• Journal of the Korean Applied Science and Technology
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• v.38 no.1
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• pp.118-125
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• 2021

In this study Orostachys japonica A. Berger used is a medicinal herb that has long been used as a folk remedy for cancer treatment. In this study, the antioxidant efficacy of the ethyl acetate fraction of Orostachys japonica A. Berger was confirmed. The results of the Orostachys japonica A. Berge ethyl acetate fraction of antioxidant activity assays showed Antioxidant effect of Orostachys japonica A. Berger EtOAc fraction extract at 0.10 mg/mL was showed a DPPH radical scavenging rate of 78.54% and ABTS+ radical scavenging rate of 73.48%. Also, the toxicity result of Orostachys japonica A. Berger EtOAc fraction extracts using alternative experimental animal model zebrafish, confirmed a 100% the survival of the zebrafish embryo was shown that there was no coagulation and no hatching delay at all concentrations. also ROS generation induced by UV-B irradiation was confirmed that the fluorescence intensity decreased as a whole in all larvae treated with Orostachys japonica A. Berger EtOAc fraction extracts. In particular, it was confirmed that ROS generation was effectively suppressed by showing a 35.7% reduction rate compared to the positive control at a concentration of 3 ㎍/mL. These results were confirmed that Orostachys japonica A. Berger EtOAc fraction extracts has the possibility of application in the cosmetics field as a natural antioxidant.

• Journal of the Korean Burn Society
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• v.22 no.2
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• pp.66-70
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• 2019

Purpose: The necrotizing fasciitis is a terrifying infectious disease that can rapidly spreads to surrounding tissues when fascia is infected and it can cause sepsis to death if not properly diagnosed and treated. The purpose of this study is to investigate the characteristics, causes, and treatment methods of necrotizing fasciitis in Korea through reviewing patients admitted to our burn center. Methods: 21 patients with necrotizing fasciitis were selected for this study among those inpatients with electronic medical records (EMR) admitted to Hallym University Hangang Sacred Heart Medical Center from Jan 1, 2008 to June 30, 2019. The medical records and wound photos of those 21 selected subjects were reviewed. Results: There were 13 male and 8 female patients and mean age was 58.76 years old. 13 of 21 subjects were survived and 8 died (38% mortality rate). The surgical treatments performed were I&D, fasciotomy, debridement, allograft, burring, STSG, flap, and amputation. The most common causes were burns in 9 subjects (6 contact burns) and cellulitis occurred on skins in 5 subjects. And other various causes were observed as fournier's gangrene, stab wound, intramuscular injection, tumor and bleu toe syndrome (toe necrosis). The infected areas were 11 feet and legs, 7 hips, 3 abdomen and trunk in 21 subjects. Of the 8 deaths, 3 were infected in feet and legs, 2 were infected in hips, and 2 were infected in abdomen and trunk. As for underlying diseases, 12 patients with hypertension or diabetes were the highest and others such as cancer and stroke were found. Conclusion: The only method to increase the survival rate is to 'suspect' the disease as much as possible and perform early extensive excision. It is advisable to treat the disease by the burn center to properly provide adequate and optimal wound management, infection control, medical care and nutritional supports.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.73-77
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• 2008

Purpose : p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL. Methods : We performed an immunohistochemical staining for p16 protein in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively. Results : Of 74 slides, 12 were negative for p16 protein. Seven were males and 5 were females with a median age at diagnosis was 5.8 (1.3-18.8) years. Initial WBC were 17,225 $(500-403,300)/{\mu}L$. By immunologic surface marker analysis, 7 patients were early pre-B CALLA (+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were $53.5{\pm}18.7%$. Conclusion : Loss of p16 protein is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 status and clinical outcomes.

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.33-45
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• 2011

Heat shock protein 90 (Hsp90) is ATPase-directed molecular chaperon and affects survival of cancer cell. Inhibitory effect of Hsp90 by inducing cell cycle arrest and apoptosis in the cancer cell was reported. However, its role during oocyte maturation and early embryo development is very insufficient. In this study, we traced the effects of Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on meiotic maturation and early embryonic development in pigs. We also investigated several indicators of developmental potential, including structural integrity, gene expression (Hsp90-, cell cycle-, and apoptosis-related genes), and apoptosis, which are affected by 17-AAG. Then, we examined the roles of Hsp90 inhibitor on viability of primary cells in pigs. Porcine oocytes were cultured in the NCSU-23 medium with or without 17-AAG for 44 h. The proportion of GV arrested oocytes was significantly different between the 17-AAG treated and untreated group (78.2 vs 34.8%, p<0.05). After completion of meiotic maturation, the proportion of MII oocytes was lower in the 17-AAG treated group than in the control group (27.9 vs 71.0%, p<0.05). After IVF, the percentage of penetrated oocytes was significantly lower in the 17-AAG treated group (25.2%), resulting in lower normal pronucleus formation (2PN of 14.6%). Therefore, the inhibition of meiotic progression by Hsp90 inhibitor played a critical role in fertilization status. Porcine embryo were cultured in the PZM-3 medium with or without 17-AAG for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without 17-AAG. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 17-AAG treated group compared with control (7.5 vs 4.4, respectively). Blastocysts that developed in the 17-AAG treated group had low structural integrity and high apoptotic nuclei than those of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. The mRNA expressions of cell cycle-related genes were down-regulated in the 17-AAG treated group compared with control. Also, the expression of the pro-apoptotic gene Bax increased in 17-AAG treated group, whereas expression of the anti-apoptotic gene Bel-XL decreased. However, the expression of ER stress-related genes did not changed by 17-AAG. Cultured pESF cells were treated with or without 17-AAG and used for MIT assay. The results showed that viability of pESF cells were decreased by treatment of 17-AAG ($2{\mu}M$) for 24 hr. These results indicated that 17-AAG decreased cell proliferation and increased cell death. Expression patterns Hsp90 complex genes (Hsp70 and p23), cell cycle-related genes (cdc2 and cdc25c) and apoptosis-related genes (Bax and Bcl-XL) were significantly changed by using RT-PCR analysis. The spliced form of pXbp-1 product (pXbp-1s) was detected in the tunicamycin (TM) treated cells, but it is not detected in 17-AAG treated cells. In conclusion, Hsp90 appears to play a direct role in porcine early embryo developmental competence including structural integrity of blastocysts. Also, these results indicate that Hsp90 is closely associated with cell cycle- and apoptosis-related genes expression in developing porcine embryos.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.213-219
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• 2009

Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.615-623
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• 2009

Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.