• Journal of Ginseng Research
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• v.48 no.1
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• pp.77-88
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• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.265-274
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• 1998

Purpose : This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aims of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. Materials and Methods : Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy Seventy eight patients (82.1$\%$) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication Probabilities (NTCP). Results : Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100$\%$ of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range; 0.17-0.43) was 68$\%$ of the mean NTCP with 2D treatment planning (range; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79$\%$), showed major response including 25 (26$\%$) with complete responses and 50 (53$\%$) with partial responses. One and two rear overall survivals of stage III patients were 62.6$\%$ and 35.2$\%$ respectively. Twenty percent (19/95) of patients had pneumonitis; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for Patients without complication was 62$\%$ of those with complications. Conclusions : This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.

• Korean Journal of Food Science and Technology
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• v.36 no.1
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• pp.141-146
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• 2004

Fungal products indirectly mediate anti-tumor effects in vitro and in vivo. To investigate whether Lentinus edodes might possess direct anti-tumor substance, L. edodes was extracted and tested on human papillomavirus (HPV) 16 oncogenes-associated animal tumor cells (TC-1) and in an animal tumor model. Only water extract displayed direct anti-proliferative effects in TC-1 tumor cells in vitro. This inhibition was dose-dependent, and inhibitory concentration ($IC_{50}$) was $800\;{\mu}g/mL$. Fungal extracts also showed growth inhibition to human cervical cancer cells (CaSki and HeLa) similarly to TC-1 tumor cells. When fungal extracts were added at a high dose (1.5 mg/mL), cell growth was inhibited within 6 hr following extract treatment. Cell growth inhibition was blocked by heat treatment, but not by low pH, which is indicative of heat sensitivity of this anti-proliferative substance. Cell growth suppression was mediated by apoptosis, as determined by Annexin V and propidium iodide staining. When challenged with TC-1 cells, direct intratumoral injection of fungal extracts resulted in some positive effect on tumor growth inhibition, as compared to oral delivery. Results suggest that heat labile substance of L. edodes suppresses growth of HPV oncogenes-associated tumor cells through apoptosis.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.41-48
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• 2002

Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

• Journal of the Korean Society of Radiology
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• v.84 no.2
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• pp.441-453
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• 2023

Purpose To evaluate the development, location, and volume of a VX2 carcinoma using four inoculation methods in a rabbit brain. Materials and Methods Inoculation of a VX2 cell suspension was performed 1) on the appointed day, 2) seven days after storing a VX2 carcinoma in a freezer or 3) seven days after storing a VX2 carcinoma in a deep freezer after sacrificing the donor rabbits. 4) Without sacrificing the rabbits, the VX2 cell suspension was obtained using a gun biopsy, inoculation was performed on the appointed day. MR imaging was performed 10 days after inoculation. Brain tissues were obtained the day after. The development, location, and volume of the tumor were evaluated. Results Seventeen of the 18 rabbits inoculated on the appointed day developed tumors (average tumor volume, 106.32 mm³). One of five inoculated seven days after storing the VX2 tumor in the freezer, and three of five inoculated seven days after storing the VX2 tumor in the deep freezer developed tumors. Inoculation with a VX2 cell suspension obtained with a gun biopsy from five rabbits revealed development of tumors in only two rabbits. The tumors mostly developed in the superficial cortex. Conclusion TVX2 rabbit brain tumor model is easy to develop and revealed variable reproducibility. This model can be applicable in radiologic imaging, treatment planning, interventional treatment and drug delivery research. VX2 cell can be successfully innoculated into the brain using variable methods under researcher's variable conditions.

• Korean Journal of Veterinary Service
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• v.21 no.3
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• pp.285-300
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• 1998

1. The number of average milking cows, clinical forms of mastitis, mastitis-developing cows, and cows killed by mastitis a year were 25.7, 1.8(7%), 6.3(26%), and 2.7(10.1%)heads, respectively. The annual grade changes of standard plate counts(SPC) and somatic cell counts(SCC) showed the grade 1A of SPC diminished sharply from April to August, we think it was due to the lack of proper management in farming season and the grade 3 of SCC indirectly influenced increased in huge during August. 2. The average number of parturitions of farms was 2.3, but 50% of below 1 parturition were 22 farms(31%), 50% of above 3 parturitions were 16(23%) out of 71 farms. According to grades of the number of parturitions of milking cows per each farm, the farms' grades recording 3 parturitions and 50% were little bit excellent. 3. The actual situation research of foremilking CMT revealed 35 out of 74 farmer didn't do CMT Among them(35 out of 74 farmers), 80% did not test thanks to the troublesome process of the CMT. SCC grade 3, among farms who did foremilking CMT once or twice a month and who did not were 29% and 40% respectively and SPC grade 1A were 55% and 9%, respectively. 4. The research of actual situation on milking management let us know 29 farms(39%) did not do lastmilking, 37 farms(49%) usually did overmilking, and 34 farms(46%) did milking for 4 or 5 minutes. Grades according to average requiring times of milking showed SCC grade 1 of farms milking within 7 minutes was 11% and SPC grade 1A was 34%, on the other side, farms milking more than 7 minutes were 0% in SCC grade 1 and 13% in SPC grade 1A. Grades according to the starting time of milking after rubbing teats showed SPC grade 1A of farms starting milking at about 1 minute and over 2 minutes were 50% and 20%, respectively. 5. The research of actual situation on hygienic milking management uncovered 65 farms(88%) were using one towel which was used in washing teats and udders to wash more than 3 to 4 cows, and 53 farms(72%) were using one dried towel to dry udders not for each cow but for more than 3 to 4 cows after washing. Also, on milking turns disclosed 30 farms(40%) were milking cows in the order of incoming without isolation of a dominant group. According to grades of towels used in washing teats and udders, farms using a towel for each cow were 56% and a towel for over 3 cows were 31% in SPC grade 1A. According to using-or-not grades of dried towels after washing udders, farms using a towel for each cow were 79% and a towel for over 3 cows were 21% in SPC grade 1A. 6. Farms doing teat-dipping before milking were 7(10%), not doing teat-dipping after milking, or doing sometimes were 9(12%), and doing right after milking were 57(77%). And farms doing teat-dipping after dry cows and before delivery were 21(28a ). Farms using bethadine as an antiseptic solution were 70(95%), 40 farms(59%) diluted it with water as weak as 5 to 10 times, and on drying cows 64 farms(87%) slowly did it more than 2 days. Grade 1A of SPC of farms doing teat-dipping at every milking was 38%, farms doing occasionally or not was 33%, and farms doing it right after milking was 37% and doing after milking more than 5 cows was 20%. Grade 1A of SPC among farms diluting bethadine 5 times and diluting 5 to 10 times with water were 36% and 33%, respectively, and Grade 3 of SCC were 35% and 32%, respectively. 7. Studies on nonlactating period medical treatment, as the cows were on dry, 54 farms treated with their own hands.73 farms(98%) had bovine mastitis treated for themselves. And on applying medicines against mastitis, 55 farmers chose them on the basis of their own experience, 42 farms(57%) were treated more than 3 days. 41 farms(55%) dumped away the mastitis infected milk separately, 24 farms(32%) were feeding and milking at the same time. 8. Fifty-six farms(76%) always washed and disinfected milking machines after milking. Farms using the milking machines at low, or variable vacuum pressures, or at the vacuum pressure, set at the moment of its installation were 31(42%), and farms that did not know pulsation ratio were 27(37%). Farms changing liners when they were torn 8(11%), 58 farms(78%) said they checked milking system when there were wrong with them, 31 farms(42%) changed milking hoses when they found out problems, and 42 farms(57%) cleaned vacuum and milking systems when they felt dirty. The SPC grade 1A of farms washing and sterilizing milking machines was 38% and farms only washing was 28%.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.219-223
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• 2010

Purpose: To test the radiosensitizing effect of the newly synthesized novel histone deacetylase inhibitor, SK-7041 in vivo. Materials and Method: The RIF-l cell line was implanted into the back of a 6-week-old female C3H mouse, intradermally, The mice were grouped into control, drug, radiation (RT), and RT+drug group. SK-7041, 4 mg/kg was administered intraperitoneally for six cycles every 12 hours for mice in the drug and RT+drug group, An identical volume of phosphate buffered saline (PBS) was administered at the same frequency to mice in the control and RT groups. A single 5 Gy fraction was delivered to mice in RT and RT+drug group 6 hours after the fourth delivery. The volume of the implanted tumor was measured every 2~3 days to formulate the growth delay curve. Results: For the control, drug, RT, and RT +drug groups, the average duration for implanted tumor to reach a volume of $1,500mm^3$ was 10 days, 10 days, 9 days, and 12 days, respectively. Moreover, the tumor volume on D14 was $276.7mm^3$, $279.9mm^3$, $292.5mm^3$, and $185.5mm^3$, respectively (p=0.0004). The difference for the change in slope for the control and drug versus the RT and RT+drug groups were borderline significant (p=0.0650). Conclusion: The results of this study indicate that SK-7041 has a radiosensitizing effect for the RIF-1 cell line in vivo at a low concentration and this effect may be synergistic. Implementing this result to clinical trial is warranted.

• Korean Chemical Engineering Research
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• v.52 no.5
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• pp.632-637
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• 2014

A microfluidic method for the in situ production of monodispersed alginate hydrogels using biocompatible polymer gelation by crosslinker mass transfer is described. Gelation of the hydrogel was achieved in situ by the dispersed calcium ion in the microfluidic device. The capillary number (Ca) and the flow rate of the disperse phase which are important operating parameters mainly influenced the formation of three distinctive flow regions, such as dripping, jetting, and unstable dripping. Under the formation of dripping region, monodispersed alginate hydrogels having a narrow size distribution (C.V=2.71%) were produced in the microfluidic device and the size of the hydrogels, ranging from 30 to $60{\mu}m$, could be easily controlled by varying the flow rate, viscosity, and interfacial tension. This simple microfluidic method for the production of monodisperse alginate hydrogels shows strong potential for use in delivery systems of foods, cosmetics, inks, and drugs, and spherical alginate hydrogels which have biocompatibility will be applied to cell transplantation.

• Polymer(Korea)
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• v.36 no.6
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• pp.789-794
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• 2012

Poly(lactic-co-glycolic acid) (PLGA) has been most widely used due to its advantages such as good biodegradability, controllable rate of degradation and metabolizable degradation products. We manufactured composite scaffolds of PLGA scaffold penetrated DBP gel (PLGA/DBP gel) by a simple method, solvent casting/salt leaching prep of PLGA scaffolds and subsequent soaking in DBP gel. Chondrocytes were seeded on the PLGA/DBP gel. The mechanical strength of scaffold, histology (H&E, Safranin-O, Alcian-blue) and immunohistochemistry (collagen type I, collagen type II) were performed to elucidate in vitro and in vivo cartilage-specific extracellular matrices. It was better to keep the characteristic of chondrocytes in the PLGA/DBP gel scaffolds than that PLGA scaffolds. This study suggests that PLGA/DBP gel scaffold may serve as a potential cell delivery vehicle and a structural basis for in vivo tissue engineered cartilage.

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.511-522
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• 2007

Introduction : The purpose of this study was to evaluate the possibility of the acellular dermal matrix (ADM) as a barrier membrane for bone regeneration, and to evaluate the osteogenic effect of ADM as a carrier system for rhBMP-2 in the rat calvarial defect model. Materials and Methods: An 8-mm, calvarial, critical-size osteotomy defect was created in each of 60 male Spraque-Dawley rats(weight $250{\sim}300g$). Three groups of 20 animals, each received either rhBMP-2(0.025mg/ml) in an ADM carrier, ADM only, or negative surgical control. And each group was divided into 2- and 8-weeks healing intervals. The groups were evaluated by histologic and histomorphometric parameters(10 animals/group/healing intervals). Data were expressed as $means{\pm}standard$ deviations($m{\pm}SD$). Comparisons between experimental and control groups were made using two-way ANOVA and post hoc t-test. Comparisons between 2 weeks and 8 weeks were made using paired t-test. The level of statistical difference was defined as P< 0.05. Results : The ADM group and rhBMP-2/ADM group results in enhanced local bone formation in the rat calvarial defect at both 2 and 8 weeks. The amount of defect closure and new bone formation were significantly greater in the rhBMP-2/ADM group relative to ADM group(P<0.05). At 8 weeks, the majority of ADM in the defect was contracted, and integrated with surrounding host tissues. In addition, host cell infiltration and neovascularization of the ADM in the absence of an inflammatory response were observed, and the newly formed bone around ADM showed a continuous remodeling and consolidation. Conclusion : The results of the present study indicated that ADM may be used as a barrier membrane for bone regeneration and that may be employed as a delivery system for BMPs.