• Molecules and Cells
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• v.41 no.9
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• pp.842-852
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• 2018

Notch signaling is an evolutionarily conserved pathway and involves in the regulation of various cellular and developmental processes. Ligand binding releases the intracellular domain of Notch receptor (NICD), which interacts with DNA-bound CSL [CBF1/Su(H)/Lag-1] to activate transcription of target genes. In the absence of NICD binding, CSL down-regulates target gene expression through the recruitment of various corepressor proteins including SMRT/NCoR (silencing mediator of retinoid and thyroid receptors/nuclear receptor corepressor), SHARP (SMRT/HDAC1-associated repressor protein), and KyoT2. Structural and functional studies revealed the molecular basis of these interactions, in which NICD coactivator and corepressor proteins competitively bind to ${\beta}-trefoil$ domain (BTD) of CSL using a conserved ${\varphi}W{\varphi}P$ motif (${\varphi}$ denotes any hydrophobic residues). To date, there are conflicting ideas regarding the molecular mechanism of SMRT-mediated repression of CSL as to whether CSL-SMRT interaction is direct or indirect (via the bridge factor SHARP). To solve this issue, we mapped the CSL-binding region of SMRT and employed a 'one- plus two-hybrid system' to obtain CSL interaction-defective mutants for this region. We identified the CSL-interaction module of SMRT (CIMS; amino acid 1816-1846) as the molecular determinant of its direct interaction with CSL. Notably, CIMS contains a canonical ${\varphi}W{\varphi}P$ sequence (APIWRP, amino acids 1832-1837) and directly interacts with CSL-BTD in a mode similar to other BTD-binding corepressors. Finally, we showed that CSL-interaction motif, rather than SHARP-interaction motif, of SMRT is involved in transcriptional repression of NICD in a cell-based assay. These results strongly suggest that SMRT participates in CSL-mediated repression via direct binding to CSL.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.77-80
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• 2009

Mucosa-associated lymphoid tissue(MALT) lymphoma is thought to originate from marginal zone B-cells. In the WHO classification, Extranodal marginal zone lymphoma of MALT is classified B-cell Non-Hodgkin lymphoma. Common sites of MALT lymphoma include stomach, lung and the ocular-adnexa. Although less common in other sites, it is the most common low-grade lymphoma of the breast, thyroid, bowel skin and soft tissue. No strong age or gender predominance exists in MALT lymphoma. Dissemination to other sites can occur. In the oral cavity, MALT lymphoma is rare. Herein, we present a case of intra-oral MALT lymphoma. 66 year-old woman without any background of immunodeficiency or autoimmune disease admitted department of oral & maxillofacial surgery in Ulsan university hospital for evaluation of long-standing mild upper lip swelling. The lesion was completely resected and biopsied. Histological and immunohistochemical stains(CD3, CD5, CD20, CD21, CK) findings were used to confirm the lesion. Bone marrow biopsy was done and no bone marrow involvement was found. She did not receive chemotherapy and radiotherapy after surgery. No recurrence has been noted in the 22 months to date.

• Journal of Chest Surgery
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• v.29 no.12
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• pp.1381-1384
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• 1996

Thymoma Is an anterior mediastinal tumor, arising from the thymus, but occasionally has ectopic focus such as neck, trachea, thyroid, pulmonary hilum, lung parenchyme and pleura. Forty-two year old male patient was admitted due to progressive development of shortness of breath in 4 months. He had a history of exposure to asbestos for About 10 years duration In recent 15 years. Radiologically, multiple pleural masses were seen rom apex to diaphrAgm, with no evidence of anterior mediastinal mass,with fluid in right pleural cavity. Closed thoracotomy drainage with open biopsy were performed. Effusion cell block showed many T cell marker positive Lymphocytes & some epithelial cells compatible with thymoma, and the tissue also showed cortical type thymoma. Pleuropneumonectomy and thymectomy followed by 60 Gy radiation therapy were done and the patient is well 8 months postoperatively. The pleura is markedly thickened by the invasion of thymoma and the interstitial space of the lung tissue,but the normal appearance of thymus was present in remote area (Masaoka classification IVa). We report a case of ectopic invasive thymoma arising from the right pleura with intact thymus.

• The Korea Journal of Herbology
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• v.31 no.6
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• pp.63-71
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• 2016

Objective : To suggest a scientific evidence of Aconitum carmichaeli Debx. (Aconiti Lateralis Radix Preparata: ALRP) as one of cooling and heating medicines on the regulation of body temperature, we investigated the effects of ALRP water extract on hypothyroidism. Methods : Hypothyroidism was induced by intradermal injection with PTU for 4 weeks in SD rats. ALRP extract or L-thyroxine as a control drug was orally administrated for 2 weeks with PTU injection in rats. The physiological and serological parameters were measured in rats. The histological change of thyroid tissues was observed by H&E staining, and also the expression of thermo-regulating proteins was determined by Western blot in dorsal root ganglia and brain tissues of rats. Results : The administration of ALRP extract in PTU-induced hypothyroidism rats was significantly increased body temperature, but did not changes on body weight, food and water intake. ALRP extract did not effect on the levels of TSH and T4 in the hypothyroidism rats. ALRP extract significantly decreased the levels of GPT, glucose, HDL-cholesterol, LDL-cholesterol, and total cholesterol in the hypothyroidism rats. In histological observation, the enlarged epithelium and atrophic follicles with higher concentration of follicular cells on hypothyroidism were improved by ALRP extract. In addition, ALRP extract increased the expression of TRPV1 and TRPM8 ion channel proteins in hypothyroidism rats. Conclusion : These results indicate that ALRP extract can improve PTU-induced hypothyroidism through regulation of body temperature and lipid accumulation. The action mechanism of ALRP extract is related with body temperature control by thermoregulation with TRP ion channels.

• BMB Reports
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• v.56 no.3
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• pp.184-189
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• 2023

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.66-74
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• 2021

Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

• Korean Journal of Ecology and Environment
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• v.35 no.3 s.99
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• pp.198-212
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• 2002

A numerical variation and abnormalities were studied on egg bags and embryos of Korean salamander, Hynobius leechii from agricultural habitat. The teratogenic and toxic effects of fungicide benomyl were also investigated with early embryos from non-agricultural habitat. We collected 144 egg bags from agricultural region, and 3418 of early embryos were contained. The lengths of egg bags were varied from 10 to 23 cm and the most frequent length was 19 cm. The number of embryos was varied from 7 to 43, and the most frequent range was 22 to 26. Spontaneous abnormalities were occurred in 406 embryos among 116 egg bags, and 24 kinds of external abnormalities were found. Individuals showing severe external defect were histologically studied and they showed optic dyspalsia, thyroid carcinoma, somatic muscular dysplasia, partial biaxial structure, decrease of red blood cells in the heart, cephalic degeneration and intestinal dysplasia. 385 embryos from non-agricultural region were exposed to 200 nM${\sim}$ 1 ${\mu}$M of benomyl at blastula or gastrula for 12 days. All embryo were dead in the concentration of 1 ${\mu}$M (LD$_{100}$) and 75% of embryos were dead in 800nM of benomyl. Speciflc effect due to benomyl was acrania or cephalic dysplasia and this restult suggests that the benomyl inhibit stongly to the development of neural tissue. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of the movement of neural crest cells.

• The Korean Journal of Nuclear Medicine
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• v.32 no.4
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• pp.374-381
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• 1998

Purpose: I-131 labeled (2'-deoxy-2'-iodo-${\beta}$-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and it's feasibility for scintigraphic tumor imaging. Materials and Methods: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected with 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was performed after 2 and 24h. Then, rat body was fixed and microtomized slice was placed on radiographic film for autoradiography. Results: %ID/g of tumor was 0.74 (0.5h),0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0.69), muscle (0.14), bone (0.33) and intestine (0.51). However, %ID/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. Conclusion: This results suggest that IAD may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.

• Korean Journal of Agricultural Science
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• v.9 no.1
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• pp.303-313
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• 1982

The study was conducted to find out the concentrations of sex hormones and the contents of metabolites in serum, and the changes of weights and tissues on ovary, thyroid gland and adrenal gland according to gestation period in rabbit. The results were summarized as follows: 1. The ovary weights were increased significantly with the time e lapse after gestation and recovered normally at 5 days after parturition. In the histological changes of ovary, the lutein cells were hypertrophied and the secretory granules were increased actively until 3 weeks after gestation, and then a trophied thereafter. 2. The thyroid gland weights at all observation times were higher than those in control group, and the significance was recognized at 1, 3 and 4 weeks after gestation. The histological features of the secretory epithelium were the hyper trophic and columnar condition stimulating the functional state from 1 week after gestation. 3. The adrenal gland weights in experimental group were recognized significantly at 4 weeks after gestation, but showed higher than those in control group at all observation times. The zona fasciculata and zona reticularis of the gland showed the slight hypertrophic condition, but the zona glomeerulosa and adrenal medulla did not find out any particular changes. 4. The serum concentrations of progesterone and LH reached a peak level at 2 weeks and 1 week after geestation respectively, and rapidly began to decline thereafter. 5. The serum concentrations of estradiol-$17{\beta}$ and FSH were not detected below 20.0 pg/ml and 1.3 mIU/ml respectively. 6. The contents of total protein and non-protein nitrogen nitrogen were decreased gradually with the time elapse after gestation, but the significant differences were recognized from 3 weeks. 7. The total lipids were not changed markedly until 3 weeks, but increased significantly at 4 weeks after gestation and at 5 days after parturition. 8. The serum cholesterol tended to be decreased until 3 weeks, but increased at 4 weeks after gestation and at 5 days after parturition. 9. The serum calcium showed a continuous decrease during the gestation period, but the significant differences were recognized at 3 and 4 weeks. The serum phosphorus also had a significant decrease at 4 weeks after gestation.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.289-297
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• 1999

Purpose: Misonidazole is a radiosensitizer that binds in hypoxic cells. The purpose of this study was to find out the feasibility of I-131-Iodomisonidazole (IMISO) for imaging of tumor hypoxia. Materials and Methods: Tosyl precursor was dissolved in acetonitrile and I-131-NaI was added to synthesize IMISO. Balb/c mice inoculated with CT-26 adenocarcinoma were injected with IMISO. Mice were sacrificed at 1, 2, 4, 24 hr and % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy and MRI, mouse bearing CT-26 adenocarcinoma was administered with IMISO and imaging was performed 4 hr after. Then, mouse body was fixed and microtomized slice was placed on radiographic film for autoradiography Results: %ID/g of tumor was 1.64 (1h), 0.98 (2h), 0.85 (4h) and 0.20 (24h), respectively. At 24h, %ID/g of tumor was higher than that of all other tissues except thyroid. Tumor to muscle ratio increased with time and tumor to blood ratio also increased with time and reached 1.53 at 24 hr. On autoradiogram, tumor was well visualized as an increased activity in central hypoxic area of the tumor which corresponds to the area of high signal intensity on T2-weighted MR image. On scintigraphy, tumor uptake was visualized. Conclusion: This results suggest that IMISO may have a potential for tumor hypoxia imaging in mouse model. However, further study is needed to improve it's localization in tumor tissue and to achieve acceptable images of tumor hypoxia.