Purpose: This study investigates the alterations in A549 human non-small-cell lung cancer (NSCLC) cells exposed to Citrus junos extract (CJE). We further examine the antiproliferative and apoptotic effects of CJE on NSCLC cells. Methods: Inhibition of proliferation was examined by applying the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) colorimetric assay on CJE-treated A549 NSCLC cells. The lactate dehydrogenase (LDH) assay was performed to measure the degree of toxicity of CJE on NSCLC cells. The effect on migratory proliferation was confirmed using the scratch wound healing assay. The antiproliferative effect of the CJE on human lung cancer cells was verified through morphological observation, fluorescence microscopy, and caspase-3 colorimetry. Results: Exposure of NSCLC cells to CJE resulted in a dose- and time-dependent decrease in cell activity and increased toxicity to the cells. In addition, microscopic observation revealed a reduced ability of the cancer cells to migrate and proliferate after exposure to the CJE, with simultaneous morphological apoptotic changes. Fluorescence staining and microscopic examination revealed that this death was a process of self-programmed cell death of NSCLC cells. Compared to unexposed NSCLC cells, the expression of caspase-3 was significantly increased in cells exposed to CJE. Conclusion: Exposure of A549 human NSCLC cells to CJE inhibits the proliferation, increases the cytotoxicity, and decreases the ability of cells to migrate and grow. Moreover, the expression of caspase-3 increases after CJE treatment, suggesting that the apoptosis of NSCLC cells is induced by a chain reaction initiated by caspase-3. These results indicate that Citrus junos is a potential therapeutic agent for human non-small-cell lung cancer.
Kim, Minjeong;Hur, Sumin;Kim, Kwang H.;Cho, Yejin;Kim, Keunyoung;Kim, Ha Ryong;Nam, Ki Taek;Lim, Kyung-Min
Biomolecules & Therapeutics
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제30권2호
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pp.126-136
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2022
Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.
Hong, Hun Pyo;Kim, Cheul Hong;Yoon, Ji Young;Kim, Yong Deok;Park, Bong Soo;Kim, Yong Ho;Yoo, Ji Uk
Journal of The Korean Dental Society of Anesthesiology
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제14권3호
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pp.157-165
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2014
Background: Incisional site of surgical operation become transient ischemic state and then occur reoxygenation due to vasodilatation by inflammatory reaction, the productive reactive oxygen species (ROS) give rise to many physiologic results. Apoptosis have major role on elimination of inflammatory cell and formation of granulation tissue in normal wound healing process. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. After cardiopulmonary bypass for coronary artery surgery, remifentanil can also inhibit the release of biomarkers of myocardial damage. Here we investigated whether remifentanil pretreatment has cellular protective effect against hypoxia-reoxygenation in HaCaT human keratinocytes, if so, the role of apoptosis and autophagy on this phenomenon. Methods: The HaCaT human keratinocytes were exposed to various concentrations of remifentanil (0.01, 0.05, 0.1, 0.5 and 1 ng/ml) for 2 h before hypoxia (RPC/HR group). These cells were cultured under 1% oxygen tension for 24h at $37^{\circ}C$. After hypoxia, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. 3-MA/RPC/HR group was treated 3-methyladenine (3-MA), autophagy inhibitor for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with thiazolyl blue tetrazoliumbromide (MTT, amresco), showing the mitochondrial activity of living cells. To investigate whether the occurrence of autophagy and apoptosis, we used fluorescence microscopy and Western blot analysis. Results: The viability against hypoxia-reoxygenation injury in remifentanil preconditioning keratinocytes were increased, and these cells were showed stimulated expression of autophagy 3-MA suppressed the induction of autophagy effectively and the protective effects on apoptosis. Atg5, Beclin-1, LC3-II and p62 were elevated in RPC/HR group. But they were decreased when autophagy was suppressed by 3-MA. Conclusions: Remifentanil preconditioning showed the protective effect in human keratinocytes, and we concluded that autophagy may take the major role in the recovery of wound from hypoxia-reoxygenation injury. We suggest that further research is needed about the cell protective effects of autophagy.
Journal of the Korea Academia-Industrial cooperation Society
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제16권9호
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pp.6425-6431
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2015
Invertase, that hydrolyzes sucrose into glucose and fructose, plays a great role in carbohydrate reallocation between the photosynthetic source tissue and various sink tissues. Invertase also occurs in a variety of isoforms for various functions in plants. Insoluble invertases were extracted only in buffer solutions containing high concentrations of salt. Within these classes, acid invertase has an optimum activity at acidic pH (pH 4-5). Induction of insoluble acid invertase (INAC-INV) in leaf, stem, and root tissues in response to physical wounding has been investigated. To detect the localization of INAC-INV within the plant, immunolocalization has been performed. In this study, the accumulation of INAC-INV was noticeable to reach maximum levels on 72 hr after mechanical injuries. INAC-INV was induced in wounded leaves 3 times more than control leaves. Immunolocalization results showed that INAC-INV accumulated in wall appositions and intercellular spaces. INAC-INV was also localized at sieve cell walls in phloem tissues close to the site of wounding. Taken together, this study suggested that INAC-INV induction upon wounding injuries can play a role on responses to the high energy demand for wound healing process.
Current acceptable methods for promoting periodontal regeneration are based on removal of diseased soft tissue. root treatment, guided tissue regeneration, introduction of new graft materials and biological mediators. Insulin-like growth factor-I(IGF-I) and Platelet-derived growth factor-BB(PDGF-BB), the members of the polypeptuyde growth factor family have been reported as the biological mediators which regulate a variety cellular matrix biologic activities of wound healing process including the cell proliferation, migration and extracellular matrix synthesis.The purposes of this study is to evaluate the combination effects of IGF-I and PDGF-BB on the cellular activity of the periodontal ligament cells to act as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM containing 10% FBS at the $37^{\circ}C$, 5% CO2 incubator. Author measured the DNA synthetic activity, and total protein, collagen and noncollagenous protein synthetic activities according to the concentration of 10,100ng/ml IGF-I and1,10 ng/ml PDGF-BB in combination. The results were as follows: Significantly increased in the 1 ng/ml PDGF-BB alone compared to the 10 ng/ml PDGF-BB alone(P<0.01) and in the 1 ng/ml PDGF-BB and 10, 100ng/ml IGF-I in combination compared to the 1 ng/ml PDGF-BB alone(P<0.05, P<0.0l). The synthetic activity of the total protein and collagen is significantly increased like to the synthetic activity of the DNA(P<0.05). The synthetic activity of the noncollagenous protein is increased according to the concentration of IGF_I, but not statistically statistically significant(P>0.05). The percent of the collagen is significantly in the 1ng/ml PDGF-BB and 10ng/ml IGF-I in combination compared to the 1ng/ml PDGF-BB alone(P<0.05) and in the 10ng/ml IGF-I in combination compared to the 10ng/ml PDGF-BB alone(P<0.05). The synthetic activity of the DNA is In conclusions, the percent study shows that PDGF-BB and IGF-I in combination have a potentiality to enhance the DNA synthesis and the total protein and collagen synthesis of The periodontal ligament cells, especially it is more significant in the low concentration of PDGF-BB compared to the high one. Thus, the PDGF-BB and IGF-I in combination may have important roles in promotion of periodontal litgment healing, and consequently, may useful for clinical application in periodontal regenerative procedures.
The use of laser in the treatment of soft tissue minimizes hemorrhage, provides better view of the operating field, and thereby minimizes operating time. Also, there will be far less post-operative swelling, pain and scar formation, and sterilizing effect are shown in some portions of the wound site. All these advantages of laser therapy contribute to its widespread use in the field of medicine and dentistry. Regarding such facts, we used CO2 laser of different watts in gingivectomy for white rats to compare initial healing process. For the control group, the least amount of output in performing gingivectomy(4watts) was offered, and for the experimental group, 6watts was given. Animals were sacrificed on the second, third days, 1 weeks, 2 weeks, and 3 weeks after operation, and their specimens were histologically analyzed. The following results were obtained: 1. Blood clot of small size was observed in both the control and experimental groups after two days, and no more thereafter. 2. In both the control and experimental groups, the inflammation zone size was the greatest after two days, and it decreased gradually to become almost invisble by the second week. The experimental group showed larger size of inflammation zone during second and third days: however, there was no difference after one week. 3. Granulation tissue in both the control and experimental groups showed gradual maturation with time, and by the second week, it was almost replaced by normal connective tissue. By the third week, complete healing pattern was observed. The experimental group showed larger granulation tissue than the control group until the third day, but there was no significant difference after one week. 4. In both the control and experimental groups, gingival epithelialization began on the second day. After one week, regeneration of rete peg and partial formation of junctional epithelium were observed: by the second week, keratinization of oral sulcular epithelium began, and it was completed by the third week.
Lee, Kyung Ju;Jang, Wookju;Kim, You Ah;Park, Byoung Jun;Kang, Hakhee
Journal of the Society of Cosmetic Scientists of Korea
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제46권3호
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pp.273-282
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2020
Aloe vera (Aloe barbadensis Miller) has been used since ancient times to improve various skin diseases such as burns, wounds, and eczema. It has been reported that Aloe vera contains vitamin, enzyme, mineral, sugar, phenolic compound, fatty acid and amino acid. Aloe vera changes its color from green to red under the extreme thermal and arid climate to protect itself. These morphological changes induce variation of composition such as increasing of aloe-emodin content. Aloe-emodin is one of the major anthraquinone in aloe family plants. Since aloe-emodin contains a polyphenolic structure, this compound may be responsible for the reported antioxidant and anti-inflammatory effects of aloe. However, there is no research on the process of increasing the compounds of Aloe vera. Therefore, the purpose of this study is to develop a pink aloe manufacturing process that increases the aloe-emodin content and enhances the antioxidant and anti-inflammatory activities of aloe. As a result of heating aloe under appropriate conditions, pink aloe increased aloe-emodin content compared to general aloe, and exhibited effects such as increasing antioxidant activity, inhibiting NO production, and promoting cell regeneration. Through this study, the applicability of pink aloe as a new anti-aging material in the cosmetic field was confirmed.
The terminology "human body" simply means a physical body but also more often, as an object in art works, carries symbolic concepts incorporating the whole history of human lives. Human body has been employed as an artistic object capturing physical body, delivering artist's idea expressing life indicators from different standpoints of times and places. This point of view about human body in art works has in fact rather short history since 1960's when modern thinking paradigm focusing upon rationality and reasoning has begun declining and on the contrary when the body used to be the servant of the mind and soul for a long time has begun attracting artist's attention as a real entity from the viewpoint of dichotomy. During the 1960's, frequent performances in Pop art and of Fluxus showed that the human body has been an important media for artistic communication after importance of body performances had been raised in Action painting in 1940's. The human body became a more determined media in body art works that had got into stride after Yves Kline's conceptual works applying body and its traces. These kinds of art works have continued and consolidated into the Feminism came into blossom in 1980's and into fragmentated and disembodied body art trend in 1990's. Through development of trends in body works, human body now might well be regarded as a clue provide from individual identity with implication over the world. This thesis is to analyse in semiotic way main works of Kiki Smith who is a representative artist devoting to Feminism and proposing extended significance of human body. In the analysis process of works done by two great artists with histrorical background of art trend in order to find and open an significance horizon of human body, semiotics and bodism are therefore perceived as pertinent and applied as basic tools. The first stage of analysis is to get the significances emerged in between expression part and contextual parts, which are separated structually from the most basic level. The study deals with body works furthermore in the way of structual cohesion of the expression and the context from the view of A J. Greimas' Structural Semantics and tried to build up a basic frame for the extended significances of human body. This thesis is, on the other hand, to attempt to contribute for extension of disembodied and fragmentated body discussed in the structural semantic frame earlier by Julia Kriesteva who delivers abjection concepts and phenomenology of Maurice Merleau-Ponty who enables to overview relationship between the body and the world from the viewpoint of Bodism, further into interpretation level. The other works are Kiki smith's that showed epics about death in mid-1980's, detailed humbleness of vulnerable human body exposed to dichotomy and fragmentation in 1990's and religion and mythology incorporating wouln healing in 2000's and henceforth. Through the analysis of Kiki Smith's representative work 'Pee body', it is verified and confirmed that fragmentated body showed beyond boundary gap of the human body and ultimately tends to imply human healing owing to divine maternity. Bodily symbols in Kiki Smith's are extended to the universal world to imply human life and death on the one hand and religion and mythology of human wound and divine healing one the other hand. This thesis through these process and results of analysis is in a broad context, to emphasize that human body as objectified text has a key indicator role to understand world as well as semiotic extension in art works in late 20th century so that we might confirm bodily symbol as a cultural context constitutes a section of contemporary visual arts.
In order to evaluate the therapeutic effect of thoracostomy on the patients with pathological changes in pleural cavity which were caused by various etiological factors, a clinical study was carried out during a period of 5 and half years from May 1972 to September 1977 in the department of thoracic surgery, Hanyang University Hospital, and the following results were obtained. Of a total of 264 patients, 205 cases were male, and 59 female, exhibiting the ratio of male to female being 3.5 to 1. The pathological changes in pleural cavity could occur at any age from 4 months after birth to 76 years old, the peak incidence being in the third decade in either male or female. The incidence decreased in the second, fifth and fourth decade in order. The type of pathological changes observed and their frequencies of occurrences were 93 cases [35.2%] in pneumothorax, 62 cases [23.5%] in hemothorax, 48 cases [18.2%] in pyothorax, 46 cases [17. 4%] in hemopneumothorax, 13 cases [4.9%] in hydropneumothorax, and one case each in hydrothorax and chylothorax. The incidence of the primary diseases which predisposed the pathological changes in pleural cavity were, 119 cases [45-1%] in trauma, 64 cases [24.2%]in lung tuberculosis, 38 cases [14.4%] in pneumonia or empyema, 14 cases [5.3%] in lung emphysema and blebs, 13 cases [4.9%] in process after thoracotomy, 3 cases [1.1%] each in lung malignant tumor and lung paragonimiasis, one case in mechanical ventilator and 9 cases [3.4%] in unknown origin. The pathological changes in pleural cavity were located in the right side of the cavity in 124 cases, in the left side in 133 cases and in both sides in 7 cases, indicating that the difference between the incidence of the left and rightside occurences was insignificant. Of 93 cases of pneumothorax studied, 63 cases were found to have been tension pneumothorax and 30 cases non-tension pneumothorax, showing greater prevalence of tension type over non-tension type. Of 119 cases of trauma observed, 82 cases were accompanied with rib fractures and 37 cases were without any fracture [non-bone fracture]. Patients with the rib fractures were characterized by multiple rib fractures and multiple double fractures of ribs, accompanying with or without fracture of bones other than ribs, and patients with non-bone fracture were characterized by penetrating stab wound and blunt trauma. Of 264 cases who received thoracostomy, 207 cases [78.4%] demonstrated that their pathological changes in pleural cavity were removed and subsided by a simple measure of thoracostomy. In 43 cases [16.3%], various surgical measures including radical operation and thoracotomy were required for complete healing, since their pathological changes were not abolished by thoracostomy alone. The rest 14 cases [5.3%] were expired following thoracostomy.
Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.
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