• 생명과학회지
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• 제18권7호
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• pp.912-917
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• 2008

유전자재조합 hG-CSF의 생리활성을 분석하기 위하여 편상의 암세포로부터 분리되어진 cDNA를 이용하여 hG-CSF 유전자를 분리하여 동물세포(CHO cell lines)를 이용하여 재조합 단백질을 생산하였다. 재조합 단백질의 체내 생리활성을 분석하기 위하여0일과 2일에 피하주사 후 5일에 혈액을 채취하여 백혈구 수를 분석하였다. 투여 전과 비교하여 5일째에 백혈구 수는 현저하게 증가하였다. 또한, pEGFP-mUII-hG-CSF벡터를 소 태아로부터 분리되어진 체세포에 형질전환을 시켜서, EGFP signal을 나타내는 세포를 confocal를 이용하여 분리하여 수립하였다. 따라서, 이러한 결과는 유전자재조합 hG-CSF는 체내에서 강력한 생리활성을 나타내며, 또한 당쇄가 첨가되어지고 이중으로 연결되어진 새로운 돌연변이체를 포함하여 고 활성 재조합체의 생산이 가능할 것으로 보이며, pEGFP-mUII-hG-CSF벡터는 복제 형질전환 가축 생산을 위하여 유용하게 사용되어질 것으로 사료된다.

• Toxicological Research
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• 제31권4호
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• Clinical and Experimental Reproductive Medicine
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• 제28권2호
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• pp.161-167
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• 2001

Objective: Granulocyte-macrophage colony stimulating factors known to be secreted in murine and human reproductive tract. The development of human, bovine and murine embryos could be promoted by addition of GM-CSF in culture medium. However, the pregnancy and implantation rate of embryos cultured in GM-CSF have not been evaluated. The aim of this study was to assess the effect of GM-CSF in embryo development, pregnancy and implantation rate. Methods: A total of 191 IVF cycles were divided into control and GM-CSF supplement group (control=96, GM-CSF=95). The embryos were cultured for three day with or without 2 ng/ml of recombinant human GM-CSF. The quality of embryo, developmental velocity, pregnancy and implantation rates were compared. Results: There was no difference in age, number of gonadotropin ampules used, number of oocytes and fertilization. The number of ICSI cycle was higher in GM-CSF group. In GM-CSF group, G-1 grade embryos were the highest in proportion (56.4%), while G-2 grade embryos were highest (44.3%) in control group. The developmental velocity of embryos were not different between GM-CSF and control group. The pregnancy and implantation rates were significantly higher in GM-CSF group than control (47.4% vs. 33.3%, 17.0% vs. 11.1% respectively). Conclusion: By adding GM-CSF in culture medium, the quality of embryo, pregnancy and implantation rate could be improved.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2523-2526
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• 2012

Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ${\leq}50$. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/$mm^3$, 34 (26%) one between 100-300 cells/$mm^3$ and 40 (31%) an ANC greater than 300 cells/$mm^3$. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/$mm^3$ were more likely to die than patients with ANC >300 cells/$mm^3$ by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

• BMB Reports
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• 제45권12호
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• pp.742-747
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• 2012

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

• 대한임상독성학회지
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• 제13권1호
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• pp.50-54
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• 2015

Podostroma cornu-damae is a rare species of fungus belonging to the Hyocreaceae family. Its fruit body is highly toxic, as it contains trichothecene mycotoxins. The morphology is similar to that of immature Ganoderma lucidum, making identification difficult for non-experts. We experienced such a case of a 56- year-old male who picked and consumed podostroma cornu-damae, and consumed. Later that day, he developed digestive system symptoms, including nausea, vomiting, and abdominal pain. He presented to the emergency room (ER), there were no abnormal physical findings, symptoms improved after gastric lavage, and the patient voluntarily discharged himself on the same day. The following day, as the symptoms gradually deteriorated, he was admitted via the ER. He was presented with severe pancytopenia, alopecia, desquamation of skin, and acute renal failure. He recovered without any complications after conservative care, antibiotics therapy, and granulocyte colony stimulating factor administration. The most commonly reported complications of podostroma cornu-damae intoxication were reported pancytopenia, infection, disseminated intravascular coagulation, acute renal failure, etc. since Prevention is especially important because its toxicity can be lethal and there is no particular treatment to date, prevention is especially important. Promotion and education for the public are needed.

• Journal of Radiation Protection and Research
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• 제15권2호
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• pp.41-49
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• 1990

Wistar rat에 $^{88}SrCl_2$를 꼬리 정맥에 주사하여 체내 기관과 혈액 내 분포, 잔존율을 조사하였고 착화제와 유기산을 투석하여 혈장 단백질에 결합하는 Sr 양의 변화를 측정하였다. 혈액내에서 Sr은 혈장에 60%, 세포에 40% 부착되어 이동하였다. 혈장에 존재하는 Sr 중 약 50%정도는 혈장 단백질과 결합한 상태였고, 세포에는 세포 표면에 가볍게 부착되어 있었다. Erythrocyte나 granulocyte보다 lymphocyte에 많은 양의 Sr이 부착되어 있었다. 투여후 초기 1시간 이내에 혈액 내에서 급격히 감소하여 뼈에 침착되었다. 이때 각 기관에서도 Sr의 잔존율은 24시간 이내에 크게 감소하였고, 뼈로 침착된 Sr은 24시간 이후에 서서히 감소하였다. 착화제 EDTA, EGTA 및 DTPA를 투여한 경우, 혈장 단백질에 결합하는 Sr의 양은 대조군의 57%에서 27-33%로 감소하였으며 citrate 및 oxalate의 투여시는 이 값이 19%와 40%로 각각 감소하였다.

• 한국약용작물학회지
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• 제25권5호
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• pp.269-281
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• 2017

Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

• Journal of Ginseng Research
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• 제37권4호
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• pp.389-400
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• 2013

Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation ($30mJ/cm^2$), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.

• Nutrition Research and Practice
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• 제16권6호
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• pp.685-699
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• 2022

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.