• BMB Reports
• /
• 제49권2호
• /
• pp.111-115
• /
• 2016

Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.

• Toxicological Research
• /
• 제25권4호
• /
• pp.181-188
• /
• 2009

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

• Journal of Microbiology and Biotechnology
• /
• 제20권6호
• /
• pp.1011-1017
• /
• 2010

A novel dioscin-glycosidase that specifically hydrolyzes multi-glycosides, such as 3-O-${\alpha}$-L-($1{\to}4$)-rhamnoside, 3-O-${\alpha}$-L-($1{\to}2$)-rhamnoside, 3-O-${\alpha}$-L-($1{\to}4$)-arabinoside, and ${\beta}$-D-glucoside, on diosgenin was isolated from the Absidia sp.d38 strain, purified, and characterized. The molecular mass of the new dioscin-glycosidase is about 55 kDa based on SDS-PAGE. The dioscin-glycosidase gradually hydrolyzes either 3-O-${\alpha}$-L-($1{\to}4$)-Rha or 3-O-${\alpha}$-L-($1{\to}2$)-Rha from dioscin into 3-O-${\alpha}$-L-Rha-${\beta}$-D-Glc-diosgenin, further rapidly hydrolyzes the other ${\alpha}$-L-Rha from 3-O-${\alpha}$-L-Rha-${\beta}$-D-Glc-diosgenin into the main intermediate products of 3-O-${\beta}$-D-Glc-diosgenin, and subsequently hydrolyzes these intermediate products into aglycone as the final product. The enzyme also gradually hydrolyzes 3-O-${\alpha}$-L-($1{\to}4$)-arabinoside, 3-O-${\alpha}$-L-($1{\to}2$)-rhamnoside, and ${\beta}$-D-glucoside from [3-O-${\alpha}$-L-($1{\to}4$)-Ara, 3-O-${\alpha}$-L-($1{\to}4$)-Rha]-${\beta}$-D-Glc-diosgenin into diosgenin as the final product, exhibiting significant differences from previously reported glycosidases. The optimal temperature and pH for the new dioscin-glycosidase is $40^{\circ}C$ and 5.0, respectively. Whereas the activity of the new dioscin-glycosidase was not affected by $Na^+$, $K^+$, and $Mg^{2+}$ ions, it was significantly inhibited by $Cu^{2+}$ and $Hg^{2+}$ ions, and slightly affected by $Ca^{2+}$ ions.

• 한국수산과학회지
• /
• 제45권2호
• /
• pp.146-153
• /
• 2012

This study examined the effect of formulated diets (composed of condensed freshwater $Chlorella$ or $Schizochytrium$ sp., $Crypthecodinium$ sp., and EPA oil sources derived from baker's yeast) on the population growth and fatty acid composition of the brackish water flea ($Diaphanosoma$ $celebensis$) to determine diet effectiveness for mass production. Results indicated that the highest maximum density, fecundity, and population specific growth rate (SGR) of the flea were observed using a diet of $Tetraselmis$ $suecica$ (control). However, results using condensed freshwater $Chlorella$ and the mixed treatment of $Schizochytrium$ sp.+$Crypthecodinium$ sp.+EPA oil did not significantly differ from the control treatment ($P$>0.05). Thus, $T.$ $suecica$ could be replaced with a combination diet of $Schizochytrium$ sp., $Crypthecodinium$ sp., and EPA oil in condensed freshwater $Chlorella$ without growth interruption of $D.$ $celebensis$. As the percentage of combination diet (mix of $Schizochytrium$ sp., $Crypthecodinium$ sp., and EPA oil) in condensed freshwater $Chlorella$ increased, the level of ARA, EPA, DHA, and n-3 HUFA in $D.$ $celebensis$ also increased. However, the population density of $D.$ $celebensis$ sharply decreased with the use of treated supplements C5M5 (CHL [50%] and $Crypthecodinium$ sp.+ $Schizochytrium$ sp. + EPA oil [MIX 50%]). The optimum proportions of CHL and MIX for $D.$ $celebensis$ within the mixture were 70% and 30%, respectively. Based on the results, the combination of $Schizochytrium$ sp., $Crypthecodinium$ sp., and EPA oil in condensed freshwater $Chlorella$ appears to be a stable and effective food source for mass production of $D.$ $celebensis$.

• Tuberculosis and Respiratory Diseases
• /
• 제49권1호
• /
• pp.93-98
• /
• 2000

Acute respiratory distress syndrome (ARDS) has been reported to be associated with a variety of medical and surgical conditions, including All-trans-retinoic acid (ATTA). ATRA is very efficaceous drug to acute promyelocytic leukemia (APL). This drug can induce complete remission at APL without fatal risk of disseminated intravascular coagulation. But ATRA treatment, sometimes, produces the symptoms of fever, weight gain and acute respiratory distress, renal function impairment. The causes of these symptoms are not fully proved, but supposed as the result of leukostasis and capillary leak syndrome from excessive leukocyte differentiation and cytokines release. Recently, we experienced a 24-year-old woman who complained gum bleeding for 6 days. At bone marrow biopsy, she was diagnosed as APL. 2 days after ATRA treatment, she was suffered from the symptoms of dyspnea and general ache. At laboratory examination, total leukocyte count was 50,400/$mm^3$, $PaO_2$ was 42.5 mm Hg and chest PA revealed the findings compatible with ARDS. Treatment with low dose ara-C, corticosteroid and general supportive cares were tried. Within 3 days after treatment, the patient recovered from ARDS by evidence of arterial blood gas study and chest radiographs. She has acquired complete remission of APL with maintenance of A TRA. And so, we present this case with a review of related literatures.

• Journal of Ginseng Research
• /
• 제44권4호
• /
• pp.570-579
• /
• 2020

Background: Many researchers reported that the various immune activities of red ginseng are due to acid polysaccharides. But, the exact structural characteristics of the acidic polysaccharide in red ginseng have not been fully elucidated. Therefore, we isolated the acidic polysaccharide from red ginseng and characterized the structural property of the active moiety of this polysaccharide, which contributes to the immunostimulatory activity of red ginseng. Methods: A polysaccharide (RGP-AP-I) was purified from red ginseng via size-exclusion chromatography using Sephadex G-100. Immunostimulatary activity of RGP-AP-I was investigated via anti-complementory and macrophage stimulatory activity. The structure of RGP-AP-I was characterized by HPLC, sugar composition, β-glucosyl Yariv reagent and methylation analysis. Results: Peritoneal macrophages stimulated using RGP-AP-I significantly augmented the production of various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-α. The primary structure of RGP-AP-I was elucidated by assessing its sugar composition and methylation analysis. RGP-AP-I is a 96 kDa acidic polysaccharide, and comprises nine different monosaccharides, which mainly include sugars such as rhamnose (Rha, 9.5%), galacturonic acid (GalA, 18.4%), galactose (Gal, 30.4%), and arabinose (Ara, 35.0%). RGP-AP-I exhibited an considerable reaction with the β-glucosyl Yariv reagent, revealing the presence of arabino-β-3,6-galactan. Methylation analysis indicated that RGP-AP-I comprises 21 different glycosyl linkages, such as 3-, 4-, 6- and 3,6-linked Galp; 5-linked Araf; 2,4-linked Rhap; and 4-linked GalAp, which are characteristics of rhamnogalacturonan I (RG-I). Conclusion: we assumed that the immunostimulatory activity of RGP-AP-I may be due to the RG-I structure, which comprises a main chain with a repeating linkage unit, [→2)-Rhap-(1→4)-GalAp-(1→] and three groups of side chains such as (1→5)-linked arabinan, (1→4)-linked galactan, and arabino-β-3,6-galactan, which branch at the C(O)4 positions of Rha residues in the main chain of RGP-AP-I.

• 한국토양비료학회지
• /
• 제17권4호
• /
• pp.415-427
• /
• 1984

수도재배(水稻栽培)(유수형성기(幼穗形成期)) 포장(圃場)에 자생(自生)하고 있는 잡초(雜草)와 벼(복광(福光)벼) 및 두과작물(荳科作物)의 근계(根系)에 협생(協生)하는 질소고정미생물(窒素固定微生物)인 Azospirillum 속(屬)의 질소고정력(窒素固定力)의 발현양상(發現樣相)과 숙주별(宿主別) 이들 균(菌)의 분포(分布)를 조사(調査)한 결과(結果)는 다음과 같다. 1. 벼, 잡초(雜草) 및 두과작물(荳科作物)의 근계(根系)(근표면(根表面), 근조직내부(根組織內部))에 협생질소고정미생물(協生窒素固定微生物)인 Azospirillum 속(屬)이 널리 공존(共存)하고 있었다. 2. 근조직내부(根組織內部)(inner root solutions)에서 Azospirillum spp. 균(菌)이 발현(發現)한 질소고정력(窒素固定力)은 16~53 n mole/tube hr의 범위(範圍)였으며, 특(特)히 돌피, 바람하늘지기 및 물닭개비의 근계(根系)에서 높은 질소고정력(窒素固定力)을 보였다. 3. 작물근계별(作沕根系別)로 Aaospirllum속(屬)의 질소고정균(窒素固定菌)을 계대배양(繼代培養)하였을 때의 질소고정력(窒素固定力)은 근조직내부(根組織內部)(histosphere; 6~39 n mole/tube hr) 보다 근표면(根表面)(rhizoplane; 1~260 n mole/tube hr)에서 분리(分離)한 균주(菌株)가 높은 질소고정력(窒素固定力)을 보였으며, 벼, 바람하늘지기, 물닭개비 및 콩 등(等)의 근표면(根表面) 분리균주(分離菌株)는 100 n mole/tube hr 이상(以上)으로 현저(顯著)히 높은 질소고정력(窒素固定力)을 나타내 있다. 4. 화본과작물(禾本科作物)(벼, 돌피), 알방동사니 및 자귀풀(근표면(根表面), 근조직내부(根組織內部))에서는 A. brasilense의 협생질소고정균(協生窒素固定菌)이 우점(優點)하였고, 그 외(外) 작물근계(作物根系)는 A. lipoferum과 A. brasiilene의 양균(兩菌)이 상호(相互) 협생(協生)하고 있었다. 한편(便) A. brasilense 균(菌)중에는 $nir^+$(탈질형균(脫窒型菌))와 $nir^-$(비탈질형균(非脫窒型菌))의 양특성형균(兩特性型菌)이 동일숙주내(同一宿主內)의 근계(根系)에 공존(共存)하였다. 5. 공시작물(供試作物) 근계(根系)에서 분리동정(分離同定)한 Azospirillum spp. 의 협생질소고정균(協生窒素固定菌)을 현미경(顯微鏡)으로 형태(形態)를 관찰(觀察) 한 결과(結果), A. lipoferum와 A. brasilense의 양균(兩菌)은 S자(字)모양의 간균(桿菌)으로 양극편모(兩極鞭毛)(single polpr flagellum)을 갖고 있었다.

• 한국식품위생안전성학회지
• /
• 제33권3호
• /
• pp.168-175
• /
• 2018

본 연구에서는 경기도내 유통되는 수산물 42품목 670건에 대한 총수은 노출량평가를 수행하고, 총수은이 0.1 mg/kg 이상 검출된 시료를 대상으로 기존의 식품공전법과 개발시험방법을 적용하여 비교하였다. 유통 수산물에 대한 총수은 모니터링 결과 총수은에 대한 주간추정섭취량(Estimated weekly intake)은 $0.0742{\mu}g/kg$ bw/week인 것으로 조사되었으며, 이는 JECFA에서 제시한 PTWI $4{\mu}g/kg$ bw/week 대비 1.9% 미만으로 수산물 섭취로 인한 수은 위해성은 안전한 수준으로 평가되었다. 전처리 방법 개선에 따른 메틸수은 분석법 개발을 위해 추출, 정제 부분을 기존 식품공전방법과 다르게 진행하였다. Microwave 추출조건은 용액, 시간, 온도 3가지 조건을 고려하였다. Microwave 추출용액은 10% NaCl, 5 N HCl 용액, 11 N HCl 및 0.1 N NaOH를 선정하여 비교한 결과 회수율이 89.8%로 가장 높고 유화현상도 발생하지 않은 10% NaCl 용액으로 선정하였다. Microwave 추출시간은 10~20분 동안 추출시간을 달리하여 회수율을 비교하였으며, 10분 이상 추출 시 회수율은 100% 이상을 나타냈으나 15분 이상 추출 시에는 유기용매와의 층분리가 어려워 추출시간을 15분으로 선정하였다. Microwave 추출온도에 따른 회수율을 알아보기 위해 $40{\sim}60^{\circ}C$에서 추출 후 회수율을 비교하였다. 추출온도가 증가함에 따라 회수율이 증가하였으나 $50^{\circ}C$ 이상의 온도에서는 회수율이 감소하여 $50^{\circ}C$로 최적화 하였다. 식품공전에서 정제과정에 사용되는 L-cystein은 매 실험마다 제조해야하는 번거로움이 있어 이를 대체하기 위해 0.05~5 N NaOH를 이용하였다. NaOH용액의 농도가 높아질수록 회수율이 증가하는 경향을 보였지만 2 N NaOH 이상의 농도에서는 재현성이 떨어지고 거품발생량이 증가하여 2 N NaOH용액을 정제용액으로 선정하였다. 이 실험들을 바탕으로 수산물 중 메틸수은 시료 전처리 방법을 제안하였다. 제안된 시료전처리 방법은 기존 시험방법에 비해 검출효율이 높고 전처리 시간을 절약할 수 있는 것으로 나타났다. 따라서 수산물 전반에 대한 모니터링 수행 시 스크리닝 분석법으로 유용하게 활용할 수 있을 것으로 생각된다. 우리나라의 수산물 섭취량이 세계에서 가장 많은 것으로 알려진 만큼 비의도적 유해물질인 메틸수은에 대한 종합적이고 체계적인 관리가 이루어져야 될 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6627-6632
• /
• 2015

Background: We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone ($20mg/m^2$ daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C $10mg/m^2$ q12h*7d, G-CSF $300{\mu}g$ qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ${\geq}$two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

• Clinical and Experimental Pediatrics
• /
• 제49권12호
• /
• pp.1329-1339
• /
• 2006

목 적 : 조혈모세포이식은 혈액암뿐만 아니라, 유전 질환, 면역질환에서 완치의 방법으로 널리 사용되고 있다. 그러나 생착 실패나 재발로 인해 조혈모세포이식이 실패하는 경우가 종종 있고, 이때는 장기 생존이 거의 불가능한 것으로 알려져 있으며, 치료방법도 정립되지 않았다. 이에 본 저자들은 1차 이식이 실패한 경우 치료법으로써 2차 이식의 의의에 대해 알아보고자 하였다. 방 법 : 1991년 5월부터 2004년 12월까지 전남대학교병원 소아과에서 조혈모세포이식을 시행한 115례 중에서 생착 실패나 재발로 2차 이식을 시행한 비혈액암 8례(재생불량성빈혈 7례, 부신백질이영양증 1례)와 혈액암 7례(급성골수성백혈병 3례, 급성림프구성백혈병 2례, 만성골수성백혈병 1례, 골수이형성증후군 1례), 총 15례의 의무기록지를 바탕으로 치료 방법, 합병증, 치료성과 등에 대해 분석 하였다. 결 과 : 비혈액암의 경우 2례는 일차성 생착 실패, 5례는 후기 이식편 거부, 1례는 Fanconi 빈혈로 1차 이식 후 급성골수성백혈병으로 전환되어 2차 이식을 시행하였다. 1차 이식 후 이식편기능 부전까지 기간은 중앙값 130.5일(범위, 59-279일)이었고, 1차와 2차 이식 사이의 간격은 중앙값 348일(범위, 86-1,875일)이었다. 전처치는 7례에서 cyclophosphamide를 기본으로 하였고, fludarabine을 3례에서, 방사선 조사를 2례에서 사용하였다. 이식원은 6례에서 조직형 일치 형제간 말초조혈모세포를, 1례에서 조직형 일치 형제간 골수를, 1례에서 제대혈을 사용하였고, 제대혈을 사용한 1례를 제외한 7례는 2차 이식의 공여자가 1차 이식 시와 동일하였다. 급성 이식대숙주병은 1례에서 Grade IV로 발생하였다. 총 8례 중 2례가 사망하였고, 1례는 생착 실패하였으나 생존하여, 5년 Kaplan-Meier(K-M)전체생존율은 75.0%, 무병생존율은 62.5%이었다. 혈액암의 경우 모두 재발로 인해 2차 이식을 시행하였다. 1차 이식 후 재발까지 기간은 중앙값 174일(범위, 90-1,474일)이었고, 1차 이식과 2차 이식 사이의 간격은 중앙값 319일(범위, 178-1,715일)이었다. 전처치는 5례에서 fludarabine, busulfan, antithymocyte globulin 병합요법을, 1례는 busulfan, ara-C, idarubicine 병합요법을, 나머지 1례는 melphalan, busulfan 병합요법을 사용하였다. 이식원은 5례는 1차 이식과 동일한 공여자의 말초조혈모세포였고, 나머지 2례는 제대혈을 사용하였다. grade II 이상의 급성 이식대숙주병은 2례에서 발생하였다. 사망한 5례 중 4례는 재발로, 나머지 1례는 이식관련 합병증으로 사망하였다. 2년 K-M 전체생존율과 무병생존율은 각각 28.6%이었다. 결 론 : 조혈모세포이식을 시행하고 이식편 거부나 재발이 된 경우 2차 이식은 일부 환자에서 장기 생존을 가능하게 하는 방법이 될 수 있다. 비혈액암 질환, 특히 재생불량성빈혈에서 생착 실패를 보이는 경우 2차 이식을 시행하는 것을 추천할 수 있지만, 적절한 전처치와 이식원에 관한 연구가 더 필요하겠고, 혈액암 질환에서 재발한 경우에는 소수에서만 장기 생존이 가능하므로 더욱 효과적인 항백혈병 치료가 필요할 것으로 사료되었다.