PURPOSE: Diallyl disulfide (DADS) is a major organosulfur compound derived from garlic. It has been reported that DADS is able to inhibit the proliferation of several tumor cells. In this study, the effect of DADS was investigated in terms of the proliferation of AGS, gastric adenocarcinoma cell line at various concentrations. METHODS: The viability of cultured cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To detect the induction of apoptosis, Annexin V-FITC/propodium iodide (PI) staining assay was performed. Analysis of reactive oxygen species (ROS) and the distribution of cells in the cell cycle were measured by a flow cytometer. And using the Western blot analysis, the change of Fas, caspase-3, Bax, Bcl-2 activity was measured. RESULTS: The percentage of live AGS cells was decreased to 23% of that in the control group after 400 microM DADS treatment for 48 hours. The Annexin V positive/PI negative (apoptosis portion) area increased from low concentration of DADS to high concentration. When comparing among the DADS treatment groups, the amount of ROS production increased in a dose dependent manner. The percentage of sub-diploid DNA content increased from 8.71% at 50 microM to 25.74% at 400 microM DADS treatment group. The expressions of Fas, caspase-3, Bax were increased and that of Bcl-2 was decreased in a dose dependent manner. CONCLUSION: DADS decreases the viability of AGS cell lines and induces apoptosis in a dose-dependent manner. But the relationship of the anti-proliferative effect of DADS and related molecular changes were not clearly proportional to the concentration of DADS.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid ; Adenocarcinoma ; Allyl Compounds ; Annexin A5 ; Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Cycle ; Cell Line ; Cells, Cultured ; Disulfides ; DNA ; Garlic ; Reactive Oxygen Species ; Stomach Neoplasms

This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Alkylating/administration & dosage ; Brain Neoplasms/diagnosis/*mortality/*therapy ; Chemoradiotherapy, Adjuvant/methods/mortality ; Comorbidity ; Dacarbazine/administration & dosage/*analogs & derivatives ; Female ; Glioblastoma/diagnosis/*mortality/*therapy ; Hematologic Diseases/*mortality ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prevalence ; Radiotherapy, Conformal/mortality ; Republic of Korea/epidemiology ; Risk Factors ; Survival Rate ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Sleep duration affects health in various ways. The objective of this study was to investigate the associations of sleep duration with chronic kidney disease (CKD) in a Korean adult population. METHODS: This cross-sectional analysis was conducted for total of 1,360 participants who completed baseline health examinations for the Korean Genome and Epidemiology Study-Kangwha study in 2010 to 2011. Sleep habits were measured by an interviewer-assisted questionnaire. Sleep duration was calculated based on the number of hours per day participants had slept over the past 1 year. CKD was defined as either proteinuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Multiple logistic regression models were applied to examine associations between sleep duration and CKD. RESULTS: Women with very long sleep duration (≥ 9 hours/day) were at significantly increased odds for having high serum creatinine (odds ratio [OR], 2.936; 95% confidence interval [CI], 1.176 to 7.326), low eGFR (OR, 3.320; 95% CI, 1.372 to 8.034), and CKD (OR, 3.112; 95% CI, 1.315 to 7.363), compared those with a typical sleep duration (7 to < 8 hours/day), after adjusting for sociodemographic status, socioeconomic status, health behaviors, comorbidities, and sleep quality. Among women, for every 1 hour increase in sleep duration per day, there was a 24.6% increase in the presence of CKD (OR, 1.246; 95% CI, 1.019 to 1.523). However, among men, sleep duration was not significantly associated with CKD. CONCLUSIONS: Very long sleep duration was independently associated with a higher prevalence of CKD among Korean women. Gender may influence this association.
Adult ; Comorbidity ; Creatinine ; Cross-Sectional Studies ; Epidemiology* ; Female ; Genome* ; Glomerular Filtration Rate ; Health Behavior ; Humans ; Logistic Models ; Male ; Prevalence ; Proteinuria ; Renal Insufficiency, Chronic* ; Social Class

High mobility group box 1 (HMGB1) is a pivotal mediator of sepsis progression. Remifentanil, an opioid agonist, has demonstrated anti-inflammatory effects in septic mice. However, it is not yet known whether remifentanil affects the expression of HMGB1. We investigated the effects of remifentanil on HMGB1 expression and the underlying mechanism in septic rats. Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups; a sham group, a cecal ligation and puncture (CLP) group, and a CLP with remifentanil treatment (Remi) group. The rat model of CLP was used to examine plasma concentrations of proinflammatory cytokines, tissue HMGB1 mRNA and the activity of nuclear factor (NF)-κB in the liver, lungs, kidneys, and ileum. Pathologic changes and immunohistochemical staining of NF-κB in the liver, lungs, and kidneys tissue were observed. We found that remifentanil treatment suppressed the level of serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α 6 hours after CLP, and serum HMGB1 24 hours after CLP. HMGB1 mRNA levels and the activity of NF-κB in multiple organs decreased by remifentanil treatment 24 hours after CLP. Remifentanil treatment also attenuated nuclear expression of NF-κB in immunohistochemical staining and mitigated pathologic changes in multiple organs. Altogether, these results suggested that remifentanil inhibited expression of HMGB1 in vital organs and release of HMGB1 into plasma. The mechanism was related to the inhibitory effect of remifentanil on the release of proinflammatory cytokines and activation of NF-κB.
Animals ; Cytokines ; HMGB1 Protein ; Humans ; Ileum ; Inflammation ; Interleukins ; Kidney ; Ligation ; Liver ; Lung ; Male ; Mice ; Models, Animal ; Plasma ; Punctures ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Sepsis ; Tumor Necrosis Factor-alpha

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods: and Results: Non-apoptotic concentrations of DEP (10 μg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 μg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.