• Title/Summary/Keyword: Histological differentiation

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Disruption of the Tff1 gene in mice using CRISPR/Cas9 promotes body weight reduction and gastric tumorigenesis

  • Kim, Hyejeong;Jeong, Haengdueng;Cho, Yejin;Lee, Jaehoon;Nam, Ki Taek;Lee, Han-Woong
    • Laboraroty Animal Research
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    • v.34 no.4
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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.

Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress

  • Kim, Tae Jin;Pyun, Do Hyeon;Kim, Myeong Jun;Jeong, Ji Hoon;Abd El-Aty, A.M.;Jung, Tae Woo
    • Journal of Ginseng Research
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    • v.46 no.3
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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.

Gintonin-enriched fraction protects against sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy in high-fat diet-fed mice

  • Jin, Heegu;Oh, Hyun-Ji;Nah, Seung-Yeol;Lee, Boo-Yong
    • Journal of Ginseng Research
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    • v.46 no.3
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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.

Effect of water extract Phellinus linteus-discard Schisandra chinensis solid fermented extracts in an Animal Model of Dexamethasone-Induced Muscle Loss (Dexamethasone으로 유도한 근감소 동물모델에서 상황버섯-오미자박 고상발효 열수추출물의 근감소 개선에 대한 효과)

  • Su-Jin, Hwang;Young-Suk, Kim;Tae Woo, Oh
    • Herbal Formula Science
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    • v.30 no.4
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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.

Effects of topical application of Phospholipid derivatives on the secretion of sebum on the skin of the fuzzy rats

  • Y. A. Hwang;Park, W. K.;Park, C. Y.;Kim, J. W.;Park, C. S.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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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.

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New established cell lines from undifferentiated pleomorphic sarcoma for in vivo study

  • Eun-Young Lee;Young-Ho Kim;Md Abu Rayhan;Hyun Guy Kang;June Hyuk Kim;Jong Woong Park;Seog-Yun Park;So Hee Lee;Hye Jin You
    • BMB Reports
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    • v.56 no.4
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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.

The optimal dosage of hyaluronic acid for bone regeneration in rat calvarial defects

  • Ling Li;Jungwon Lee;Young-Dan Cho;Sungtae Kim;Yang-Jo Seol;Yong-Moo Lee;Ki-Tae Koo
    • Journal of Periodontal and Implant Science
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    • v.53 no.4
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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).

Characterization of age- and stage-dependent impaired adult subventricular neurogenesis in 5XFAD mouse model of Alzheimer's disease

  • Hyun Ha Park;Byeong-Hyeon Kim;Seol Hwa Leem;Yong Ho Park;Hyang-Sook Hoe;Yunkwon Nam;Sujin Kim;Soo Jung Shin;Minho Moon
    • BMB Reports
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    • v.56 no.9
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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.

MRI Findings and Differential Diagnosis of Benign and Malignant Tumors of the Uterine Corpus (자궁체부의 양성 및 악성 종양의 자기공명영상 소견과 감별 진단)

  • Jihyun Kim;Suk Hee Heo;Sang Soo Shin;Yong Yeon Jeong
    • Journal of the Korean Society of Radiology
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    • v.82 no.5
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    • pp.1103-1123
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    • 2021
  • The uterus can be largely divided into the uterine corpus and uterine cervix. Diseases that can occur in the uterine corpus, composed of the endometrium and myometrium, vary from benign to malignant tumors. Ultrasound and CT are the primary non-invasive evaluation methods to differentiate between benign and malignant tumors, but in some cases, they are difficult to differentiate due to their non-specific imaging findings. However, magnetic resonance imaging (MRI), which has high resolution, helps not only in locating lesions but also in evaluating histological characteristics and staging of malignant tumors. In this review article, the characteristic MRI findings that radiologists should be aware of regarding various benign and malignant tumors detected in the uterine corpus are summarized with their points of differentiation.

Primary Radiation Therapy of Malignant Salivary Gland Tumors by Conventional Megavoltage Irradiation -Korea Cancer Center Hospital- (악성 타액선 종양의 방사선 치료 성적에 대하여 -원자력 병원의 10년 경험 ($1975.1{\sim}1984.12$)-)

  • Cho Chul Koo;Koh Kyoung Hwan;Yoo Seong Yul;Park Young Hwan;Park Woo Yoon;Shim Young Sang;Oh Kyung Kyoon
    • Radiation Oncology Journal
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    • v.8 no.1
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    • pp.35-43
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    • 1990
  • Retrospective analysis of survival rates was undertaken in the patients of 58 cases treated with conventional radiation therapy for malignant salivary gland tumors between January 1975 and December 1984 in Korea Cancer Center Hospital (KCCH). They were patients whose long-term follow-up was possible and who had refused surgery or had had recurrences postoperatively. Out of 58 patients, 25 patients ($43.1\%$) had mucoepidermoid carcinomas and 24 patients ($41.3\%$) adenoid cystic carcinoma. Total actuarial survival rates at 5 years and 10 years were $68.2\%\;and\;31.8\%$ respectively, but disease-free survival rates, $43.2\%\;and\;13.0\%$, respectively. According to TNM stage, the survival rates at 5 years were $86.5\%$ in $T_1,\;40.0\%\;in\;T_2+T_3,\;and\;0\%\;in\;T_4$. In terms of histologic types, 5 years disease-free survival rate of adenoid cystic carcinomas ($40.1\%$) was lower than that of mucoepidermoid carcinomas ($49.8\%$) but overall survival rate ($77.3\%$) was much higher than that of mucoepidermoid carcinomas ($51.5\%$). There-fore, we concluded that the patients, who had had disease after failure of treatment, could survive during a certain period of time and their alive times were 2 years on the average. There was a difference in survival rates in the mucoepidermoid carcinomas in terms of histological grade of differentiation and it was a arbiter in prognosis: 5 YSR of low-grade was $78.8\%$ and higher 2 times than that of high-grade. There was no difference in survival rates according to location and sex. The number of patients having minor salivary gland tumors was 6 cases and their actuarial 5 YSR was $32.3\%$. Consequently, prognostic factors which influence the survival rates of patients with malignant salivary gland tumors are thought to be 1) histological subtypes 2) T and N staging (AJCC) 3) histological grade, especially in mucoepidermoids.

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