• BMB Reports
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• v.55 no.5
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• pp.244-249
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• 2022

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.745-757
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• 1994

Superovulatory treatment with exogenous gonadotropins adversely affects the uterus through the disruption of the delicate balance of ovarian steroids (estrogens, progestins, androgens). To examine the uterine effects of this treatment, 189 rats were given 4IU, 20IU or 40IU pregnant mare',s serum gonadotropin(PMSG) at 28 days of age and sacrificed every 24h until day 10(D10) post injection. Long term uterine effects were examined in 12 rats treated with 4IU or 40IU PMSG and killed on D30. Adult rat uteri were examined to provide a reference for comparisons. Morphological and histological changes of control (4IU) uteri mimicked those of the adult on a comparable time-course form D2 to D5. Administration of superovulatory doses(20IU, 40IU) of PMSG produced stromal hypertrophy by D2 and focal papillary hyperplasia of the luminal epithelia by D3. Levels of $17{\beta}$-estradiol following 20IU and 40IU PMSG treatment were significantly(p<0.05, p<0.005) elevated above those of controls after D1. Androgen levels of both groups(20IU, 40IU) significantly p<0.05, p<005 increased from baseline on D1 and were maximum between D2 and D3. In the 20IU PMSG group, the hyperplasia gradually regressed after D3 and was absent by D10. The hyperplasia in the 40IU PMSG group, however, had become extensive by D6. It is suspected that preceding elevated levels of estrogen may be responsible for this progressive change. On D 4, the levels of $17{\beta}$-estradiol reached a maximum, which was significantly(p<0.001) greater than both the controls and 20IU PMSG-treated rats. Between D6 and D10, the hyperplasia in 40IU PMSG-treated rats partially regressed. Examination of uteri from D30 revealed no evidence of the hyperplasia. It is suggested that previous exposure to high levels of estrogen and androgens, secondary to superovulation, is possible cause for the observed hyperplasia.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4491-4501
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• 2016

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the 'First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity' held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named 'Exophytic Verrucous Hyperplasia'. Previously described clinical features of OVH such as the 'blunt' or 'sharp' variants; and the 'mass' or 'plaque' variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of 'Exophytic Verrucous Hyperplasia' as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1495-1499
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• 2015

Background: c-Kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker for demonstrating thrombocyte function. We aimed to investigate whether c-kit is expressed in benign, preneoplastic and neoplastic endometrial tissues and whether MPV has a relation with c-kit expression and its intensity. Materials and Methods: c-Kit expression was investigated immunohistochemically in 10 samples of normal endometrium (n=10), simple endometrial hyperplasia (5 cases with atypia and 10 cases without atypia), complex endometrial hyperplasia (10 cases with atypia and 10 cases without atypia) and endometrial cancer (EC) (10 cases grade I and 10 cases grade II) and MPV of all cases was checked. Results: c-Kit expression was observed at very low rates in cases with normal endometrial tissues (NE) and in hyperplasia without atypia. c-Kit expression and immunostaining were strong in endometrial atypia and EC. MPV levels of complex atypical endometrial hyperplasia (CAEH) (p:0.002), EC grade I (ECG I) (p<0.001) and EC grade II (ECG II) (p<0.001) were significantly elevated when compared with the NE group. Both c-kit expression and intensity of immunostaining had a positive correlation with MPV level. Conclusions: While c-kit expression and intensity of immunostaining were mildly positive in NE and hyperplasia without atypia, they were clearly observed in EC and hyperplasia with atypia. As c-kit expression is related to the mutagenesis a long-term followup may be needed in these cases. A high MPV level may be a good test for demonstrating c-kit expression and intensity of immunostaining.

• Journal of Life Science
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• v.19 no.11
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• pp.1514-1521
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• 2009

To evaluate the feasibility of cathepsin-B levels in preoperatively screening patients with thyroid cancer, we assigned these patients to either the thyroid cancer group (n=32) or the nodular hyperplasia group (n=7). Five healthy volunteers served as controls (n=5). We quantified cathepsin-B expressions in cancerous lesions with follicular carcinoma and hyperplastic lesions with nodular hyperplasia, and compared the degrees to those of normal thyroid tissue, which was obtained from matched contralateral lobe. The activity of serum cathepsin B was significantly higher in patients with thyroid carcinoma ($284.87{\pm}79.32$, ${\times}10^{-2}\;mU$) and those with nodular hyperplasia ($255.45{\pm}95.68$, ${\times}10^{-2}\;mU$) than compared to normal control ($168.94{\pm}15.10$, ${\times}10^{-2}\;mU$) (p<0.05). Based on the results of immunoassay, the concentrations of cathepsin B in the thyroid cancer group ($15.50{\pm}7.86\;ng/ml$) and the nodular hyperplasia group ($17.64{\pm}7.49\;ng/ml$) were higher than those of the control group ($4.85{\pm}0.61\;ng/ml$). The degree of cathepsin-B mRNA expression was significantly higher in cancerous or hyperplastic lesions than normal thyroid tissues from matched contralateral lobe with follicular carcinoma or non-neoplastic thyroid disease. Our results indicate that the activity of serum cathepsin B is a useful indicator in screening patients with nodular hyperplasia or neoplastic thyroid disease and it may be involved in the abnormal proliferation of cells.

• Journal of Chest Surgery
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• v.51 no.2
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• pp.133-137
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• 2018

Pulmonary nodular lymphoid hyperplasia is a reactive lymphoproliferative disease. It is very rare, which means that many aspects of the disease are unknown or have not been proven. Pulmonary nodular lymphoid hyperplasia can be symptomatic or asymptomatic, progressive or not, and solitary or multiple, and a surgical approach is the current treatment of choice. We present a case of pulmonary nodular lymphoid hyperplasia that was visualized as multiple ground glass opacities on a computed tomography (C T) scan, and observed for 1 year because the patient was pregnant. Over this period, the number and extent of the opacities progressed, but no symptoms were reported. A surgical biopsy was done and some remaining lesions regressed on follow-up CT scans, while others progressed, without any appearance of symptoms.

• Journal of Nutrition and Health
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• v.28 no.10
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• pp.1031-1039
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• 1995

Dietary mehaden oil enhances mucosal hyperplasia that normally occurs after massive small bowel resection. In contrast, dexamethasone and aspirin inhibit the adaptation response. In order to gain insight on the mechanism of these effects, male Sprague-Dawley rats weighing approximately 150gram were randomly divided into two groups and fed diet containing either 15% safflower oil or 14% menhaden oil and 1% safflower oil. Ten days later they were subjected to 70% jejunoilear resection. Immediately after surgery each group was further divided into two groups and receive either vehicle or 125ug/kg/day dexamethasone subcutaneously. All animals were sacrificed seven days after the surgery, and the remaining intestine was removed and divided at the anastomotic site. Dexamethasone, which decreased gut hyperplasia in both dietary groups, decreased both serum IGF-I levels and ileral PGE2 synthesis. Menhaden oil enhanced gut hyperplasia, but did not increase IGF-I or IGF-II levels in serum. PGE2 synthesis was lower in the ileum of menhaden oil-fed rats compared to that of safflower oil-fed rats. The effects of menhaden oil on adaptation did not apper to be mediated either through IGFs or PGE2 synthesis. Other factors could have played a role in enhancing adaptation following menhaden oil feeding.

• International Journal of Vascular Biomedical Engineering
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• v.1 no.1
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• pp.41-47
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• 2003

The patency rates of small diameter vascular grafts are disappointing because of the formation of thrombus and intimal hyperplasia. Among the various factors influencing the success of graft surgery, the compliance and the size of a graft are believed to be the most important physical properties of a vascular graft. Mismatch of compliance and size between an artery and a graft alters anastomotic flow characteristics, which may affect the formation of intimal hyperplasia. Among the hemodynamic factors influencing the development of intimal hyperplasia, the wall shear stress is suspected as the most important one. The wall shear stress distributions are experimentally measured near the end-to-end anastomosis models in order to clarify the effects of compliance and diameter mismatch on the hemodynamics near the anastomosis. The effects of radial wall motion, diameter mismatch and impedance phase angle on the wall shear rate distributions near the anastomosis are considered. Compliance mismatch generates both different radial wall motion and instantaneous diameter mismatch between the arterial portion and the graft portion during a flow cycle. Mismatch in diameter seems to be affecting the wall shear rate distribution more significantly compared to radial wall motion. The impedance phase angle also affects the wall shear rate distribution.

• Journal of Pharmacopuncture
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• v.11 no.2
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• pp.125-130
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• 2008

Objective The purpose of this study was to report the efficiency of Bee Venom Pharmacopunture Therapy by managering of Benign Prostatic Hyperplasia patients. Method Two patients were treated with Bee Venom Pharmacopunture and another Korean Medicine therapy for six weeks and compared with I-PSS(International Prostate Symptom Score) before and after. Results After treated with Bee Venom Pharmacopunture Therapy, 'I-PSS' values decreased significantly all the patients. Conclusions Bee Venom Pharmacopunture Therapy was shown fairly effective to Benign Prostatic Hyperplasia.