Protective effects of gomisin N against hepatic steatosis through AMPK activation.

Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. It has been reported to exert a protective effect against hepatic steatosis by attenuating endoplasmic reticulum (ER) stress. However, the detailed mechanism by which GN inhibits hepatic steatosis remains to be elucidated. In this study, we examined whether GN activates AMP-activated protein kinase (AMPK) and exerts therapeutic effects on liver X receptor (LXR)- or palmitic acid (PA)-induced triglyceride (TG) accumulation in HepG2 cells. Furthermore, in vivo protective effects of GN against hepatic steatosis were assessed in high-fat diet (HFD)-induced obese mice. GN stimulated the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c) in HepG2 cells. It decreased the expression of lipogenesis genes, but increased the expression of fatty acid oxidation genes. Additionally, GN decreased the expression of lipogenesis genes induced by the LXR agonist T0901317 or PA in HepG2 cells, resulting in reduced intracellular TG content. However, preincubation with compound C, an AMPK inhibitor, prevented GN-mediated effects. Administration of GN to HFD-induced obese mice decreased HFD-induced liver weight, hepatic TG accumulation, and cytoplasmic lipid droplet. These findings demonstrate that GN activates the AMPK pathway and ameliorates HFD-induced hepatic steatosis.

Risk factors associated with difficult gastric endoscopic submucosal dissection: predicting difficult ESD.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) is a widely accepted treatment for superficial gastric neoplasms. Difficult ESD can lead to complications, such as bleeding and perforation. To predict difficult ESD procedures, we analyzed the factors associated with difficult ESD. PATIENTS AND METHODS: The medical records of 1052 ESD procedures were retrospectively reviewed. Difficult ESD was defined by any one of three end points: longer procedure time (≥60 min), piecemeal resection, incomplete (R1) resection, or gastric wall perforation. To determine the factors associated with difficult ESD, clinical and pathologic features and endoscopic findings were analyzed. RESULTS: The rates of en bloc resection and curative (R0) resection were 93.3 and 92.4 %, respectively. The mean procedure time was 27.7 ± 16.7 min. After multivariate analysis, larger tumor size (≥20 mm) was an independent risk factor for longer procedure time (OR 4.1, P < 0.001), for piecemeal resection (OR 2.3, P = 0.003) and incomplete (R1) resection (OR 2.1, P = 0.005). Location of the lesion (upper third) was an independent risk factor for longer procedure time (OR 5.8, P < 0.001), for piecemeal resection (OR 4.1, P < 0.001) and incomplete (R1) resection (OR 4.5, P < 0.001). Submucosal fibrosis was an independent risk factor for longer procedure time (OR 9.7, P < 0.001), for piecemeal resection (OR 2.4, P < 0.001) and incomplete (R1) resection (OR 2.6, P < 0.001). Finally, submucosal invasive gastric cancer was an independent risk factor for piecemeal resection (OR 2.6, P = 0.008), for perforation (OR 19.3, P = 0.001) and for incomplete (R1) resection (OR 2.7, P = 0.001). CONCLUSIONS: Difficult ESD procedures are a function of the lesion size and location, submucosal fibrosis, and submucosal invasive cancer. When a difficult ESD procedure is expected, appropriate preparations should be considered, including consultation with more experienced endoscopists.

Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill. (SC) is a traditional Chinese herbal medicine with diverse pharmacological activities for treatment of various human diseases. Endoplasmic reticulum (ER) stress is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of methanol extract of Schisandra chinensis (SC extract) against ER stress-induced NAFLD in vitro and in vivo. MATERIAL AND METHODS: The protective effects of SC extract were examined in tunicamycin- or palmitate-treated HepG2 cells in vitro, and in tunicamycin-injected mice or high fed diet (HFD) obese mice in vivo. Expression of ER stress markers including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride accumulation were measured in HepG2 cells and in the liver of mice. RESULTS: SC extract significantly inhibited expression of tunicamycin-induced ER stress markers in tunicamycin-treated HepG2 cells and in the liver of tunicamycin-injected mice, and it also inhibited tunicamycin-induced triglyceride accumulation. Similar observations were made under physiological ER stress conditions such as in palmitate-treated HepG2 cells and in the liver of HFD obese mice. In addition, SC extract repressed the expression of inflammatory genes and lipogenic genes in palmitate-treated HepG2 cells. Schisandrin, an abundant bioactive lignan in SC extract, inhibited the expression of ER stress markers in tunicamycin-or palmitate-treated HepG2 cells, whereas Gomisin J did not affect ER stress markers. CONCLUSIONS: SC attenuates ER stress and prevents development of NAFLD. SC may be useful as a pharmacological agent for protection against ER stress-induced human diseases.

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis.

Gomisin N is a physiological substance derived from Schisandra chinensis. In the present study, the in vitro and in vivo effects of gomisin N on endoplasmic reticulum (ER) stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride (TG) accumulation, in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced expression of markers of ER stress and increased TG levels; Gomisin N reversed these effects, reducing the expression of markers of ER stress and TG levels. Similar effects were seen following palmitate pretreatment of HepG2 cells. The inhibitory effects of gomisin N were further confirmed in mice injected with tunicamycin. Gomisin N reduced expression of markers of ER stress and decreased TG levels in mouse liver after tunicamycin injection. Furthermore, gomisin N decreased expression of inflammatory and lipogenic genes in palmitate-incubated HepG2 cells. These results suggest that gomisin N inhibits ER stress and ameliorates hepatic steatosis induced by ER stress.

A case of midazolam anaphylaxis.

Midazolam is a type of anesthetic agent frequently used for conscious sedation during a variety of medical procedures. Anaphylactic reactions to midazolam are rarely reported. However, we observed a case of midazolam hypersensitivity in which emergency measures were required to ensure patient recovery after administration of midazolam as a sedative. The occurrence of the anaphylactic reaction to midazolam was confirmed by elevated serum tryptase levels. The current case report presents a discussion of our findings.

[How medical students perform academically by admission types?].

PURPOSE: Despite the importance of selecting students whom are capable for medical education and to become a good doctor, not enough studies have been done in the category. This study focused on analysing the medical students' academic performance (grade point average, GPA) differences, flunk and dropout rates by admission types. METHODS: From 2004 to 2010, we gathered 369 Konyang University College of Medicine's students admission data and analyzed the differences between admission method and academic achievement, differences in failure and dropout rates. Analysis of variance (ANOVA), ordinary least square, and logistic regression were used. RESULTS: The rolling students showed higher academic achievement from year 1 to 3 than regular students (p < 0.01). Using admission type variable as control variable in multiple regression model similar results were shown. But unlike the results of ANOVA, GPA differences by admission types were shown not only in lower academic years but also in year 6 (p < 0.01). From the regression analysis of flunk and dropout rate by admission types, regular admission type students showed higher drop out rate than the rolling ones which demonstrates admission types gives significant effect on flunk or dropout rates in medical students (p < 0.01). CONCLUSION: The rolling admissions type students tend to show lower flunk rate and dropout rates and perform better academically. This implies selecting students primarily by Korean College Scholastic Ability Test does not guarantee their academic success in medical education. Thus we suggest a more in-depth comprehensive method of selecting students that are appropriate to individual medical school's educational goal.

Estrogen receptor beta stimulates Egr-1 transcription via MEK1/Erk/Elk-1 cascade in C6 glioma cells.

The Egr-1 is an immediate early response gene encoding a transcription factor that functions in the regulation of cell growth, differentiation, and apoptosis. Estrogen has diverse physiological effects, including cellular proliferation and neuroprotection against brain injury. There are two types of estrogen receptors (ERs), ERα and ERß. ERα-induced Egr-1 expression has been extensively studied; however, the role of ERß is yet not known. In the present study, we investigated whether or not ERß induces Egr-1 expression in C6 rat glioma cells, which express ERß but not ERα. Our results show that ERß promoted up-regulation of Egr-1 expression via a non-genomic mechanism involving the Raf/MEK1/Erk/Elk-1 signaling cascade.

Evaluation of an immunochromatographic assay for the detection of anti-hepatitis A virus IgM.

BACKGROUND: Hepatitis A virus (HAV) is a causative agent of acute hepatitis, which is transmitted by person-to-person contact and via the faecal-oral route. Acute HAV infection is usually confirmed by anti-HAV IgM detection. In order to detect anti-HAV IgM in the serum of patients infected with HAV, we developed a rapid assay based on immunochromatography (ICA) and evaluated the sensitivity of this assay by comparing it with a commercial microparticle enzyme immunoassay (MEIA) that is widely used for serological diagnosis. RESULTS: The newly developed ICA showed 100% sensitivity and specificity when used to test 150 anti-HAV IgM-positive sera collected from infected patients and 75 negative sera from healthy subjects. Also, the sensitivity of ICA is about 10 times higher than MEIA used in this study by determining end point to detect independent on infected genotype of HAV. In addition, the ICA was able to detect 1 positive sample from among 50 sera from acute hepatitis patients that had tested negative for anti-HAV IgM using the MEIA. CONCLUSION: Conclusively, ICA for the detection of anti-HAV IgM will be very effective for rapid assay to apply clinical diagnosis and epidemiological investigation on epidemics due to the simplicity, rapidity and specificity.

Are medical students satisfied with their medical professionalism education?

PURPOSE: This study aims to examine the satisfaction of undergraduate medical students with their medical professionalism education. METHODS: Two hundred and one premedical students and 1,287 medical students (from year 1 to 4) participated in a five-point Likert scale survey. There were 27 items in the premedical students' survey and 31 items in the medical students' questionnaire. Statistical analysis including one-way ANOVA was performed. RESULTS: Among the 27 items concerning premedical professionalism education, only six topics scored "average" level. In the survey of medical students only nine items out of 31 were rated "average" which did not reach the satisfactory level. Nine items from the medical students' survey showed significant positive improvements in satisfaction as the academic year increased; however, the changes were not large enough for any of the topics to receive a satisfactory score. CONCLUSION: Overall students were dissatisfied with their professionalism education. The reasons for these results and possible approaches for improving students' satisfaction should be considered in future research.

Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma.

Lignans isolated from Schisandria chinensis have been prescribed as anti-cancer and anti-hepatitis treatments in Chinese medicine. To investigate the applications of lignans isolated from Schisandria chinensis in hepatic carcinoma therapy, their apoptotic ability was screened using a cell proliferation assay. Compared to the other lignans, gomisin N induced high apoptotic levels in hepatic carcinoma. Cell morphology and flow cytometric analysis demonstrated that this lignan induced cell death at high concentrations, but did not induce any changes at low concentrations. In addition, the expression levels of Bcl-2 and Bax proteins, which are involved in the apoptotic pathway, were markedly increased in only the 320 µM-treated group compared to the vehicle and other concentration groups, while the expression level of p53 protein remained unchanged in this group. These results suggest that gomisin N is an anti-cancer drug candidate capable of inhibiting the proliferation and inducing the apoptosis of human hepatic carcinomas.

Elevation of CRABP-I in the cerebrospinal fluid of patients with Moyamoya disease.

BACKGROUND AND PURPOSE: The etiology of moyamoya disease (MMD) remains obscure. This study was undertaken to identify specific proteins associated with the pathogenesis of MMD. METHODS: We studied cerebrospinal fluid (CSF) from 20 patients with angiographically confirmed MMD (4 boys and 16 girls; age range, 3 to 13 years; mean, 7.5 years) and 4 control patients with cerebral palsy who underwent selective dorsal rhizotomy (2 boys and 2 girls; age range, 5 to 10 years; mean, 7.3 years). CSF proteins were analyzed by 2-dimensional polyacrylamide gel electrophoresis, and protein identification was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The presence of specific CSF protein in patients with MMD was confirmed by Western blotting. In addition, cerebral CSF was also tested in 7 patients who had other brain diseases but no MMD (2 boys and 5 girls; age range, 1 to 12 years; mean, 6.9 years). RESULTS: We identified 1 polypeptide spot (Mr of 13 to 15 kDa and isoelectric point of 5 to 5.5) that was differentially expressed in the CSF samples of MMD patients (mean optical density intensity, 0.36+/-0.24; range, 0.05 to 0.92) and control spinal CSF samples (mean, 0.03+/-0.04; range, 0 to 0.08; P=0.002). This polypeptide was identified as cellular retinoic acid-binding protein (CRABP)-I. High levels of expression of CRABP-I in the CSF from 17 MMD children were confirmed by Western blotting. CONCLUSIONS: The analysis of the CSF of MMD patients reveals high CRABP-I expression. The present study suggests that the elevation of CRABP-I in CSF may be a candidate for pathogenesis of MMD.