• BMB Reports
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• v.54 no.2
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• pp.142-147
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• 2021

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

• Journal of Acupuncture Research
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• v.39 no.1
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• pp.40-48
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• 2022

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

• Journal of Convergence Korean Medicine
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• v.5 no.1
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• pp.5-23
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• 2023

Objectives: This study was conducted to evaluate the effect of combination treatment of herbal medicine for external use and western medicine for atopic dermatitis (AD). Methods: We searched randomized controlled trials (RCTs) which assess the effect of combination treatment of herbal and western medicine for AD through 8 electronic databases from the start to December 2022. The data synthesis was conducted by using Review Manager (RevMan, ver.5.4.1) and Cochrane risk-of-bias tool was used to evaluate the risk of bias. Results: 13 RCTs were included. The combination treatment group had significantly higher total efficacy rate(p<0.0001) and lower SCORAD score (p<0.00001) than the western medicine treatment group. The adverse event rate was also significantly lower in the combination treatment than the western medicine treatment group (p<0.0001). But there was no significant difference in recurrence rate (p=0.09). Conclusion: This study demonstrates that the combination treatment of herbal and western medicine could be safe and effective for AD. However, due to limits of included studies such as high heterogeneity between the literature and unclear risk of bias, further studies are warranted.

• The Journal of Korean Medicine
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• v.40 no.1
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• pp.63-77
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• 2019

Objectives: The purpose of this study is to examine the effect of water and fermentation extracts of KMS (Kami-Mihudeongsikjang-tang) on AD (atopic dermatitis). Additionally, by applying the fermentation extracts of KMS at the first sensitization and latency period, I investgated whether it could prevent AD. Methods: In this study, to test the effect and preventive efficacy of KMSs on AD. DNCB-induced BALB/c mice of AD model was used. Through histological observation, epidermis and dermis thickness, the infiltration of eoshiphils and mast cells in epidermis and dermis were examined. We measured the serum level of IgE and IL-6, TNF-alpha, and the expressions of $NF-{\kappa}B$ and MAPK protein. In order to examine the effect of KMSs on keratinocyte, HaCaT cells were treated TNF-alpha and IFN-gamma to induce an inflammatory response. The KMSs were applied at various concentration in the experimental group. We investigated TARC expression. Results: The treatment groups were reduced epidermis and dermis thickness, inhibited the infiltration of eosinophils and mast cells, reduced the serum level of IL-6. Moreover, sfKMS group reduced serum level of TNF-alpha, inhibited the protein expressions of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. Especially sfKMS-pre group were reduced the serum level of IgE, show significant inhibition on the protein expression of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. In the experiment on HaCaT cells, sfKMS group were reduced expression of TARC. Conclusions: These result suggest that wKMS and sfKMS was effective in the treament on AD, and sfKMS would prevent AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.37 no.2
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• pp.25-29
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• 2023

This study was designed to establish an atopic dermatitis (AD) model using MC903 and was conducted to find out the optimal challenge concentration that can cause dermatitis symptoms enough to be experimentally verified while reducing adverse effects such as weight loss. MC903 was treated at concentrations of 2, 3, and 4 nmol/day, and evaluation of skin surface symptoms, water contents, histopathological changes, body weight changes, and spleen/body weight ratio was conducted. In addition, the expression level of thymic stromal lymphopoietin (TSLP) was also observed. In our results, MC903 induced AD skin lesions such as erythema, scab and fissure and lowered skin moisture level significantly. In addition, water holding capacities in the 3 or 4 nmol groups were diminished significantly compared to that in the control group. On the other hand, 4 nmol treatment induced a weight loss of up to 20% compared to control group. Finally, a higher level of TSLP expression was observed in the 3 nmol group than in the 2 nmol group or the 4 nmol group. Taken together, we propose a total 14-day protocol consisting of 3 days of sensitization (2 nmol/day) and 6 days of challenge (3 nmol/day).

• Clinical and Experimental Pediatrics
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• v.49 no.5
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• pp.545-551
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• 2006

Purpose : The gene-encoding cytotoxic T lymphocyte-associated antigen-4(CTLA-4) is one of the candidate genes for conferring susceptibility to atopic dermatitis(AD). The aim of the study was to investigate the association between Korean children with AD and the polymorphisms of CTLA-4 gene promoter(-318) and exon 1(＋49). Methods : The CTLA-4 promoter(-318 T/C) and exon 1(＋49 A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 145 children with atopic eczema, 69 children with non-atopic eczema, and 96 healthy controls. Results : There was no significant difference in genotype and allele frequencies of the CTLA-4 promoter -318 T/C and exon 1 ＋49 A/G polymorphisms when the atopic eczema, non-atopic eczema, and control groups were compared. Additionally the CTLA-4 promoter -318 T/C and exon 1 ＋49 A/G polymorphisms were not shown to be associated with severity, IgE level, or eosinophil counts. Conclusion : Our data show that the polymorphisms within the CTLA-4 promoter(-318 T/C) and exon 1(＋49 A/G) genes are not associated with susceptibility to AD in Korean children.

• Journal of Microbiology and Biotechnology
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• v.16 no.11
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• pp.1699-1705
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• 2006

Recent studies have suggested that oral bacteriotherapy with probiotics might be useful for preventing and managing childhood atopic dermatitis (AD). The purpose of this investigation was to evaluate the efficacy and safety of oral treatment with probiotics for adolescent and adult AD patients as well as for childhood AD patients. Sixty-four patients with mild to moderate AD were recruited for treatment with a mixture of four probiotic strains (Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus casei, and Biftdobacterium lactis) twice daily for 8 weeks. The degree of pruritus was determined by a 10-point visual analog scale every other week, and the patients' global assessments of their clinical responses (i.e., better, unchanged, or worse) was done at the end of intervention. The clinical severity of the eczema was evaluated by eczema area and severity index (EASI) score every other week. As laboratory markers, total immunoglobulin E (IgE), eosinophil cationic protein (ECP) in the serum, and cytokine production [interleukin-4 (IL-4), interleukin-10 (IL-10), and $interferon-{\gamma}\;(IFN-{\gamma})$ by the peripheral blood mononuclear cells (PBMCs) were measured at the beginning and at the end of intervention. Of the 64 enrolled AD patients, only 50 patients finally completed the 8-week study. After 8-week treatment with probiotics, the EASI score was significantly improved (p<0.0001), 50% of the patients experienced improvement of their eczema, and significant improvement of the pruritus was also observed (p=0.0002). The effect was more pronounced for the patients with very high IgE levels (>1,000 ku/l) or for the patients with moderate disease severity. There was no significant difference in the therapeutic effects between the childhood AD and adolescent and adult AD patients. There were no significant changes of cytokines, as well as the total IgE and ECP levels, in the patients' serum. Treatment with the mixture of four probiotic strains was generally well tolerated. Our results suggest that the treatment with the mixture of four probiotic strains is beneficial for the management of the adolescent and adult AD patients, as well as for the childhood AD patients.

• The Journal of Pediatrics of Korean Medicine
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• v.31 no.1
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• pp.43-51
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• 2017

Objectives Hataedock method is a Korean medical therapy which removes fetal toxin by orally administering herbal decoction to neonates. This study was to observe skin damage and anti-inflammatory effect via regulating IL-4 activity in NC/Nga mice which were induced atopic dermatitis (AD)-like skin lesion by Dermatophagoides (D.) farinae after applying Douchi Hataedock method. Methods NC/Nga mice with 3 weeks of gestational age were used. Each 10 mice were allocated to the control group (Ctrl), the AD-induced group (AE), and the group which induced AD after administering Douchi extract (GT). After 4 weeks from administering Douchi extract to the mice, the primary AD was induced by applying D. farinae extract 6 times per week for 3 weeks and then the secondary AD was induced by the same method after 1 week from the primary AD induction. To identify the skin damage and anti-inflammatory effect, we observed LxR, IL-4, Fc ${\varepsilon}$ receptor, substance P, and $NF-{\kappa}B$. Results The GT group showed alleviation of skin injury and decrease in capillary angiogenesis. Stratum corneum damage, epithelial cell hyperplasia, lymphocyte infiltration, and capillary distribution relatively decreased in the GT group. LxR-positive reaction in the GT group were increased by 53% than that of the AE group. IL-4 production, $Fc{\varepsilon}$ receptor activity, and substance P-positive reaction in the GT group were decreased by 82%, 42%, and 82% respectively compare to those of the AE group. $NF-{\kappa}B$-positive reaction in the GT group were decreased by 15% compare to that of the AE group. Conclusions Hataedock method with Douchi extract alleviated AD via reducing inflammatory cytokines secreted at the early stage of AD. Thus, Douchi Hataedock method has a beneficial effect for the prevention and treatment of AD.

• Journal of Haehwa Medicine
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• v.18 no.1
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• pp.29-41
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• 2009

Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

• Journal of Nutrition and Health
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• v.37 no.8
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• pp.669-674
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• 2004

The purpose of this study was to develop the antiallergic and hypoallergic fennented soybean foods without side effect. We manufactured Chungkukjang with addition of herbal (aloe, cinamon, licorice root) extract. Sensory evaluation was performed to evaluate the acceptability by the consumer. Clinical evaluation was performed with 10 atopic dermatitis (AD) patients who showed positive reaction with specific IgE and skin prick test. Cross-over study between nonnal Chungkukjang and Chungkukjang with aloe extract was performed. In sensory evaluation, Chungkukjang with aloe extract obtained best score overall. In clinical evaluation, 7 out of 10 AD patients showed positive reaction to soy-bean and 4 out of 10 AD patients showed positive reaction to normal Chungkukjang. 2 out of 10 AD patients showed positive reaction to Chungkukjang with aloe extract. In conclusion, Chungkukjang could be recommended as functional food with hypoallergic effect. As adding aloe extract to Chungkukjang, hypo allergic effect was increased.