• Molecules and Cells
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• v.24 no.3
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• pp.431-436
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• 2007

Stem cell-based therapy is being considered as an alternative treatment for cardiomyopathy. Hence understanding the basic molecular mechanisms of cardiomyocyte differentiation is important. Besides BMP or Wnt family proteins, $TGF-{\beta}$ family members are thought to play a role in cardiac development and differentiation. Although $TGF-{\beta}$ has been reported to induce cardiac differentiation in embryonic stem cells, the differential role of $TGF-{\beta}$ isoforms has not been elucidated. In this study, employing the DMSO-induced cardiomyocyte differentiation system using P19CL6 mouse embryonic teratocarcinoma stem cells, we investigated the $TGF-{\beta}$-induced signaling pathway in cardiomyocyte differentiation. $TGF-{\beta}1$, but not the other two isoforms of $TGF-{\beta}$, was induced at the mRNA and protein level at an early stage of differentiation, and Smad2 phosphorylation increased in parallel with $TGF-{\beta}1$ induction. Inhibition of $TGF-{\beta}1$ activity with $TGF-{\beta}1$-specific neutralizing antibody reduced cell cycle arrest as well as expression of the CDK inhibitor $p21^{WAF1}$. The antibody also inhibited induction of the cardiac transcription factor Nkx2.5. Taken together, these results suggest that $TGF-{\beta}1$ is involved in cardiomyocyte differentiation by regulating cell cycle progression and cardiac gene expression in an autocrine or paracrine manner.

• Herbal Formula Science
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• v.12 no.2
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• pp.163-173
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• 2004

Chelidonii Herba (CHE, Baek-gul-chae in Korean), which has its original description in Gu-Hwang-Bon-Cho, a classic book of oriental Herbal book, is widely used in the treatment of stomach cancer, jaundice, gasrtic ulcer, edema and stomach pain, in Korea, Japan and China. The present study was conducted to evaluate the effect of CHE on the nitric oxide (NO) production, iNOS and COX-2 expression in lipopolysaccharide - activated Raw 264.7 cells. After the treatment of CHE, NO production was monitored by measuring the nitrite content in culture medium, cell viability was measured by MIT assay. COX-2 and iNOS were determined by lmmunoblot analysis. The production of nitric oxide was significantly inhibited by pretreatment (1h) with CHE (0.1-0.3 mg／ml) on LPS-activated Raw264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein were up-regulated by LPS, but the increased levels of iNOS and COX-2 were inhibited by pretreatment of CHE (0.1-0.3 mg／ml), respectively. Thus, the present data suggest that CHE may play an important role in adjunctive therapy in Gram-negative bacterial infections.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.386-398
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• 2020

Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.321-329
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• 2007

The present study was conducted to evaluate the effect of Yongdamsagantang (YST) on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in RAW 264.7 cells. After the treatment of YST water extract, cell viability was measured by MTT assay, and NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) and phospholylation of inhibitor of nuclear factor kappa B alpha ($p-I{\kappa}B{\alpha}$) were determined by Immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidences that YST inhibited the production of NO. iNOS, and interleukin-6, and the activation of $p-I{\kappa}B{\alpha}$ in RAW 264.7 cells activated with lipopolysaccharide. These findings showed that YST could have some anti-inflammatory effects which might play a role in therapy in Gram-negative bacterial infections.

• Toxicological Research
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• v.31 no.1
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• pp.33-40
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• 2015

Bee venom (BV) has long been used in traditional Eastern and Western medicine for chronic inflammation, pain and skin therapy. Human exposure to BV, however, often causes unwanted adverse effects and is even fatal in some cases. Phospholipase $A_2$ ($PLA_2$) of BV is now suspected to play a key role in these adverse effects. We investigated the potential use of $PLA_2$-free bee venom (PBV) as a replacement for BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration exhibits a superior profile in comparison with regular BV, by inhibiting elastase activity and suppressing the induction of nitric oxide (NO) and metalloproteinase-9 (MMP-9), while retaining the effects of cell proliferation and protection against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV thus appears to be more promising than BV as a cosmetic ingredient with a reduced potential for adverse reactions in the recipient.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Molecules and Cells
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• v.42 no.6
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• pp.448-459
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• 2019

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is a promising target for gastric cancer (GC) treatment; however the efficacy of PI3K/mTOR dual inhibitors in GC has not yet been maximized. Additionally, the effect of autophagy regulation by PI3K/mTOR dual inhibitors has not been clearly elucidated in GC treatment. We aimed to show that our newly developed PI3K/mTOR dual inhibitor, CMG002, when combined with an autophagy inhibitor, chloroquine (CQ), potently induces effective cancer cell death in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells, where both the PI3K/AKT/mTOR and autophagy pathways play important roles in disease pathogenesis. EBV- and mock-infected AGS and NUGC3 GC cell lines were treated with CMG002 +/- CQ. PI3K/AKT/mTOR signaling pathway mediators, cellular apoptosis and autophagy markers were confirmed by Western blot assay. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. CMG002 effectively blocked the PI3K/AKT/mTOR pathway by markedly decreasing phosphorylation of AKT and its downstream mediator S6. CMG002 induced G0/G1 cell cycle arrest and enhanced apoptotic cell death in AGS and NUGC3 cells, particularly EBV-infected cells compared with mock-infected cells, as confirmed by flow cytometric analyses and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays. The combination of CMG002 plus CQ synergistically increased apoptotic cell death in EBV-infected GC cell lines when compared with CMG002 alone (P < 0.05). Our results suggest that the new PI3K/mTOR dual inhibitor, CMG002, when used in combination with the autophagy inhibitor, CQ, provides enhanced therapeutic efficacy against EBVaGC.

• Korean Journal of Play Therapy
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• v.21 no.4
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• pp.427-448
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• 2018

The study examined the mediated-moderation effect of parental reflection levels from maternal childhood experiences by the parents to mother's reaction to negative emotions of their preschoolers by examining it through the lens of parental role satisfaction. The participants in this study were 327 mothers who and their infants aged 3-6 years. They completed questionnaires on the maternal childhood experiences scale, parental reflection scale, parental role satisfaction scale and mother's reaction to negative emotions of their preschoolers scale. The results of the structural equation model analysis are as follows. First, a mediating model revealed that the relationship between maternal childhood experiences by parents and mother's reactions to negative emotions of their preschoolers was mediated by parental role satisfaction. Second, the results revealed the moderation effect of parents reflection levels on the relationship between maternal childhood experiences by parents and parental role satisfaction. Finally, parental reflection levels were also seen to have a mediated moderation effect of parental reflection level from maternal childhood experiences to mother's reaction to negative emotions of their preschoolers through parental role satisfaction. These results indicate the importance of parental reflection and parental role satisfaction.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.161-166
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• 2014

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

• Herbal Formula Science
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• v.13 no.1
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• pp.145-159
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• 2005

Objective : Juglandis Semen has a function that to invigorate the lung and kidney. And It is commonly used as a supporting agent in the treatment of coughing and bronchitis. This study was performed to investigate the effect of oral administration of Juglandis Semen Extract (JSE) against the experimental asthma induced by ovalbumin. Methods : Asthma was induced to Balb/c mouse by i.p. injection and aerosol immunization with ovalbumin. It was observed the change of the cell number in the BAL fluid. Concentrations of IL-4, IL-5 in splenoc yte were assessed by ELISA, IgG and IgE from serum were calculated by same method. Results : 1. Number of macrophage in BAL fluid was significantly decreased in JSE group compared with control group, but not eosinophil and lymphocyte. 2. Levels of IgG and IgE in serum were significantly decreased in JSE group compared with control group, respectively. 3. Concentration of IL-4 in culture supernatant of splenocyte was significantly decreased in JSE group compared with control group, but there was no significant in IL-5. Conclusion : We found that the effect of JSE extract in asthma was implicated in reduction of IL4released from Th2 cell, and decreases of IgG and IgE from plasma cell. These findings suggest that JSE can produce anti-asthmatic effect, which may play a role in allergen-induced asthma therapy.