• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.386-395
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• 2010

Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.

• BMB Reports
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• v.50 no.5
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• pp.263-268
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• 2017

${\beta}$-Agarase cleaves the ${\beta}$-1,4 linkages of agar to produce neoagarooligosaccharides (NAO), which are associated with various physiological functions. However, the immunological functions of NAO are still unclear. In this study, we demonstrated that ${\beta}$-agarase DagA-produced neoagarohexaose (DP6), an NAO product, promoted the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4). DP6 directly and indirectly enhanced the activation of natural killer (NK) cells in a TLR4-dependent manner in vitro and in vivo. Finally, the antitumor activity of DP6 against B16F1 melanoma cells was inhibited in NK cell-depletion systems by using NK-cell depleting antibodies in vivo. Collectively, the results indicated that DP6 augments antitumor immunity against B16F1 melanoma cells via the activation of DC-mediated NK cells in a TLR4-dependent manner. Thus, DP6 is a potential candidate adjuvant that acts as an immune cell modulator for the treatment of melanoma.

• The Korean Journal of Food & Health Convergence
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• v.5 no.2
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• pp.27-34
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• 2019

RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

• Journal of Life Science
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• v.21 no.2
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• pp.286-291
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• 2011

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

• CELLMED
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• v.13 no.2
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• pp.2.1-2.9
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• 2023

CPS219, a new concept compound composed of coffee (CO), Pueraria Tomsonii flower (PF), and Sambou bamboo salt^TM (BS), was developed as a coffee beverage to alleviate menopausal symptoms. The purpose of this study is to evaluate the anti-oxidant and menopausal alleviating effects of CPS219 combined as the optimal ratio of each component selected through sensory evaluation and blind consumer test. For CPS219, the optimal ratio of CO, PF, and BS was determined to be 1:0.1:0.017 through various sensory evaluations and blind consumer tests. CPS219 significantly enhanced the superoxide dismutase-like activity compared to the CO or CO plus PF (CP). The proliferation of MCF-7 cells was considerably increased after 24 hours by treatment with CO, CP, or CPS219, but only CPS219 significantly boosted the proliferation of MCF-7 cells after 48 hours. Moreover, CPS219 had an estrogen-like effect by dramatically increasing the expression of estrogen receptor-β mRNA in MCF-7 cells but not CO and CP. Treatment of MCF-7 cells with CO, CP, or CPS219 did not cause any cytotoxicity. In conclusion, these findings imply that anti-oxidant and estrogen-like properties of CPS219 can be used to prevent and cure postmenopausal symptoms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1647-1655
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• 2005

Gamimahaenggamsuk-tang (GMHGST) is used for treatment of inflammatory diseases including rheumatoid arthritis (RA). Here, regulatory activity of GMHGST on RA-mediated inflammatory responses was investigated in cultured human fiDroblast-like synoviocytes (FLS), Levels of mRNAs encoding for inflammatory cytokines such as $IL-1{\beta}$, IL-6 and IL-8 and NOS-II enzyme, which had been induced by $TNF-{\alpha}$ and $IL-1{\beta}$ cotreatment, were decreased to the similar levels as those in cells treated with anti-inflammatory agent MTX. mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases (TIMPs) as well as intercellular adhesion molecule (ICAM) were also downregulated by increasing doses of GMHGST in activated FLS. Moreover, GMHGST appeared to protect cells by decreasing NO levels, and inhibited cell proliferation which had been induced by inflammatory stimulation by $TNF-{\alpha}$ and IL-1. These results suggest that GMHGST is effective as an inhibitory agent for regulating inflammatory responses in activated FLS.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.2
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• Journal of Physiology & Pathology in Korean Medicine
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• v.37 no.2
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• pp.36-44
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• 2023

Essential oils and aromatherapy have traditionally been used for the treatment of anxiety and depression with few side effects. This study aimed to investigate the effects of essential oils from six herbal prescriptions known to be effective in treating anxiety and depression in Korean medicine. The neuroprotective and anti-neuroinflammatory effects of six essential oils, including Gamisachil-tang (GMSCT), Guibi-tang (GBT), Sihogayonggolmoryeo-tang (SYM), Danchisoyosan (DCSYS), Sihosogansan (SHSGS), and Soyosan (SYS), were examined in PC12 and BV2 cells. In corticosterone (CORT)-stimulated PC12 cells, all six essential oils ameliorated the CORT-induced decrease in cell viability at a concentration of 10 ㎍/ml. GMSCT, GBT, and SHSGS recovered CORT-induced cytotoxicity at concentrations of 1 ㎍/ml and 10 ㎍/ml. In lipopolysaccharide (LPS)-stimulated BV2 cells, GBT (10 ㎍/ml) decreased interleukin (IL)-1β production, whereas SHSGS (1 ㎍/ml) inhibited tumor necrosis factor (TNF)-α production. In the MK-801-induced anxiety in zebrafish, electroencephalogram (EEG) assessment indicated that GMSCT and SHSGS induced recovery in the delta and beta power densities and reduced theta/beta and delta/beta ratios. DCSYS and SYS decreased theta power density and theta/beta ratio, whereas GBT and SYM showed no effects on EEG signals. In the tail suspension test (TST) in mice, GBT, DCSYS, SHSGS, and SYS exhibited antidepressant-like effects by decreasing immobility time. These results suggest that the essential oils from the six herbal prescriptions, except SYM, may have beneficial effects on anxiety and/or depression. Further studies should be conducted to investigate the molecular signaling pathways that mediate the effects of these essential oils on anxiety and depression.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.4
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• pp.308-313
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• 2011

Purpose: Beta-tricalcium phosphate (${\beta}$-TCP) is a synthetic calcium phosphate ceramic that has widely been used as a bone material to repair bone defects. Despite many clinical studies, the molecular mechanism whereby this biomaterial alters the gene expression in osteoblasts to promote bone formation is poorly understood. Thus, we attempted to address this question by using microarray techniques to identify the genes that are differentially regulated in osteoblasts exposed to ${\beta}$-TCP. Methods: By using DNA microarrays, we identified several genes whose expression levels were significantly up- or down-regulated in osteoblast-likeMG-63cells cultured with ${\beta}$-TCP at a concentration of 100 mg/10 ml for 24 hours. Results: The differentially expressed genes covered a broad range of functional activities: signal transduction, transcription, cell cycle regulation, vesicular transport, apoptosis, immunity, cytoskeletal elements and cell proliferation and differentiation. Conclusion: The gene expression changes related to cell proliferation and differentiation, vesicle transport, immunity and defense could affect the osteogenic activities of osteoblasts for bone regeneration. However, further studies will be required to verify the relative importance of these genes in bone formation, their temporal and spatial expression patterns and their interactions with each other.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.1
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• pp.23-35
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• 2009

Objectives The purpose of this study is to investigate the effect of Kakamsodokum (KKSDU) on atopic dermatitis in an in-vitro experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the condition in humans. Methods We evaluated $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$, IL-10 mRNA, CD4+/$IFN-{\gamma}+$, and CD4+CD25+foxp3+ in B and T cells of NC/Nga atopic dermatitis mouse by real-time PCR and intracellular staining in vitro. Results KKSDU medicines supressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$ mRNA and increased IL-10 mRNA in B cells. CD4+/$IFN-{\gamma}+$ and CD4+CD25+foxp3+ in T cells were increased by KKSDU. Conclusions KKSDU on atopic dermatitis might be very effective to the atopic dermatitis treatment.