Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells.

Ryu, Chung Heon,Park, Sang-Hoon,Park, Soon A,Kim, Seong Muk,Lim, Jung Yeon,Jeong, Chang Hyun,Yoon, Wan-Soo,Oh, Won-il,Sung, Young Chul,Jeun, Sin-Soo Mary Ann Liebert 2011 Human gene therapy Vol.22 No.6

<P>Clinical trials of gene therapy using a viral delivery system for glioma have been limited. Recently, gene therapy using stem cells as the vehicles for delivery of therapeutic agents has emerged as a new treatment strategy for malignant brain tumors. In this study, we used human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) as delivery vehicles with glioma-targeting capabilities, and modified interleukin-12 (IL-12p40N220Q; IL-12M) as a novel therapeutic gene. We also engineered UCB-MSCs to secret IL-12M (UCB-MSC-IL12M) via tetrameric cell-permeable peptide (4HP4)-mediated adenoviral transduction. We confirmed the migratory capacity of UCB-MSC-IL12M toward GL26 mouse glioma cells by an in vitro migration assay and in vivo injection of UCB-MSC-IL12M into the ipsilateral hemisphere of implanted gliomas in C57BL/6 mice. In vivo efficacy experiments showed that intratumoral injection of UCB-MSC-IL12M significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with control mice. Antitumor effects were associated with increased local IL-12M levels, followed by interferon-γ secretion and T-cell infiltration in intracranial gliomas, as well as antiangiogenesis. Interestingly, tumor-free mice after UCB-MSC-IL12M treatment were resistant to ipsilateral and contralateral tumor rechallenge, which was closely associated with tumor-specific long-term T-cell immunity. Thus, our results provide the rationale for designing novel experimental protocols to induce long-term antitumor immunity against intracranial gliomas using UCB-MSCs as an effective delivery vehicle for therapeutic cytokines including IL-12M.</P>

Inhibitory Effect of Farfarae Flos Water Extract on COX-2, iNOS Expression and Nitric Oxide Production in lipopolysaccharide - activated RAW 264.7 cells

Yoon Tae Gyoung,Byun Boo Hyeong,Kwon Teag Kyu,Suh Seong Il,Byun Sung Hui,Kwon Young Kyu,Kim Sang Chan The Physiological Society of Korean Medicine and T 2004 동의생리병리학회지 Vol.18 No.3

Farfrae Flos has been clinically used for the treatment of asthma in traditional oriental medicine. There is lack of studies regarding the effects of Farfrae Flos on the immunological activities. The present study was conducted to evaluate the effect of Farfrae Flos on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, Farfrae Flos water extract inhibited nitric oxide production in a dose-dependent manner and abrogated inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Farfrae Flos water extract did not affect on cell viability. To investigate the mechanism by which Farfrae Flos water extract inhibits iNOS and COX-2 gene expression, we examined the on the phospholylation of inhibitor κBα and production of TNF-α, IL-1β and IL-6. Results provided evidence that Farfrae Flos inhibited the production of interleukin-1β (IL-1β) and the activation of phospholylation of inhibitor κBα in Raw 264.7 cells activated with LPS. These findings suggest that Farfrae Flos can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet's disease

Yoon, Jeong-Yun,Lee, Yeojin,Yu, Seong-Lan,Yoon, Hee-Kyung,Park, Ha-Yan,Joung, Chung-Il,Park, Seok-Rae,Kwon, Mihye,Kang, Jaeku D.A. Spandidos 2017 Biomedical reports Vol.7 No.6

<P>Despite extensive studies, the pathogenesis of Behçet's disease (BD) remains unclear. In particular, the roles of B cells in patients with BD have not been elucidated. Activation-induced cytidine deaminase (AID) is a critical enzyme for immunoglobulin (Ig) heavy chain class switching and somatic hypermutation in B cells and the abnormal expression of AID in various immune conditions has previously been studied. B10 cells, an interleukin (IL)-10-secreting subset of regulatory B cells, function to downregulate inflammation and autoimmunity. Thus, in the present study, the relevance of B cells in patients with BD was investigated. The plasma levels of IL-10 and IgA and the proportions of cluster of differentiation (CD)43<SUP>+</SUP> B cells, excluding naïve B cells, were measured in 16 patients with BD and 16 age- and sex-matched healthy controls (HCs). Additionally, the mRNA levels of IL-10 and AID were assessed in B cells from fresh peripheral blood samples of the BD patients and HCs. The plasma level of IL-10 in patients with BD did not differ significantly from that in HCs. Similarly, there was no significant difference in the plasma level of IgA, although a slight increase was observed in patients with BD compared with that in HCs. There were no differences in CD43<SUP>+</SUP>CD19<SUP>+</SUP> B cell numbers between patients with BD and HCs. However, IL-10 mRNA levels were significantly reduced (P<0.05), while AID mRNA levels were significantly increased (P<0.01) in the B cells of patients with BD compared with those in HCs. These results provide insight into the role of B cells in patients with BD.</P>

Fermented Milk Containing Lacticaseibacillus rhamnosus SNU50430 Modulates Immune Responses and Gut Microbiota in Antibiotic-Treated Mice

Yoon Sunghyun,Park SungJun,Jung Seong Eun,Lee Cheonghoon,Kim Woon-Ki,Choi Il-Dong,Ko GwangPyo 한국미생물·생명공학회 2024 Journal of microbiology and biotechnology Vol.34 No.6

Antibiotics are used to control infectious diseases. However, adverse effects of antibiotics, such as devastation of the gut microbiota and enhancement of the inflammatory response, have been reported. Health benefits of fermented milk are established and can be enhanced by the addition of probiotic strains. In this study, we evaluated effects of fermented milk containing Lacticaseibacillus rhamnosus (L. rhamnosus) SNUG50430 in a mouse model with antibiotic treatment. Fermented milk containing 2 × 105 colony-forming units of L. rhamnosus SNUG50430 was administered to six weekold female BALB/c mice for 1 week. Interleukin (IL)-10 levels in colon samples were significantly increased (P < 0.05) compared to water-treated mice, whereas interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were decreased, of mice treated with fermented milk containing L. rhamnosus SNUG50430-antibiotics-treated (FM+LR+Abx-treated) mice. Phylum Firmicutes composition in the gut was restored and the relative abundances of several bacteria, including the genera Coprococcus and Lactobacillus, were increased in FM+LR+Abx-treated mice compared to PBS+Abxtreated mice. Interestingly, abundances of genus Coprococcus and Lactobacillus were positively correlated with IL-5 and IL-10 levels (P < 0.05) in colon samples and negative correlated with IFN-γ and TNF-α levels in serum samples (P < 0.001). Acetate and butyrate were increased in mice with fermented milk and fecal microbiota of FM+LR+Abx-treated mice were highly enriched with butyrate metabolism pathway compared to water-treated mice (P < 0.05). Thus, fermented milk containing L. rhamnosus SNUG50430 was shown to ameliorate adverse health effects caused by antibiotics through modulating immune responses and the gut microbiota.

Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation

Kim, Seong-Ryeol,Song, Jae-Hyoung,Ahn, Jae-Hee,Lee, Geun-Shik,Ahn, Huijeong,Yoon, Sung-il,Kang, Seung Goo,Kim, Pyeung-Hyeun,Jeon, Sang-Min,Choi, Eun-Ji,Shin, Sooyoung,Cha, Younggil,Cho, Sungchan,Kim, Elsevier 2018 Antiviral research Vol.151 No.-

<P>Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor. Intranasal administration of budesonide lowered the pulmonary HRV load and the levels of IL-1 beta cytokine leading to decreased lung inflammation. Budesonide regulates IL-1 beta production following HRV infection independent of inflammasome activation. Instead, budesonide induces mitochondrial reactive oxygen species followed by activation of autophagy. Further, the inhibition of autophagy following chloroquine or bafilomycin Al treatment reduced the anti-viral effect of budesonide against HRV, suggesting that the antiviral activity of budesonide was mediated via autophagy. The results suggest that budesonide represents a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection.</P>

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

미슬토 추출물(Mistletoe Extract)이 위암환자의 수술 후 면역기능에 미치는 효과

양성우,신동규,김일명,윤성민,이용직,허수학,김태희,Yang, Sung-Woo,Shin, Dong-Gue,Kim, Il-Myung,Yoon, Seong-Min,Lee, Yong-Jik,Heo, Su-Hak,Kim, Tae-Hee 대한위암학회 2007 대한위암학회지 Vol.7 No.3

목적: 미슬토 추출물은 서양에서 오래전부터 사용되어진 면역치료 물질로 위암에 대해서는 연구가 부족한 실정이다. 본 연구에서 수술 받은 위암환자를 대상으로 항암제와 미슬토 추출물의 병합투여가 면역기능에 미치는 효과를 파악하기 위해 시행되었다. 대상 및 방법: 원발성 위암으로 진단받고 근치적 수술을 받은 10명의 환자를 선정하여 항암화학요법과 병행하여 수술 후 7일째부터 미슬토 추출물(ABNOVA viscum-Q)을 주 3회, 총 16주간 피하주사 하였다. 면역기능에 미치는 효과는 환자의 말초혈액에서 백혈구수와 그 분획, 백혈구에 대한 총림프구의 분율 그리고 시토카인들(Interleukin-$1{\beta}$, Interleukin-2, Interleukin-6, Interferon-$\gamma$, Tumor necrosis factor-$\alpha$)의 변화를 분석하였다. 상기 항목들은 수술 전과 수술 후 8주, 16주 총 3회 측정되었다. 결과: 남녀비는 9 : 1이며, 평균연령은 55.9세(range $33{\sim}74$세)였다. 병기는 stage Ib가 4명, II가 6명이었다. 백혈구수와 총호중구수는 기저치에 비해 치료 후 8주와 16주에 유의한 감소를 보였다. 총호산구수는 기저치에 비해 8주와 16주에 증가하는 경향을 보였지만 통계적 유의성은 없었다(P=0.15). 총림프구의 수치는 치료 전후 유의한 감소를 보이지만 백혈구 수에 대한 총 림프구의 분율은 유의하지는 않지만(P=0.91) 오히려 증가하고 있다. 각각의 시토카인들은 치료전후 큰 변화를 보이지 않았다. 결론: 치료 전후 의미있는 면역반응의 증가는 관찰하기 어려웠다. 이것은 미슬토 추출물과 항암제의 병용투여에 의한 면역활성과 억제의 상쇄반응으로 생각된다. 총호산구수가 증가하였고, 백혈구에 대한 림프구의 분율이 감소하지 않고 증가하는 양상을 보인 것은 미슬토 추출물에 의해 유발된 면역반응으로 생각된다. Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

일조분석용 공용 데이터 모델 및 해석 모듈 개발

성윤복,고일두,김광우 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.1

The existing daylight analysis systems using computers are system independent, which means each system constructs own data for the daylight analysis in a separate way, and the data and information exchange between systems is not possible. If a single case of daylight analysis is compared, analyzed and evaluated in different systems, each system will repeat unnecessary process of producing, constructing and analyzing the same data. This causes a waste of resources and expenses in these works, and interferes with accurate, clear comparison and evaluation of the results owing to the possible errors and mistakes in the process of producing and constructing the data needed in each systems. Accordingly, this study aimed 1) to develop "Common Data Model & Analysis Module" for Daylight Analysis in order to share, exchange, analyze data between various systems that are operated independently, Also 2) aimed to consider the future extensibility of those applications on the web. And 3) aimed to propose this "Common Data Model & Analysis Module" as a prototype & protocol standard for daylight analysis system.

수서 환경독성 평가와 어류 Cytochrome P450 1A(CYP1A) 유전자

윤석주,김일찬,윤용달,이재성 한국환경생물학회 2003 환경생물 : 환경생물학회지 Vol.21 No.1

CYP1A 유전자는 cytochrome P450 약물대사효소에 속하며 다이옥신 등의 내분비계 장애물질에 의해 농도 의존적으로 유도되어 환경오염물질에 의해 유도되는 특성을 이용하여 환경오염물질에 대해 반응하는 생물체의 유전자 발현 변화 뿐만 아니라 이를 토대로 특정지역의 환경오염에 관한 정보를 얻을 수 있다. 본 논문에서는 수서환경오염과 관련하여 CYP1A 유전자의 응용성을 다 각도로 논의하였다. The CYPlA gene is one of Cytochrome P450 drug-metabolizing enzymes with dose-dependant manner of gene expression and is useful to get the information of alterations on gene expression upon environmental contaminants as well as the biomarker of environmental contamination at the specific places. In this report, we further discuss the usefulness of CYPlA gene in relation to aquatic environmental contamination at several aspects.