Caffeic acid (CA) is a phenolic compound found naturally in plants and foods. CA and its natural derivatives are reported to have anti-cancer effects on many cancers, including melanoma. (E)-N-(4-Butylphenyl)-3-(3,4-dihydroxyphenyl)acrylamide (4-BPCA) is an amide derivative of CA. Thus far, the anti-cancer effect and mechanism of 4-BPCA in melanoma cells remain unknown. Here we investigated whether 4-BPCA inhibits the growth of B16F10 cells, a mouse melanoma cell line. Of note, treatment of 4-BPCA at 5 M for 24 or 48 h significantly reduced the growth (survival) of B16F10 cells. On mechanistic levels, treatment with 4-BPCA for 24 h led to the activation of caspase-9/3, but not caspase-8, in B16F10 cells. 4-BPCA treatment for 2 or 4 h also decreased the expression levels of myeloid B-cell lymphoma 1 (Mcl-1) in B16F10 cells. However, 4-BPCA treatment for the times tested did not influence the expression levels of X-linked inhibitor of apoptosis protein (XIAP) in B16F10 cells. Of interest, treatment of 4-BPCA for 2 or 4 h greatly reduced the phosphorylation levels of JAK-2 and STAT-5 without altering their total protein expression levels. 4-BPCA also had abilities to increase the expression and phosphorylation levels of glucose-regulated protein-78 (GRP-78) and eukaryotic translation initiation factor-2α (eIF-2α) in B16F10 cells. In summary, these results demonstrate firstly that 4-BPCA has a strong growth-inhibitory effect on B16F10 melanoma cells, mediated via activation of the intrinsic caspase pathway, inhibition of JAK-2 and STAT-5, and triggering endoplasmic reticulum (ER) stress.

No abstract available.
Carcinoma, Hepatocellular*

OBJECTIVES: Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. METHODS: PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. RESULTS: Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. CONCLUSIONS: Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.
Animals ; Genes, Reporter ; Humans ; Lithium Chloride ; Lithium* ; PC12 Cells* ; Pheochromocytoma ; Phosphorylation* ; Phosphotransferases ; Signal Transduction ; Transcription Factors ; Valproic Acid*

PURPOSE: The incidence of colonic diverticular disease is increasing, and several grading systems based on CT findings have been developed. The objective of this study was to define the impact of various CT findings of colonic diverticulitis and to demonstrate which factors affect the need for operative treatment. METHODS: Three hundred fifty-seven patients diagnosed with colonic diverticulitis from January 2010 to July 2016 were retrospectively evaluated. Patients were excluded if pure diverticulosis, diverticular bleeding, colon cancer, or relevant data deficiencies, and the remaining patients (n = 178) were reviewed. Patients were categorized into a successful nonoperation group and an operation group. The operation group was then matched 1:2 with the nonoperative group based on age, gender, American Society of Anesthesiologists physical status classification, and body mass index. RESULTS: After propensity score matching, there were no significant differences regarding patients' demographic characteristics between the 2 groups. Left location was more associated with need for operation than the right side (79.2% vs. 31.3%, P < 0.001). CT findings such as distant intraperitoneal air, pericolic air, and free fluid were significantly more apparent in the operation group. When these factors were evaluated in a multivariate analysis, distant intraperitoneal air showed statistical significance (P = 0.046) and pericolic air and left location a significant trend (P = 0.071 and P = 0.067, respectively). CONCLUSION: This study suggests that distant intraperitoneal air is the most important factor in the need for surgery in patients with colonic diverticulitis. Further study will be able to identify more detailed CT findings and verify their significance, and will be helpful in designing practical scoring and classification systems.
Body Mass Index ; Classification ; Colon ; Colonic Neoplasms ; Diverticulitis* ; Diverticulitis, Colonic ; Diverticulum ; Hemorrhage ; Humans ; Incidence ; Intraabdominal Infections ; Multivariate Analysis ; Propensity Score ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVE: To find out the distinctive topographic EEG profiles of subject with attention deficit hyperactivity disorder comparing with age & sex matched control. METHOD: The quantitative electroencephalographies(QEEGs) of 20 drug-naive ADHD patients without any other psychiatric diagnosis were analyzed and compared to age and sex-matched controls using spectral analysis. RESULTS: 1) Slow waves(delta and theta) bipolar relative powers of the diverse areas in both hemispheres increased in drug-free ADHD patients, compared to controls. 2) Delta and theta bipolar relative powers of localized centro-temporal areas in left hemispheres increased in drug-free ADHD patients compared to controls. 3) Interhemispheric coherence and asymmetry are increased in diverse areas in ADHD patient compared to controls. CONCLUSION: We confirmed QEEG abnormalities in pure ADHD patients, especially in frontal and parietal areas. These results are compatible with other structural and functional imaging studies of ADHD.
Attention Deficit Disorder with Hyperactivity ; Electroencephalography ; Humans ; Mental Disorders ; Rabeprazole

Objective: The risk of suicide is assessed by identifying the relationship between alcohol-use patterns and suicidal ideation in Korean employees. Methods: The study involved 13,858 employees who underwent workplace mental health screening at the Workplace Mental Health Institute of Kangbuk Samsung Hospital over a 6-year period between 2014 and 2019. Analysis was performed separately for Alcohol Use Disorders Identification Test-Korea (AUDIT-K) items related to the frequency/volume of alcohol consumption (items 1 to 3, AUDIT-C) and those regarding alcohol dependence/related problems (items 4 to 10, AUDIT-D/P). Subjects were then classified into three groups on the basis of the presence or absence of clinical depression and suicidal ideation. The groups’ sociodemographic factors and clinical features of depression, anxiety, and alcohol-use patterns were analyzed with a chi-square test as well as one-way analysis of variance, followed by a post hoc test using the Bonferroni correction. Results: AUDIT-K and AUDIT-D/P scores were significantly associated with the presence or absence of clinical depression as well as the presence or absence of suicidal ideation (p<0.05). However, no significant differences were found among the three groups with regard to the AUDIT-C score (p=0.054). Conclusion Identifying or treating alcohol dependence/related problems can help lower the occurrence of mental health problems, and suicidal ideation in particular, in employees and reduce social costs.

OBJECTIVES: This study was conducted to develop the Korean version of Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS) for measuring neuroleptic side effects by self-rating method and to examine the reliability and validity in the schizophrenic patients medicated by neuroleptics and normal controls. METHODS: We made 51-item, 4-point scale of Korean version LUNSERS through translation, reverse translation and supervision by specialists. Sixty two schizophrenics diagnosed by DSM-IV criteria and medicated with neuroleptics completed LUNSERS twice with one week interval. Second LUNSERS and UKU side effect rating scale (UKU) by psychiatrist were administered to the schizophrenics at the same time. Normal controls also completed LUNSERS. RESULTS: The test-retest reliability (r=0.86, p<0.01) of LUNSERS and the concurrent validity (r=0.81, p<0.001) against UKU were good. But the neuroleptic doses and total scores of side effect items didn't show significant correlation. By the ROC curve analysis, the total scores of side effect items differentiated the medicated patients from non-medicated controls but not for the red herring items. CONCLUSION: Korean-version of LUNSERS has good reliability and validity. And it was also proved to be an useful assessment tool for measuring the extent of neuroleptic side effects systematically instead of UKU in clinical trials.
Antipsychotic Agents ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Organization and Administration ; Psychiatry ; Reproducibility of Results ; ROC Curve ; Specialization

BACKGROUND: The occurrence of atrial fibrillation after ablation of atrial flutter is clinically important. We investigated variables predicting this evolution in ablated patients without a previous atrial fibrillation history. MATERIALS AND METHODS: Thirty-six patients (Male=28) who were diagnosed as atrial flutter without previous atrial fibrillation history were enrolled in this study. Group 1 (n=11) was defined as those who developed atrial fibrillation after atrial flutter ablation during 1 year follow-up. Group 2 (n=25) was defined as those who has not occurred atrial fibrillation during same follow-up term. Echocardiogram was performed to all patients. We measured left atrial size, left ventricle end diastolic and systolic dimension, ejection fraction and left atrial volume index before and after ablation of atrial flutter. The differences of each variables were compared and analyzed between two groups. RESULTS: The preablation left ventricular ejection fraction (preLVEF) and postablation left ventricular ejection fraction (postLVEF) are 54+/-14%, 56+/-13% in group 1 and 47+/-16%, 52+/-13% in group 2. The differences between each two groups are statistically insignificant (2.2+/-1.5 in group 1 vs 5.4+/-9.8 in group 2, p=0.53). The preablation left atrial size (preLA) and postablation left atrial size (postLA) are 40+/-4 mm, 41+/-4 mm in group1 and 44+/-8 mm, 41+/-4 mm in group 2. The atrial sizes of both groups were increased but, the differences of left atrial size between two groups before and after flutter ablation were statistically insignificant (0.6+/-0.9mm in group 1 vs -3.8+/-7.4 mm in group 2, p=0.149). The left atrial volume index before flutter ablation was significantly reduced in group 1 than group 2 (32+/-10 mm3/m2, 35+/-10 mm3/m2 in group 1 and 32+/-10 mm3/m2, 29+/-8 mm3/m2 in group 2, p<0.05). CONCLUSION: The difference between left atrial volume index before and after atrial flutter ablation is the robust predictor of occurrence of atrial fibrillation after atrial flutter ablation without previous atrial fibrillation.
Atrial Fibrillation* ; Atrial Flutter* ; Catheter Ablation* ; Follow-Up Studies ; Heart Atria ; Heart Ventricles ; Humans ; Stroke Volume

OBJECTIVE: cDNA microarray is a convenient molecular technology that enables to search for gene expression in large scale. To explore the effect of antipsychotics on the gene expression in the brain, we applied cDNA microarray and searched for differentially expressed genes in the olanzapine-treated rat frontal cortex. METHODS: We administered olanzapine (4 mg/kg/day, IP) to S-D rats for 14days, and dissected the frontal cortex to examine. We analyzed altered gene expression from microarray, and screened up- or down-regulated genes. Their changes were confirmed by RT-PCR. RESULTS: Three down-regulated and one up-regulated genes were screened by triplicate cDNA microarray analysis. Among them, translocase of the inner mitochondrial membrane 23 (TIM23) was confirmed in RT-PCR. The expression of TIM23 mRNA was significantly increased in olanzapine-treated rat frontal cortex. CONCLUSION: This is the first report of up-regulated gene expression of TIM23 by antipsychotics in the rat brain. TIM23 is the essential component of mitochondrial biogenesis. From this result, we suggest that antipsychotic effect may be related to the improvement of mitochondrial dysfunction in the brain.
Animals ; Antipsychotic Agents ; Brain ; DNA, Complementary* ; Gene Expression* ; Mitochondrial Membranes ; Organelle Biogenesis ; Oligonucleotide Array Sequence Analysis* ; Rats* ; RNA, Messenger ; Schizophrenia

Background/Aims: Although fecal microbiota transplantation (FMT) has been proven as one of the promising treatments for patients with ulcerative colitis (UC), potential prognostic markers regarding the clinical outcomes of FMT remain elusive. Methods: We collected fecal samples of 10 participants undergoing FMT to treat UC and those from the corresponding donors. We categorized them into two groups: responders and nonresponders. Sequencing of the bacterial 16S rRNA gene was conducted on the samples to explore bacterial composition. Results: Analyzing the gut microbiota of patients who showed different outcomes in FMT presented a distinct microbial niche. Source tracking analysis showed the nonresponder group had a higher rate of preservation of donor microbiota, underscoring that engraftment degrees are not one of the major drivers for the success of FMT. At the phylum level, Bacteroidetes bacteria were significantly depleted (p<0.003), and three genera, including Enterococcus, Rothia, and Pediococcus, were enriched in the responder group before FMT (p=0.003, p=0.025, and p=0.048, respectively). Furthermore, we applied a machine learning algorithm to build a prediction model that might allow the prediction of FMT outcomes, which yielded an area under the receiver operating characteristic (ROC) curve of 0.844. Notably, the microbiota-based model was much better at predicting outcomes than the clinical features model (area under the ROC curve=0.531). Conclusions This study is the first to suggest the significance of indigenous microbiota of recipients as a critical factor. The result highlights that bacterial composition should be evaluated before FMT to select suitable patients and achieve better efficiency.