• The Journal of Korean Physical Therapy
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• 제20권3호
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• pp.61-68
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• 2008

Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.

• Childhood Kidney Diseases
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• 제22권1호
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• pp.1-6
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• 2018

Rituximab (RTX) is a chimeric monoclonal antibody that inhibits CD20-mediated B-cell proliferation and differentiation. Several studies have examined its use in intractable nephrotic syndrome (NS) with some positive results. However, those studies examined such effects for a short-term period of 1 year, and some patients continued to relapse after a lapse in RTX treatment. Our use of RTX as a maintenance therapy (RTX injection when the CD19 cell count exceeded $100-200/{\mu}L$ before relapse) showed some noticeable efficacy. We used RTX in 19 patients with steroid-dependent NS (SDNS). In 12 patients treated with RTX maintenance therapy, only one relapse occurred. The mean treatment period was $23.4{\pm}12.7months$, and the mean number of RTX administrations was $3.9{\pm}1.6$. The relapse rates were decreased (from 2.68/year to 0.04/year), and the drug-free period also increased (from 22.5 days/year to 357.1 days/year) during maintenance therapy. The other seven patients were treated with one cycle of RTX or additional cycles in case of relapse (non-maintenance therapy). Relapse rates were significantly decreased after RTX treatment (from 1.76/year to 0.96/year, P=0.017). The relapse-free period was $15.55{\pm}7.38$ (range, 5.3-30.7) months. No severe side effects of RTX were found except for a hypersensitivity reaction such as fever and chills during its infusion. In conclusion, RTX is considered an effective and safe option to reduce the relapse rate by a single- or maintenance-interval therapy in SDNS.

• The Journal of Korean Physical Therapy
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• 제26권2호
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• pp.56-61
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• 2014

Purpose: The aim of this study was to investigate relationship between the angle of the first metatarsophalangeal joint (1st MPJ) and the dimensions of the abductor hallucis; dorso-plantar (DP) thickness, medio-lateral (ML) width, and cross-sectional area (CSA), in subjects with and without hallux valgus. Methods: Sixty feet, mean (SD) age of 22.5 (2.1) years old, were included in this study (hallux valgus = 30; control = 30). An X-ray device was used for measurement of the angle of the 1st MPJ, and an ultrasound system was used for determination of mean (SD) DP thickness, ML width, and CSA of the abductor hallucis muscle in each foot from three trials. Results: The results showed the DP thickness, ML width, and CSA of the abductor hallucis did not differ significantly between subjects with and without hallux valgus. In addition, the correlations between the angle of the 1st MPJ and DP thickness, ML width, and CSA of the abductor hallucis showed poor correlation (Pearson r=-0.09, -0.20, and -0.18, respectively). Conclusion: Based on these findings, we speculate that morphological changes to the abductor hallucis muscle cannot be representative of the angle of the 1st MPJ, and also cannot be used in differentiation between subjects with and without hallux valgus.

• 대한한의학원전학회지
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• 제27권4호
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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.

• 한국발생생물학회지:발생과생식
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• 제21권1호
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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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• 제47권3호
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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.

• 생체재료학회지
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• 제22권4호
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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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• 제19권1호
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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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• 제16권17호
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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.

• 한국동물생명공학회지
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• 제35권1호
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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.