• 제목/요약/키워드: human-to-human (H2H)

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Effect of Ginseng Saponins on the Biosynthesis of Prostaglandins (인삼 사포닌 성분이 프로스타글란딘류 생성에 미치는 영향)

  • 이선희;박찬웅
    • Journal of Ginseng Research
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    • v.13 no.2
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    • pp.202-210
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    • 1989
  • The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

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NMR Studies on the Structure of Human Annexin I

  • Han, Hee-Yong;Bang, Keun-Su;Na, Doe-Sun;Lee, Bong-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.182-182
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    • 1996
  • Annexin I is a member of the annexin family of calcium dependent phospholipid binding proteins and has anti-inflammatory activity by inhibiting phospholipase A$_2$ (PLA$_2$). Recent X-ray crystallographic study of annexin I identified six Ca$\^$2+/ binding bites, which was different types (type II, III) from the well-known EF-hand motif (type I). In this work, the structure of annexin I was studied at atomic level by using $^1$H, $\^$15/N and $\^$l3/C NMR(nuclear magnetic resonance) spectroscopy, and the effect of Ca$\^$2+/ binding on the structure of annexin I was studied, and compared with that of Mg$\^$2+/ binding, When Ca$\^$2+/ was added to annexin I, NMR peak change was occured in high- and low-field regions of $^1$H-NMR spectra. NMR peak change by Ca$\^$2+/ binding was different from that by Mg$\^$2+/ binding. Because annexin I is a larger protein with 35 kDa molecular weight, site-specific (amide-$\^$15/N, carbonyl-$\^$l3/C) labeling technique was also used. We were able to detect methionine, tyrosine and phenylalanine peaks respectively in $\^$13/C-NMR spectra, and each residue was able to be assigned by the method of doubly labeling annexin I with [$\^$13/C] carbonyl-amino acid and [$\^$15/N] amide-amino acid. In $\^$l3/C-NMR spectra of [$\^$13/C] carbonyl-Met labeled annexin I, we observed that methionine residues spatially located near Ca$\^$2+/ binding Sites Were Significantly effected by Ca$\^$2+/ binding. From UV spectroscopic data on the effect of Ca$\^$2+/ binding, we knew that Ca$\^$2+/ binding sites of annexin I have cooperativity in Ca$\^$2+/ binding. The interaction of annexin I with PLA$_2$ also could be detected by using heteronuclear NMR spctroscopy. Consequently, we expect that the anti-inflammatory action mechanism of annexin I may be a specific protein-protein interaction. The residues involved in the interaction with PLA$_2$ can be identified as active site by assigning NMR peaks effected by PLA$_2$ binding.

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Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats

  • Zhang, Weiqian;Liu, Yan;Ge, Ming;Jing, Jiang;Chen, Yan;Jiang, Huijie;Yu, Hongxiang;Li, Ning;Zhang, Zhigang
    • Nutrition Research and Practice
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    • v.8 no.2
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    • pp.220-226
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    • 2014
  • BACKGROUND/OBJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide ($As_2O_3$)-induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg $As_2O_3$ (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before $As_2O_3$ treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS: Rats treated with $As_2O_3$ had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content ($0.805{\pm}0.059{\mu}g/g$) of kidneys in rats treated with $As_2O_3$. However, resveratrol had no effect on zinc level in the kidney relative to $As_2O_3$-treated groups. CONCLUSIONS: Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.

A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy

  • Naseer, Muhammad Imran;Alwasiyah, Mohammad Khalid;Abdulkareem, Angham Abdulrahman;Bajammal, Rayan Abdullah;Trujillo, Carlos;Abu-Elmagd, Muhammad;Jafri, Mohammad Alam;Chaudhary, Adeel G.;Al-Qahtani, Mohammad H.
    • Genes and Genomics
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    • v.40 no.11
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    • pp.1149-1155
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    • 2018
  • Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.

Effects of ultraviolet light B irradiation on nitric oxide activity in the sprague-dawley rat in vivo (I) (흰쥐에 조사한 자외선B가 Nitric Oxide의 활성에 미치는 효과 (I))

  • Min, Kyung-Ok;Kim, Jung-Hwan
    • Journal of Korean Physical Therapy Science
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    • v.6 no.3
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    • pp.63-82
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    • 1999
  • Recent studies have revealed that Nitric oxide(NO) was one of the demonstration for the physiological regulator, endothelial derived relaxing factor(EDRF) and that NO was produced by ultraviolet irradiation in human. Thus, the present author have carried out a experimental study on the change of hematological, histological value of ultraviolet irradiation in sprague-dawley rats. The subjects were divided into four groups of ten rats each selected at random. There were 4 groups: 1. no irradiation control; 2. ultraviolet $75mJ/cm^2$ irradiation group; 3. ultraviolet $150mJ/cm^2$ irradiation group; 4. ultraviolet $225mJ/cm^2$ group. After a irradiation, hematological and histological tests were performed to observe erythrocyte, hemoglobin, hematocrit, MCH, MCHC, MCV, $O_2$ saturation, pH, $PO_2,\;PCO_2$ value and to observe histological changes. In hematological tests, erythrocyte, hemoglobin, hematocrit significantly increased in $75mJ/cm^2$ than control group and more $150mJ/cm^2$ ultraviolet irradiation group respectively. Also In blood gas tests, $PO_2$ significantly increased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group. Whereas $PCO_2$ significantly decreased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group (Duncan-Tukey test, P<0.05). In histological tests, control and $75mJ/cm^2$ group unchanged, but more $150mJ/cm^2$ group changed that it was cytolysis, cytotoxic effect, acanthosis, proliferation of keratinocyte, appearance of amorphous cell and pyknotic nucleus, production of sunburn cell. In conclusion, the present author results support the importance of the relation between NO effect and hematological, histological value by ultraviolet B irradiation.

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Implementation a Physical Ear Model for Determinating Location of the Microphone of Fully Implantable Middle Ear Hearing Device (완전 이식형 인공중이용 마이크로폰의 위치 결정을 위한 물리적 귀 모델의 구현)

  • Kim, D.W.;Seong, K.W.;Lim, H.K.;Kim, M.W.;Jung, E.S.;Lee, J.W.;Lee, M.W.;Lee, J.H.;Kim, M.N.;Cho, J.H.
    • Journal of rehabilitation welfare engineering & assistive technology
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    • v.2 no.1
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    • pp.27-33
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    • 2009
  • Generally, implantable microphone has been implanted in the temporal bone for implantable middle ear hearing devices (IMEHDs). In this case, the microphone's membrane can be damaged and can be generated biological noise. In order to overcome the these problems, the location of implanted microphone should be changed. As an alternative, the microphone can be implanted in the external auditory canal. However, the sound emission can be produced because of vibration transducer toward reverse direction from the tympanic membrane to the external auditory canal. In this paper, an amount of the emitted sound is measured using a probe microphone as the changing the position of microphone in the external auditory canal of a physical ear model, which is similar to acoustical and vibratory properties of the human ear. Through the measured value, the location of the microphone was assumed in the external auditory canal. According to the analysis, the microphone input sound can be decreased when microphone position become more distance from the tympanic membrane in the auditory canal. However, the external auditory canal is not appropriated to implantable microphone position, because sound emission is not completely eliminated.

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Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

  • Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4031-4036
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    • 2012
  • Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

The Effect of Franchisor's On-going Support Services on Franchisee's Relationship Quality and Business Performance in the Foodservice Industry (외식 프랜차이즈 가맹본부의 사후 지원서비스가 가맹점의 관계품질과 경영성과에 미치는 영향)

  • Lee, Jae-Han;Lee, Yong-Ki;Han, Kyu-Chul
    • Journal of Distribution Research
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    • v.15 no.3
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    • pp.1-34
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    • 2010
  • Introduction The purpose of this research is to develop overall model which involves the effect of ongoing support services by franchisor on franchisee's relationship quality(trust, satisfaction, and commitment) and business performance(financial and non-financial performance), and to investigate the relationships among trust, satisfaction, commitment, financial and non-financial performance. This study also suggests franchise business or franchise system should be based on long-term orientation between franchisor and franchisee rather than short-term orientation, or transactional relationship, and proposes the most effective way of providing on-going support services by franchisor with franchisee thru symbiotic relationship among franchisor and franchisee Research Model and Hypothesis The research model as Figure 1 shows the variables on-going support services which affect the relationship quality between franchisor and franchisee such as trust, satisfaction, and commitment, and also analyze the effects of relationship quality on business performance including financial and non-financial performance We established 12 hypotheses to test as follows; Relationship between on-going support services and trust H1: On-going support services factors (product category & price, logistics service, promotion, information providing & problem solving capability, supervisor's support, and education & training support) have positive effect on franchisee's trust. Relationship between on-going support services and satisfaction H2: On-going support services factors (product category & price, logistics service, promotion, information providing & problem solving capability, supervisor's support, and education & training support) have positive effect on franchisee's satisfaction. Relationship between on-going support services and commitment H3: On-going support services factors (product category & price, logistics service, promotion, information providing & problem solving capability, supervisor's support, and education & training support) have positive effect on franchisee's commitment. Relationship among relationship quality: trust, satisfaction, and commitment H4: Franchisee's trust has positive effect on franchisee's satisfaction. H5: Franchisee's trust has positive effect on franchisee's commitment. H6: Franchisee's satisfaction has positive effect on franchisee's commitment. Relationship between relationship quality and business performance H7: Franchisee's trust has positive effect on franchisee's financial performance. H8: Franchisee's trust has positive effect on franchisee's non-financial performance. H9: Franchisee's satisfaction has positive effect on franchisee's financial performance. H10: Franchisee's satisfaction has positive effect on franchisee's non-financial performance. H11: Franchisee's commitment has positive effect on franchisee's financial performance. H12: Franchisee's commitment has positive effect on franchisee's non-financial performance. Method The on-going support services were defined as an organized system of continuous supporting services by franchisor for the purpose of satisfying the expectation of franchisee based on long-term orientation and classified into six constructs such as product category & price, logistics service, promotion, providing information & problem solving capability, supervisor's support, and education & training support. The six constructs were measured agreement using a 7-point Likert-type scale (1 = strongly disagree to 7 = strongly agree)as follows. The product category & price was measured by four items: menu variety, price of food material provided by franchisor, and support for developing new menu. The logistics service was measured by six items: distribution system of franchisor, return policy for provided food materials, timeliness, inventory control level of franchisor, accuracy of order, and flexibility of emergency order. The promotion was measured by five items: differentiated promotion activities, brand image of franchisor, promotion effect such as customer increase, long-term plan of promotion, and micro-marketing concept in promotion. The providing information & problem solving capability was measured by information providing of new products, information of competitors, information of cost reduction, and efforts for solving problems in franchisee's operations. The supervisor's support was measured by supervisor operations, frequency of visiting franchisee, support by data analysis, processing the suggestions by franchisee, diagnosis and solutions for the franchisee's operations, and support for increasing sales in franchisee. Finally, the of education & training support was measured by recipe training by specialist, service training for store people, systemized training program, and tax & human resources support services. Analysis and results The data were analyzed using Amos. Figure 2 and Table 1 present the result of the structural equation model. Implications The results of this research are as follows: Firstly, the factors of product category, information providing and problem solving capacity influence only franchisee's satisfaction and commitment. Secondly, logistic services and supervising factors influence only trust and satisfaction. Thirdly, continuing education and training factors influence only franchisee's trust and commitment. Fourthly, sales promotion factor influences all the relationship quality representing trust, satisfaction, and commitment. Fifthly, regarding relationship among relationship quality, trust positively influences satisfaction, however, does not directly influence commitment, but satisfaction positively affects commitment. Therefore, satisfaction plays a mediating role between trust and commitment. Sixthly, trust positively influence only financial performance, and satisfaction and commitment influence positively both financial and non-financial performance.

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Promoter Cloning of Human SETDB1 Gene Utilizing Bioinformatic Programs (생물정보 프로그램을 활용한 SETDB1 유전자 프로모터 클로닝)

  • Noh, Hee-Jung;Kim, Keun-Cheol
    • Journal of Life Science
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    • v.24 no.1
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    • pp.1-7
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    • 2014
  • Eukaryotic gene expression is an important process, which is initiated by several transcription factors and RNA polymerases that occupy the promoter region of genomic DNA. Although there are many experiments to identify the promoter region in a gene, it is time and labor consuming to finalize it. In this study, we utilized bioinformatic programs, including Ensembl, NCBI, and CpG plots, to identify the cloning promoter region in SETDB1 genomic DNA. We performed PCR amplification to obtain the SETDB1 promoter on an approximately 2 kb region upstream from the TSS named SETDB1-P1. The PCR product was ligated with TA cloning vectors, and we confirmed the insert size using restriction enzyme digestion. Sequentially, the insert was subcloned into a pGL3-luc vector to produce pGL3-SETDB1- P1-luc and then confirmed by DNA sequencing. We also obtained a fragmented PCR product called P2 and P3 and performed a luciferase assay using pGL3-SETDB1-P1-luc transfection. We found that several anticancer drugs, including taxol, 4-FU, and doxorubicin, decreased the promoter activity of SETDB1. We obtained consistent data on the regulation of SETDB1 gene expression after anticancer drug treatment using Western blot analysis and RT-PCR. Our results suggest that promoter cloning of the human SETDB1 gene utilizing bioinformatics is a very useful and timesaving approach to study gene expression.

The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.