• 동의생리병리학회지
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• 제22권2호
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• pp.315-320
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• 2008

This study investigated the signaling mechanisms contributed to the vasodilatory effects of HMC05, a herbal prescription. HMC05 acted in an endothelium-independent manner. To elucidate the fundamental mechanisms of its vascular actions, we focused on the signaling molecules involved in actin-myosin filament regulation including 20 kDa myosin light chains (LC20), Rho-associated kinase (ROCK), PKC, JNK and extracellular signal-regulated protein kinase (ERK) in the endothelium-denuded thoracic aorta or isolated smooth muscle cells (SMCs). It lowered the phosphorylation level of LC20 and showed that ROCK, ERK, JNK and $PKC{\alpha}$ pathways played important roles in the effects, as confirmed by the observations with a specific inhibition or activation, and with the activity and the subcellular localization of these molecules. In particular, HMC05 dramatically inhibited the activity of ERK and the downstream signaling of ROCK. It also changed the subcellular localization of the phophorylated $PKC{\alpha}$ as well as the amount of phosphorylation. Taken together, these data indicate that the vascular relaxation effects of HMC05 are attributed to the regulation of these signaling mechanisms.

• 대한병리학회지
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• 제52권6호
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• pp.416-419
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• 2018

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-${\alpha}$, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, ${\alpha}$-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.

• Journal of Microbiology and Biotechnology
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• 제13권6호
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• pp.841-845
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• 2003

In order for engineered tissues to find clinical utility, the engineered tissues must function appropriately. However, smooth muscle (SM) tissues engineered in vitro with a conventional tissue engineering technique may not exhibit contractile functions, because smooth muscle cells (SMCs) cultured in vitro typically revert from a contractile, differentiated phenotype to a synthetic, nondifferentiated phenotype and lose their ability to contract. SMCs in vivo typically reside in mechanically dynamic environments. We hypothesized that cyclic mechanical stretch induces the features of SMCs in in vitro engineered tissues to be similar to those of SMCs in native tissues. To test the hypothesis, aortic SMCs were seeded onto elastic, three-dimensional scaffolds and cultured in vitro under a cyclic mechanical stretching condition for 4 weeks. A significant cell alignment in a direction parallel to the cyclic stretching direction was found in the SM tissues exposed to cyclic stretching. The cellular alignment and alignment direction were consistent with those of native vascular SM tissues, in which SMCs in vivo align in the radial direction (parallel to stretching direction). In control tissues (SM tissues engineered without stretching), cells randomly aligned. The expression of SM ${\alpha}-actin$ and SM myosin heavy chain, phenotypic markers of SMCs in a contractile state, was upregulated in the stretched tissues by 2.5- and 2.0-fold, respectively, compared to SMCs in the control tissues. The cellular features of alignment and contractile phenotype of SMCs in the SM tissues engineered under a mechanically dynamic environment could allow the engineered SM tissues to exhibit contractile functions.

• Molecules and Cells
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• 제23권2호
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• pp.175-181
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• 2007

The present study was undertaken to determine whether $SM22{\alpha}$ participates in the regulation of vascular smooth muscle contractility using $SM22{\alpha}$ knockout mice and, if so, to investigate the mechanisms involved. Aortic ring preparations were mounted and equilibrated in organ baths for 60 min before observing contractile responses to 50 mM KCl, and then exposed to contractile agents such as phenylephrine and phorbol ester. Measurement of isometric contractions using a computerized data acquisition system was combined with molecular or cellular experiments. Interestingly, the aortas from $SM22{\alpha}$-deficient mice ($SM22^{-/-LacZ}$) displayed an almost three-fold increase in the level of $SM22{\beta}$ protein compared to wild-type mice, but no change in the levels of caldesmon, actin, desmin or calponin. $Ca^{2+}$-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the $SM22{\alpha}$-deficient mice, whereas in the presence of $Ca^{2+}$ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCl was significantly affected. A decrease in phosphorylation of extracellular signal regulated kinase (ERK) 1/2 was observed in the $SM22{\alpha}$-deficient mice and this may be related to the decreased vascular contractility. Taken together, this study provides evidence for a pivotal role of $SM22{\alpha}$ in the regulation of $Ca^{2+}$-independent vascular contractility.

• Archives of Pharmacal Research
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• 제27권12호
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• pp.1238-1244
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• 2004

The suppressive effects of Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae), on the progress of acute carbon tetrachloride $(CCl_4)$-induced hepatic fibrosis were investigated in the rat. CK significantly suppressed $(CCl_4)$-induced hepatic necrosis and inflammation, as determined by the serum enzymatic activities of alanine and aspartate aminotransferase and serum tumor necrosis factor-${\alpha}$ levels, in dose-dependent manners. In addition, the increased hepatic fibrosis after acute $(CCl_4)$ treatment was suppressed by the administration of CK. CK also significantly prevented the elevation of hepatic ${\alpha}$ 1(I) procollagen (type I collagen) mRNA and ${\alpha}$ -smooth muscle actin (${\alpha}$ -SMA) expressions in the liver of $(CCl_4)$-intoxicated rats and also suppressed the induction of ${\alpha}$ -SMA and type I collagen in cultured hepatic stellate cells, in dose-dependent manners. These results suggest that the suppressive effects of CK against the progress of acute $(CCl_4)$-induced hepatic fibrosis possibly involve mechanisms related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.

• The Journal of Korean Physical Therapy
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• 제27권3호
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• pp.140-146
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• 2015

Purpose: To determine the effects of 630 nm light emitting diode (LED) on full-thickness wound healing. Methods: Twelve male Sprague-Dawley rats were randomly divided into LED (n=6) and control group (n=6). Two $19.63mm^2$ wounds were created on the mid dorsum. LED group received a 630 nm LED irradiation with $3.67mW/cm^2$ for 30 minutes ($6.60J/cm^2$) for 7 days, while control group received sham LED irradiation. Epithelial gap, collagen density, ${\alpha}$-SMA fibroblast and PCNA keratinocyte were measured on histochemical and immunohistochemical staining using image analysis system. An independent t-test was conducted to compare the difference between groups. Results: The wound closure rate, collagen density, ${\alpha}$-SMA fibroblast number, epithelial gap and PCNA keratinocyte number have shown no significant difference between LED and control group at day 3 after the treatment. At day 7 after the treatment, the wound closure rate in LED group was increased when compared with control group (p<0.05). The collagen density (p<0.05) and ${\alpha}$-SMA immunoreactive fibroblast number (p<0.001) were increased when compared with control group at day 7. The epithelial gap in LED group was significantly shorten than control group at day 7 (p<0.01). The PCNA positive cell number in LED group was higher than control group at day 7 (p<0.01). Conclusion: 630 nm LED with $3.67mW/cm^2$, $6.60J/cm^2$ accelerate collagen deposition by stimulating fibroblasts, and enhance wound contraction by differentiating myofibroblasts in the dermis, and accelerate keratinocyte proliferation by facilitating DNA synthesis in the epidermis. It may promote the healing process in proliferation stage of wound healing.

• 대한임상검사과학회지
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• 제44권4호
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• pp.229-238
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• 2012

Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

• Nutrition Research and Practice
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• 제4권5호
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• pp.369-374
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• 2010

Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by ${\alpha}$-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.

• 한국임상수의학회지
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• 제33권1호
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• pp.43-47
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• 2016

A 7-year-old castrated male Schnauzer was presented with melena and inappetence. Laboratory examination revealed mild anemia. Abdominal ultrasonography showed abnormal enlargement of intestinal segment and a oval mass with soft tissue density. After surgical resection of the enlarged intestine including the mass, histopathologic examination showed that the mass was tentatively diagnosed as synchronous occurrence of gland cell- and mesenchymal cell-origin tumors. Subsequently, immunohistochemistry showed positivity to cytokeratin AE1/AE3 in the gland cells and positivity to ${\alpha}-smooth$ muscle-specific actin, but negative expression of c-Kit, suggesting the co-existence of adenocarcinoma and leiomyosarcoma. Follow-up examination after 3-year of the surgery confirmed that the dog remained healthy and did not show recurrence of the tumors.

• Asian-Australasian Journal of Animal Sciences
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• 제31권3호
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• pp.439-448
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• 2018

Objective: Myogenic satellite cells were isolated from semitendinosus muscle of prepubertal Korean black goat to observe the differential effect of linolenic and retinoic acid in thepresence of thiazolidinediones (TZD) and also to observe the production insulin sensitive preadipocyte. Methods: Cells were characterized for their stemness with cluster of differentiation 34 (CD34), CD13, CD106, CD44, Vimentin surface markers using flow cytometry. Cells characterized themselves as possessing significant (p<0.05) levels of CD13, CD34, CD106, Vimentin revealing their stemness potential. Goat myogenic satellite cells also exhibited CD44, indicating that they possessed a % of stemness factors of adipose lineage apart from their inherent stemness of paxillin factors 3/7. Results: Cells during proliferation stayed absolutely and firmly within the myogenic fate without any external cues and continued to show a significant (p<0.05) fusion index % to express myogenic differentiation, myosin heavy chain, and smooth muscle actin in 2% horse serum. However, confluent myogenic satellite cells were the ones easily turning into adipogenic lineage. Intriguingly, upregulation in adipose specific genetic markers such as peroxisome proliferation-activated receptor ${\gamma}$, adiponectin, lipoprotein lipase, and CCAAT/enhancer binding protein ${\alpha}$ were observed and confirmed in all given treatments. However, the amount of adipogenesis was found to be statistically significant (p<0.01) with linolenic acid as compared to retinoic acid in combination with TZD's. Conclusion: Retinoic acid was found to produce smaller preadipocytes which have been assumed to have insulin sensitization and hence retinoic acid could be used as a potential agent to sensitize tissues to insulin in combination with TZD's to treat diabetic conditions in humans and animals in future.