• Title/Summary/Keyword: AdBlue

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Searching for blue ocean of Alzheimer's disease drug discovery

  • MookJung, In-Hee
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.04a
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    • pp.109-120
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    • 2006
  • Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

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Characteristic Comparison of the Composition Classification on Potash Glass Beads Excavated in Korea (한국 포타쉬 유리구슬의 조성 분류에 따른 특성 비교)

  • KIM, Na-Young;KIM, Gyu-Ho
    • Journal of Conservation Science
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    • v.31 no.3
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    • pp.255-265
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    • 2015
  • In this study, the potash glass beads of 281 samples in 30 sites analyzed until now were classified according to the chemical composition. And the color, size, manufacturing technique and distribution period were compared. Korea potash glass beads are divided into 3 types depending on the stabilizer content. I, II type is the CaO and $Al_2O_3$ content of less than 5%. Relatively, I type has a high CaO and II type has a high $Al_2O_3$. In contrast, III type comprises more than CaO 5%. I, II type is the saltpetre, III type is estimated using plant ash as row material of flux. A review of the properties by type, I type is cobalt blue, copper blue and purple beads. The outer diameter is sized to the range 1.4~7.4mm. Also it was produced by the drawing technique. It was used continuously from BC 1C until around AD 6C. On the other hand, II type is outer diameter of 1.9~3.6mm and a copper blue beads. manufacturing technique is the same as the I type. This seems to have been in use since around AD 1C to 4C. Finally, III type is brown, colorless, amber beads and an outer diameter of about 10mm. It was formed by winding technique and appeared in the tombs of Goryeo and Joseon Dynasty. As a result, 3 types of potash glass beads distributed in Korea is likely to flowing through the various trade routes from different provenances.

A Probiotic Preparation Alleviates Atopic Dermatitis-Like Skin Lesions in Murine Models

  • Kim, Min-Soo;Kim, Jin-Eung;Yoon, Yeo-Sang;Seo, Jae-Gu;Chung, Myung-Jun;Yum, Do-Young
    • Toxicological Research
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    • v.32 no.2
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    • pp.149-158
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    • 2016
  • Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that encompasses immunologic responses. AD is frequently associated with elevated immunoglobulin (Ig) E levels, and common environmental factors contribute to its pathogenesis. Several recent studies have documented the role of specific lactic acid bacteria in the treatment and prevention of AD in humans and mice. In this study, the efficacy of Duolac ATP, a probiotic preparation, was determined in a mouse model with AD-like skin lesions. Alterations in the cytokine levels and histological staining suggested the alleviation of AD. The in vivo test showed that T helper (Th)2 cytokines, IgE, interleukin (IL)-4, and IL-5, were significantly downregulated, whereas Th1 cytokines, IL-12p40 and interferon (IFN)-${\gamma}$, were upregulated in all groups of mice treated with Duolac ATP compared to that observed in the group of mice treated with 1-chloro-2,4-dinitrobenzene (DNCB) alone. Moreover, the scratch score decreased in all mice treated with Duolac ATP. Staining of the dorsal area of the mice in each group with hematoxylin and eosin and toluidine blue further confirmed the alleviation of AD in mice orally treated with Duolac ATP. These results suggest that Duolac ATP inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Thus, Duolac ATP is beneficial and effective for the treatment of AD-like skin lesions.

Protective effect of Lycium barbarum leaf extracts on atopic dermatitis: in vitro and in vivo studies

  • Han Sol Lee;Eun Young Bae;Sun Yung Ly
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.855-869
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    • 2023
  • BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

Dioscorea japonica Thunb. Ethanolic Extract Attenuated Oxazolone-Induced Atopic Dermatitis-like Skin Lesions in BALB/c Mice

  • Jegal, Jonghwan;Park, No-June;Jo, Beom-Geun;Kim, Su-Nam;Yang, Min Hye
    • Natural Product Sciences
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    • v.25 no.3
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    • pp.261-267
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    • 2019
  • The rhizomes of Dioscorea japonica Thunb. are widely consumed as food and also used to treat diabetes and polyuria in Korea. This study was undertaken to study the anti-atopic dermatitis effects of a 95% ethanolic extract (DJE) of D. japonica in an oxazolone-stimulated murine model of atopic dermatitis (AD). The therapeutic effects of DJE on AD-like skin lesions were assessed on both ears. DJE (1%) or dexamethasone (0.5%; the positive control) were applied to skin lesions for three weeks. Serum levels of IgE and IL-4 were assessed by ELISA (enzyme-linked immunosorbent assay). Histopathological examinations were performed by hematoxylin and eosin (H&E) and toluidine blue staining and revealed DJE significantly reduced dermal thickness and inflammatory cell infiltration when applied to oxazolone-treated ear skin. DJE-treated AD mice also showed lower serum levels of IgE and IL-4 than oxazolone-stimulated controls. Our findings demonstrate DJE might be a useful safe, topical agent for the treatment of atopic diseases.

Therapeutic Effects of LED Fusion of Two Wavelength Bands on Atopic Dermatitis of NC/Nga Mice (융합 LED 광선치료가 아토피 피부염에 미치는 영향)

  • Lee, Sangmin;Choi, Ji-Hye;Koo, Bon-Jun;Kwon, Jungkee
    • Journal of the Korean Applied Science and Technology
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    • v.39 no.4
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    • pp.552-559
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    • 2022
  • Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching, mainly before five. The aim of this study is to investigate the effects of 405 nm+850 nm LED light therapy on AD-like symptoms in NC/Nga mice. The mice were randomly placed in the normal (Vehicle), atopic dermatitis-induced (CON), and 405 nm + 850 nm LED light therapy (LED) groups. The LED experimental group conducted 405 nm+850 nm wavelength LED ray therapy for 10 minutes a day for seven days. LED light therapy research confirmed the improvement and improvement of Dermatics score and observed the reduction of epidermal tissue thickness caused by dermatitis. Based on the significant decrease of serum IL-1𝛽 and transdermal moisture loss and serum IgE concentration due to LED light therapy, LED light therapy can help restore normal skin conditions in mice that cause atopic dermatitis. This study showed the anti-atopic effect of infrared light and blue light. Light in mice with atopic dermatitis led to the simultaneous use of circular LEDs with two wavelengths.

Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways

  • Kwon, Yujin;Cho, Su-Yeon;Kwon, Jaeyoung;Hwang, Min;Hwang, Hoseong;Kang, Yoon Jin;Lee, Hyeon-Seong;Kim, Jiyoon;Kim, Won Kyu
    • BMB Reports
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    • v.55 no.6
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    • pp.275-280
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    • 2022
  • The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

Numerical Investigation of the Urea Melting and Heat Transfer Characteristics with Three Different Types of Coolant Heaters (냉각수 순환 방식 가열원 형상에 따른 요소수 해동 특성에 관한 수치적 연구)

  • Lee, Seung-Yeop;Kim, Man-Young;Lee, Chun-Hwan;Park, Yun-Beom
    • Transactions of the Korean Society of Automotive Engineers
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    • v.20 no.4
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    • pp.125-132
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    • 2012
  • Urea-SCR system, which converts nitrogen oxides to nitrogen and water in the presence of a reducing agent, usually AdBlue urea solution, is known as one of the powerful NOx reduction systems for mobile as well as stationary applications. For its consistent and reliable operation in mobile applications, such various problems as transient injection, ammonia slip, and freezing in cold weather have to be resolved. In this work, therefore, numerical study on three-dimensional unsteady heating problems were analyzed to understand the melting and heat transfer characteristics such as urea liquid volume fraction, temperature profiles and generated natural convection behavior in urea solution by using the commercial software Fluent 6.3. After validating by comparing numerical and experimental data with pure gallium melting phenomena, numerical experiment for urea melting is conducted with three different coolant heating models named CH1, 2, and 3, respectively. Finally, it can be found that the CH3 model, in which more coolant is concentrated on the lower part of the urea tank, has relatively better melting capability than others in terms of urea quantity of $1{\ell}$ for start-up schedule.

Medicinal Herb Extracts Attenuate 1-Chloro-2,4dinitrobenzene-induced Development of Atopic Dermatitis-like Skin Lesions (한약재 단일 추출물 및 복합 추출물을 이용한 아토피성 피부염 억제 효과)

  • Lee, Moon Hee;Han, Min Ho;Yoon, Jung Jeh;Song, Myung Kyu;Kim, Min Ju;Hong, Su Hyun;Choi, Byung Tae;Kim, Byung Woo;Hwang, Hye Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.851-859
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    • 2014
  • The present study was designed to investigate whether ethanol extracts of Sophora flavescens (GS), Glycyrrhiza uralensis (GC), Dictamnus dasycarpus (BSP), and their mixtures (GGB-1, -2, -3, and -4) inhibit 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in a mouse model. DNCB was topically applied on the dorsal surface of Balb/c mice to induce AD-like skin lesions. The pathological phenotypes of AD, such as erythema, ear thickness, edema, scabs, and discharge, were significantly decreased in the GGB (DNCB + GS:GC:BSP = 3:1:1 mixture)-1-treated groups compared with the other treated groups. The weight of the spleen in immune organs was significantly decreased in the GGB-1-treated groups, whereas the weight of the liver in a control group was similar to that of the groups treated with the samples. Furthermore, toluidine blue staining analysis, a method used to specifically identify mast cells, showed that master cell infiltration into the dermis of the GGB-1-treated group was significantly decreased. The immunoglobulin E concentration was lower in the GGB-1-treated group. In addition, the levels of inflammatory cytokines (interferon-${\gamma}$, interleukin-1, 4, 5, 6, and 13, $1{\beta}$, and tumor necrosis factor-${\alpha}$) were also significantly reduced in the GGB-1-treated group. Taken together, these results suggest that a mixture of GS, GC, and BSP in a proportion of 3:1:1 (GGB-1) may contribute to the relief of AD symptoms and may be considered an excellent candidate for an AD therapeutic drug.

Protective Effect of Acanthopanax senticosus on Oxidative Stress Induced PC12 Cell Death

  • Choi, Soo-Jung;Yoon, Kyung-Young;Choi, Sung-Gil;Kim, Dae-Ok;Oh, Se-Jong;Jun, Woo-Jin;Shin, Dong-Hoon;Cho, Sung-Hwan;Heo, Ho-Jin
    • Food Science and Biotechnology
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    • v.16 no.6
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    • pp.1035-1040
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    • 2007
  • Epidemiologic studies have shown important relationships between oxidative stress and Alzheimer's disease (AD) brain. In this study, free radical scavenging activity and neuronal cell protection effect of aqueous methanol extracts of Acanthopanax senticosus (A. senticosus) were examined. $H_2O_2$-induced oxidative stress was measured using 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. Pretreatment with the phenolics of A. senticosus prevented oxidative injury against $H_2O_2$ toxicity. Since oxidative stress is known to increase neuronal cell membrane breakdown, leading to cell death, lactic dehydrogenase release, and trypan blue exclusion assays were utilized. We found that phenolics of A. senticosus have neuronal cell protection effects. It suggests that the phenolics of A. senticosus inhibited $H_2O_2$-induced oxidative stress and A. senticosus may be beneficial against the oxidative stress-induced risk in AD.