OBJECTIVE: Post-traumatic stress disorder (PTSD) is a psychiatric disorder characterized by depression and anxiety, that arises due to an imbalance of neurotransmitters in response to excessive stress. Hesperidin (HSD) is a naturally occurring flavonoid shown to exert a variety of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. METHODS: This study was used the open field test (OFT) and forced swimming test (FST) to examine the effects of HSD on the depression-like response of rats after exposure to a single prolonged stress (SPS) leading to the dysregulation of the serotonergic activation system. Male rats were given HSD (20, 50, and 100 mg/kg, intraperitoneal injection, n=6-7 per group) once daily for 14 days after exposure to SPS. The influence of administration of HSD on SPS-induced behavioral responses and concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and monoamine oxidase-A (MAO-A) in the rat brain were also investigated using enzyme-linked immunoassays (ELISAs). RESULTS: Daily HSD administration signifificantly improved depression-like behaviors in the FST (P0.05), increased the number of lines crossed in the central zone of the OFT (P0.01), and reduced freezing behavior both in contextual and cued fear conditioning. HSD treatment also attenuated the reduction in SPS-induced 5-HT concentrations in the hippocampus and amygdala. This increase in 5-HT concentrations during HSD treatment was partially attributed to a decrease in the 5-HIAA/5-HT ratio in the hippocampus of rats with PTSD. Furthermore, HSD treatment inhibited activity of MAO-A and decreases of tryptophan hydroxylase-1 expression in the hippocampus. CONCLUSION HSD was shown to exert antidepressant effects in rats exposed to SPS, suggesting that this natural flflavonoid may be an effective medicine for PTSD.

BACKGROUND: Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. METHODS: We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. RESULTS: In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. CONCLUSIONS: These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers.
Breast Neoplasms ; Cell Line ; Cell Movement ; Epithelial-Mesenchymal Transition ; Humans ; Lung ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Phosphorylation ; Phosphotransferases ; Prostatic Neoplasms ; Sequence Analysis, RNA

The original version of this article contained error in the URL of the SUPPLEMENTARY MATERIALS.

Eleven compounds (1–11) were isolated from the rhizomes of Osmunda japonica, and their structures were elucidated based on 1H, 13C-NMR and LC-IT-TOF MS data. Of these compounds, all compounds (1 – 11) have been previously reported, although five (6 – 9, 11) have not previously been isolated from this plant. The antioxidant activities of isolated compounds (1 – 11) were measured by DPPH and ABTS assays, and compound 10 showed the high antioxidant activity.
Plants ; Rhizome*

PURPOSE: Recently, a nomogram predicting overall survival after gastric resection was developed and externally validated in Korea and Japan. However, this gastric cancer nomogram is derived from large-volume centers, and the applicability of the nomogram in smaller centers must be proven. The purpose of this study is to externally validate the gastric cancer nomogram using a dataset from a medium-volume center in Korea. MATERIALS AND METHODS: We retrospectively analyzed 610 patients who underwent radical gastrectomy for gastric cancer from August 1, 2005 to December 31, 2011. Age, sex, number of metastatic lymph nodes (LNs), number of examined LNs, depth of invasion, and location of the tumor were investigated as variables for validation of the nomogram. Both discrimination and calibration of the nomogram were evaluated. RESULTS: The discrimination was evaluated using Harrell's C-index. The Harrell's C-index was 0.83 and the discrimination of the gastric cancer nomogram was appropriate. Regarding calibration, the 95% confidence interval of predicted survival appeared to be on the ideal reference line except in the poorest survival group. However, we observed a tendency for actual survival to be constantly higher than predicted survival in this cohort. CONCLUSIONS: Although the discrimination power was good, actual survival was slightly higher than that predicted by the nomogram. This phenomenon might be explained by elongated life span in the recent patient cohort due to advances in adjuvant chemotherapy and improved nutritional status. Future gastric cancer nomograms should consider elongated life span with the passage of time.
Calibration ; Chemotherapy, Adjuvant ; Cohort Studies ; Dataset* ; Discrimination (Psychology) ; Gastrectomy ; Humans ; Japan ; Korea ; Lymph Nodes ; Nomograms* ; Nutritional Status ; Retrospective Studies ; Stomach Neoplasms*

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1beta is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1beta production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1beta in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Co-treatment with WA decreased IL-1beta production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1beta and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IkappaB-alpha phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1beta, as well as increased procaspase-1 and pro IL-1beta protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit ac tivation of the NLRP3 inflammasome. NLRP3 activators induced IL-1beta secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1beta and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1beta production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer.
Blotting, Western ; Caspase 1 ; Dendritic Cells* ; Down-Regulation ; Gastritis ; Gene Expression ; Helicobacter pylori ; Helicobacter* ; Humans ; Interleukin-1beta ; Interleukin-6 ; Macrophages ; NF-kappa B* ; Peptic Ulcer ; Phosphorylation ; Stomach Neoplasms ; Withania

Paraplegia secondary to spinal cord infarction is a recognized complication of open thoracic and thoracoabdominal aortic aneurysm (TAA) repair. TAA is serious and unpredictable condition. Therefore, aortic repair requires thorough information on managing the potential complications will facilitate improve control the problem. We report the symptoms and management of paraplegia in a patient who underwent stent insertion as TAA.
Aortic Aneurysm, Abdominal ; Aortic Aneurysm, Thoracic ; Humans ; Infarction ; Paraplegia ; Spinal Cord ; Spinal Cord Ischemia ; Stents

PURPOSE: The wild-type p53 protein participates in suppressing cell transformations while its mutant forms has tumorigenic potential. Alterations in the structure of the p53 protein are one of the most common changes associated with human cancers. CREB-binding protein (CBP) and its homologue, p300, are transcriptional co-activators of various sequence-specific DNA-binding transcription factors and are involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis. Several studies suggested that an association between p53 and p300 might account for the p53-responsible negative regulation. This study examined the relationship between p53 and CBP expression in terms of the clinicopathological factors and significance. METHODS: The level of p53 protein and CBP expression was measured in 150 gastric adenocarcinoma patients, who had undergone a gastrectomy, and the relationship between p53 and CBP was examined. Immunohistochemical stain was performed on formalin-fixed paraffin-embedded sections using monoclonal anti-p53 and anti-CBP antibody. RESULTS: 1. p53 protein was expressed in 46.3% (31/67) of early gastric cancers (EGC), 69.9% (58/83) of advanced gastric cancers (AGC)(P<0.05), 69.1% (65/94) of the intestinal type, 42.9% (24/56) of the diffuse type (P<0.05), 78.5% (55/70) of patients with a lymph node metastasis and 42.5% (34/80) of patients without a lymph node metastasis (P<0.01). 2. CBP expression was observed in 65% (61/94) of intestinal type, 51% (29/56) of the diffuse type (P>0.05), 47.8% (32/67) of EGC, 69.8% (58/83) of AGC (P<0.05), 68.6% (48/70) of patients with a lymph node metastasis and 52.5% (42/80) of patients without a lymph node metastasis (P>0.05). 3. p53 protein and CBP expression was coincidentally observed in 66.7% of gastric adenocarcinomas, and there was a significant correlation between the expression of both (P<0.05). CONCLUSION: That the expression of the p53 protein and CBP indirectly indicate the malignant potential of a cell, and may play an indirect role in the CBP and p53-mediated tumorigenic potential.
Adenocarcinoma* ; Apoptosis ; CREB-Binding Protein* ; DNA Repair ; Gastrectomy ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Stomach ; Stomach Neoplasms ; Transcription Factors

PURPOSE: We examined the expressions of claudin-4 and E-cadherin, which are known as cell adhesion-associated proteins, in stomach cancer. The relationship of their expression with the clinicopathologic factors was examined to investigate the roles of these proteins in the invasion or metastasis of stomach adenocarcinoma. METHODS: The expressions of claudin-4 and E-cadherin were examined in 73 cases of adenocarcinoma of the stomach by performing immunohistochemical staining. RESULTS: The expressions of claudin-4 and E-cadherin in the stomach adenocarcinoma were both correlated with the histologic grade, the T-stage and nodal metastasis, respectively (P<0.05). The expression of claudin-4 was significantly associated with the expression of E-cadherin. CONCLUSION: Our data suggests that claudin-4 and E-cadherin are involved in the processes of histologic differentiation, invasion and metastasis of stomach adenocarcinoma.
Adenocarcinoma ; Cadherins* ; Claudin-4* ; Neoplasm Metastasis ; Stomach Neoplasms* ; Stomach*

PURPOSE: Laparoscopic cholecystectomy has replaced open cholecystectomy as the standard treatment and it has widely gained rapid acceptance. However, laparoscopic cholecystectomy has many complications and it can require conversion to open cholecystectomy or further management. We reviewed our cases for determining the complications and clinical results in order to improve the efficacy and safety of laparoscopic cholecystectomy in our hospital. METHODS: The data from 3,224 laparoscopic cholecystectomies that were performed at our hospital from January 1995 to December 2004 were reviewed retrospectively. The pre-operative laboratory data, operative findings, post-operative pathologic findings, complications and proper treatment were evaluated. RESULTS: 52 of all the patients developed complications. The median patient age was 51.8+/-11.6 years, and the median admission time was 29.9+/-10.6 days. The most common complications were post operative bleeding (20 case), and bile duct injury (15 cases). A collection of bile was noted in 12 cases. The treatment of complications were operations (16 case) radiologic interventions (14 case), and observation with conservative management (22 case). CONCLUSION: There were various complications of laparoscopic cholecystectomy, and these patients needed a longer hospital stay and operative treatment. So, improvement of surgeons' skill with a carefully approach and better understanding of the anatomical variations of the biliary tree and vascular system, recognition of pre-operative patients' general condition and the severity of inflammation, and prompt and proper management for complications should be done to prevent serious problems.
Bile ; Bile Ducts ; Biliary Tract ; Cholecystectomy ; Cholecystectomy, Laparoscopic* ; Hemorrhage ; Humans ; Inflammation ; Length of Stay ; Retrospective Studies