• Journal of Korean Medical classics
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• v.27 no.4
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• pp.15-20
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• 2014

Objectives : We search the contents about Bi disease in Huang Di Nei Jing(黃帝內經), to analyze the significance of Bi disease, etiopathogenisis and pathogenesis of Bi disease, treatment of Bi disease. Methods : We find that the key feature of Bi disease is joint pain induced by impatency of Qi and blood. Exterior and interior etiological factors are involved in, such as exogenous evil of cold and dampness, emotional disorders, intemperance of taking food, dysfunction of yingqi and weiqi, strong or weak constitution, etc. Results : The important pathogenesis are invaded by exogenous evil because of deficiency, disharmony of yingqi and weiqi and disharmony of five viscera. The key points of treatments are the individual concerned therapy and climate concerned therapy, selecting the acupoint according to the differentiation of symptoms and signs. Conclusions : The combined therapy should be used such as acupuncture and moxibustion, hot application of medicine, massage, Daoyin, outside apply, etc. These supply the theory foundation for etiological factor, pathogenesis, syndrome and treatment, and to direct the diagnosis and treatment of Bi disease later generations.

• Development and Reproduction
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• v.21 no.1
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• pp.1-10
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• 2017

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

• BMB Reports
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• v.47 no.3
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• pp.135-140
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• 2014

The mesenchymal stem cells (MSCs), which are derived from the mesoderm, are considered as a readily available source for tissue engineering. They have multipotent differentiation capacity and can be differentiated into various cell types. Many studies have demonstrated that the MSCs identified from amniotic membrane (AM-MSCs) and amniotic fluid (AF-MSCs) are shows advantages for many reasons, including the possibility of noninvasive isolation, multipotency, self-renewal, low immunogenicity, anti-inflammatory and nontumorigenicity properties, and minimal ethical problem. The AF-MSCs and AM-MSCs may be appropriate sources of mesenchymal stem cells for regenerative medicine, as an alternative to embryonic stem cells (ESCs). Recently, regenerative treatments such as tissue engineering and cell transplantation have shown potential in clinical applications for degenerative diseases. Therefore, amnion and MSCs derived from amnion can be applied to cell therapy in neuro-degeneration diseases. In this review, we will describe the potential of AM-MSCs and AF-MSCs, with particular focus on cures for neuronal degenerative diseases.

• Biomaterials Research
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• v.22 no.4
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• pp.311-318
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• 2018

Background: Tissue regeneration includes delivering specific types of cells or cell products to injured tissues or organs for restoration of tissue and organ function. Stem cell therapy has drawn considerable attention since transplantation of stem cells can overcome the limitations of autologous transplantation of patient's tissues; however, it is not perfect for treating diseases. To overcome the hurdles associated with stem cell therapy, tissue engineering techniques have been developed. Development of stem cell technology in combination with tissue engineering has opened new ways of producing engineered tissue substitutes. Several studies have shown that this combination of tissue engineering and stem cell technologies enhances cell viability, differentiation, and therapeutic efficacy of transplanted stem cells. Main body: Stem cells that can be used for tissue regeneration include mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. Transplantation of stem cells alone into injured tissues exhibited low therapeutic efficacy due to poor viability and diminished regenerative activity of transplanted cells. In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases. Conclusion: The combination of stem cell and tissue engineering techniques overcomes the limitations of stem cells in therapy of human diseases, and presents a new path toward regeneration of injured tissues.

• Genomics & Informatics
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• v.19 no.1
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• pp.2.1-2.10
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• 2021

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7671-7674
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• 2015

Background: Overexpression of HER2-neu has been reported in many epithelial malignancies, including cancers of the breast, ovaries, lungs, prostate, bladder, pancreas, colorectum and stomach as well as osteosarcomas. The aim of this study was evaluation of expression of HER2-neu immunohistochemistry (IHC) status and clinicopathologic features in a series of colonic adenocarcinomas. Materials and Methods: In this descriptive and analytical study, we surveyed 211 samples of colon adenocarcinoma from 182 patients (86.3%) undergoing total or partial colectomy and 29 (7.13%) with biopsies by colonoscopy. A sufficient sample size was obtained from all cases and the slides were stained with hematoxylin and eosin and also by IHC (HER2) staining. Results: The mean age for the patients at diagnosis was 57.9 years (range, 15-88 years). One hundred and twenty one patients (57.3%) were male. Of all patients, 201 samples (95.3%) were conventional adenocarcinomas (159, 29 and 13 cases were well, moderately and poorly differentiated, respectively) and 10 (4.7%) were mucinous type. Out of 211 cases, 171 were checked for lymph nodes metastasis and 64 were positive. There is a correlation between HER2 scores and differentiation, most score 3 cases being well differentiated (P<0.05). Conclusions: In patients with advanced colon cancer, surgery alone is not curative and other forms of therapy may be required to prolong patient survival. HER2 overexpression was found in some cases and this could be a guideline to new adjuvant therapy for these patients.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.42-49
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• 2020

As a preclinical study, many researchers have been attempted to convert the porcine PSCs into several differentiated cells with transplantation of the differentiated cells into the pigs. Here, we attempted to derive neuronal progenitor cells from pig embryonic germ cells (EGCs). As a result, neuronal progenitor cells could be derived directly from pig embryonic germ cells through the serum-free floating culture of EB-like aggregates (SFEB) method. Treating retinoic acid was more efficient for inducing neuronal lineages from EGCs rather than inhibiting SMAD signaling. The differentiated cells expressed neuronal markers such as PAX6, NESTIN, and SOX1 as determined by qRT-PCR and immunostaining. These data indicated that pig EGCs could provide valid models for human therapy. Finally, it is suggested that developing transgenic pig for disease models as well as differentiation methods will provide basic preclinical data for human regenerative medicine and lead to the success of stem cell therapy.

• Journal of Life Science
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• v.26 no.12
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• pp.1355-1359
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• 2016

Human bone marrow mesenchymal stem cells (hBM-MSCs) can differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Previous studies, including our own, have shown that MSCs can also differentiate into neuron-like cells. However, their rate of neuronal differentiation is not sufficient for application to stem cell therapy, which requires well-defined cell types. For this purpose, we first examined the expression of neuronal lineage markers (GFAP, MAP-2, KCNH1, Nestin, NF-M, and Tuj-1) by real-time PCR, western blot, and immunocytochemical staining. The expressions of the astrocyte marker GFAP and neuronal markers NF-M and Tuj-1 increased in neuronal differentiated MSCs (dMSCs). To improve the neuronal differentiation efficiency, PDE4, an important signaling intermediator in the progression of neuronal differentiation, was modulated using well-known inhibitors such as rolipram or resveratrol and then differentiated into neuronal cells (Roli- or RSV-dMSCs). The expressions of NF-M, Tuj-1 were increased while that of GFAP decreased in Roli- and RSV-dMSCs, which were examined by real-time PCR, western blot, and immunocytochemical staining. From these experiments, we have found that the neuronal differentiation efficiency can be ameliorated by the modulation of PDE4 activity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.459-466
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• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Korean Journal of Family Social Work
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• no.55
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• pp.91-128
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• 2017

The purpose of this study is to develop an effective intervention strategy for marriage migrant woman in family therapy. For this purpose, we collected counseling cases of professional counselors who successfully completed counseling and attempted the qualitative analysis of treatment intervention strategies and effects. The results of the study were obtained by dividing the meaning units in the immigrant woman's statements made during the counseling process composed of a total of 6 sessions. The counselors were analyzed to have tried the following intervention strategies. They attempted the following six strategies: Helping emotional differentiation by searching for unresolved emotional problems, dealing with undifferentiation due to family projection process and love triangle, dealing with multi-generational transfer process of the original family relationship patterns and coping mechanism, shedding lihgt on ineffectiveness of inconsistent communication due to emotional oppression applying a communication model of MRI, switching client's awareness through reorganization, suggesting a way of communication that leads to real self. Such counselors' attempts resulted in positive changes and treatment effects were found to include first, cognitive insights and motivation for change, second, improved communication skills and third, anxiety reduction and self-differentiation. Due to their husbands' refusal to participate in counseling, marriage migrant women often get involved in counseling alone, so they tend to worry that the effectiveness of family therapy may be low but it was found that the proper intervention of the counselor could improve the ability of the wife to resolve conflicts, which would be a great help in solving problems such as family violence and this study is meaningful in that it provided the appropriate therapeutic intervention strategies needed.