• Radiation Oncology Journal
• /
• 제18권4호
• /
• pp.314-320
• /
• 2000

목적 :폐암으로 확진되어 근치적 방사선 치료를 받은 환자에서 방사선페렴이 발생할 수 있는 위험군을 사전에 예측해 보고자 혈장내 TGF-$\beta$1, TNF-$\alpha$, IL-6의 농도를 측정하여 페렴 발생과의 상관관계를 분석하고자 하였다. 재료 및 방법 : 1998년 5월부터 1999년 7월까지 폐암으로 확진되어 근치적 방사선 치료를 받은 17명의 환자(비소세포암 11명, 소세포암 6명)을 대상으로 하였다. 방사선 치료는 주 5회 매일 1.8 Gy씩 실시하였고 비소세포암과 소세포암에서 각각 평균 60 Gy와 져 Gy를 조사하였다. 모든 환자에서 방사선치료 전, 방사선치료 중 주 1회, 치료 후 추적관찰로 내원시마다 혈액을 채취하여 혈장 TGF-$\beta$1, TNF-$\alpha$ 및 IL-6의 양을 ELISA법으로 측정하였다. 모든 환자에서 단순흉부촬영(치료중 주1회, 치료 후 추적관찰 시마다 촬영) 및 방사선 폐렴과 연관된 증세를 관찰하여 방사선 페렴의 징후가 발견되면 즉시 고해상도 컴퓨터 단층 촬영(HRCT)를 촬영하여 방사선 폐렴 발생여부를 확진하고자 하였다. 결과: 17명의 환자 중 13명에서 방사선 폐렴과 연관된 증세가 발현되었고 단순 흉부 촬영과 고해상도 컴퓨터 단층 찰영에서 이를 확인할 수 있었다. 방사선 폐렴이 발생한 환자에서 측정한 TGF-$\beta$1의 경우 특징적인 수치 변화를 보여 치료 전 평균값은 38.45 ng/ml로 방사선 페렴이 발생하지 않은 군에 비해 상승되어 나타났고(0.7T ng/ml) 방사선치료 중 13.66 ng/ml의 평균값을 보인 후 다시 점진적으로 상승하여 치료 2$\~$4주 후까지 평균 60.63 ng/ml로 상승되어 유지되었고 이 수치는 폐렴이 발생하지 않은 군과 비교할 때(12.77 ng/ml) 통계적으로 의미가 있었다(p<0.05). TNF-$\alpha$와 IL-6의 수치도 방사선 폐렴군에서 더 높게 측정되었으나 수치변화의 양상은 특징적이지 못하였으며 통계학적 의미도 찾을 수 없었다. 결론: 방사선 치료를 받은 폐암환자에서 치료 전과 치료 기간 중 및 치료 후 측정한 혈장 TGF-$\beta$1,의 수치는 향후 방사선 페렴이 발생할 위험군을 예측할 수 있는 지표로 사용할 수 있을 것으로 사료된다.

• Radiation Oncology Journal
• /
• 제23권3호
• /
• pp.161-168
• /
• 2005

목적: 강력한 항산화 효과를 지닌 melatonin을 전처치하였을 때 방사선유도성 섬유증 과정에서 중요한 사이토카인인 $TGF-{\beta}1$의 변화된 발현양상을 마우스 폐에서 연구하였다. 대상 및 방법: C57BL/6 마우스를 실험군에 따라 세 군(대조군, 방사선조사 단독군, melatonin 전처치군(방사선조사 1시간 전에 300 mg/kg 복강주사))으로 분류하고 양측 흉곽에 12 Gy의 선량을 단일조사하였다. 방사선조사 후 2주와 4주의 폐조직에서 $TGF-{\beta}1$ mRNA 발현수준을 측정하기 위해 semiquantitive RT-PCR를 시행하였고, $TGF-{\beta}1$ protein 발현의 수준과 위치를 보기 위해 면역조직화학염색을 시행하였다. 결과: 2주 후에 측정된 mRNA 발현은 방사선조사 단독군과 melatonin 전처치군에서 각각 대조군의 1.92배와 1.80배 증가된 수준을 보였고(p=0.064), 4주 후에는 각각 2.38배와 1.94배 수준의 증가된 발현을 보였다(p=0.004). $TGF-{\beta}1$ protein의 발현은 조직병리학적으로 방사선손상 영역에서 주로 관찰되었는데 폐포 대식세포와 폐포벽의 상피세포들이 주요 근원이었다. 발현수준은 2주완 4주 후에 각각 $15.8\%\;vs\;16.9\%$ (P=0.565), 그리고 $36.1\%\;vs\;25.7\%$ (p=0.009)이었다. 결론: Melatonin 전처치로 방사선조사에 의한 $TGF-{\beta}1$ mRNA와 protein의 발현이 4주 후에 유의하게 감소됨을 관찰하였다. 따라서 방사선으로 인한 폐손상 시에 항섬유증 약물로의 사용가능성을 확인하였다.

• Journal of Ginseng Research
• /
• 제37권4호
• /
• pp.425-434
• /
• 2013

UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-${\beta}$1 level, while accelerated procollagen type I, transforming growth factor-${\beta}$1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes.

• Animal Bioscience
• /
• 제36권1호
• /
• pp.29-42
• /
• 2023

Objective: Pigs, an ideal biomedical model for human diseases, suffer from about 50% early embryonic and fetal death, a major cause of fertility loss worldwide. However, identifying the causal variant remains a huge challenge. This study aimed to detect single nucleotide polymorphisms (SNPs) and candidate genes for the number of mummified (NM) piglets using the imputed whole-genome sequence (WGS) and validate the potential candidate genes. Methods: The imputed WGS was introduced from genotyping-by-sequencing (GBS) using a multi-breed reference population. We performed genome-wide association studies (GWAS) for NM piglets at birth from a Landrace pig populatiGWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase on. A total of 300 Landrace pigs were genotyped by GBS. The whole-genome variants were imputed, and 4,252,858 SNPs were obtained. Various molecular experiments were conducted to determine how the genes affected NM in pigs. Results: A strong GWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase 8 (CDK8) gene, which plays a crucial role in embryonic retardation and lethality. Based on the molecular experiments, we found that Y-box binding protein 1 (YBX1) was a crucial transcription factor for CDK8, which mediated the effect of CDK8 in the proliferation of porcine ovarian granulosa cells via transforming growth factor beta/small mother against decapentaplegic signaling pathway, and, as a consequence, affected embryo quality, indicating that this pathway may be contributing to mummified fetal in pigs. Conclusion: A powerful imputation-based association study was performed to identify genes associated with NM in pigs. CDK8 was suggested as a functional gene for the proliferation of porcine ovarian granulosa cells, but further studies are required to determine causative mutations and the effect of loci on NM in pigs.

• 대한치과교정학회지
• /
• 제42권4호
• /
• pp.207-217
• /
• 2012

Objective: This study aimed to evaluate the effect of an intentionally created socket on bone remodeling with orthodontic tooth movement in rabbits. Methods: Eighteen male rabbits weighing 3.8 - 4.25 kg were used. An 8-mm deep and 2-mm wide socket was drilled in the bone 1 mm mesial to the right mandibular first premolar. The left first premolar was extracted to serve as an extraction socket. A traction force of 100 cN was applied to the right first premolar and left second premolar. Sections were obtained at the middle third of the moving tooth for both the drilled and extraction sockets and evaluated with hematoxylin and eosin staining and immunohistochemical analyses. The amount of tooth movement and tartrate-resistant acid phosphatase (TRAP)-positive cell count were compared between the 2 groups using the Mann-Whitney U test. Results: At week 2, the distance of tooth movement was significantly higher in the intentional socket group (p < 0.05) than in the extraction socket group. The number of TRAP-positive cells decreased in week 2 but increased in week 3 (p < 0.05). However, there were no significant differences between the groups. Furthermore, results of transforming growth factor (TGF)-${\beta}$ staining revealed no significant differences. Conclusions: The intentional socket group showed greater distance of tooth movement than did the extraction socket group at week 2. Osteoclast counts and results of immunohistochemical analyses suggested elevated bone remodeling in both the groups. Thus, osteotomy may be an effective modality for enhancing tooth movement in orthodontic treatment.

• 대한두개안면성형외과학회지
• /
• 제18권1호
• /
• pp.9-15
• /
• 2017

Background: Relaxin is a transforming growth factor ${\beta}1$ antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. Methods: Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. Results: Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. Conclusion: Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated.

• BMB Reports
• /
• 제53권11호
• /
• pp.594-599
• /
• 2020

Lin28a has diverse functions including regulation of cancer, reprogramming and regeneration, but whether it promotes injury or is a protective reaction to renal injury is unknown. We studied how Lin28a acts in unilateral ureteral obstruction (UUO)-induced renal fibrosis following unilateral ureteral obstruction, in a mouse model. We further defined the role of Lin28a in transforming growth factor (TGF)-signaling pathways in renal fibrosis through in vitro study using human tubular epithelium-like HK-2 cells. In the mouse unilateral ureteral obstruction model, obstruction markedly decreased the expression of Lin28a, increased the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin. In TGF-β-stimulated HK-2 cells, the expression of Lin28a was reduced and the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin was increased. Adenovirus-mediated overexpression of Lin28a inhibited the expression of TGF-β-stimulated type I collagen, α-SMA, vimentin and fibronectin. Lin28a inhibited TGF-β-stimulated SMAD3 activity, via inhibition of SMAD3 phosphorylation, but not the MAPK pathway ERK, JNK or p38. Lin28a attenuates renal fibrosis in obstructive nephropathy, making its mechanism a possible therapeutic target for chronic kidney disease.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7091-7095
• /
• 2014

Background: The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. Materials and Methods: Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. Results: The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). Conclusions: CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.

• Parasites, Hosts and Diseases
• /
• 제50권4호
• /
• pp.385-390
• /
• 2012

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of $CD4^+CD25^+Foxp3^+$ T (regulatory T; $T_{reg}$) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-${\gamma}$, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-${\beta}$, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of $T_{reg}$ cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and $T_{reg}$ cells recruitment.

• 대한수의학회지
• /
• 제58권4호
• /
• pp.211-217
• /
• 2018

Mesenchymal stem cells (MSCs) are useful candidates for tissue engineering and cell therapy. Physiological cell environment not only connects cells to each other, but also connects cells to the extracellular matrix that provide mechanical support, thus exposing the entire cell surface and activating signaling pathways. Hydrogel is a polymeric material that swells in water and maintains a distinct 3-dimensional (3D) network structure by cross linking. In this study, we investigated the optimized cellular function for canine adipose tissue-derived MSCs (cAD-MSCs) using hydrogel. We observed that the expression levels of Ki67 and proliferating cell nuclear antigen, which are involved in cell proliferation and stemness, were increased in transwell-hydrogel (3D-TN) compared to the transwell-normal (TN). Also, transforming growth factor-${\beta}1$ and SOX9, which are typical bone morphogenesis-inducing factors, were increased in 3D-TN compared to the TN. Collagen type II alpha 1, which is a chondrocyte-specific marker, was increased in 3D-TN compared to the TN. Osteocalcin, which is a osteocyte-specific marker, was increased in 3D-TN compared to the TN. Collectively, preconditioning cAD-MSCs via 3D culture systems can enhance inherent secretory properties that may improve the potency and efficacy of MSCs-based therapies for bone regeneration process.