• Biomolecules & Therapeutics
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• 제23권5호
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2022년도 춘계학술대회
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• pp.279-282
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• 2022

급성 림프모구성 백혈병은 골수 내 미성숙 림프구 과다증식으로 인해 골수 기능이 억제되어 발생하는 급성 백혈병이다. 성인 급성 백혈병의 30% 비율을 차지하고 있으며, 소아는 항암화학요법으로 80% 이상의 완치율을 보이는 반면, 성인은 20%~50%로 저조한 생존율을 보이고 있다. 그러나 급성 림프모구성 백혈병 진단을 위한 의료영상 데이터 기반 머신러닝 알고리즘에 관한 연구가 초동 단계이다. 본 논문에서는 신속하고 정확한 진단을 위해 CNN 알고리즘모델들을 비교분석한다. 네 가지 모델을 사용하여 급성 림프모구성 백혈병 진단 모델들을 비교분석하기 위한 실험 환경을 구축하고 주어진 의료영상 데이터에 대해 정확도가 가장 우수한 알고리즘을 선택하였다. 실험 결과에 따르면 네 가지의 CNN 모델들 중에서 InceptionV3모델이 98.9%의 정확도로 가장 우수한 성능을 보였다.

• IMMUNE NETWORK
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• 제20권5호
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• pp.38.1-38.12
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• 2020

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3⁺ induced Treg (iTreg) differentiation in ovalbumin-specific CD4⁺ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제18권2호
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• pp.286-297
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• 1996

The proliferation of bone marrow stem cell compartment is thought to be under both positive and negative controls by cytokines and colony stimulation factors. Macrophage inflammatory $protein-1{\alpha}(MIP-1{\alpha})$ has been assessed for its potential to protect hematopoietic stem cells from cytotoxic effects of a cycle-specific antineoplastic agents. We have tested the ability of $MIP-1{\alpha}$ to suppress the proliferation of stem cell line Du.528.101 in variety of active status by using $[^{3}H]-thymidine$ incorporation test. The results were as follows. 1. The effect of $MIP-1{\alpha}$ on steady-state Du.528.101 cell represented the cell growth suppression at the concentration of 10, 50, 100nM of $MIP-1{\alpha}$(P<0.001). 2. $MIP-1{\alpha}$ stimulated the proliferation of Du.528.101 cells previously treated with IL-1 at the concentration of 5, 50nM of $MIP-1{\alpha}$(P<0.01). 3. The suppression effect of MIP-1 on Du.528.101 cells at the concentration of 5, 50nM was shown when cells were treated with $MIP-1{\alpha}$ before activation with $IL-1{\beta}(P<0.01)$. 4. The growth rate of synchronized cells were slower than that of non-synchronized ones, and $MIP-1{\alpha}$ represented the similar suppression effect on both synchronized and non-synchronized cells.

• Archives of Pharmacal Research
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• 제14권1호
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• pp.73-77
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• 1991

The effects of pyridoxine (PN) on rifampicin (RMF) toxicity were investigated by both in vivo and in vitro methods. RMF (30 mg/kg) was injected intraperitoneally and PN(150 mg/kg) was administered orally to rats for 10 consecutive days. After treatment, clinical chemistry and hematologic profiles were measured. RMF and PN plus RMF did not show any adverse effects at this in vivo experimental condition. Thymidine incorporations of mice bone marrow cells were examined in vitro. RMF showed a decrease in thymidine uptake in a dose-dependent manner, but PN showed a reversal of the thymidine uptake suppression caused by RMF (p<0.01). On the other hand, PN showed a decrease in thymidine uptake at a high concentration level.

• 대한예방한의학회지
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• 제10권1호
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• pp.13-32
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• 2006

In order to indentify the effect of Astragali Radix(A.R) on cyclophosphamide(C.Y) induced leukopenia, A.R. extracts(EAR) were treated to mice orally, and blood sampling was done by periods. For the in vivo experiments, mice were divided into 4 groups, which treated EAR before, or after C.Y injection, or both, or none. Rapid normalization in the peripheral blood count of WBC, neutrophils, lymphocytes, RBC, and platelets observed in every EAR treated group regardless of the treatment periods of EAR. These studies suggest that, A.R. premedication can be effective in protection of bone marrow suppression during anticancer therapy.

• 대한임상독성학회지
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• 제6권2호
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• pp.138-141
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• 2008

A 47-year-old woman ingested about 12 mg of colchicine with suicidal intent. Colchicine, a highly poisonous alkaloid, is a commonly used treatment for gout, Bechet's disease, and familial Mediterranean fever. Despite the knowledge of its side effects, the risk of a significant overdose is under-appreciated. She suffered from acute multisystem toxicity, including gastrointestinal disorders, bone marrow suppression, alopecia, and probable pancreatitis, but she ultimately recovered with supportive therapy. We report a case of acute colchicine toxicity from a single overdose with a review of the literature.

• IMMUNE NETWORK
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• 제2권1호
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• pp.53-59
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• 2002

Background: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-${\gamma}$) and TNF-${\alpha}$ can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Methods: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-${\gamma}$, TNF-${\alpha}$, or macrophage inflammatory protein 1-${\alpha}$ (MIP-$1{\alpha}$). Results: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-${\gamma}$, TNF-${\alpha}$, or MIP-$1{\alpha}$ increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-${\gamma}$, TNF-${\alpha}$, or MIP$1{\alpha}$ mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-${\gamma}$ enhanced apoptosis most strongly via Fas-caspase-3 pathway. Conclusion: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-${\gamma}$ can induce apoptosis of bone marrow progenitors in part by Fas induction.

• 대한핵의학회지
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• 제27권1호
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• pp.112-117
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• 1993

연구배경 :핵사고시 가장 중요한 유출방사성핵종의 하나이며, 갑상선암 및 갑상선 기능항진증 치료에 없어서는 안되는 치료제인 방사성옥소($^{131}I$)는 과량 투여시 백혈병 또는 유전이상을 나타낼 것으로 추측되고 있으나, 이에 대해서는 아직 논란의 여지가 있다. 방법 : 실험군은 방사성옥소를 투여하지 않고 위장수술만을 시행한 대조군과, 갑상선 기능항진증의 치료용량인 10mCi/60Kg(0.17mCi/Kg)을 투여하는 군, 갑상선암의 치료용량인 100 mCi/60 Kg (1.67 mCi/Kg)을 투여하는군, 그리고 골수억제 등의 부작용 때문에 치료를 중단하게 되는 1000 mCi/60 Kg(16.67 mCi/Kg)를 투여하는 군으로 나누어 실험을 시행하였다. 각 군은 생후 6주(30g)전후의 생쥐 10마리로 구성되었으며, 방사성옥소는 복강에 투여하였다. 투여 1일 및 3일 후 생쥐를 희생시켜 골수를 채취하고, 이를 대상으로 미소핵검사를 시행하였다. 미소핵은 골수세포 중핵이 없는 정염성 및 다염성적헐구에서 관찰하며, 1000개의 세포 중 미소핵이 나타난 세포수를 %로 표시하였다. 결과 : 다염성 적혈구 (괄호안은 정염성 적혈구)에서의 미소핵 발현은 대조군의 경우 1일째 $0.25{\pm}0.07$ ($0.23{\pm}0.07$)%, 3일째 $0.24{\pm}0.07$ ($0.21{\pm}0.07$)%, 치료용량의 방사성옥소를 투여한 군 중 0.17 mCi/Kg을 투여한 군에서는 1일째 $0.27{\pm}0.1$ ($0.23{\pm}0.09$)%, 3일째 $0.28{\pm}0.07$ ($0.25{\pm}0.06$)%, 1.67 mCi/Kg을 투여한 군에서는 1일째 $0.29{\pm}0.08$ ($0.26{\pm}0.09$)%, 3일째 $0.31{\pm}0.05$ ($0.29{\pm}0.06$)%, 16.67mCi/Kg를 투여하는 군에서는 1일째 $0.32{\pm}0.06$ ($0.25{\pm}0.09$)%, 3일째 $0.33{\pm}0.08$ ($0.3{\pm}0.06$)%를 보였다. 투여한 방사성옥소의 양이 많을수록 미소핵 빈도수가 증가하는 경향을 보였으나, 각 군간에 통계학적으로 유의한 차이는 없었다(p>0.05). 결론 : 임상적으로 치료를 중단하게 되는 1000mCi/60 Kg(16.67 mCi/Kg)를 투여한 군에서도 생쥐 골수내 미소핵이 발현되지 않는 것으로 보아, 방사성옥소는 비교적 안심하고 치료에 사용할 수 있는 제제로 사료되었다.

• Molecules and Cells
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• 제40권10호
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• pp.752-760
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• 2017

A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis, but its regulatory mechanisms in osteoclast formation are less well-defined. Here, we demonstrate the effect of A2BAR stimulation on osteoclast differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived monocyte/macrophage (BMM) and RANKL increased A2BAR expression during osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and $NF-{\kappa}B$ by RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast differentiation. Stimulation of A2BAR suppressed the expression of osteoclast marker genes, such as c-Fos, TRAP, Cathepsin-K and NFATc1, induced by RANKL, and transcriptional activity of NFATc1 was also inhibited by stimulation of A2BAR. A2BAR stimulation caused a notable reduction in the expression of Atp6v0d2 and DC-STAMP related to cell-cell fusion of osteoclasts. Especially, a decrease in bone resorption activity through suppression of actin ring formation by A2BAR stimulation was observed. Taken together, these results suggest that A2BAR stimulation inhibits the activation of ERK1/2, p38 and $NF-{\kappa}B$ by RANKL, which suppresses the induction of osteoclast marker genes, thus contributing to the decrease in osteoclast cell-cell fusion and bone resorption activity.