. The aim of this study is to investigate whether the cationic polycation PEI could increase the transfection efficiency of BMP expressing DNA using a vector-loaded collagen sponge model. BMP-2/pcDNA3.1 plasmid was constructed by subcloning human BMP-2 cDNA into the pcDNA3.1 plasmid vector. PEI/DNA complexes were prepared by mixing PEI and BMP-2/pcDNA3.1 and the constructed complexes were loaded into the collagen sponges. In vitro studies, BMSCs were transfected with the PEI/BMP-2/pcDNA3.1 complexes from collgen sponge. The level of secreted BMP-2 and alkaline phosphatase activities of transfected BMSCs were significantly higher in PEI/BMP-2/pcDNA3.1 group than in BMP-2/pcDNA3.1 group (p<0.05). Transfected BMSCs were cultured and mineralization was observed only in cells treated with PEI/BMP-2/pcDNA3.1 complexes. In vivo studies, PEI/BMP-2/pcDNA3.1/collagen, BMP-2/pcDNA3.1/collagen and blank collagen were grafted in skeletal muscle of nude mice. Ectopic bone formation was shown in PEI/BMP-2/pcDNA3.1/collagen grafted mouse 4 weeks postimplantation, while not in BMP-2/pcDNA3.1 grafted tissue. This study suggests that PEI-condensed DNA encoding for BMP-2 is capable of inducing bone formation in ectopic site and might increase the transfection rate of BMP-2/pcDNA3.1. As a non-viral vector, PEI offers the potential in gene therapy for bone engineering.

Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

  • Feng, Sen-Ling;Luo, Hai-Bin;Cai, Liang;Zhang, Jie;Wang, Dan;Chen, Ying-Jiang;Zhan, Huan-Xing;Jiang, Zhi-Hong;Xie, Ying
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.247-257
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    • 2020
  • Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

Abrogation of the Circadian Nuclear Receptor REV-ERBα Exacerbates 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration

  • Kim, Jeongah;Jang, Sangwon;Choi, Mijung;Chung, Sooyoung;Choe, Youngshik;Choe, Han Kyoung;Son, Gi Hoon;Rhee, Kunsoo;Kim, Kyungjin
    • Molecules and Cells
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    • v.41 no.8
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    • pp.742-752
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    • 2018
  • Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.