• Journal of Physiology & Pathology in Korean Medicine
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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.

• Journal of Veterinary Clinics
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• 제37권2호
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• pp.109-113
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• 2020

A 5-year-old female lion-head rabbit weighing 2 kg was brought to a local animal hospital with hematuria. Radiography showed a mass in the uterus, which was removed by ovariohysterectomy. Macroscopic examination showed several masses in both uterine horns. These masses, which invaded the deep uterine walls, were firm to the touch, and their cut surfaces were greyish-white in color. Histopathologically, these masses were nonencapsulated and were composed of spindle cells arranged in cellular, large interlacing bundles or streams. The tumor cells had elongate nuclei with prominent nucleoli, granular chromatin and eosinophilic cytoplasm. Moderate anisocytosis and anisokaryosis were observed. Severe and extensive inflammation and necrosis were present within the masses. Immunohistochemically, the neoplastic cells were positive for vimentin, desmin, and α-smooth muscle actin, but negative for cytokeratin. These uterine masses were diagnosed as leiomyosarcoma. To our knowledge, this is the first report of a uterine leiomyosarcoma in the rabbit in Korea.

• Journal of Gastric Cancer
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• 제17권3호
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• pp.277-281
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• 2017

Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report a case of asymptomatic gastric PAMT that was pathologically confirmed after surgical resection. The tumor had a multinodular plexiform growth pattern, bland-looking spindle cells, and an Alcian bluepositive myxoid stromal matrix rich in small blood vessels. Immunohistochemistry analysis revealed that the tumor cells of the PAMT were positive for smooth muscle actin (SMA) and negative for c-kit, CD34, S-100 protein, epithelial membrane antigen (EMA), and desmin. PAMT should be differentiated from other submucosal tumors of the stomach by immunohistochemical findings. Considering the benign features of this tumor, observation without resection may be an option for the treatment of PAMT if the tumor is asymptomatic.

• Journal of Pathology and Translational Medicine
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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.

• Annals of dermatology
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• 제30권6호
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• pp.712-715
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• 2018

Desmoplastic fibroblastoma is a rare fibrous tumor that usually presents as a painless, slow-growing mass in the subcutaneous tissues and skeletal muscles. It has a wide anatomic distribution, with the most common involvement being the arm and shoulder. Here, we report a case of a tiny painful desmoplastic fibroblastoma arising on the scalp. According to a microscopic examination, this tumor was composed of spindle-shaped fibroblasts in the dense collagenous stroma. On immunohistochemical staining, tumor cells were positive for vimentin and negative for smooth muscle actin, CD34, and S100. Our case is unique in that desmoplastic fibroblastoma developed on the scalp and there was presence of pain despite its small size.

• Biomedical Science Letters
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• 제24권4호
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• pp.341-348
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• 2018

The polyherbal drug Gyeongshingangjeehwan 18 (GGEx18) from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) has traditionally been used as an antiobesity drug in Korean local clinics. This study investigates the effects of GGEx18 on pancreatic fibroinflammation in high-fat diet (HFD)-fed obese C57BL/6J mice and the molecular mechanism involved in this process. After HFD-fed obese C57BL/6J mice were treated with GGEx18 (125, 250, and 500 mg/kg) for 12 weeks, variables and determinants of obesity, pancreatic inflammation, and fibrosis were measured using histology, immunohistochemistry, and real-time polymerase chain reaction. Administration of GGEx18 at 500 mg/kg/day to obese mice decreased body weight gain, mesenteric adipose tissue mass, and adipocyte size. GGEx18 treatment not only reduced mast cells and CD68-immunoreactive cells, but also decreased collagen levels and ${\alpha}$-smooth muscle actin-positive cells in the pancreas of HFD-fed mice. Concomitantly, GGEx18 decreased the expression of genes for inflammation (i.e., CD68 and tumor necrosis factor ${\alpha}$) and fibrosis (i.e., collagen ${\alpha}1$ and transforming growth factor ${\beta}$) in the pancreas of obese mice. These results suggest that GGEx18 may inhibit visceral obesity and related pancreatic fibroinflammation in HFD-fed obese mice.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.209-220
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• 2023

This study is to determine the regulation of nitric oxide synthase 3 (NOS3) by edaravone in mice with hypoxic pulmonary hypertension (HPH). C57BL/6J mice were reared in a hypoxic chamber. HPH mice were treated with edaravone or edaravone + L-NMMA (a NOS inhibitor). Lung tissue was collected for histological assessment, apoptosis analysis, and detection of malondialdehyde, superoxide dismutase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and NOS3. The levels of serum TNF-α and IL-6 were also measured. Immunohistochemistry was used to visualize the expression of α-smooth muscle actin (SMA) in pulmonary arterioles. Edaravone treatment improved hemodynamics, inhibited right ventricular hypertrophy, increased NOS3 expression, and reduced pathological changes, pulmonary artery wall thickness, apoptotic pulmonary cells, oxidative stress, and the expression of TNF-α, IL-6, and α-SMA in HPH mice. L-NMMA treatment counteracted the lung protective effects of edaravone. In conclusion, edaravone might reduce lung damage in HPH mice by increasing the expression of NOS3.

• BMB Reports
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• 제57권2호
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• pp.116-121
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• 2024

We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease.

• BMB Reports
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• 제57권3호
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• pp.143-148
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• 2024

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

• Journal of Convergence for Information Technology
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• 제10권10호
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• pp.143-149
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• 2020

This study tried to observe the ability to inhibit vasocontriction in phloretin - the primary ingredient of apple tree leaves and the Manchurian apricot - through ROCK(Rho-associdated, coiled-coil containing protein kinase) inactivation in rat aortae. A piece of artery that was separated from Sprague-Dawley male rats and retained or damaged the endothelium was suspended in myograph tank with two metal rings, the lower ring fixed to the bottom of the tank, and the upper ring connected to the isotonic force transducer. Interestingly, phloretin inhibited fluoride- or phorbol ester-provoked contraction implying that additional pathways dissimilar from endothelial nitric oxide synthesis such as ROCK or MEK (mitogen activated protein kinase kinase) inactivation might be involved in the vasorelaxation. Therefore, this study provides that phloretin participates in the reduction of ROCK or MEK activity in smooth muscle in addition to the endothelial-dependent action of the endotheliuim in complete blood vessels, and consequently inhibits actin-myosin interaction in smooth muscle. Furthermore, phloretin inhibited thromboxane A2-induced contraction suggesting the mechanism including inhibition of ROCK and MEK.