BACKGROUND: Caveolin, a family of integral membrane proteins are a principal component of caveolae membranes. In this study, we investigated the effect of p38 kinase on differentiation and on inflammatory responses in sodium nitroprusside (SNP)- treated chondrocytes. METHODS: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. SNP was used as a nitric oxide (NO) donor. In this experiments measuring SNP dose response, primary chondrocytes were treated with various concentrations of SNP for 24 h. The time course of the SNP response was determined by incubating cells with 1 mM SNP for the indicated time period (0~24 h). The cyclooxygenase-2 (COX-2) and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin E2 (PGE2) assay was used to measure the COX-2 activity. The tyrosine phosphorylation of caveolin-1 was determined by immunoblot analysis and immunostaining. RESULTS: SNP treatment stimulated tyrosine phosphorylation of caveolin-1 and activation of p38 kinase. SNP additionally caused dedifferentiation and inflammatory response. We showed previously that SNP treatment stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase with SB203580 reduced caveolin-1 tyrosine phosphorylation and COX-2 expression but enhanced dedifferentiation, whereas inhibition of ERK with PD98059 did not affect caveolin-1 tyrosine phosphorylation levels, suggesting that ERK at least is not related to dedifferentiation and COX-2 expression through caveolin-1 tyrosine phosphorylation. CONCLUSION: Our results indicate that SNP in articular chondrocytes stimulates dedifferentiation and inflammatory response via p38 kinase signaling in association with caveolin-1 phosphorylation.
Cartilage ; Caveolae ; Caveolin 1 ; Chondrocytes* ; Collagen Type II ; Cyclooxygenase 2* ; Digestion ; Dinoprostone ; Humans ; Membrane Proteins ; Membranes ; Nitric Oxide ; Nitroprusside ; Phosphorylation ; Phosphotransferases* ; Rabbits ; Tissue Donors ; Tyrosine

Purpose: This study investigated the anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl. (SS) in vitro and in vivo. Methods: The extracts of Syzygium aromaticum extract (SA) and Sorbus commixta extract (SC) were prepared individually using distilled water. They were mixed in a 1:2 ratio for use in the experiment. To assess the anti-obesity potential of SS in vitro, we examined cell proliferation, cellular triglyceride (TG), and total cholesterol (TC) levels, as well as lipogenesis and β-oxidation in 3T3-L1 cells. To confirm its anti-obesity potential in vivo, C57BL/6J mice were fed a 60% high-fat diet (HFD) to induce obesity. SA alone, SC alone, and their combination compound, SS (at a dosage of 200 mg/kg) were orally administered for 6 weeks. Thereafter, to conduct a comparative evaluation, serum analysis, western blotting of liver tissues, and histopathological analysis were performed. Results: Both SS200 and SS400 significantly inhibited the cellular TG and TC contents in the 3T3-L1 cells. Furthermore, treatment of the cells with SS (at a dose 200 and 400 μg/mL) also led to a noticeable regulation of key lipogenic and β-oxidation factors. Treatment of obese mice with SS resulted in a greater reduction in serum leptin and TG levels compared to treatment with the individual compounds (SA and SC). Furthermore, activation of AMPactivated protein kinase α by SS treatment resulted in the suppression of sterol regulatory element-binding proteins (SREBP)-1, leading to the inhibition of acetyl-CoA carboxylase (ACC) expression. Conclusion Our results suggest that SS may have the potential to prevent obesity through a reduction in the TG and TC levels and regulation of lipogenesis and β-oxidation.

PURPOSE: Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis. METHODS: The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry. RESULTS: A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells. CONCLUSION: Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.
Apoptosis ; Blotting, Western ; Breast ; Breast Neoplasms ; Cell Death ; Cell Survival ; Humans ; MCF-7 Cells ; Milk Thistle ; Prostate ; Silymarin ; Skin

PURPOSE: Circular stapled hemorrhoidopexy (CSH) is widely used to treat patients with grades III–IV hemorrhoids because of less pain and short hospital stay. However, this procedure is associated with some complications, such as urge to defecate, anal stenosis, staple line dehiscence, abscess and sepsis. To avoid these complications, surgeons perform a partial stapled hemorrhoidopexy (PSH). The aim of this study is to present our early experience with the PSH. METHODS: We retrospectively reviewed the medical records of 58 patients with hemorrhoids who were treated with a PSH at Busan Hang-Un Hospital from January 2016 to June 2016. A specially designed tri-window anoscope was used, and a purse string suture was made at the mucosae of the protruding hemorrhoids through the window of the anoscope. The hemorrhoidopexy was done by using a circular stapler. RESULTS: Of the 58 patients included in this study, 34 were male and 24 were female patients (mean age, 50.4 years). The mean operation time was 12.4 minutes, and the mean postoperative hospital stay was 3.8 days. Three patients experienced bleeding (5.1%) 5 urinary retention (8.6%) and 5 skin tags (8.6%). Urge to defecate, tenesmus, abscess, rectovaginal fistula, anal stricture, incontinence, and recurrence did not occur. CONCLUSION: PSH is a minimally invasive, feasible, and safe technique for treating patients with grades III–IV hemorrhoids. A PSH, instead of a CSH, can be used to treat certain patients with hemorrhoids.
Abscess ; Busan ; Constriction, Pathologic ; Female ; Hemorrhage ; Hemorrhoids* ; Humans ; Length of Stay ; Male ; Medical Records ; Mucous Membrane ; Rectovaginal Fistula ; Recurrence ; Retrospective Studies ; Sepsis ; Skin ; Surgeons ; Sutures ; Urinary Retention

Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5′ UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.
Antigens, Surface* ; Brain Diseases ; Neural Stem Cells ; Neurons* ; Stem Cells

Despite a high mortality rate, no specific treatment for severe fever with thrombocytopenia syndrome (SFTS) has been established. This study compared the clinical outcomes of SFTS patients treated with plasma exchange (PE group) with those who were not treated (non-PE group) at nine Korean hospitals between May 2013 and August 2015. A total of 53 SFTS patients were included: 24 (45.3%) PE cases and 29 (54.7%) non-PE cases. The overall in-hospital mortality rate was 32.1% (17/53). The in-hospital mortality rate of the PE group did not differ from that of the non-PE group (29.3% vs. 34.5%, p=0.680). Of the 24 PE cases, 16 (66.7%) were treated with PE within 7 days of symptom onset (early PE group). The early PE group survived longer than the non-PE group (mean 28.4 days vs. 22.6 days, p=0.044). Multivariate analysis showed an inverse association between early PE implementation and 30-day mortality (adjusted hazard ratio 0.052, 95% confidence interval 0.004–0.678, p=0.024). The results of this study suggest that early PE implementation may have a beneficial effect on the clinical outcome of SFTS patients.
Fever* ; Hospital Mortality ; Humans ; Mortality ; Multivariate Analysis ; Phlebovirus ; Plasma Exchange* ; Plasma* ; Thrombocytopenia*

OBJECTIVES: The objective of the present study was to determine the effects of the widely used combination hormone therapy, drospirenone and 17beta-estradiol on the blood pressure, body weight, lipid profiles, and major side effects in postmenopausal Korean women. METHODS: Four hundred seventeen menopausal patients who were being treated with drospirenone/17beta-estradiol at the Asan Medical Center between December 2007 and October 2010 underwent a retrospective chart review. One hundred twenty-five patients were divided into 2 groups based on blood pressure, as follows: group 1 (normal blood pressure, n = 76); and group 2 (stage 1 hypertension and pre-hypertension, n = 49). The systolic and diastolic blood pressure and the body weight were checked before the treatment, and 1, 2, 3, 6, 9, 12, 18 and 24 months after taking the medication. RESULTS: The median days of administration were 279. The combination of drospirenone and 17beta-estradiol had a blood pressure-lowering effect in groups 1 and 2. However, the body weight did not show a statistically significant change. Only the level of triglycerides decreased with time and the change was statistically significant. The low density lipoprotein (LDL)-cholesterol and triglycerides levels had a statistically significant decrease 18 months after the medication. The most common reasons for discontinuouing medication were vaginal spotting (28%), fear of side effects (27%), and ineffectiveness (26%). CONCLUSION: The combination of drospirenone/17beta-estradiol caused a decrease in systolic and diastolic blood pressure and the body weight showed no statistically significant decrease. Furthermore, triglycerides showed statistically significant decrease and there were no severe side effects of the medication reported.
Androstenes ; Blood Pressure ; Body Weight ; Female ; Hormone Replacement Therapy ; Humans ; Hypertension ; Lipoproteins ; Menopause ; Metrorrhagia ; Prehypertension ; Retrospective Studies ; Triglycerides

TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells.
Up-Regulation/*drug effects ; Tumor Necrosis Factor-alpha/*pharmacology ; Signal Transduction/*drug effects ; PTEN Phosphohydrolase/genetics/*metabolism ; NF-kappa B/genetics/*metabolism ; Leukemia/genetics/*metabolism ; Humans ; Gene Expression ; Cell Line, Tumor

A 23-year old woman was admitted to our hospital with hemoptysis. The chest X-ray showed reticulonodular opacity and multiple cysts throughout the entire lung field. The chest CT scan revealed numerous bilateral cysts with various sizes, some of them with thickened walls. An open lung wedge resection was performed. The resected specimen showed scattered small nodules, 0.3 to 0.6 cm in size. Microscopically, each nodule was composed of atypical glands with an occasional papillary architecture spreading to the alveolar septa, which were morphologically consistent with a papillary adenocarcinoma with a bronchioloalveolar carcinoma growth pattern. Immunochemically, the tumor cells were negative for the S-100 protein. The patient was diagnosed with an adenocarcinoma of the lung. A variety of diseases can produce or mimic multiple, thin-walled cysts in the lung. Lung cancer with multiple cysts is quite rare. Nevertheless, adenocarcinoma should be a diagnostic consideration. We report a case of a multiple cystic adenocarcinoma of the lung.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Adenocarcinoma, Papillary ; Female ; Hemoptysis ; Humans ; Hydrazines ; Lung ; Lung Neoplasms ; S100 Proteins ; Thorax

PURPOSE: The most common risk factor for fecal incontinence (FI) is obstetric injury. FI affects 1.4%–18% of adults. Most patients are unaware when they are young, when symptoms appear suddenly and worsen with aging. Autologous fat graft is widely used in cosmetic surgical field and may substitute for injectable bulky agents in treating FI. Authors have done fat graft for past several years. This article reports the effectiveness of the fat graft in treating FI and discusses satisfaction with the procedure. METHODS: Fat was harvested from both lateral thighs using 10-mL Luer-loc syringe. Pure fat was extracted from harvests and mixed with fat, oil, and tumescent through refinement. Fats were injected into upper border of posterior ano-rectal ring, submucosa of anal canal and intersphincteric space. Thirty-five patients with FI were treated with this method from July 2016 to February 2017 in Busan Hangun Hospital. They were 13 male (mean age, 60.8 years) and 22 female patients (mean age, 63.3 years). The Wexner score was checked before procedure. We evaluated outcome in outpatients by asking the patients. For 19 patients we checked the Wexner score after procedure. RESULTS: Symptom improved in 29 (82.9%), and not improved in 6 (17.1%). In 2 of 6 patients, they felt better than before procedure, although not satisfied. No improvement in 4. Mean Wexner score was 9.7 before procedure. There were no serious complications such as inflammation or fat embolism. CONCLUSION: Autologous fat graft can be an effective alternative treatment for FI. It is safe and easy to perform, and cost effective.
Adult ; Aging ; Anal Canal ; Busan ; Embolism, Fat ; Fats ; Fecal Incontinence ; Female ; Humans ; Inflammation ; Male ; Methods ; Outpatients ; Risk Factors ; Syringes ; Thigh ; Transplants