• Laboraroty Animal Research
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• 제34권4호
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• pp.257-263
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• 2018

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. Tff1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated Tff1-knockout (KO) mice, without a neomycin resistant ($Neo^R$) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our Tff1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established Tff1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that Tff1 expression influences gender differences.

• Journal of Ginseng Research
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• 제46권3호
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• pp.444-453
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• 2022

Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. Methods: C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4-5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. Results: CK treatment attenuated ER stress markers, such as eIF2a phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. Conclusion: These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity.

• Journal of Ginseng Research
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• 제46권3호
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• pp.454-463
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• 2022

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.

• 대한한의학방제학회지
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• 제30권4호
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• pp.269-280
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• 2022

Objectives : In this study, it was investigated the effects of solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis extract (PS) and its action mechanism on dexamethasone-induced muscle atrophy in mice. Methods : In mice, muscle atrophy model was induced by dexamethasone (5 mg/kg, I.p) once daily for 2 weeks and with PS extract administration (100 and 300 mg/kg, p.o.) as treatment groups. The changes in body weights, grip strength, Treadmill test, muscle weights, and the expression of atrophy-related genes were measured in muscle atrophy mice. The histological changes of gastrocnemius tissues were also observed by H&E staining with measurement of myofiber size. Results : The administration of PS extract increased significantly body weights, grip strength, treadmill test and muscle weights in muscle atrophy mice. PS extract administration increased significantly the area of myofibers and inhibited structural damages of muscle and increased significantly the expression of myogenin and decreased significantly the expression of MuRF1, Atrogin1 and phosphorylation of AMPK and PGC1α in muscle tissues of muscle atrophy mice. Conclusions : These results indicate that PS extract has a improvement effects on muscle atrophy with stimulation of myogenic differentiation and inhibition of mRNA degradation that could be related with the activation of AMPK and PGC1α signaling pathways in muscle. This suggests that PS extract can apply to treat muscle atrophy in clinics.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.578-589
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• 2003

The fuzzy rat that expresses hypersecretion of sebum and hyperplastic sebaceous glands is a genetic mutant for the study of many pharmacological aspects especially human acne. Through this model, we examined the effects of several phospholipids on the secretion of sebum after topical application. The phospholipid derivatives were phosphatidylcholine (PC), hydrogenated phosphatidylcholine (HPC), phosphati dylserine (PS) and hydrogenated phosphatidylserine(HPS). All agents were dissolved into the vehicle (1, 3-Butanediol, ethanol and water) at 0.5％ weight volume and applied on the dorsal area of the fuzzy rat. To observe histological changes, the skin biopsies were stained with Oil Red O and the size and morphology of sebaceous gland was observed under microscope. Topical treatment with PC and/or HPC showed a marked decrease in sebum excretion. Especially hydrogenated PC (HPC) appeared to have more predominant sebosuppressive function than any other treatment. The other agents such as PS and HPS showed a marginal effect on sebum secretion. With the sebosuppressive activity, HPC and PC seem to have a good potential application on acne treatment. In order to obtain more insights into possible mechanisms behind the above observations, effects of each phospholipid on the expression of peroxisome proliferator-activated receptor (PPAR) genes were investigated. Recently, it has been demonstrated that expression and activation of PPAR subtypes appear to modulate the accumulation of cytoplasmic fat droplets that characterizes the sebocyte differentiation(1). It was also previously suggested that PPAR${\gamma}$ antagonist would seem possible to interfere sebum production without side effects (2). In this study we examined the diverse effects of the tested phospholipids on the expression of several PPAR genes based on reverse transcription-polymerase chain reaction (RT-PCR) from the topically treated skin of fuzzy rats. The results and possible implications are discussed.

• BMB Reports
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• 제56권4호
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• pp.258-264
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• 2023

As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS.

• Journal of Periodontal and Implant Science
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• 제53권4호
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• pp.259-268
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• 2023

Purpose: Hyaluronic acid (HA) affects angiogenesis and promotes the migration and differentiation of mesenchymal cells, thereby activating the osteogenic ability of osteoblasts. Although studies on the action of HA during bone regeneration are being actively conducted, the optimal dose of HA required for bone regeneration remains unclear. Therefore, the purpose of this study was to elucidate the most effective HA dose for bone formation using a rat critical-size defect model. Methods: Thirty rats were randomly divided into 5 groups, with 6 rats in each group. An absorbable collagen sponge soaked with HA or saline was used to fill an 8-mm defect, which was then covered with a collagen membrane. Different treatments were performed for each group as follows: (1) saline control, (2) 1 mg/mL HA, (3) 25 mg/mL HA, (4) 50 mg/mL HA, or (5) 75 mg/mL HA. After a healing period of 4 weeks, micro-computed tomography and histological analysis were performed. The obtained values were analyzed using analysis of variance and the Tukey test (P<0.05). Results: At week 4, the 75 mg/mL HA group had the highest bone volume/total volume ratio, new bone, and bone fill among the 5 groups, and these values were significantly different from those observed in the control group (P<0.01) and 1 mg/mL HA group (P<0.001). More active bone formation was observed in the higher-dose HA groups (25 mg/mL, 50 mg/mL, and 75 mg/mL HA), which included a large amount of woven bone. Conclusions: The 75 mg/mL HA group showed better bone formation than the other groups (1, 25, and 50 mg/mL HA and control).

• BMB Reports
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• 제56권9호
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• 대한영상의학회지
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• 제82권5호
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• pp.1103-1123
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• 2021

자궁은 크게 자궁체부와 자궁경부로 나뉜다. 이 중 자궁내막과 자궁근층으로 이루어진 자궁체부에는 양성에서 악성 종양까지 다양한 질환이 발생한다. 비침습적인 일차적 평가로 초음파와 컴퓨터단층촬영이 있으나 비특이적인 영상 소견으로 감별이 어려운 경우가 있다. 반면 높은 해상도와 병리학적 특성 파악이 가능한 자기공명영상은 병변의 위치 확인뿐만 아니라 조직학적 특징, 그리고 악성 종양의 병기 설정에도 도움을 준다. 이 종설에서는 영상의학과 의사들이 알아야 할 자궁체부에서 볼 수 있는 다양한 양성과 악성 종양들의 특징적인 자기공명영상 소견들과 이들의 감별점에 대해 정리했다.

• Radiation Oncology Journal
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• 제8권1호
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• pp.35-43
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• 1990

1975년 1월부터 1984년 12월까지 원자력병원 치료 방사선과에서 악성 타액선 종양으로 방사선 치료를 받은 58명의 환자를 대상으로 하여 이들의 생존율을 후향적으로 분석하였다. 이들은 수술후 재발했거나, 수술이 불가능한 환자들이었다. 58명의 환자중 mucoepidermoid carcinoma를 가진 환자가 $43.1\%$, adenoid cystic carcinoma를 가진 환자는 $41.3\%$였다. 주 타액선 종양의 5년 보험생존율은 $68.2\%$, 10년 생존율은 $31.8\%$였으나, 무병생존율은 각각 $43.2\%\;13.0\%$로써 치료 후 재발된 상태에서도 비교적 오래 산다는 것을 알 수 있었다. TNM staging에 의한 생존율도 $T_1$의 5년 생존율이 $86.5\%,\;T_2+T_3$가 $40.0\%,\;T_4$가 $0\%$로, T stage가 높아지면 질수록 생존율도 현저히 감소하였다. 병리조직학적 관점에서 볼 때, adenoid cystic carcinoma의 5년 무병생존율은 $40.1\%$로써, mucoepidermoid ca.의 $49.8\%$보다 낮았으나, 전체적인 생존율은 $77.3\%$로써, mucoepidermoid ca.의 $51.5\%$보다 현저히 높았다. 따라서, adenoid cystic carcinoma는 치료실패후 병을 가진 상태에서도 상당 기간 생존할 수 있다는 것을 알았으며, 평균 생존기간은 2년 이었다. 또한 mucoepidermoid ca.인 경우에는 세포의 분화정도에 따라 생존율이 달라졌는데, 저등도 분화세포의 5년 생존율이 $78.8\%$로 고등도 분화세포의 $38.2\%$보다 거의 2배나 높았다. 암의 위치와 성별에 따른 생존율의 차이는 없었다. Minor salivary gland tumor는 6명으로 5년 보험생존률은 $32.3\%$였다. 따라서 주 타액선 종양의 생존율에 영향을 끼칠 수 있는 예후 인자는 1) 병리조직학적 세포종류, 2) T와 N stages (AJCC), 3) mucoepidermoid carcinoma에 있어서 분화 정도 였다.