• 생명과학회지
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• 제24권12호
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• pp.1356-1363
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• 2014

28개의 아미노산으로 이루어져 있는 Ghrelin은 위 기저부의 X/A-유사 신경내분비 세포에서 주로 합성 분비되는 물질로 음식의 섭취나 비만, 에너지 항상성 등을 조절하는 역할을 하며, 이러한 Ghrelin 활성화는 수용체인 G-protein coupled growth hormone secretagogue receptor-1a (GHS-R1a)와 결합을 통해 일어난다. 최근 보고된 자료에 따르면, ghrelin과 수용체는 위나 시상하부, 뇌하수체 등뿐만 아니라 T 세포나 단핵구 및 대식세포 등 면역 세포에서도 생성되며, 염증반응을 유도하는 사이토카인의 생성을 억제하는 역할을 한다. 또한 흉선의 퇴화 등 면역기관에 있어서도 중요한 호르몬으로 보고되고 있지만 그 기전이나 기능에 대한 연구가 아직 미미한 실정이다. 본 연구에서는 흉선에서 T 세포의 성숙이나 세포활성을 억제하는 물질로 알려져 있는 덱사메타손(Dexamethasone; DEX)으로 세포사멸을 유도시킨 흉선세포에 ghrelin을 처리하여 세포사멸 억제효과를 알아보았다. 그 결과 Ghrelin은 세포사멸에 중요 단백질인 Caspase-3와 PARP 및 Bim의 활성화가 in vivo 및 in vitro 모두에서 효과적으로 저해됨을 확인할 수 있었으며, 이러한 세포사멸의 억제효과는 ghrelin을 처리할 경우 DEX에 의해 활성화된 Glucocorticoid 수용체(GR)의 인산화의 억제와 HSP90 등과 복합체를 이루고 있는 GR이 활성화되면서 분해되는 과정을 억제시켜 결과적으로 핵 안으로 이동하는 과정을 억제하는 기전을 통해 나타남을 알 수 있었다. 이러한 결과 등을 통해 볼 때, ghrelin은 약물이나 체내 생리적 스트레스 등으로 인해 발생하는 흉선 내 면역세포들의 세포사멸에 도움을 줄 것으로 사료되며, 나아가 이로 인한 흉선위축을 보호할 수 있는 치료 후보물질로서의 연구를 기대할 수 있으리라 사료된다.

• 생명과학회지
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• 제19권8호
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• pp.1067-1072
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• 2009

성체흰쥐의 경우 항암제인 싸이클로포스파마이드(CY)처리로 퇴축된 가슴샘은 2주 후에 정상조직으로 재생된다. 가슴샘 발생과정에서 이미 알려진 SDF-1 신호전달의 중요성과는 달리 성체의 가슴샘 재생과정에서 그 역할에 관해서는 알려진 바 전혀 없다. 본 연구의 목적은 발생중인 가슴샘에서 발현이 증가된다고 이미 알려져 있는 SDF-1이 성체의 가슴샘재생과정에서 어떤 발현 양상을 보이는지를 조사하는 것이다. 본 연구에서는 사이클로포스파마이(cyclophosphamide: CY)를 투여하여 가슴샘의 급성 퇴축을 유발시킨 후, 가슴샘 재생과정동안 SDF-1의 발현 특성을 면역조직화학, 이중면역염색 형광법, 역전사 중합효소 연쇄반응법을 이용하여 조사하였다. 그 결과, SDF-1은 가슴샘의 급성 퇴축 이후 7일째 되는 시기에 mRNA와 단백질의 양이 급격히 증가하였으며, 이중면역염색 형광법을 통해 큰포식 세포와 위치적 분포가 일치함을 확인하였다. 따라서, 본 연구 결과들을 통해 SDF-1은 가슴샘의 급성 퇴축 초기 과정에서 나타나는 손상된 세포를 처리하는 큰포식 세포의 기능 조절에 관여할 것으로 생각된다.

• Journal of Chest Surgery
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• 제2권2호
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• pp.167-167
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• 1969

Two groups of esophagus graft were done in canine esophagus in 34 adult mongrel dogs. For the first group segmental replacement graft was done with fresh autologous pericardium tube, and for the second, patch graft was done utilizing fresh autologous pericardium, fresh homologous pericardium,and dacron piece. All eight dogs in the first segmental replacement graft group died 2 to 5 days after operation with severe empyema caused by anastomosis disruption. Among 26 patch graft dogs 2 died during operation and 7 died 13 to 18 days after operation. For the 17 long-term patch grafted survivors esophagography and postoperative weight check were done. Postoperative stool was collected and examined for dacron patch excretion. One, two, three, and four months postoperative long-term survivors were sacrificed to obtain specimens in each group respectively and the following observations were made.I. Survival; Autologous pericardium patch group showed no mortality but in homologous pericardium and dacron patch group only two thirds were long-term survivors. II. Postoperative swallowing; There was no case which demonstrated postoperative dysphagia. About half of the cases showed postoperative weight increase and in only 3 cases weight decrease followed operation. III. Dacron patch was excreted in the stool 8 to 23 days after operation. Animals which excreted dacron patch up to 9 days after operation all died of empyema due to anastomosis disruption.IV. Postoperative esophagogram; All esophagograms in each group showed no leakage of barium, no passage disturbances and no remarkable stenotic signs.V. Morphological findings; [A] Macroscopical findings; In one month group specimens of each group dense adhesion with surrounding structures was noted and luminal surface was smooth with contraction of the patched area. In two month groups anastomosis sutures were still exposed but patched area showed lesser abnormality. In three to four months groups sutures were covered completely and patched area showed only very slight signs of contraction. [B] Microscopic findings; In one month group luminal surface of the replaced tissue [transplanted tissue] showed almost complete epithelial covering that is composed of several layers of squamous cells with no evidence of keratinization. Basement membrane was also well distinct throughout. Slight to minimal inflammatory cells comprising of large mononuclears, lymphocytes and plasma cells were observed in the subepithelial fibrous stroma consisted entirely of loose fibrous tissue containing many newly formed capillaries and fibroblastic proliferation. Scattered suture granulomas were found, few of which became acutely inflamed. In two months group repairing process progressed with lesser degree of inflammatory cell infiltration and young capillary proliferation. Fibrous tissue was more matured showing even focal collagenization.Suture granuloma persisted but with lesser reactive changes. Epithelial covering was that of a mature non-keratinizing stratified squamous epithelium. In three and four months groups the replaced area showed essentially similar histological findings. However, subepithelial stroma still consisted entirely of connective tissue without evidence of smooth muscle regeneration. In this group, inflammatory cell infiltration was minimal or negligible. Among these patch materials autologous pericardium group showed the most satisfactory repairing process.The above mentioned results may signify the feasibility of autogenous pericardium patch graft in clinical esophageal surgery.

• Journal of Chest Surgery
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• 제2권2호
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• pp.168-186
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• 1969

Two groups of esophagus graft were done in canine esophagus in 34 adult mongrel dogs. For the first group segmental replacement graft was done with fresh autologous pericardium tube, and for the second, patch graft was done utilizing fresh autologous pericardium, fresh homologous pericardium,and dacron piece. All eight dogs in the first segmental replacement graft group died 2 to 5 days after operation with severe empyema caused by anastomosis disruption. Among 26 patch graft dogs 2 died during operation and 7 died 13 to 18 days after operation. For the 17 long-term patch grafted survivors esophagography and postoperative weight check were done. Postoperative stool was collected and examined for dacron patch excretion. One, two, three, and four months postoperative long-term survivors were sacrificed to obtain specimens in each group respectively and the following observations were made. I. Survival; Autologous pericardium patch group showed no mortality but in homologous pericardium and dacron patch group only two thirds were long-term survivors. II. Postoperative swallowing; There was no case which demonstrated postoperative dysphagia. About half of the cases showed postoperative weight increase and in only 3 cases weight decrease followed operation. III. Dacron patch was excreted in the stool 8 to 23 days after operation. Animals which excreted dacron patch up to 9 days after operation all died of empyema due to anastomosis disruption. IV. Postoperative esophagogram; All esophagograms in each group showed no leakage of barium, no passage disturbances and no remarkable stenotic signs. V. Morphological findings; [A] Macroscopical findings; In one month group specimens of each group dense adhesion with surrounding structures was noted and luminal surface was smooth with contraction of the patched area. In two month groups anastomosis sutures were still exposed but patched area showed lesser abnormality. In three to four months groups sutures were covered completely and patched area showed only very slight signs of contraction. [B] Microscopic findings; In one month group luminal surface of the replaced tissue [transplanted tissue] showed almost complete epithelial covering that is composed of several layers of squamous cells with no evidence of keratinization. Basement membrane was also well distinct throughout. Slight to minimal inflammatory cells comprising of large mononuclears, lymphocytes and plasma cells were observed in the subepithelial fibrous stroma consisted entirely of loose fibrous tissue containing many newly formed capillaries and fibroblastic proliferation. Scattered suture granulomas were found, few of which became acutely inflamed. In two months group repairing process progressed with lesser degree of inflammatory cell infiltration and young capillary proliferation. Fibrous tissue was more matured showing even focal collagenization. Suture granuloma persisted but with lesser reactive changes. Epithelial covering was that of a mature non-keratinizing stratified squamous epithelium. In three and four months groups the replaced area showed essentially similar histological findings. However, subepithelial stroma still consisted entirely of connective tissue without evidence of smooth muscle regeneration. In this group, inflammatory cell infiltration was minimal or negligible. Among these patch materials autologous pericardium group showed the most satisfactory repairing process. The above mentioned results may signify the feasibility of autogenous pericardium patch graft in clinical esophageal surgery.

• 동의생리병리학회지
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• 제20권6호
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• pp.1636-1648
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• 2006

There are detailed descriptions of the clinical experiences and prescriptions of asthma in traditional Korean medicine. Zedoariae rhizoma is one of the Korean herbal medicines used to treat bronchial asthma and allergic rhinitis for centuries. However, the therapeutic mechanisms of this medication are still far from clear, In this study, a house-dust-mite (Dermatophagoides pteronyssinus [Der p])-sensitized murine model of asthma was used to evaluate the immunomodulatory effect of Zedoariae rhizoma on the allergen-induced airway inflammation in asthma. Three different protocols were designed to evaluate the treatment and/or long-term prophylacitic effect of Zedoariae rhizoma in Der p-sensitized mice. Cellular infiltration and T-cell subsets in the bronchoalveolar lavage fluid (BALF)of allergen-challenged mice were analyzed. Intrapulmonary lymphocytes were also isolated to evaluate their response to allergen stimulation. When Zedoariae rhizoma was administered to the sensitized mice before AC (groups A and C), it suppressed airway inflammation by decreasing the number of total cells and eosinophil infiltration in the BALF, and downregulated the allergen- or mitogen-induced intrapulmonary lymphocyte response of sensitized mice as compared to those of controls. This immunomodulatory effect of Zedoariae rhizoma may be exerted through the regulation of T-cell subsets by elevation or activation of the CD8+ and double-negative T-cell population in the lung. However, the administration of Zedoariae rhizoma to sensitized mice 24 h after AC (group B) did not have the same inhibitory effect on the airway inflammation as Zedoariae rhizoma given before AC. Thus, the administration of Zedoariae rhizoma before AC has the immunomodulatory effect of reducing bronchial inflammation in the allergen-sensitized mice. On the other hand, to determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Zedoariae rhizoma, for the control of allergic disease, we examined the effects of oral administration of Zedoariae rhizoma on a murine model of asthma allergic responses. When oral administration of Zedoariae rhizoma was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of Zedoariae rhizoma dichotomously modulates allergic inflammation in murine model for asthma, thus offering a different approach for the treatment of allergic disorders.

• Gut and Liver
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• 제12권6호
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

• Nutrition Research and Practice
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• 제15권6호
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• pp.673-685
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether in vitro treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice. MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)₂D₃ or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured. RESULTS: Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D₃ treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy. CONCLUSIONS: Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.

• 생명과학회지
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• 제31권7호
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• pp.686-697
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• 2021

프로폴리스는 꿀벌에 의해 생산된 수지 물질로 벌집을 보호하기 위해 사용되어 왔다. 꿀벌은 다양한 나무와 식물에서 배출된 수분을 침과 밀랍과 섞어서 프로폴리스를 생산한다. 프로폴리스는 기원전 300년경부터 상처를 치료하는 민간요법으로 사용되어 왔다. 프로폴리스에는 플라보노이드, 페놀계 화합물, 밀랍과 같은 많은 생리 활성 화합물이 포함되어 있다. 프로폴리스의 기능적 요소들 때문에, 프로폴리스에는 생물학적 응용을 위한 넓은 스펙트럼이 있다. 프로폴리스와 프로폴리스의 생물학적 활동의 화합물은 각각 과즙의 출처와 추출 방법에 따라 달라질 수 있다. 프로폴리스의 박테리아, 바이러스, 곰팡이를 포함한 반미생물 활동이 가장 잘 알려진 특징이다. 면역조절 메커니즘의 경우 아르테필린 C와 카페인산 페네틸에스테르가 주로 조절 화합물로 확인되었으며 각 화합물은 염증 반응을 감소시키고 T 림프구에 면역억제 반응을 일으킨다. 프로폴리스는 항염증 효과를 통해 암세포 증식 억제, 종양 신호 전달 캐스케이드 차단, 항혈관신생 등 항종양 활성을 보였다. 그러나 프로폴리스의 더 많은 응용을 위해서는 과즙의 원천 분석, 프로폴리스 화합물의 식별, 프로폴리스 분자 메커니즘, 화합물 시너지 효과의 조사가 더 필요할 것으로 보인다.

• 한국자원식물학회지
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• 제23권5호
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• pp.415-422
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• 2010

홍삼은 인삼을 증숙하는 과정에서 생겨나는 화학적으로 변화된 생리활성물질들에 의해 인삼과 차별화된 효과를 보여준다. 또한 홍삼은 장내미생물의 생물학적 전환에 의해 변화되어 생체내 약리활성을 보이는데, 이는 개인의 장내 미생물의 분포 차이에 의해 약리작용의 차이를 보일 수 있다. 최근 이 같은 차이를 극복하기 위해 인위적으로 장내미생물에 의해 사전 발효시킨 발효홍삼은 홍삼과 다른 성분량의 차이를 보임으로써 독특한 약리작용을 보인다고 알려져 있다. 이에 본 연구는 홍삼과 발효홍삼의 추출물이 알러지 및 염증반응에 끼치는 영향에 대해 알아보기 위해 비만세포의 탈과립 과정에서 분비되는 $\beta$-hexosaminidase 분비량 비교, 염증매개 세포부착물질인 ICAM-1 발현비교, 생쥐림프구의 증식능, 각질형성세포 증식능을 상호 비교하였다. 실험결과 홍삼은 1, $10\;{\mu}g/ml$에서 $\beta$-hexosaminidase 분비량 억제 및 ICAM-1 발현 억제 조절 효과를 나타내었으며, 발효 홍삼은 모든 농도에서 유의적인 억제 효과를 나타내었다. 그러므로 홍삼과 발효홍삼에서는 모두 항알러지 및 항염증 효과가 있다고 사료된다. 그러나 LPS에 의한 B세포의 증식능에서 홍삼 $1\;{\mu}g/ml$은 증가효과를 발효홍삼에서는 $100\;{\mu}g/ml$에서 억제효과를 나타내었고, ConA에 의한 T세포의 증식능에서는 홍삼 $100\;{\mu}g/ml$에서 증가효과를 발효홍삼 $100\;{\mu}g/ml$에서는 억제효과를 나타냄으로써 림프구 증식능에 관한 실험에서는 두 추출물간에 상반된 효과를 나타내었다. HaCaT세포를 이용한 각질형성세포 증식능에서는 발효홍삼 1, $10\;{\mu}g/ml$에서만 효과를 나타내었다. 이러한 결과를 종합해 볼 때, 홍삼과 발효홍삼에 존재하는 성분량의 변화에 따라 그 효능에서 차이를 나타내고 있는 것으로 사료되며, 홍삼 및 발효홍삼의 고농도 $100\;{\mu}g/ml$에서는 저농도와는 다른 효과를 보이는 경향을 나타내고 있으므로 홍삼 및 발효홍삼의 사용에 있어 적절한 적응증과 주성분의 검증 및 유효 농도에 대한 연구가 더욱 필요하다고 판단된다.

• 한국방사선학회논문지
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• 제16권3호
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• pp.335-341
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• 2022

본 연구는 블루베리의 방사선 방호효과를 알아보고자 하였다. 실험동물은 SD계 Rat 8주령 280~300 g 수컷 21마리를 사용하여 7마리를 하나의 군으로 정상군(A), 5 Gy 대조군(B), 5 Gy 실험군(C)으로 설정하였고, 생리식염수 경구투여량(200 mg/kg/day)로 1일 2회씩 50 mg/kg/day로 흰쥐에 7일 동안 경구투여 한 후 방사선 조사는 5 Gy를 조사 하였다. 그 결과 본 연구에서는 백혈구에서 유의성이 있음을 확인할 수 있었다(p<0.000). 적혈구나, 혈소판에서는 유의한 차이를 보이지 않았다. 세부적으로 살펴보았을 때 백혈구(WBC)는 호중구에서 정상군, 대조군, 실험군, 세 집단간 유의성이 있었다(p<0.004). 림프구에서도 통계적으로 세 집단간 유의성이 있었다(p<0.000). 단핵구에서는 통계적으로 유의성이 없었다(p<0.483). 적혈구(RBC)를 살펴보면, 혈색소(HGB)는 통계적으로 세 집단간 유의성은 없었다(p<0.291). 적혈구용적백분율(HCT)에서도 세 집단간 통계적으로 유의성은 없었다(p<0.564). 평균적혈구용적(MCV)에서는 통계적으로 세 집단간에 유의한 차이를 보였다(p<0.001). 평균적혈구혈색소양(MCH)에서 통계적으로 세 집단간 유의한 차이가 있었다(p<0.028). 평균적혈구혈색소농도(MCHC)에서 세 집단간 통계적으로 유의한 차이가 있었다(p<0.020). 적혈구분포폭(RDW)은 유의성이 없었다(p<0.09). 혈소판(PLT)에서 세부적으로 살펴보면, 평균혈소판용적(MpV)에서 통계적으로 세 집단간 유의성이 있었다.(p<0.04). 결론적으로 본 연구를 통하여 블루베리가 방사선 방호효과가 있는 것으로 사료된다.