• Journal of Society of Preventive Korean Medicine
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• v.13 no.1
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• pp.13-27
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• 2009

This study aimed to validate neuroprotective effect of Chungpaesagan-tang on the early stage of cerebral ischemic damage. Cerebral ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours in the Sprague-Dawley rats. Water extract of Chungpaesagan-tang(8.7g/kg) was administered orally twice at 1 and 4 hours after the MCAO. Neurological score was tested at 3 and 24 hours after the MCAO and Chungpaesagan-tang administration. At 24 hours after the MCAO, infarct volume and edema ratio was evaluated with the TTC staining. Apoptotic cell death in cerebral cortex and caudate putamen was observed with cresyl violet staining and TUNEL labeling. Bax expression in the MCAO rat brain was stained with immunohistochemistry. Chungpaesagan-tang improved neurological and behavioral impairment of the MCAO rats and reduced infarct area, infarct volume and brain edema formation. Chungpaesagan-tang attenuated cell death percentage in cortex penumbra and reduced TUNEL positive cells in cortex penumbra and in caudate putamen of the MCAO rats. Chungpaesagan-tang reduced Bax positive neurons in caudate putamen and reduced c-Fos positive neurons in cortex penumbra of the MCAO rats. Chungpaesagan-tang intensified neuronal HSP72 expression in cortex penumbra of the MCAO rats. In results, Chunpaesagan-tang reduces infarct volume and edema formation through anti-apoptotic effect. This result suggests that Chunapaesagan-tang has an adequate neuroprotective effect on the early stage of cerebral ischemic damage.

• Archives of Pharmacal Research
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• v.21 no.1
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• pp.46-53
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• 1998

When NIH3T3 cells were exposed to mild heat and recovered at $37^{\circ}C$ for various time intervals, they were thermotolerant and resistant to subsequent stresses including heat, oxidative stresses, and antitumor drug methotrexate which are apoptotic inducers. The induction kinetics of apoptosis by stresses were determined by DNA fragmentation and protein synthesis using $[35^S]$methionine pulse labeling. We investigated the hypothesis that thermotolerant cells were resistant to apoptotic cell death compared to control cells when both cells were exposed to various stresses inducing apoptosis. The cellular changes in thermotolerant cells were examined to determine which components are involved in this resistance. At first, the degree of resistance correlates with the extent of heat shock protein synthesis which were varied depending on the heating times at $45^{\circ}C$ and recovery times at $37^{\circ}C$after heat shock. Secondly, membrane permeability change was observed in thermotolerant cells. When cells prelabeled with $[^{3}H]$thymidine were exposed to various amounts of heat and recovered at $37^{\circ}C$ for 1/2 to 24 h, the permeability of cytosolic $[^{3}H]$thymidine in thermotolerant cells was 4 fold higher than that in control cells. Thirdly, the protein synthesis rates in thermotolerant and control cells were measured after exposing the cells to the same extent of stress. It turned out that thermotolerant cells were less damaged to same amount of stress than control cells, although the recovery rates are very similar to each other. These results demonstrate that an increase of heat shock proteins and membrane changes in thermotolerant cells may protect the cells from the stresses and increase the resistance to apoptotic cell death, even though the exact mechanism should be further studied.

• Proceedings of the Korea Society of Environmental Biology Conference
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• 2002.11a
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• pp.33-37
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• 2002

The present was performed to identify the effects of tributyltin (TBT) in the immature mice testes. 3-week-old male ICR mice were orally administrated on one time basis of TBT dose of O (Vehicle control, VC), 25 (TBT 25 mg/kg, T$_{25}$ ), 50 (TBT 50 mg/kg, T$_{50}$ ), 100 (TBT 100 mg/kg, T$_{100}$ ) mg/kg per each one. After 3 days the time treated of TBT, mice were sacrified and wighted body, testis, epididymis, seminal vesicle, vas deferens, and prostate. As the result of weighing, wights of each oragan and gonad index were tendency decresed in comparing groups of TBT treated with that (C) of unteated (p <0.05). As the result of examination of steroid hormones in the immature male mice, The concentrations of serum and intratesticular testosterone were significatly increased rather than the control group. But concentrations of estradiol were decresed objectly. A group of the highest change of concentrations of steroid hormones is T$_{100}$ . The high dose group, T$_{100}$ , was decreased all of concentrations of steroid hormones rather than those of T$^{25}$ . The result of observation with histological changes in testis showed a tendency for innercellular wall to increase damage and extinction in seminiferous tubles. As the result of investigation apoptotic cell numbers in the testis using teminal deoxy-nucleotidyl transferase -mediated dUTP-digoxygenin nick end-labeling immunohistochemical straia, The ratio of Apoptic cells significantly was incensed in depending on treatment of TBT does. In conclusion, these results shows that TBT triggers apoptosis on reproductive cell in testis and changes level of concentrations of steroid hormones in the immature male mice , as endocrine disruptors (EDs).

• Molecules and Cells
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• v.19 no.3
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• pp.408-417
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• 2005

Nitric oxide (NO) occurs in various types of cells in the central nervous system. We studied the distribution and morphology of neuronal nitric oxide synthase (NOS)-containing neurons in the visual cortex of mouse and rabbit with antibody immunocytochemistry. We also compared this labeling to that of calbindin D28K, calretinin, and parvalbumin. Staining for NOS was seen both in the specific layers and in selective cell types. The densest concentration of intense anti-NOS immunoreactive (IR) neurons was found in layer VI, while the weak anti-NOS-IR neurons were found in layer II/III in both animals. The NOS-IR neurons varied in morphology. The large majority of NOS-IR neurons were round or oval cells with many dendrites coursing in all directions. Two-color immunofluorescence revealed that only 16.7% of the NOS-IR cells were double-labeled with calbindin D28K in the mouse visual cortex, while more than half (51.7%) of the NOS-IR cells were double-labeled with calretinin and 25.0% of the NOS-IR cells were double-labeled with parvalbumin in mouse. By contrast, 92.4% of the NOS-IR neurons expressed calbindin D28K while only 2.5% of the NOS-IR neurons expressed calretinin in the rabbit visual cortex. In contrast with the mouse, none of the NOS-IR cells in the rabbit visual cortex were double-labeled with parvalbumin. The results indicate that neurons in the visual cortex of both animals express NOS in specific layers and cell types, which do not correlate with the expression of calbindin D28K, calretinin or parvalbumin between the two animals.

• Journal of Radiation Industry
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• v.9 no.4
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• pp.193-198
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• 2015

Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.77-85
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• 2022

The Td05 and Sgc8c, DNA-based aptamers, are well-known to target internalized surface markers (IGHM and PTK7) of Burkitt's lymphoma and acute lymphoblastic leukemia (ALL). Thus, Td05 and Sgc8c labeled with metallic radioisotope ⁶⁴Cu can be evaluated as potential diagnostic PET imaging agents. In this study, we modified the carbon chain length of the last adenosine of aptamer (n = 3, 6, 12) to increase tumor cell uptake and select the best candidate among six types of aptamer analogues and one adenosine of aptamer. After labeling of ⁶⁴Cu, [⁶⁴Cu]Cu-DOTA-aptamer analogues were evaluated in vitro studies (serum stability, Log P values, cell uptake, biodistribution). Then, we evaluate in vivo PET imaging study for two candidates (⁶⁴Cu-DOTA-C12-Sgc8c, ⁶⁴Cu-DOTA-C6-Td05). PET images clearly visualize tumors at 24 h post-injection rather than at an early time point and the tumor-to-background ratio also increases at the delay time point. ⁶⁴Cu-DOTA-C12-Sgc8c and ⁶⁴Cu-DOTA-C6-Td05 could be used as potential radiotracers for lymphoma.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.181-189
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• 2024

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

• Animal Bioscience
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• v.37 no.2
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• pp.284-294
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• 2024

Objective: Pork is an important source of animal protein in many countries. Subtle physiochemical changes occur during pork postmortem aging. The changes of apoptosis and autophagy in pork at 6 h to 72 h after slaughter were studied to provide evidence for pork quality. Methods: In this article, morphological changes of postmortem pork was observed through Hematoxylin-eosin staining, apoptotic nuclei were observed by TdT-mediated dUTP nick end labeling assay, protein related to apoptosis and autophagy expressions were tested by western blot and LC3 level were expressed according to immunofluorescence assay. Results: In this study, we found the occurrence of apoptosis in postmortem pork, and the process was characterized by nucleus condensation and fragmentation, formation of apoptotic bodies, increase in apoptosis-related Bax/Bcl-2 levels, and activation of caspases. Autophagy reached its peak between 24 and 48 h after slaughter, accompanied by the formation of autophagosomes on the cell membrane and expression of autophagy-related proteins beclin-1, P62, LC3-I, LC3-II, and ATG5. Conclusion: Obvious apoptosis was observed at 12 h and autophagy reached its peak at 48 h. The present work provides the evidence for the occurrence of apoptosis and autophagy during postmortem aging of pork. In conclusion, the apoptosis and autophagy of muscle cells discovered in this study have important implications for pork in the meat industry.

• Journal of Korean Ophthalmic Optics Society
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• v.21 no.1
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• pp.69-76
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• 2016

Purpose: The study was conducted to determine that photoreceptors of mouse having pigment in RPE(retinal pigment epithelium) can be damaged by blue-light and apoptosis of specific cells among photoreceptors are induced by blue-light, and to assist the investigation of AMD(Age-related macular degeneration) mechanisms and development of AMD drugs. Methods: C57Black mice were injured by irradiating $2800{\pm}10lux$ of 463 nm LED for 6 hours after 24 hours dark adaptation and eyes were enucleated 1, 3, 7 days. Damage of retina induced by blue-light was determined by western blotting GFAP(Glial fibrillary acidic protein) expression. In the light-injured retina, cell death of photoreceptors was determined by TUNEL(Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. ERK(Extracellular signal-regulated kinases), JNK, and SRC(sarcoma) expression were assessed by western blotting to determine regulated pathway. Blue light-injured retina were immunostained with antibodies against Opsin and Rhodopsin as markers of photoreceptors to compared the damage cone cells with rod cells. Results: After 1, 3 and 7 days from exposure to blue-light, thickness of retina was more decreased than control, and more decreased at nuclear layer than at outer plexiform layer and GFAP expression was increased day 1 after blue-light injured. While phosphorylated ERK and SRC protein expressions at day 1 were increased after blue-light injured, phosphorylated c-JUN was decreased. Fluorescence intensity analysis showed that markers of cone and rod cells were decreased after blue-light injured and Opsin was more decreased than Rhodopsin. Conclusions: The study suggests possibilities that the blue-light promotes retinal damage and causes apoptotic cell death via ERK and SRC pathway in mouse retina, and blue-light retinal damage is more induced cone cells apoptosis than rod cells directly.

• Journal of Life Science
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• v.24 no.1
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• pp.86-91
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• 2014

Trichoplusia ni cells are used as a host permissive cell line in the baculovirus expression system, which is useful for large-scale production of human sugar transport proteins. However, the activity of endogenous sugar transport systems in insect cells is extremely high. Therefore, the transport activity resulting from the expression of exogenous transporters is difficult to detect. Furthermore, very little is known about the nature of endogenous insect transporters. To exploit the expression system further, the effect of D-fructose on 2-deoxy-D-glucose (2dGlc) transport by T. ni cells was investigated, and T. ni cell-expressed human transporters were photolabeled with [$^3H$] cytochalasin B to develop a convenient method for measuring the biological activity of insect cell-expressed transporters. The uptake of 1 mM 2dGlc by uninfected- and recombinant AcMPV-GTL infected cells was examined in the presence and absence of 300 mM of D-fructose, with and without $20{\mu}M$ of cytochalasin B. The sugar uptake in the uninfected cells was strongly inhibited by fructose but only poorly inhibited by cytochalasin B. Interestingly, the AcMPV-GTL-infected cells showed an essentially identical pattern of transport inhibition, and the rate of 2dGlc uptake was somewhat less than that seen in the non-infected cells. In addition, a sharply labeled peak was produced only in the AcMPV-GTL-infected membranes labeled with [$^3H$] cytochalasin B in the presence of L-glucose. No peak of labeling was seen in the membranes prepared from the uninfected cells. Furthermore, photolabeling of the expressed protein was completely inhibited by the presence of D-glucose, demonstrating the stereoselectivity of labeling.