• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• Tuberculosis and Respiratory Diseases
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• 제43권1호
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• pp.75-87
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• 1996

연구배경: 폐암은 우리나라 남자들의 악성종양중에서 2번째로 많으며, 수술요법이 가장 좋은 치료이나 대부분의 환자들이 진단당시 수술을 받을 수 없을 정도로 진행되어서 방사선치료(RT)나 항암치료를 동반한 RT를 받게되는데, 방사선-폐렴 및 폐섬유증의 발생이 제일 중요한 부작용이다. 방사선-폐렴은 대개 치료부위에 국한되어 발생하나 때로는 반대쪽에서까지 생기기도하며, Gibson 등은 RT후 양쪽폐에서 BAL액내 세포수 및 임파구가 증가한다고 보고하였다. 방사선-폐렴이 RT의 가장 중요한 제한요소이기 때문에 이의 발생을 조기에 진단하는 것이 환자의 예후에 매우 중요한 영향을 미친다. 이에 연구자들은 염증반응을 야기하는데 중요한 역할을 한다고 알려진 접착분자(ICAM-1, CD18)들이 방사선-폐렴의 발생에도 작용을 하는지, 만일 한다면 이를 방사선-폐렴의 진단 및 예측인자로 사용할 수 있을 가를 살펴보고, 또 방사선-폐렴이 양측성으로 오는 가를 보기위하여 본 연구를 시행하였다. 대상: 조직학적으로 확인된 폐암으로 RT를 받을 환자 29예를 대상으로 하였는데 RT 전에는 16예에서, RT후 1~2개월에는 18예에서 BAL및 혈중 sICAM 농도를 측정하였다. 5예에서는 RT전 및 후에 BAL을 시행하였다. 결과: 7예에서 임상적으로 유의한 방사선-폐렴이 발생하였다. 전 환자군에서 보면, BAL 액내 총 세포수가 $20.2{\pm}10.2{\times}10^6\;cells/L$에서 $35.3{\pm}21.6{\times}10^6\;cells/L$(p=0.0344)로 증가하였으며, 임파구도 $5.3{\pm}4.2%$에서 $39.6{\pm}23.4%$로 유의하게 증가하였다(p=0.0001). 이러한 변화는 RT를 받은 쪽 뿐 아니라 받지 않은 쪽에서도 같이 일어났으며, 방사선-폐렴이 생긴 환자와 생기지 않은 환자 사이에서도 차이가 없었다. 혈중 sICAM농도와 BAL애내 농도는 RT전후로 유의한 차이가 없었으나(혈청: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$) 방사선-폐렴이 발생한 환자들에서는 방사선-폐렴이 생기지 않은 환자에 비해 sICAM 유의하게 증가되었다(혈청: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). 또한 폐포대식세포(AM)에서의 ICAM-1 발현도도 RT후에 증가하는 추세를 보였으나 통계적 유의성은 없었는데(RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), 방사선-폐렴이 생긴 환자들에서($2.10{\pm}0.390$) 방사선-폐렴이 생기지 않은 환자에 비해($1.28{\pm}0.31$, p=0.0002) 유의하게 높았다. 이상의 BAL 결과로 미루어 RT후에 대부분의 환자들에서 양측성으로 subclinical alveolitis가 발생한 확인하였다. 그러나 임상적인 방사선-폐렴은 훨씬 드물게 발생하고, AM의 ICAM발현도 및 혈중 sICAM농도는 이러한 임상적인 방사선-폐렴발생의 좋은 지표가 될 수 있다고 사료된다.

• Journal of Periodontal and Implant Science
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• 제29권4호
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• pp.873-893
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• 1999

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue and repair of function. For more than a decade there have been many efforts to develop materials and bioactive molecule(such as growth factor and differentiation factors) to promote periodontal wound healing. Among the bioactive molecules, bone morphogenetic protein(BMP) was studied for periodontal wound healing. Since Urist demonstrated that demineralized bone matrix could induce the formation of cartilage and bone in ectopic site, many studies on BMP have been reported. Among those BMPs, it was reported that rhBMP-2 enhanced the healing of bone defects in animal studies and clinical studies. However, its efficacy in periodontal regeneration, especially 1-wall intrabony defects is still unknown. The purpose of this study was to examine the effect of rhBMP-2/ACS on the epithelial migration, gingival connective tissue adhesion, cementum formation, alveolar bone regeneration in intrabony defects of dogs. Four millimeter deep and four millimeter wide 1-wall defects were surgically created in the mesial aspects of the 3rd incisors. The test group received rhBMP-2/ACS with a flap procedure and the control underwent buffer/ACS with a flap procedure. Histologic analysis after 8 weeks of healing revealed the following results: 1. The length of epithelial growth(the distance from alveolar crest to the apical end of JE) was $0.9{\pm}1.5mm$ in the control group and $1.2{\pm}1.4mm$ in the test group. There was no statistically significant difference between the two groups. 2. The length of connective tissue adhesion was $2.4{\pm}1.3mm$ in the control group and $1.2{\pm}1.1mm$ in the test group. The control group showed significantly enhanced adhesion(P<0.05). 3. The length of new cementum was $0.9{\pm}1.0mm$ in the control group and $1.7{\pm}0.8mm$ in the test group. The test group showed significantly enhanced cementum regeneration(P<0.05). 4. The length of new bone height was $1.9{\pm}0.6mm$ in the control group and $2.4{\pm}0.9mm$ in the test group. There was no statistically significant difference between the two groups. 5. The new bone area was $4.7{\pm}1.7mm^2$ in the control group and $8.0{\pm}2.0mm^2$ in the test group. The test group showed significantly enhanced bone formed area(P<0.05). 6. The new bone density was $73.0{\pm}8.6%$ in the control group and $66.6{\pm}15.3%$ in the test group. There was no statistically significant difference between the two groups. These results suggest that the use of rhBMP-2 in 1-wall intrabony defects has significant effect on new cementum and new bone formation area, but doesn't have any significant effect on the prevention of junctional epithelium migration and new bone formation height.

• Molecules and Cells
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• 제38권6호
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• pp.528-534
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• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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• pp.453-459
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• 2010

Introduction: Ameloblastic carcinoma is a rare malignant lesion, and may arise from either carcinoma ex-ameloblastoma or de novo carcinoma. Aberrant promoter hypermethylation of the tumor-associated genes leading to their inactivation is a common event in many cancer types. The p16/CDKN2/INK4A gene and p16 5 protein are involved directly in regulating the cell cycles. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. The aim of this study was to evaluate the roles of p16 and E-cadherin methylation and loss of p16 and E-cadherin expression in the malignant transformation of an ameloblastoma. Materials and Methods: Eight cases of ameloblastoma, including 4 benign ameloblastomas without recurrence, 2 benign ameloblastomas with recurrence and 2 carcinoma ex-ameloblastomas, were examined. The promoter hypermethylation profile of the p16 and E-cadherin genes was studied using methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining for p16 and E-cadherin expression. Results: 1) Aberrant CpG island methylation of the p16 gene was detected in 3 of the 4 benign ameloblastomas without recurrence and 1 of the 2 benign ameloblastomas with recurrence. 2) Aberrant CpG island methylation of the E-cadherin gene was found in 1 of the 4 benign ameloblastomas without recurrence. 3) A loss of p16 expression was noted in 1 of 4 benign ameloblastomas without recurrence and 1 of 2 carcinoma ex-ameloblastomas. 4) A loss of E-cadherin expression was noted in 2 of the 4 benign ameloblastomas without recurrence, 1 of the 2 benign ameloblastomas with recurrence and 2 of the 2 carcinoma ex-ameloblastomas. 5) A loss of p16 expression was observed in 1 of the 4 cases showing aberrant methylation of the p16 gene. 6) A loss of E-cadherin expression was observed in 3 benign ameloblastoma case showing aberrant methylation of the E-cadherin gene. Conclusion: These results suggest that loss of E-cadherin expression related to the other genetic pathway (not methylation) might be an adjuvant indicator predicting the malignant transformation of an ameloblastoma. However, the number of samples in this study was too small and the relationship between the treatment methods and clinical course were not defined. Therefore, further study will be needed.

• Tuberculosis and Respiratory Diseases
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• 제43권4호
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• pp.527-535
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• 1996

연구배경 : 내피세포와 백혈구 및 상피세포에서 주로 발견되는 sICAM-1은 백혈구 표면의 배위자인 (ligand)인 LFA-1과 결합함으로서 염증성 질환 이외에 악성 종양의 전이와 진행에 중요한 역할을 하는 것으로 알려졌다. 최근에는 혈청내 sICAM-1의 농도가 악성 흑세포종의 전이와 비례하여 증가되는 것으로 보고되었으며, 또한 sICAM-1의 이형이 여러 질환에서 발견되고 이들의 혈청 농도의 증가는 위암, 대장암, 담낭암, 췌장암의 간전이와 관련되며, 악성 흑세포종 환자의 생존율의 감소와 관련되는 것으로 보고하였으나 폐암에서는 이에 대한 보고는 거의 없다. 이에 저자들은 폐암 환자의 혈청에서 sICAM-1을 측정하여 폐암의 조직학적 분류와 진행 및 전이의 정도에 따른 변화를 알아보고 폐암의 진단적 가치에 대하여 알아 보고자 하였다. 방법 : 1995년 1월부터 1996년 3월까지 전북대학교병원 내과에 입원하여 폐암을 진단 받은 환자 38명을 대상으로 하였으며, 정상 대조군은 비슷한 연령의 다른 질환을 갖고 있지 않은 8명을 대상으로 하였으며, 기관지 내시경을 통한 조직 생검이나 경피적 세침 흡입술을 이용하여 확진을 하였으며, 각 조직학적 분류에 따른 진행정도를 알기 위하여 TNM system 을 이용하여 분류하였고, 소세포 폐암은 limited stage와 extensive stage로 분류하였다. Genzyme사의 Predicts sICAM-1 ELISA kit를 이용하여 혈청 sICAM-1농도를 측정하였다. 결과 : 1. 소세포 폐암군에서 혈청 sICAM-1은 정상 대조군에 비해 유의한 증가가 없었으나, extensive stage군에서 limited stage군에 비해 유의한 증가를 보였다. 2. 편평상피암군에서 혈청 sICAM-1은 정상 대조군에 비해 유의한 증가를 보였으며, stage IIIa기 이하군에 비해 stage IIIb기 이상군에서 유의한 증가를 보였다. 3. 선폐암 환자군에서 혈청내 sICAM-1은 정상 대조군에 비해 유의한 증가를 보였다. 결론 : 혈청 sICAM-1농도의 변화는 폐암의 조직학적 분류에 따라 다르게 나타나며, 폐암의 전이 및 진행과 관련이 있을 것으로 보인다. 폐암 환자에서 혈청 sICAM-1농도의 측정은 폐암에서 진행의 정도를 평가하는 데 지표로서 이용될 수 있을 것으로 사료된다.

• 한국환경과학회지
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• 제18권3호
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• pp.299-308
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• 2009

We manufactured PVA-derived hydrogels using a foam generation technique that has been widely used to prepare colloidal gas aphrons(CGA). These gels were differentiated to the conventional gels such as for medical or pharmaceutical applications, which have tiny pores and some crystalline structure. Rather these should be used in de-pollution devices or adhesion of cells or biomolecules. The crosslinkers used in this work were amino acid, organic acid, sugars and lipids(vitamins). The structures of the gels were observed in a scanned electron microscope. Amino acids gels showed remarkably higher swelling ratios probably because their typical functional groups help constructing a highly crosslinked network along with hydrogen bonds. Boric acid and starch would catalyze dehydration while structuring to result in much lower water content and accordingly high gel content, leading to less elastic, hard gels. Bulky materials such as ascorbic acid or starch produced, in general, large pores in the matrices and also nicotinamide, having large hydrophobic patches was likely to enlarge pore size of its gels as well since the hydrophobicity would expel water molecules, thus leading to reduced swelling. Hydrophilicity(or hydrophobicity), functional groups which are involved in the reaction or physical linkage, and bulkiness of crosslinkers were found to be more critical to gel's cross linking structure and its density than molecular weights that seemed to be closely related to pore sizes. Microscopic observation revealed that pores were more or less homogeneous and their average sizes were $20{\mu}m$ for methionine, $10-15{\mu}m$ for citric acid, $50-70{\mu}m$ for L-ascorbic acid, $30-40{\mu}m$ for nicotinamide, and $70-80{\mu}m$ for starch. Also a sensory test showed that amino acid and glucose gels were more elastic meanwhile acid and nicotinamide gels turned out to be brittle or non-elastic at their high concentrations. The elasticity of a gel was reasonably correlated with its water content or swelling ratio. In addition, the PVA gel including 20% ascorbic acid showed fair ability of cell adherence as 0.257mg/g-hydrogel and completely degraded phenanthrene(10 mM) in 240 h.

• Journal of Oral Medicine and Pain
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• 제33권1호
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• pp.35-40
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• 2008

고농도 세포외 포도당이 치주인대세포의 integrin 발현과 cathepsin-B 및 -L의 발현에 미치는 영향을 살펴보기 위하여 사람 치주인대로부터 일차배양을 통해 얻은 치주인대세포를 1,000 mg/L 농도의 포도당이 포함된 배양액(대조군)과 4,500mg/L 농도의 포도당이 포함된 배양액(실험군)으로 나누어 24시간과 48시간 배양하였다. 그 후, RT-PCR을 통하여 integrin, cathepsin-B 및 -L의 발현을 평가하여 다음과 같은 결론을 얻었다. 1. 대조군에 비해 실험군에서 ${\alpha}5$ intergrin 발현이 증가하였다. 2. Cathepsin-B는 24시간 배양 실험군에서 발현이 증가하였으나, 48시간 배양후에는 발현이 감소하였다. 3. Cathepsin-L은 24시간과 48시간 배양군 모두에서 대조군에 비해 실험군에서 발현이 감소하였다. 이상의 결과로 보아, 고농도 포도당 조건은 치주인대세포의 integrin 발현을 증가시키며, 이는 세포활성에 영향을 미쳐 치주조직의 재생을 지연시킬 것으로 추측된다. 또한, 이 과정은 cathepsin 발현의 감소로 인해 촉진될 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.871-876
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• 2014

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters. Methods: The mRNA expression of DSGs, as well as ${\gamma}$-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens. Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p=0.000). DSG3 mRNA expression highly correlated with histological grade (p=0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p=0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of ${\gamma}$-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules. Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

• Asian-Australasian Journal of Animal Sciences
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• 제31권4호
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.