• 대한한방부인과학회지
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• 제26권1호
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• pp.59-68
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• 2013

Objectives: This study was conducted to investigate the acute toxicity of Pyungwi-san(Pingwei-san in Chinese) in ICR mice, according to KFDA and OECD guideline. Methods: In the present study, 15 male and female ICR mice administrated singly by gavage at dose levels of 0 and 2000 mg/kg of Pyungwi-san. During the experimental period, no treatment-related death was observed. There were no adverse effects on clinical signs, body weight, and gross findings at all treatment groups. Results: These results showed that the single oral adminstration of Pyungwi-san (Pingwei-san) did not cause any toxic effect at the dose levels of 2000 mg/kg in rats. Conclusions: Taken together, the median lethal dose($LD_{50}$) of Pyungwi-san (Pingwei-san) was considered to be over 2000 mg/kg body for both sexes.

• Journal of Korean Neurosurgical Society
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• 제44권4호
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• pp.185-189
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• 2008

Objective : The authors present their experiences with stereotactic multiplanar reformatted (MPR) computed tomography (CT)-guided catheter placement for thrombolysis of spontaneous intracerebral hematoma (sICH) and their clinical results. Methods : In 23 patients with sICH, MPR CT-guided catheter placement was used to select the trajectory and target point of hematoma drainage. This group was comprised of 11 men and 12 women, and the mean age was 57.5 years (range, 31-79 years). The patients' initial Glasgow Coma Scale scores ranged from 7 to 15 with a median of 11. The volume of the hematoma ranged from 24 mL to 86 mL (mean 44.5 mL). A trajectory along the main axis of the hematoma was considered to be optimal for thrombolytic therapy. The trajectory was calculated from the point of entry through the target point of the hematoma using reformatted images. Results : The hematoma catheter was left in place for a median duration of 48.9 hours (range 34 to 62 hours). In an average of two days, the average residual hematoma volume was 6.2 mL (range 1.4 mL to 10.2 mL) and was reduced by an average of 84.7% (range 71.6% to 96.3%). The residual hematoma at postoperative seven days was less than 5 mL in all patients. There was no treatment-related death during hospitalization. Conclusion : The present study indicates that stereotactic MPR CT-guided catheter placement for thrombolysis is an accurate and safe procedure. We suggest that this procedure for stereotactic removal of sICH should be considered for the optimization of the trajectory selection in the future.

• BMB Reports
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• 제50권2호
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• pp.60-70
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• 2017

Glaucoma is characterized by a slow and progressive degeneration of the optic nerve, including retinal ganglion cell (RGC) axons in the optic nerve head (ONH), leading to visual impairment. Despite its high prevalence, the biological basis of glaucoma pathogenesis still is not yet fully understood, and the factors contributing to its progression are currently not well characterized. Intraocular pressure (IOP) is the only modifiable risk factor, and reduction of IOP is the standard treatment for glaucoma. However, lowering IOP itself is not always effective for preserving visual function in patients with primary open-angle glaucoma. The second messenger cyclic adenosine 3',5'-monophosphate (cAMP) regulates numerous biological processes in the central nervous system including the retina and the optic nerve. Although recent studies revealed that cAMP generated by adenylyl cyclases (ACs) is important in regulating aqueous humor dynamics in ocular tissues, such as the ciliary body and trabecular meshwork, as well as cell death and growth in the retina and optic nerve, the functional role and significance of cAMP in glaucoma remain to be elucidated. In this review, we will discuss the functional role of cAMP in aqueous humor dynamics and IOP regulation, and review the current medications, which are related to the cAMP signaling pathway, for glaucoma treatment. Also, we will further focus on cAMP signaling in RGC growth and regeneration by soluble AC as well as ONH astrocytes by transmembrane ACs to understand its potential role in the pathogenesis of glaucoma neurodegeneration.

• 동의생리병리학회지
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• 제27권6호
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• pp.764-770
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• 2013

Stevia rebaudiana is a traditional herb used as a sweetener in Brazil and Paraguay as well as Korea and China. This study investigated the efficacy of Stevia rebaudiana methanol extract (SRE) to protect cells against the mitochondrial dysfunction and apoptosis in hepatocyte. To determine the effects of SRE on oxidative stress, we used the human derived hepatocyte cell line, HepG2 cell. Treatment of arachidonic acid (AA)+iron in HepG2 cells synergistically amplified cytotoxicity, as indicated by the excess reactive oxygen species (ROS) and mitochondrial permeability transition by fluorescence activated cell sorter (FACS) and immunoblot analysis. Treatment with SRE protected hepatocytes from AA+iron-induced cellular toxicity, as shown by alterations in the protein levels related with cell viability such as procaspase-3. SRE also prevented the mitochondrial dysfunction induced by AA+iron, and showed anti-oxidant effects as inhibition of $H_2O_2$ production and GSH depletion. Moreover, we measured the effects of SRE on AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death. Acetyl-CoA Carboxylase (ACC), a direct downstream target of AMPK. SRE increased phosphorylation of ACC, and prevented the inhibition of ACC phosphorylation by AA+iron. These results indicated that SRE has the ability to protect cells against AA+iron-induced $H_2O_2$ production and mitochondrial impairment, which may be mediated with AMPK-ACC pathway.

• Toxicological Research
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• 제22권2호
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• pp.95-102
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• 2006

Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

• 대한암한의학회지
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• 제14권1호
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• pp.13-20
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• 2009

Lung cancer remains the leading cause of cancer-related death throughout the world. Non-small cell lung cancer(NSCLC) is the most deadly form of lung cancer. Patients with non-small cell lung cancer are often found to be unavailable for operation at primary diagnosis. They are typically given conventional chemotherapy. When the tumor progresses during chemotherapy, a change in regimen is considered. The average period of administration differs with the regimen. In this case report, the authors introduce two cases of non-small cell lung cancer patients treated with allergen removed Rhus verniciflua stokes based herbal medicine along with pemetrexed($Alimta^{(R)}$) and erlotinib($Tarceva^{(R)}$). The authors report this case because these molecular-targeted agents were used for longer periods than expected, while improving the performance and other symptoms. Further studies illuminating the synergistic effects through conjunctive treatment with both conventional and Eastern medicine in lung cancer treatment should be performed in the future.

• 대한한의학원전학회지
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• 제27권4호
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• pp.55-72
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• 2014

Objectives : King Hyojong (1619-1659) was the 17th king of the Joseon Dynasty. He was on the throne from 1649 to 1659. The king was a center of state rule in ancient times. This meant that the physical and mental status of a king was very confidential information. In the royal court of Joseon Korea, the treatment process for the king had to be performed under the surveillance of close associates, and this whole process had to be recorded by the official secretary. This is the reason that I referred to the Daily Records of Royal Secretariat of Joseon Dynasty. Methods : Relevant articles were extracted from Daily Records of Royal Secretariat of Joseon Dynasty and analyzed according to the main arguments of this paper. Some other related sources were referred in terms of King Hyojong's ailments and treatments. Results & Conclusions : King Hyojong suffered from various diseases during his time on the throne. Fever was the most frequent ailment; he also often had diarrhea followed by poor appetite. I assume that he must have suffered from diabetes considering his ailments. Additionally, his final treatment records clearly show that his ailments were similar to diabetic complications.

• BMB Reports
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• 제51권10호
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• pp.508-513
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• 2018

Fibronectin fragments found in the synovial fluid of patients with osteoarthritis (OA) induce the catabolic responses in cartilage. Nuclear high-mobility group protein Box 1 (HMGB1), a damage-associated molecular pattern, is responsible for the regulation of signaling pathways related to cell death and survival in response to various stimuli. In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in normal cartilage. Although 29-kDa FN-f significantly reduced the HMGB1 expression at the mRNA and protein levels 6 h after treatment, the cytoplasmic level of HMGB1 was increased in chondrocytes treated with 29-kDa FN-f, which significantly inhibited the interaction of HMGB1 with Beclin-1, increased the interaction of Bcl-2 with Beclin-1, and decreased the levels of Beclin-1 and phosphorylated Bcl-2. In addition, the level of microtubule-associated protein 1 light chain 3-II, an autophagy marker, was down-regulated in chondrocytes treated with 29-kDa FN-f, whereas the effect was antagonized by mTOR knockdown. Furthermore, prolonged treatment with 29-kDa FN-f significantly increased the release of HMGB1 into the culture medium. These results demonstrated that 29-kDa FN-f inhibits chondrocyte autophagy by modulating the HMGB1 signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6417-6421
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• 2015

Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1581-1584
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• 2014

Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$, day 1) and cisplatin ($75mg/m^2$, day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.