• 제목/요약/키워드: differentiation-resistance

검색결과 133건 처리시간 0.021초

C2C12 골격근 세포에서 백출의 분화 조절 효능 (Effect of Root of Atractylodes macrocephala Koidzumi on Myogenesis in C2C12 Cells)

  • 송미영
    • 한방비만학회지
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    • 제15권1호
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    • pp.38-44
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    • 2015
  • Objective: Skeletal muscle is a crucial tissue from the perspectives of mitochondrial dysfunction and insulin resistance, it is formed by myogenesis which is dynamic multistep process to be myotubes. The authors could found that root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) enhanced glucose and lipid metabolism in C2C12 myotubes via mitochondrial regulation. However its action in myogenesis process is not known. The aim of this work was the study of ARA on proliferation, differentiation and hypertrophy in C2C12 cells. Methods: To study proliferation phase, cells were incubated in growth medium with or without ARA (0.2 or 1.0 mg/ml) for 24 hours. To examine differentiation, at 70% confluence, cells were transferred in differentiation medium both with/without ARA (0.2 or 1.0 mg/ml) for 96 hours. And after 72 hours of differentiation, cells were treated with or without ARA (0.2 or 1.0 mg/ml) for 24 hours, the genesis of hypertrophy in myotubes were analyzed. Results: In proliferation phase, ARA could make difference in morphologic examination. In differentiation phase, it also made morphologic difference furthermore ARA (1.0 mg/ml) increased mRNA expressions of Myogenic regulatory factors and muscle-specific proteins synthesis. In late differentiation, ARA induced hypertrophic morphological changes in neo-formed myotubes. Conclusions: ARA might control cell cycle promoting myogenesis and hypertrophy in C2C12 cells.

감귤 잿빛곰팡이병균의 살균제에 대한 저항성 및 유전적 다양성 (Fungicide Resistance and Genetic Diversity of Botrytis cinerea of Citrus)

  • 고영진;이재군;서정규;문두길;한해룡
    • 한국식물병리학회지
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    • 제14권6호
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    • pp.682-688
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    • 1998
  • Fungicide resistance of 48 isolates of Botrytis cinerea collected from citrus in Cheju was investigated and genetic diversity was analyzed with random amplified polymorphic DNA(RAPD). High levels of resistance to benzimidazole fungicides benomyl and thiophanate-methyl and N-phenylcarbamate fungicide diethofencarb were observed. Negative cross resistance was clear between benzimidazole and N-phenylcarbamate fungicides, and multiple resistance to the fungicides was also observed. There was cross resistance among the dicarboximide fungicides procymidione, vinclozolin and iprodione as it was observed between the benzimidazole fungicides benomyl and thiophanate-methyl. The lowest levels of resistance were to the dicarboximide fungicides, but no sensitive isolate to polyoxin B was observed. The isolates showed genetically diverse RAPD profiles according to the geographic origin collected, but there was no significant correaltion between RAPD profiles of genomic DNA and the levels of fungicide resistance of the isolates. The isolates showed genetically diverse RAPD profiles, indicating that genetic differentiation had already occurred in the populations of B. cinerea distributed in Cheju.

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Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

  • Chang, Youjin;Kim, Seon Ye;Choi, Yun Jung;So, Kwang Sup;Rho, Jin Kyung;Kim, Woo Sung;Lee, Jae Cheol;Chung, Jin-Haeng;Choi, Chang-Min
    • Tuberculosis and Respiratory Diseases
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    • 제75권3호
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    • pp.95-103
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    • 2013
  • Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

RAPD 및 약제저항성을 이용한 감귤 검은점무늬병균의 유전적 다양성 분석 (Genetic Diversity of Phomopsis citri with Random Amplified Polymorphic DNA (RAPD) and Fungicide Resistance)

  • 고영진;서정규;이태선;송장훈;권혁모;문덕영;문두길;한해룡
    • 한국식물병리학회지
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    • 제14권2호
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    • pp.171-176
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    • 1998
  • Gentic diversity of 42 isolates of Phomopsis citri was analyzed with random amplified polymorphic DNA(RAPD) and fungicide resistance. RAPD profiles of genomic DNA of the isolates of P. citri and the degrees of their resistance to the fungicides mancozeb and propineb suggested the occurrence of genetic differentiation of P. citri distributed in Cheju. The isolates showed genetically diverse RAPD profiles according to the host species collected even from the same collection site and also according to the geographic origin collected even from the same host species. High levels of resistance to fungicides mancozeb and propineb were observed among the isolates of P. citri. However, there was no correlation between RAPD profiles of genomic DNA and levels of fungicide resistance of the isolates, suggesting that fungicide resistance of P. citri occurred irrespective of the host and geographic origin.

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GLUT4 상향조절을 통한 Allium hookeri 추출물의 3T3-L1 세포 내 포도당 흡수 증진 효과 (Allium Hookeri Extract Enhances Glucose Uptake through GLUT4 Up-regulation in 3T3-L1 Cells)

  • 강영은;최경미;박은진;정원범;정희진;유환수
    • 생명과학회지
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    • 제27권3호
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    • pp.289-294
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    • 2017
  • 삼채(Allium species)는 전통적인 약재나 건강 증진 식품으로 사용되어 왔다. 특히, Allium hookeri (A. hookeri)는 제 2형 당뇨병 모델 마우스에서 혈당 감소 효과가 보고되었다. 본 연구에서는 A. hookeri 추출물이 3T3-L1 세포에서 인슐린 민감성을 증진시키는지 시험하였다. 3T3-L1 지방세포분화가 불완전하게 유도되는 저농도의 인슐린 조건에서, A. hookeri 추출물은 세포 내 지방 함량을 증가시키고, 분화 유도 전사인자인 $PPAR{\gamma}$의 발현을 상승시켰다. 또한, A. hookeri 추출물은 포도당 수송체 4(GLUT4)의 발현을 증가시킴으로써 세포 내 포도당 흡수(glucose uptake)를 향상시켰다. 이러한 결과들은 A. hookeri 추출물이 인슐린 민감성을 증진시켜 $PPAR{\gamma}$와 GLUT4를 활성화하고, 세포 내 포도당 흡수를 촉진한다는 사실을 보여준다. 따라서, A. hookeri 추출물은 당뇨병의 예방 및 치료에 임상적으로 응용될 수 있을 것으로 생각된다.

Differential Resistance of Radish Cultivars against Bacterial Soft Rot Caused by Pectobacterium carotovorum subsp. carotovorum

  • Soo Min Lee;Jin Ju Lee;Hun Kim;Gyung Ja Choi
    • The Plant Pathology Journal
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    • 제40권2호
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    • pp.151-159
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    • 2024
  • Bacterial soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) is one of the most severe diseases in radish cultivation. To control this plant disease, the most effective method has been known to cultivate resistant cultivars. Previously, we developed an efficient bioassay method for investigating resistance levels with 21 resistant and moderately resistant cultivars of radish against a strain Pcc KACC 10421. In this study, our research expanded to investigate the resistance of radish cultivars against six Pcc strains, KACC 10225, KACC 10421, ATCC 12312, ATCC 15713, LY34, and ECC 301365. To this end, the virulence of the six Pcc strains was determined based on the development of bacterial soft rot in seedlings of four susceptible radish cultivars. The results showed that the Pcc strains exhibited different virulence in the susceptible cultivars. To explore the race differentiation of Pcc strains corresponding to the resistance in radish cultivars, we investigated the occurrence of bacterial soft rot caused by the six Pcc strains on the 21 resistant and moderate resistant cultivars. Our results showed that the average values of the area under the disease progress curve were positively correlated with the virulence of the strains and the number of resistant cultivars decreased as the virulence of Pcc strains increased. Taken together, our results suggest that the resistance to Pcc of the radish cultivars commercialized in Korea is more likely affected by the virulence of Pcc strains rather than by race differentiation of Pcc.

Inhibitory Effects of Saururus Chinensis Extracts on Osteoclast Differentiation

  • Shim, Ki-Shuk;Kim, Soon-Nam;Kim, Myung-Hee;Kim, Young-Sup;Ryu, Shi-Yong;Min, Yong-Ki;Kim, Seong-Hwan
    • Natural Product Sciences
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    • 제14권2호
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    • pp.113-117
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    • 2008
  • Saururus chinensis is a commonly used folk herb for the treatment of edema and liver diseases in Korea. To study the biological activity of Saururus chinensis in bone metabolism, we evaluated the effect of its extracts on osteoclast differentiation in vitro using primary mouse bone marrow-derived macrophages. Methanol extract (ME) from dried roots of Saururus chinensis was partitioned into methylene chloride (MF), ethyl acetate (EF), n-butanol (BF) and water fractions (WF). Tartrate-resistance acid phosphatase (TRAP) activity assay and western blot analysis were performed to determine the effect on osteoclast differentiation and mitogen-activated protein (MAP) kinases activation. ME, MF and EF dramatically inhibited receptor activator of ${NF-kB}$ ligand (RANKL)-induced formation of multinucleated osteoclasts and activation of MAP kinases. This study firstly demonstrated that ME, MF and EF of Saururus chinensis have the potential to inhibit the osteoclast differentiation, which results from the inhibition of MAP kinases activations in part.

Effects of different calcium-silicate based materials on fracture resistance of immature permanent teeth with replacement root resorption and osteoclastogenesis

  • Gabriela Leite de Souza;Gabrielle Alves Nunes Freitas;Maria Tereza Hordones Ribeiro;Nelly Xiomara Alvarado Lemus;Carlos Jose Soares;Camilla Christian Gomes Moura
    • Restorative Dentistry and Endodontics
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    • 제48권2호
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    • pp.21.1-21.15
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    • 2023
  • Objectives: This study evaluated the effects of Biodentine (BD), Bio-C Repair (BCR), and mineral trioxide aggregate (MTA) plug on the fracture resistance of simulated immature teeth with replacement root resorption (RRR) and in vitro-induced osteoclastogenesis. Materials and Methods: Sixty bovine incisors simulating immature teeth and RRR were divided into 5 groups: BD and BCR groups, with samples completely filled with the respective materials; MTA group, which utilized a 3-mm apical MTA plug; RRR group, which received no root canal filling; and normal periodontal ligament (PL) group, which had no RRR and no root canal filling. All the teeth underwent cycling loading, and compression strength testing was performed using a universal testing machine. RAW 264.7 macrophages were treated with 1:16 extracts of BD, BCR, and MTA containing receptor activator of nuclear factor-kappa B ligand (RANKL) for 5 days. RANKL-induced osteoclast differentiation was assessed by staining with tartrate-resistant acid phosphatase. The fracture load and osteoclast number were analyzed using 1-way ANOVA and Tukey's test (α = 0.05). Results: No significant difference in fracture resistance was observed among the groups (p > 0.05). All materials similarly inhibited osteoclastogenesis (p > 0.05), except for BCR, which led to a lower percentage of osteoclasts than did MTA (p < 0.0001). Conclusions: The treatment options for non-vital immature teeth with RRR did not strengthen the teeth and promoted a similar resistance to fractures in all cases. BD, MTA, and BCR showed inhibitory effects on osteoclast differentiation, with BCR yielding improved results compared to the other materials.

Elucidating molecular mechanisms of acquired resistance to BRAF inhibitors in melanoma using a microfluidic device and deep sequencing

  • Han, Jiyeon;Jung, Yeonjoo;Jun, Yukyung;Park, Sungsu;Lee, Sanghyuk
    • Genomics & Informatics
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    • 제19권1호
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    • pp.2.1-2.10
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    • 2021
  • BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

Effects of Parafibromin Expression on the Phenotypes and Relevant Mechanisms in the DLD-1 Colon Carcinoma Cell Line

  • Zhao, Shuang;Sun, Hong-Zhi;Zhu, Shi-Tu;Lu, Hang;Niu, Zhe-Feng;Guo, Wen-Feng;Takano, Yasuo;Zheng, Hua-Chuan
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권7호
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    • pp.4249-4254
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    • 2013
  • Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, $GSK3{\beta}$-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.