• Advances in nano research
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• v.12 no.3
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• pp.301-317
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• 2022

Many studies have shown that Mg-Nd-Zn-Zr (abbreviated as JDBM) alloy has good biocompatibility and biodegradability as well as promotion of cell adhesion, proliferation and differentiation, and Wnt/β-catenin signaling pathway may play a unique role in joint tissue by controlling the function of chondrocytes, osteoblasts and synoviocytes. However, it is not clear whether the JDBM alloy induces osteochondral repair through Wnt/β-catenin signaling pathway. This study aims to verify that JDBM alloy can repair osteochondral defects in rats, which is realized by Wnt/β-catenin signaling pathway. In this study, the osteochondral defect model of the right femoral condyle non-weight-bearing area in rats was established and randomly divided into three groups: Control group, JDBM alloy implantation group and JDBM alloy implantation combined with signaling pathway inhibitor drug ICRT3 injection. It was found that after JDBM alloy implantation, the bone volume fraction (BVF) became larger, the bone trabeculae were increased, the relative expression of osteogenesis gene Runx2, Bmp2, Opn, Ocn and chondrogenesis gene Collagen II, Aggrecan were increased, and the tissue repair was obvious by HE and Masson staining, which could be inhibited by ICRT3.

• Molecules and Cells
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• v.46 no.11
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• pp.675-687
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• 2023

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

• Herbal Formula Science
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• v.17 no.2
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• pp.151-162
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• 2009

Herba Artemisiae Capillaris is the dried bud of Artemisia capillaris Thunb, which has been used for expelling heat to loosen the bowels and normalizing gallbladder function to cure jaundice in traditional oriental medicines. In the present study, we evaluated the anti-inflammatory effects of the aqueous extracts of Herba Artemisiae Capillaris (HAC) in LPS-activated Raw 264.7 cells. Cells were treated with $1\;{\mu}g/ml$ of LPS 1 h before adding HAC extract. Cell viability was determined by MTT assay, and the relative level of NO was measured with Griess reagent. TNF-$\alpha$, IL-$1{\beta}$, and IL-6 cytokines were detected by ELISA. During the entire experimental period, all three doses of HAC extract (0.03, 0.10 and 0.30 mg/ml) had no significant cytotoxicity. LPS-activated cells showed increased NO levels and iNOS expressions compared to control. However, these increases were dramatically attenuated by treatment with HAC extract. Moreover, the inhibitory effects of HAC extract occurred in a dose-dependent manner. In addition, HAC extract reduced the translocation of $NF{\kappa}B$ into nuclear. HAC reduced production of IL-$1{\beta}$ and IL-6 by LPS, although it had no effects on TNF-$\alpha$. These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of $NF{\kappa}B$ activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Taken together, these results indicate that the aqueous extracts of Herba Artemisiae Capillaris warrant further development as an anti-inflammatory agent for the treatment of gram-negative bacterial infections.

• Journal of Life Science
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• v.24 no.1
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• pp.61-66
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• 2014

The purpose of this study was to investigate the immunomodulatory effects of Alpina officinarum (AO) ethanol extract on immunocompromised mice. The mice were injected intraperitoneally with an immunosuppressive drug, cyclophosphamide, and then administrated orally with 30, 100, and 300 mg/kg of ethanol extract of AO (AO 30, AO 100, and AO 300, respectively). The concentrations of cytokines and immunoglobulins (IgM, IgA, IgG) in serum were measured. The body weight of the mice and spleen cell number of the AO-fed group showed no significant difference compared to a control group. The concentrations of several cytokines, including IL-2, IFN-${\gamma}$, and TGF-${\beta}$, in serum showed a significant increase in the AO 100 group compared to the control and other groups (p<0.05). The IL-4 level showed no significant difference in the experimental groups. The supplementation of AO (30, 100, 300 mg/kg) significantly increased the concentration of IgM (p<0.05). The concentration of IgA was significantly increased in the AO 100 group (p<0.05) compared to the control group. It can be concluded that AO ethanol extract enhances immune function by promoting the production of cytokines and immunoglobulins.

• Journal of Embryo Transfer
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• v.18 no.3
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• pp.243-248
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• 2003

Sperrnatogenesis, the process by which the male germ-line stem cells(GSCs; type A spermatogonia) divide and differentiate to produce the mature spermatozoa, occurs in the seminiferous tubules of the testis. The GSCs proliferate actively to produce two types of cells: other GSCs and differentiating spermatogonia. GSCs have unipotentcy, devoted solely to the generation of sperm. The function of GSCs has broad implications for development, disease, and evolution. Spermatogenesis is fundamental for propagation of species and the defects of this system can result in infertility or disease. The ability to identify, isolate, culture, and alter GSCs will allow powerful new approaches in animal transgenesis and human gene therapy relating to infertility. Until recently, research on stem cells in the testis has been limited because of technical difficulties in isolating and identifying these cell populations. Here, we were trying to find out optimal conditions for in vitro culture of GSCs for identifying and isolating GSCs. We collected mouse GSCs from 3-days old mouse by two-step enzyme digestion method. GSCs were plated and grown on mouse embryonic fibroblasts in Dulbecco's modified Eagle's medium (DMEM) containing 15％ fatal bovine serum, 10 mM 2-mercaptoethanol, 1％ non-essential amino acids, 1 ng/$m\ell$ bFGF, 10 $\mu$M forskolin, 1500 U/$m\ell$ human recombinant leukemia inhibitory factor (LIF). Over a period 3∼5 days, GSCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells. After 5th passages, cells within the colonies continued to be alkaline phosphatase and Oct-4 positive and tested positive against a panel of two immunological markers(Integrin $\alpha$ 6 and Integrin $\beta$ 1) that have been recognized generally to characterize GSCs. SSEA-1, SSEA-3, and SSEA-4 also showed positive signals. Based on our data, these GSCs-derived cultures meet the criteria for GSCs itself and even other pluripotent stem cells. We reported here the establishment of in vitro cultures from mouse male GSCs.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.1
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• pp.1-8
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• 2005

This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.2
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• pp.89-100
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• 2009

SLE 등의 자가면역질환 병인론에 있어서 $CD4^+$ T 조력 림프구 (T helper cell)의 기능과 항상성 조절의 이상이 중요하다는 것은 알려진 사실이지만 $CD4^+$ T 조력 림프구 (T helper cell)의 발달과 기능에 대한 성호르몬의 정확한 역할에 대하여는 아직 확립되어 있지 않은 실정이다. 에스트로겐의 $CD4^+$ T 림프구에 대한 여러 방면의 작용에 대한 결과는 에스트로겐 매개 신호가 전달되는 정황에 매우 의존적이라고 할 수 있으며, 또한 에스트로겐이 B 림프구와 항원발현세포들 같이 T 림프구 기능을 변화시킬 수 있는 다른 분획 세포들의 기능에 대해서도 영향을 미칠 수 있다는 사실을 고려한다면, 에스트로겐이 $CD4^+$ T 림프구매개반응에 미치는 작용은 매우 복잡하다고 할 수 있다. 현재로선 이런 과정들과 관련된 에스트로겐의 정확한 기전에 대한 연구 성과는 현재로선 아직걸음마 단계에 지나지 않는다고 볼 수 있다. 일부 분자학적 표적들의 발견에도 불구하고 ER-$\alpha$와 ER-$\beta$, 또는 이런 표적들의 조절에 대한 유전자적 또는 비유전자적 경로의 상대적 역할에 대해서는 현재로선 알려진 바가 많지 않은 것 또한 사실이며, T 림프구 자체의 미세 환경과 ER 매개 전사반응에 영향을 미칠 수 있는 방법 역시 아직까진 알려진 바가 없다. 따라서 에스트로겐의 $CD4^+$ T 림프구에 대한 다각적 영향을 규명하는 데 있어 이런 경로들에 대한 보다 체계적이고 상세한 연구가 반드시 필요하다. 최근 골다공증의 병인에 있어 에스트로겐에 의한 TNF 및 RANK-RANKL계 억제에 대해 연구가 심도 있게 진행됨으로써 결과적으로 다른 시토카인과 면역세포들에 대한 영향이 간접적으로 규명되고 있는 점은 매우 고무적인 현상이라고 여겨진다. 이러한 연구들은 추후 에스트로겐의 면역 및 염증체계에 대한 특징적 작용을 규명하는데 있어서 밑거름이 될 수 있을 것이다. 나아가 호르몬 자체, 또는 SERM 같은 준호르몬제제들이 면역계에 미치는 영향을 분자학적으로 규명함으로써 향후 이러한 지식들이 또한 류마티스성 자가면역질환이나 만성염증성질환, 또는 전신성 감염질환에 있어 면역글로불린이나 기타 다른 기존 치료 약제들을 대체 보완할 수 있는 호르몬 치료로 이어질 수 있는 결정적인 단서를 제공할 수 있을 것이라 기대할 수 있을 것이다.

• Journal of Energy Engineering
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• v.5 no.1
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• pp.56-64
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• 1996

The objective of this investigation is to establish the rejection characteristics of caesium and cobalt from radioactive liquid waste by chemical/ultrafiltration process. An extensive experimental investigation was conducted with inactive caesium and cobalt ions, utilizing ultrafiltration stirred cell. Caesium and cobalt could be effectively removed from waste solution using copper ferrocyanide and polyarcylic acid(PAA). The rejection dependence of the caesium was found to be a function of caesiun to potassium copper ferrocyanide feed molar ratio. The binding behavior of caesium on K$_2$Cu$_3$(Fe(CN)$\sub$6/)$_2$, particles was explained in terms of a Langmuir adsorption isotherm. When Cs/K$_2$Cu$_3$(Fe(CN)$\sub$6/)$_2$molar ratio was 1.5, the removal of caesium was the most efficient. The rejection efficiency of cobalt is dependent upon various parameters such as pH, cobalt concentration and PAA concentration. The rejection behavior of cobalt was explained in term of a equilibrium model taking into account the reaction between the ligand group, the proton and the cobalt ion. At the conditions of PAA/Co ratio of 2 and pH of 5.6, the removal of cobalt was over 90%. Also, the effect of chemical addition sequence for the simultaneously removal of caesiun and cobalt was discussed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.684-691
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• 2008

As part of studies to develop new materials to lower blood glucose levels using crude polysaccharide, this study was attempted to analyze the characteristics of crude polysaccharide obtained from the extracts of a mixed herbal medium(OCM) where Trichloloma matsutake mycelium and Cordyceps militaris mycelium were cultured together and to look into the influence of administering these by concentration upon the blood glucose and serum lipid levels of rats with diabetes which was induced by STZ(Streptozotosin). Experimental group was divided into 6 groups: first, it was divided into normal control group(NC group) and diabetes-induced group, and diabetes-induced group was subdivided into diabetic control group(DC group), acarbose-treated group(PC group), 100 mg/kg/body weight-treated by crude polysaccharide of OCM(UE) group(UE100 group), 200 mg/kg/body weight-treated group(UE200 group), and 300 mg/kg/body weight-treated group(UE300 group). In diabetic-induced groups, after streptozotocin was melted in 0.01M citrate buffer at 50 mg/kg/body weight, when the non-fasting blood glucose level not on an empty stomach was 300 mg/dl or more in blood collected from the tail vein, it was regarded as diabetic induction and then such diabetic-induced experimental animals were used in this experiment. The yield of crude polysaccharide obtained from OCM was found to be 0.31% and the ${\beta}$-glucan content 39.40%. As a result of analyzing NO on immune function, which is known as major physiological activity of crude polysaccharide, high NO viability was shown; when 1 mg/ml LPS was treated at 1 ug/ml, it was found to be 50.77 uM, and when LPS was treated at 10 ug/m, it was found to be 53.78 uM. Also, regarding cancer cells, cell count was decreased by about 26% in proportion to sample concentration, while for normal cells, it was a little decreased in proportion to concentration, however, cell count was maintained in the range of $81.92{\sim}98.16%$ at all concentrations. In case of blood glucose level, it was decreased in all extract-treated groups compared to DC group and in the cases of ALT and AST, they were found to be lower in extract-treated groups compared to PC group and for serum lipid, it was found to be lower in UE100 group compared to PC group. Thus this study tried to utilize these results as fundamental data for development of preventive and therapeutic agents against diabetes as well as functional foods using the crude polysaccharide of mushrooms.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.776-784
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• 2014

Tuna cooking juice concentrate (TCJC) is by-produced during the canning processing of skipjack tuna Katsuwonus pelamis and it is well known that TCJC contains various nutritional components. Therefore, the immuno-stimulating activity of TCJC was investigated using macrophage RAW 264.7 cell line and the spleen cell isolated from BALB/c mice. The TCJC increased the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ in a dose-dependent manner compared to the control in RAW 264.7 cells without any toxicity. In particular, the production of TNF-${\alpha}$ was increased over 300-fold. The production of both Th1 cytokine (such as IFN-${\gamma}$, TNF-${\alpha}$, IL-2, and IL-12) and Th2 cytokine (IL-4, IL-6, IL-10) was also increased by TCJC treatment in splenocytes. Moreover, the TCJC increased the splenocyte proliferation in a concentration-dependent manner compared to control. These results indicate that TCJC may enhance immune function by promoting various cytokine production.