The novel herbal cocktail MA128 suppresses tumor growth and the metastatic potential of highly malignant tumor cells

KIM, AEYUNG,IM, MINJU,YIM, NAM-HIU,HWANG, YOUN-HWAN,YANG, HYE JIN,MA, JIN YEUL Spandidos Publications 2015 ONCOLOGY REPORTS Vol.34 No.2

<P>MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inhibiting tyrosinase activity via the p38 MAPK and protein kinase A signaling pathways in B16F10 cells. In the present study, we examined whether oral administration of MA128 suppressed the in vivo tumor growth of HT1080 cells in athymic nude mice. The results showed that the daily oral administration of 75 and 150 mg/kg MA128 suppressed the tumorigenic growth of HT1080 cells efficiently. Since metastasis is a major cause of cancer-associated mortality and the greatest challenge during cancer treatment, we investigated the effect of non-toxic concentrations of MA128 on the metastatic potential of HT1080 cells. MA128 inhibited anchorage-independent colony formation, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity under resting and PMA-stimulated conditions was decreased in a dose-dependent manner by MA128 in HT1080 cells. In addition, the daily oral administration of MA128 at doses of 75 and 150 mg/kg efficiently blocked the lung metastasis of B16F10 cells that had been injected into the tail veins of C57BL/6 mice. In particular, none of the mice treated with MA128 exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. MA128 also inhibited tumor-induced angiogenesis. Taken together, the results suggest that MA128 is a potential therapeutic agent and a safe herbal medicine for controlling malignant and metastatic cancer.</P>

A Novel Herbal Medicine KIOM-MA Exerts an Anti-Inflammatory Effect in LPS-Stimulated RAW 264.7 Macrophage Cells

Oh, You-Chang,Cho, Won-Kyung,Jeong, Yun Hee,Im, Ga Young,Kim, Aeyung,Hwang, Youn-Hwan,Kim, Taesoo,Song, Kwang Hoon,Ma, Jin Yeul Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P>KIOM-MA was recently reported as a novel herbal medicine effective for atopic dermatitis and asthma. In this study, we have demonstrated the inhibitory effect of KIOM-MA on proinflammatory mediator produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. KIOM-MA significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as nitric oxide (NO) and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>). Consistent with the inhibitory effect on PGE<SUB>2</SUB>, KIOM-MA suppresses the LPS-induced migration of macrophages and gelatinase activity and the expression of matrix metalloprotease-9 (MMP-9) in a dose-dependent manner. Additionally, KIOM-MA showed a strong suppressive effect on the inflammatory cytokines production such as tumor necrosis factor-<I><I>α</I></I> (TNF-<I><I>α</I></I>) and interleukin-6 (IL-6). We also found that KIOM-MA inhibits the activation of nuclear factor-<I><I>κ</I></I>B (NF-<I><I>κ</I></I>B) and represses the activity of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH<SUB>2</SUB>-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Taken together, we elucidated the mechanism of anti-inflammatory effect of KIOM-MA using RAW 264.7 cells stimulated by LPS.</P>

대식세포에서 수련환(茱連丸) 물추출물의 항염증작용에 관한 연구

윤여환 ( Yeo Hwan Yoon ),김성배 ( Sung Bae Kim ),강옥화 ( Ok Hwa Kang ),문수현 ( Su Hyun Mun ),서윤수 ( Yun Soo Seo ),양다운 ( Da Wun Yang ),강다혜 ( Da Hye Kang ),위경 ( Gyeong Wi ),임재수 ( Jae Soo Lim ),김마룡 ( Ma Ryong Kim ) 대한본초학회 2014 大韓本草學會誌 Vol.29 No.6

Objectives : Suryeon-hwan (SRH) exhibits potent anti-inflammatory activity with an unknown mechanism. However, there has been a lack of studies regarding the effects of SRH on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. So, the investigation focused on whether SRH inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. Methods : Cells were treated with 200 ng/mL of LPS 30 min prior to the addition of SRH. Cell viability was measured by MTS assay. The production of nitric oxide (NO) was determined by reacting cultured medium with Griess reagent. The content of level of cytokines (PGE, IL-6) in media from LPS-stimulated Raw 264.7 cells was analyed by ELISA kit. The expression of COX-2, iNOS and MAPKs was investigated by Western blot, RT-PCR. Results : We found that SRH inhibited LPS-induced NO, PGE2 and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, SRH suppressed the LPS-induced phosphorylation of MAPK and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation. Conclusions : These results suggest that SRH has inhibitory effects on LPS-induced PGE2, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the phosphorylation of MAPKs following activation.

IL6ST regulates liver tumorigenesis via the regulation of mitophagy

Hwan Ma,Jeong-Su Park,Feng Wang,Yeo-Jin Lee,Gyu-Rim Lee,Ekihiro Seki,Hwan-Soo Yoo,Yoon-Seok Roh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer in the world and the third largest cause of cancer mortality. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including HCC. Cytokines are released in response to a diverse range of cellular stresses, including carcinogen-induced injury, infection, and inflammation. A number of cytokines that are produced in the tumor microenvironment have an important role in cancer pathogenesis. Among them, there are IL-6 family cytokines that share the common receptor subunit IL6ST. IL6ST regulates cell survival, growth, and proliferation through the regulation of JAK-Stat3 and PI3K-mTORC1. Both downstream pathways have been linked with autophagy and mitochondrial function. Moreover, mitophagy contributes to metabolic dysfunction syndrome and chronic liver diseases such as NAFLD, NASH, and HCC. However, the mechanism of how IL6ST modulates hepatocyte mitophagy and HCC development remains unclear. IL6ST activated Stat3 and mTORC1 signaling in HCC, as evidenced by the controls phosphorylation of Stat3 (Tyr705), P70S6K(T389), EIF4E(S209), and RPS6(S235). Interestingly, IL6ST prevents mitochondrial stress and improves cell viability by inhibition of Stat3 and mTORC1-ULK1 mediated mitophagy and apoptosis. In genetically engineered mouse models of HCC (TAK1ΔHep), hepatocyte-specific deletion of IL6ST suppressed the multiplicity and maximum size of naturally occurring cancer. In conclusion, IL6ST governs parallel activation of carcinogenic STAT3 along with mTORC1 in the pathogenesis of HCC by regulation of mitophagy-dependent apoptosis and cancer cell survival.

CMX inhibits inflammation and cell proliferation via the regulation of JAK/STAT signaling in macrophages and keratinocytes

Ma Yuanqiang,Jeong su Park,Wang Feng,Hwan Ma,Gyu rim Lee,Yeo jin Lee,Yoon-seok Roh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Psoriasis, a chronic inflammation-mediated skin disease, affects 2-3% of the total populations in the world. It is characterized by keratinocytes hyperproliferation and immune cell infiltration. The JAK/STAT3 and JAK/STAT1 signaling pathways triggered by IL-6 and IFN- γ from dendritic cell and T lymphocytes, play important roles in psoriasis. Thus, blockade of JAK/STAT signaling will be potential strategy in psoriasis. CMX, an extract of Centipeda minima enriched in Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C which have already been reported in anti-inflammation, anti-cancer, antiallergy, and suppression of proliferation. We established chronic inflammatory and cell proliferating models in macrophages and keratinocytes with LPS (250ng/mL), rh-IL-6 (10ng/mL), or rh-IFN-γ (10ng/mL) to evaluate the effect of CMX. CCK-8 was used for cell proliferation assay, and the protein and RNA were collected and analyzed by western blot and RT-qPCR. We found that CMX inhibited pro-inflammatory cytokines production by inhibiting LPS-induced JAK1/2 and STAT1/3 phosphorylation in macrophages. Moreover, CMX down-regulated chemokines and cell proliferation in HaCaT cell induced by rh-IL-6 and rh-IFN-γ, respectively. Consistently, we demonstrated that reduction of chemokines expression and hyperproliferation was medicated by the regulation of IFN-γ-activated JAK/STAT1 and IL-6-activated JAK/STAT3 signaling. In conclusion, CMX inhibited JAK/STAT-mediated inflammatory responses and cell proliferation in macrophages and keratinocytes, consequently CMX may improve psoriasis development as an important therapeutic approach.

Substitution Possibilities for Raw Materials in the U . S . Paper and Paperboard Industry

Hwan Ok Ma 한국산림과학회 1993 한국산림과학회지 Vol.82 No.1

In this paper a model of the production structure for the U.S. paper and paperboard industry is estimated, emphasizing the use the industry makes of raw materials inputs. The model differs from previous models in two respects. (i) The study disaggregates raw material inputs into woodpulp and wastepaper since there are likely to be important differences in the relationship between woodpulp and wastepaper and other inputs. (ii) In order to representing the characteristics of paper and paperboard production in the absence of data on the market price of pulp, the study treats pulp as a restricted input. The approach estimates a translog profit function with annual time series data between 1958 to 1987 for two outputs(paper and paperboard), three variable inputs(labor, energy, wastepaper), one quasi-fixed (pulp) and one restricted (pulp) inputs. Simple tests for exogeneity(of output prices, wastepaper input price, and quasi-fixed and restricted inputs) and the static equilibrium test of capital are implemented and three stage least squares with instrumental variables is employed on base the results of hypotheses. Using the theoretical relationship between the restricted profit function and the total profit function following the approach of Brown and Christensen (1981), which is further applied by Halvorsen and Smith(1986), the study obtains important economic information with regard to pulp which is representing the highest proportion of the variable cost. A central finding is that pulp and wastepaper respond very differently to changes in input and output prices, which suggests that they should be regarded as different inputs. Pulp is much more responsive to price changes than wastepaper. The implication of this finding is that rising pulp price will induce significant shifts in the mix of raw material inputs. Another important finding is that. $quot;virgin fiber materials$quot;, pulp, and $quot;recycled fiber materials$quot;, wastepaper, are substitutes in both the Allen partial elasticity of substitution(AES) and the Morishima elasticity of substitution(MES). This result is encouraging implications for recycling wastepaper.

무도장 내후성 강 교량의 밀폐형 박스거더 내부의 부식에 대한 고찰

마승환(Ma, Seung-Hwan),노영태(Noh, Young-Tai),장건익(Jang, Gun-Ik) 한국산학기술학회 2015 한국산학기술학회논문지 Vol.16 No.4

내후성 강재는 대기환경에서 내식성이 우수하여 강교량의 재료로 많이 사용되고 있다. 그러나 내후성 강은 해수와 가까운 지역, 음지 및 습도가 높은 환경에서는 안정된 녹층이 형성되지 않고, 일반녹이 발생하고 있다. 따라서 열악한 대기 환경을 가지는 일본에서는 무도장으로 사용하지 않고, 녹안정화 처리를 하고 있는 상황이다. 그러나 국내에서 건설된 내후성 강은 대부분 무도장으로 건설되었고, 건습의 주기적인 반복이 일어나기 어려운 밀폐형 박스거더형으로 건설되었다. 특히, 한강수변위에 건설된 강교량의 경우, 수분의 증발, 온도차에 의한 결로 및 우수에 의한 체수 등으로 내후성강의 부동태 피막 형성에 해로운 영향을 미치고 있다. 이에 따라, 본 연구에서는 상수도 보호구역에 무도장 내후성 강으로 건설된 교량의 밀폐 형 박스거더 내부의 부식 특성을 분석하기 위하여, 육안에 의한 관찰, 셀로판 테이프 시험, 강재 두께 측정, 표면 부식 전위 측정, 채취한 녹의 전자현미경 분석 및 X선 회절 분석을 실시하였다. 분석을 통하여, 밀폐형 박스거더 내부에서 불안정녹층 이 관찰되었으며, 특히, 상부 및 하부 플랜지의 경우 우수에 의한 체수, 결로 및 제설제에 의한 영향 등으로 부식 정도가 심하게 관찰되었다. Weather proof steels are used for steel bridges due to its high corrosion resistance under atmospheric conditions. However, instead of forming stabilized rust layers, general rust occurs on weather proof steels under high humidity condition close to seawater or shady places. In Japan, therefore, they perform rust stabilization treatment instead of unpainted treatment due to severe atmospheric conditions. However, most of domestic weather proof steels were constructed unpainted in the form of closed box-girder, which makes the periodical repetition of dry and wet hard to occur. For the steel bridges constructed on the Han river, the evaporation of water, dew condensation due to temperature change, and stagnant water due to rain affect harmfully on the formation of passive film on weather proof steels. Thus, in this research, in order to analyze corrosion properties inside the closed box-girder for the unpainted weather proof steel bridge in the waterworks safety zone, multiple ways of analysis such as observation with eyes, cellophane-tape test, steel thickness measurement, surface corrosion potential measurement, electron microscope analysis, and X-ray diffraction analysis of the rust were performed. As a result, unstable rust layer was observed inside the closed box-girder, and severe corrosion was observed on the top and bottom of the flanges due to the effects of stagnant water caused by rain, dew condensation, and de-icing materials.

Effect of ultrasonic on morphology and hardness of Ni-P-Al₂O₃ electroless composite coatings

Seung-Hwan Ma,Young-Tai Noh,Young-Min Byoun 한국표면공학회 2017 한국표면공학회 학술발표회 초록집 Vol.2017 No.11

Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

( Seung-hwan Kwon ),( Shi-xun Ma ),( Yong-hyun Ko ),( Jee-yeon Seo ),( Bo-ram Lee ),( Taek Hwan Lee ),( Sun Yeou Kim ),( Seok-yong Lee ),( Choon-gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE₂ and LPS-mediated upregulation of iNOS and COX-2 expression in a dosedependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB- α, phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

Ni-Mn-B 삼원합금도금 가속수명 및 신뢰성 평가에 대한 연구

마승환(Ma, Seung-Hwan),노영태(Noh, Young-Tai),장건익(Jang, Gun-Ik) 한국산학기술학회 2015 한국산학기술학회논문지 Vol.16 No.5

강 제조 회사들은 연속주조금형의 표면을 보호하기 위해 Ni-B 또는 Ni-Co 합금 도금을 적용하고 있으며, 도금 층에 균열이 생기게 하는 황을 함유한 사카린 윤활제를 사용하고 있다. 균열 및 인장 응력을 유발하는 것은 Ni-S 화합물로 여겨진 다. Ni-Mn-B 삼원합금은 Ni-S 화합물이 형성되기 이전에 Mn-S 화합물을 형성하여 균열을 억제하기 위해서 개발되었으나, Ni-Mn-B 합금 도금에 관한 국내나 해외 기준이 없다. 그리하여 새로이 개발된 Ni-Mn-B 도금을 평가하기 위한 신뢰성 평가 기준을 개정하려한다. 가속수명시험을 개발하기 위해 FMEA(고장형태 영향분석)가 사용되어 도금의 주요 파괴 원인을 분석 하였다. Ni-Mn-B 신뢰성 기준은 가속수명시험 방법을 포함하였고, 기본 성능 시험과 환경시험, 가속수명시험으로 분류되었 으며, 80% 신뢰수준으로 B10수명 1 000시간을 보장하도록 고안되었다. Steel companies are applying Ni-B or Ni-Co alloy plating to protect the surface of Continuous casting mold, and they are using saccharin polish which causes crack on plating layer due to sulfur in saccharin. It is considered that the Ni-S compound causes the cracking and additional tensile stresses. The Ni-Mn-B ternary alloy plating was developed for suppression of crack by forming Mn-S compound before Ni-S compound is formed, but there were no domestic or international standard on the Ni-Mn-B alloy plating. Therefore, reliability evaluation standard was established to evaluate the newly developed Ni-Mn-B plating. To develop accelerating life testing method, FMEA(Failure Mode & Effective analysis) was used to analyze the cause of the main failure in plating. The Ni-Mn-B reliability standard included accelerating life test method, and it was categorized by the fundamental performance test, environment test, and accelerated life test, and was designed to guarantee 1 000 hours of B10 life with 80 % reliable level.