Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.
Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Connective Tissue Growth Factor* ; Connective Tissue* ; Cyclin D1 ; Extracellular Matrix* ; Fibrosis ; Genes, Regulator ; Glycosylation End Products, Advanced ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Muscle, Smooth, Vascular* ; Phosphotransferases ; RNA, Messenger ; Vascular System Injuries

OBJECTIVES: With the rapid increase in the prevalence of diabetes, the age groups of diabetic patients are becoming diversified. This study will examine the degree of obesity, insulin resistance, and insulin secretion ability among patients first diagnosed with diabetes according to age and gender. METHODS: The subjects of this study included 616 patients who were first diagnosed with diabetes during a routine physical examination. This sample was obtained from a total of 28,075 adults aged 19 years and older who received the examination among 33,829 participants in the Korea National Health & Nutrition Examination Survey (KNHANES) from 2007–2010. The subjects were categorized by age into young age (age: 19 – 39 years), middle age (age: 40 – 59 years), and old age (age: 60 years and older). The degree of obesity was categorized according to body mass index (BMI) into normal weight (BMI: 18.5 ~ 22.9), overweight (BMI: 23 ~ 24.9), and obesity (BMI: 25 or above). Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: It was found that 14.1% (n = 87) of a total of 616 subjects (324 men, 292 women) were in the young age group, 43.8% (n = 270) were in the middle age group, and 42.1% (n = 259) were in the old age group. In addition, 83.3% of men that were overweight or obesity were in the young age group, while 79.2% and 60.5% were in the middle age and old age groups, respectively. A total of 82.2% of women that were overweight or obesity were in the young age group, while 79.5% and 77% were in the middle age and old age groups, respectively. For men, the more obesity they were in all age groups, the higher their HOMA-IR. For women, the more obesity they were in the young age and middle age groups, the higher their HOMA-IR; however, women in the old age group showed the highest HOMA-IR when they were of normal weight. CONCLUSION: Among diabetic patients first diagnosed with the disease in Korea, the youth population had the highest obesity rate. Insulin resistance increases as an individual's weight increases among those patients who are first diagnosed with diabetes; the only exception noted is for elderly women.
Adolescent ; Adult ; Aged ; Bodily Secretions ; Body Mass Index ; Female ; Humans ; Insulin Resistance* ; Insulin* ; Korea* ; Male ; Middle Aged ; Obesity* ; Overweight ; Physical Examination ; Prevalence

PURPOSE: This study aimed to identify the factors influencing human papillomavirus (HPV) vaccination adoption stages using the Precaution Adoption Process model. METHODS: A total of 173 female university students from B metropolitan city participated. Demographics, factors contributing to action, knowledge, health beliefs, and self-efficacy related to the HPV vaccination were measured. The collected data were analyzed using descriptive statistics and multiple logistic regression analysis using SPSS for Windows version 21.0. RESULTS: Factors that contributed to the transition from the unaware and unengaged stages to the undecided about action stage included age, economic status, experience of recommendation from doctors, perceived severity of cervical cancer, and perceived barriers. Factors that contributed to the transition from the undecided about action stage to the deciding to act stage were perceived benefit and self-efficacy of the HPV vaccination. Factors that contributed to the transition from the deciding to act stage to the acting and maintenance stages were experience of recommendation from doctors and perceived severity of cervical cancer. CONCLUSION: These results suggest that aggressive HPV vaccination campaigns increase awareness. Further studies should develop tailored strategies for promoting HPV vaccination that emphasize health beliefs and self-efficacy.
Demography ; Female ; Humans ; Logistic Models ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms ; Vaccination*

Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II-stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension.
Angiotensin II ; Angiotensins ; Arteries ; Cell Proliferation ; Heart ; Hypertension ; Hypertrophy ; Insulin-Like Growth Factor Binding Protein 5* ; Kidney ; Lung ; Muscle, Smooth, Vascular ; Vascular Diseases

In patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as first treatment option. Because adenosquamous carcinoma (ASC) is a rare histologic subtype, evidences about EGFR-TKIs as first treatment option for advanced ASC are lacking. We report a case of an advanced ASC patient with the EGFR mutation, who showed good responses during 4-month treatment with gefitinib. And we will review about a necessity of EGFR mutation test and efficacy of EGFR-TKIs in ASC patients from the recent studies.
Carcinoma, Adenosquamous ; Carcinoma, Non-Small-Cell Lung ; Epidermal Growth Factor ; Humans ; Lung* ; Phosphotransferases ; Receptor, Epidermal Growth Factor

BACKGROUND: In this study, we tried to investigate whether carbenoxolone, prunetin, and silibinin affect tumor necrosis factor (TNF)-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with each agent (carbenoxolone, prunetin, and silibinin) for 30 min and then stimulated with TNF-alpha for 24 hours. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. RESULTS: Carbenoxolone, prunetin and silibinin inhibited the production of MUC5AC mucin protein induced by TNF-alpha; the 3 compounds also inhibited the expression of MUC5AC mucin gene induced by TNF-alpha. CONCLUSION: This result suggests that carbenoxolone, prunetin and silibinin can inhibit mucin gene expression and production of mucin protein induced by TNF-alpha, by directly acting on airway epithelial cells.
Carbenoxolone ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Gene Expression ; Humans ; Isoflavones ; Mucin 5AC ; Mucins ; Necrosis ; Silymarin ; Tumor Necrosis Factor-alpha

OBJECTIVE: Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. METHODS: MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by 3H-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. RESULTS: At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. CONCLUSION: Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.
Anthracenes ; Blotting, Western ; Butadienes ; Cell Proliferation ; Diterpenes ; Down-Regulation ; Epoxy Compounds ; Imidazoles ; Neurons ; Nitriles ; p38 Mitogen-Activated Protein Kinases ; Phenanthrenes ; Phosphorylation ; Protein Kinases ; Pyridines ; RNA, Small Interfering ; Vanadates

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in alphavbeta3 and alpha5beta1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.
Angiogenesis Inhibitors/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Base Sequence ; Benzocaine/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chloramphenicol/chemistry/*pharmacology ; DNA Primers ; Drug Combinations ; Factor VIII/chemistry/*pharmacology ; Humans ; Integrin alpha5beta1/*physiology ; Integrin alphaVbeta3/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Nitrofurazone/chemistry/*pharmacology ; Recombinant Fusion Proteins/chemistry/*pharmacology

PURPOSE: This study was conducted to develop Web-based multimedia contents for supporting student nurses' clinical practice on critical care, and to evaluate learners' responses. METHODS: Based on the steps of Assessment, Design, Development, Implementation, & Evaluation(ADDIE) model, a total of 13 self-directed learning modules including live lectures and real video clips were developed through faculty collaboration of nine nursing colleges in Gwangju and Chonnam province. The finally developed multimedia contents were published on the Web of the learning management system at a local e-learning center. RESULTS: The Web contents were evaluated after self-learning by 81 junior college nursing students who were encouraged to study it at their own pace during their two-week clinical practice at a medical or surgical intensive care unit of a university hospital and two hospitals. The knowledge (t = -27.66, p < .001) and self-evaluated clinical performance level(t = 7.54, p < .001) were significantly increased after learning of the Web contents and clinical practice, and satisfaction level that measured post-test only was 4.0 out of 5 point. CONCLUSION: The use of Web contents for critical care need to be extended as a complimentary material in a class room lecture or clinical practice of students to increase their self-learning ability and understandings of clinical knowledge and situation.
Computer-Assisted Instruction ; Cooperative Behavior ; Critical Care ; Humans ; Critical Care ; Learning ; Lectures ; Multimedia ; Students, Nursing

PURPOSE: As increasing overseas kidney transplant recipients, the post-transplantation management of these recipients is not unusual. Shortage of donor information and operative findings is an obstacle to post-transplant evaluation and management of overseas transplant recipients. We retrospectively reviewed the post-transplant clinical manifestation of overseas transplant recipient, and compared with those of domestic deceased donor transplant recipient. METHODS: Sixty overseas transplant recipients and 39 deceased donor transplant recipient in our center from January 2002 to August 2006 were enrolled in this study. Among the post-transplant outcomes, we focused the episodes of post-transplant complication, acute rejection and graft functional status. RESULTS: In comparison of pre-transplant clinical manifestation, overseas transplant recipients were more elderly, male predominant and less retransplantation than domestic deceased transplant cases. Remarkable surgical complications (35%, 21/60) were observed in overseas transplant recipients which was significantly higher than those of domestic transplant recipients (5.1%, 2/39 cases)(P=0.03). The urologic complication was major (14 cases) complication, and intraoperative hematoma (5 cases) and vascular complication (2 cases) succeed. Interventional procedure or surgical correction was performed in six recipients with urinary leakage obstruction. Excluding post-transplant acute tubular necrosis, the post-transplant outcomes, such as incidence of acute rejection, graft survival rate and graft function within post-transplant 3 year, of overseas transplant recipient were statistically similar with these of domestic deceased donor recipients. CONCLUSION: Considering that overseas transplant recipient had high incidence of surgical or urologic complication, the initial evaluation of post-transplant recipient was focused on completion of surgical procedure by using radiologic imaging study.
Aged ; Graft Rejection ; Hematoma ; Humans ; Incidence ; Kidney Transplantation* ; Kidney* ; Male ; Necrosis ; Retrospective Studies ; Survival Rate ; Tissue Donors* ; Transplantation ; Transplants