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Purpose: The purpose of this study was to investigate the cellular activities of MG63 osteoblast-likecells on modified titanium surfaces. Materials and Methods: MG63 osteoblast-like cells were cultured on titanium disks (n = 20 in each group) with turned, resorbable blast media (RBM)-treated, or anodized surfaces. The surfaces of commercially available implants of Osstem (Osstem Implant) were reproduced for the titanium disks. The morphology of cells cultured on these disks was examined using scanning electron microscopy. X-ray photoelectron spectroscopy (XPS) was employed for the analysis of surface chemistry. Specimens were also evaluated with an initial cell adhesion assay to compare initial adhesion, with a methyl tetrazol sulfate (MTS) assay to compare the proliferation ability, and with an alkaline phosphatase (ALP) assay to compare the differentiation ability. Statistical significance of the differences was determined using the Kruskal-Wallis test for the cell adhesion assay and analysis of variance for the MTS and ALP assays. Results: Attached cells with more defined lamellopodia and flattened morphology were observed on the anodized and RBM surfaces than on the turned surfaces. The titanium surfaces were all oxidized as titanium oxide and polluted by carbon determinants, as determined by XPS. Anodized titanium surfaces exhibited calcium and phosphorus peaks. Initial cell attachment activity, cell proliferation activity, and ALP activity were higher on the anodized surfaces than on the other surfaces. Cell differentiation on the anodized surfaces at culture day 10 was significantly higher (P < .05) than on the other surfaces. Conclusions: Surface treatment by anodization may improve initial attachment of cells, proliferation ability, and differentiation activity, which play important roles in providing better osseointegration of implants. More rapid and stronger osseointegration of implants may make it possible to offer the best anchorage and shorten the healing time required prior to functional loading. [ABSTRACT FROM AUTHOR]

Purposes: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer.Methods: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; and level 5, 85/180/100 mg/m2. Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity.Results: Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %.Conclusions: The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan, and 100 mg/m2 of S-1 every 2 weeks. [ABSTRACT FROM AUTHOR]

Background: In patients with a mediastinal tumor, video-assisted thoracic surgery (VATS) is considered to be associated with more postoperative advantages compared to open procedures. However, open procedures are still preferred in cases with large or malignant tumors. Therefore, in order to determine the appropriate surgical strategies for resection of teratomas, we here review our experience with such cases.Methods: Between January 2000 and February 2014, we experienced 132 patients diagnosed with mediastinal teratoma. By using data from a retrospective review of the patients' medical records, we compared the demographic characteristics, hospital stay duration, chest tube indwelling time, operative time, and mass size of the VATS group with those of the patients in the open group. Moreover, we also analyzed the postoperative complications and recurrence. Finally, based on our findings, we created a '∆V (volume of the mass-volume of the cyst in the mass)' capable of determining the appropriate surgical strategy, measured by preoperative computed tomography scan.Results: We excised the mass using VATS in 79 patients, while 53 patients underwent open procedures, including thoracotomy (n = 10) and median sternotomy (n = 43). The operative times, the hospital stay duration, and the chest tube indwelling time were significantly shorter in the VATS group compared to in the open group (Table 1). Four cases were converted to thoracotomy. The mean mass sizes were 6.53 ± 2.20 cm and 8.58 ± 3.45 cm in the VATS and open groups, respectively. The '∆V' of the VATS group was higher than that of the open group. There were three postoperative complications. Table 1 Comparison of the perioperative variables between the VATS group and open groups VATS (n = 79) Open (n = 53) p value Preoperative variables Age (years) 32.34  ±  13.44 29.30 ± 14.76 0.223 Female 63 28 0.001 BMI 22.07 ± 3.34 22.59 ± 3.91 0.409 ASA class 0.272 Class 1 39 21 Class 2 40 32 Mass size (cm) 6.53 ± 2.20 8.58 ± 3.45 <0.001 ∆V (cm(3)) 988.15 ± 1590.85 3093.22 ± 4947.33 0.001 Intraoperative variable Operative time (min) 129 ± 46 170 ± 45 <0.001 Postoperative variable Hospitalization (days) 6.00 ± 3.03 8.94 ± 3.99 <0.001 ICU stay (days) 0 0.42 ± 0.50 <0.001 CTD time (days) 2.00 ± 1.24 3.8 ± 3.63 <0.001 Median F/U duration (months) 47.16 ± 43.60 27.52 ± 34.00 The data are presented as mean ± standard deviation VATS video-assisted thoracic surgery, CTD chest tube indwellingConclusion: VATS for mediastinal teratoma can be performed safely in selected patients with large or malignant masses. The proposed '∆V' appears to be a useful method for determining the appropriate surgical strategy in the large size teratoma cases. [ABSTRACT FROM AUTHOR]

Purpose: Despite the development of molecular targeted therapies, few advances have been made in the treatment of lung squamous cell carcinoma (SCC). SOX2 amplification is one of the most common genetic alterations in SCC. Here, we investigated the effects of THZ1, a potent cyclin-dependent kinase 7 (CDK7) inhibitor that plays a key role in gene transcription, in SCC. Methods: Lung SCC-derived cell viabilities were assessed using a CCK-8 assay. SOX2 expression and RNAPII-CTD phosphorylation levels after THZ1 treatment were determined by Western blotting. The effect of SOX2 suppression using shRNA was assessed by flow cytometry. Gene expression patterns after THZ1 treatment of lung SCC-derived cells were identified using microarray-based mRNA profiling. Results: We found that THZ1 treatment led to suppression of cell growth and apoptotic cell death in SOX2-amplified SCC-derived cells only, whereas the modest growth-inhibitory effect of cisplatin did not differ according to SOX2 amplification status. We also found that THZ1 decreased the phosphorylation of the carboxyl-terminal domain of RNA polymerase II and the expression of several genes. Specifically, we found that the expression of transcription-associated genes, including SOX2, was down-regulated by THZ1 in SOX2-amplified SCC cells. This inhibition of SOX2 expression resulted in suppression of the growth of these cells. Conclusions: From our data, we conclude that THZ1 may effectively control the proliferation and survival of SOX2-amplified SCC cells through a decrease in global transcriptional activity, suggesting that CDK7 inhibition leading to transcription suppression may be a promising therapeutic option for lung SCC with a SOX2 amplification. [ABSTRACT FROM AUTHOR]

The conventional method for impressions of flabby tissue uses modified trays and highly flowable materials, but mucostatic impressions are difficult to achieve due to the viscous and the elastic natures of impression materials. In this report, a technique is presented in which conventional impression and intraoral scanning for a fully edentulous patient with flabby tissue are combined. The definitive impression was obtained by applying appropriate pressure to each tissue area, and the denture can be maintained passively and stable at rest and during function. [ABSTRACT FROM AUTHOR]

Objective: To determine the synergistic effect of parathyroid hormone (PTH) [1–34] in combination with hyperbaric oxygen (HBO) on bone graft in a rat calvarial bone defect model under impaired osteogenic conditions. Materials and Methods: Twenty‐four rats were divided into three groups. Localized radiation with a single 12 Gy dose was administered to the calvaria. Four weeks after radiation, calvarial circular defects were created in the parietal bones. All defects were filled with biphasic calcium phosphate. After the bone graft, PTH [1–34] was injected subcutaneously, and HBO was administered. At 6 weeks after the bone graft, the rats were sacrificed, and specimens were harvested. Results: Histomorphometric evaluation showed that the percentage of new bone area was higher in the PTH and PTH/HBO groups than in the control group. The percent residual material area was decreased in the PTH/HBO group compared with the control group. The percentage blood vessel number was highest in the PTH group. Micro‐CT evaluation showed that the new bone volume was highest in the PTH/HBO group. The residual material volume was lowest in the PTH/HBO group. Conclusion: Within the limitations of this study, our data indicate that PTH combined with HBO may reverse radiation‐induced impairment of bone healing. [ABSTRACT FROM AUTHOR]

Background: Anastomotic stricture following colorectal cancer surgery is not a rare complication, but proper management of anastomotic stricture located close to the anal verge is uncertain. This study aimed to investigate risk factors and management strategies for anastomotic stricture after ultralow anterior resection (ULAR).Methods: We retrospectively reviewed a database of patients with rectal cancer who underwent surgery between January 2007 and June 2015, and included patients with an anastomosis within 4 cm from the anal verge. Clinical outcomes and risk factors for anastomotic stricture were investigated.Results: Among the 586 patients included, 46 (7.8%) were diagnosed as having anastomotic stricture. Multivariable logistic regression analysis revealed that intersphincteric resection (ISR) with hand-sewn anastomosis (odds ratio [OR] = 3.070; 95% confidence interval [CI] 1.247-7.557) and postoperative radiotherapy (OR 6.237; 95% CI 1.961-19.841) were independent risk factors of anastomotic stricture. Forty-one (89.1%) underwent anastomotic dilatation with a Hegar dilator; while three patients (6.5%) underwent endoscopic balloon dilatation and two (4.3%) underwent surgery initially. Among the patients with initial nonoperative management (n = 44), 21 (47.7%) were completely cured with nonoperative management alone, 12 (27.3%) experienced complications, such as bowel perforation, anastomotic rupture, and perirectal abscess; and 21 (47.7%) underwent further surgical management. Fifteen patients (32.6%) eventually had permanent stoma.Conclusion: ISR with a hand-sewn coloanal anastomosis, compared to ULAR with double-stapling anastomosis, and postoperative radiotherapy were independent risk factors of anastomotic stricture after surgery for very low-lying rectal cancer. Nonoperative anastomotic dilatation showed poor clinical outcome, with high complication rates, and subsequent surgical management. Therefore, nonoperative management of such patients should be carefully selected. [ABSTRACT FROM AUTHOR]

Due to their widely known therapeutic benefits, mesenchymal stem cells have been proposed as a novel treatment option for a wide range of diseases including Alzheimer's disease. To maximize these benefits, critical factors such as delivery route, cell viability, and cell migration must be accounted for. Out of the various delivery routes to the brain, the intracerebroventricular (ICV) route stands out due to the widespread distribution that can occur via cerebrospinal fluid flow. The major objective of this present study was to observe how altering cell concentration influences the migration and viability of human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs), delivered via ICV injection, in the brains of wild-type (WT) mice. C3H/C57 WT mice were divided into three groups and were injected with 1 × 10 5 hUCB-MSCs suspended in varying volumes: high (3 μl), middle (5 μl), and low (7 μl) concentrations, respectively. Lowering the concentration increased the migratory capabilities and elevated the viability of hUCB-MSCs. These results suggest that cell concentration can affect the physiological state of hUCB-MSCs, and thus the extent of therapeutic efficacy that can be achieved. [ABSTRACT FROM AUTHOR]

Objectives Drug therapy is the mainstay of treatment for overactive bladder ( OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life ( HR-QoL) through an analysis of EQ-5D questionnaire. Methods This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. Results One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 ( P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Conclusions Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. [ABSTRACT FROM AUTHOR]

Paradols are unsaturated ketones produced by biotransformation of shogaols in gingers. Among them, 6-paradol has been investigated as a new drug candidate due to its anti-inflammatory, apoptotic, and neuroprotective activities. In this study, the inhibitory effects of 6-paradol on the activities of cytochrome P450 (CYP) enzymes were investigated with human liver microsomes and recombinant CYP isozymes. 6-Paradol showed concentration-dependent inhibitory effects on CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 isozymes, with IC 50 values ranging from 3.8 to 21.4 µM in recombinant CYP isozymes. However, the inhibition was not potentiated following pre-incubation, indicating that 6-paradol is not a mechanism-based inhibitor. These results suggest that pharmacokinetic drug-drug interactions might occur with 6-paradol, which must be considered in the process of new drug development. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease is a major cause of chronic liver disease worldwide, and cannabinoid receptor type 1 ( CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 ( BTG2) and yin yang 1 ( YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. Micro RNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression. The level of bile acid and the expression of Cb1r, Btg2, Yy1, and bile acid synthetic enzymes were significantly elevated in the livers of Lieber-DeCarli alcohol-fed mice. The overexpression of Btg2 enhanced Yy1 gene expression and bile acid production, whereas disrupting the CB1R- BTG2- YY1 cascade protected against the bile acid synthesis caused by alcohol challenge. We identified an alcohol-mediated YY1 binding site on the cholesterol 7α-hydroxylase ( Cyp7a1) gene promoter using promoter deletion analysis and chromatin immunoprecipitation assays. Notably, melatonin attenuated the alcohol-stimulated induction of Btg2, Yy1 mRNA levels and bile acid production by promoting miR-497. Overexpression of a miR-497 mimic dramatically diminished the increase of Btg2 and Yy1 gene expression as well as bile acid production by alcohol, whereas this phenomenon was reversed by miR-497 inhibitor. These results demonstrate that the upregulation of miR-497 by melatonin represses alcohol-induced bile acid synthesis by attenuating the BTG2- YY1 signaling pathway. The melatonin-miR497 signaling network may provide novel therapeutic targets for the treatment of hepatic metabolic dysfunction caused by the alcohol-dependent pathway. [ABSTRACT FROM AUTHOR]

Background: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. Methods: Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m and oxaliplatin at 105 mg/m were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m on days 1-14 of every 21-day cycle. Results: Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. Conclusion: These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer. [ABSTRACT FROM AUTHOR]

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients. [ABSTRACT FROM AUTHOR]

Purpose: A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). Methods: Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks. Results: Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6 %), intrahepatic and extrahepatic bile ducts in 23 (60.5 %), and the ampulla of Vater in 3 (7.9 %) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6 % (95 % CI 8.5-36.7] in the per-protocol (PP) population, and 18.4 % (95 %CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5 % (95 %CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95 %CI 1.8-6.9), and the median overall survival was 9.0 months (95 %CI 4.0-13.9) with a 1-year survival rate of 44.7 % (95 %CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1 %), 9 (25.7 %), 2 (5.7 %), and 2 (5.7 %) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4 %), anorexia (2.9 %), and renal toxicity (2.9 %). Conclusion: Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to evaluate the efficacy and safety of the combination of capecitabine and oral leucovorin (LV) as a third-line chemotherapy for patients with metastatic colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens. Method: Patients who showed disease progression while receiving or within 6 months of discontinuing irinotecan- and oxaliplatin-containing regimens received capecitabine 825 mg/m in combination with oral LV at a fixed dose of 30 mg, twice a day for 2 weeks followed by a 1-week rest. Results: Twenty-five patients were enrolled from July 2011 to June 2014. Three patients achieved PR, and 11 showed SD. The overall response rate was 12 %, and disease control rate was 56 %. With a median follow-up of 6.8 months, the median time to progression was 2.8 months and the median overall survival was 7.1 months. The most common non-hematologic toxicity was hand-foot syndrome (40 %), followed by mucositis (28 %) and diarrhea (12 %). Grade 3 hand-foot syndrome occurred in two patients (8 %), and grade 3 mucositis in one. Hematologic toxicities were mild, and only one patient developed grade 3 thrombocytopenia. Conclusion: The combination of capecitabine and oral LV showed a modest activity and tolerable toxicity profile in metastatic CRC patients pretreated with irinotecan- and oxaliplatin-containing regimens. Oral LV seems to be able to reduce the usual dose of capecitabine when the two drugs are combined. [ABSTRACT FROM AUTHOR]

Background: Early postoperative small bowel obstruction is associated with considerable morbidity and mortality but has not been well documented in the era of laparoscopic surgery for colorectal cancer. Subjects and Methods: Consecutive patients who had undergone laparoscopic resection for colorectal cancer were studied. Results: In total, 1787 patients (105 with and 1682 without early postoperative small bowel obstruction) with colorectal cancer requiring laparoscopic colorectal surgery were evaluated in this study. Ten patients (0.56% among the total patient population, 9.5% among patients who experienced early postoperative small bowel obstruction) who did not respond to conservative treatment for more than 14 days required surgical intervention. Multivariate analysis showed that male sex (adjusted odds ratio [AOR]=2.27), combined operation (AOR=2.23), and diverting stoma (AOR=4.79) were associated with a higher early postoperative small bowel obstruction rate. For factors related to surgical difficulty, open conversion (AOR=2.85), blood transfusion (AOR=3.51), and an operation time longer than 180 minutes (AOR=1.91) were independent factors associated with an increased early postoperative small bowel obstruction rate. Conclusions: Early postoperative small bowel obstruction following laparoscopic resection for colorectal cancer occurred in 5.9% of patients. Factors for predicting the development of early postoperative small bowel obstruction in patients with colorectal cancer are variables reflective of a more difficult surgery, rather than pathologic disease severity or anatomical location. In addition, most patients with early postoperative small bowel obstruction improved with conservative treatment, and surgical treatment was rarely needed. [ABSTRACT FROM AUTHOR]

Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation. [ABSTRACT FROM AUTHOR]

Objective. Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is one of the active components present in the root and rhizome of Rheum palmatum. It has been shown to contain biological activity (antitumour, antibacterial, diuretic and vasorelaxant effects). However, the mechanisms underlying the anti-arthritic effect of emodin have not been elucidated. Here we investigated whether emodin treatment would modulate the severity of the disease in an experimental arthritis model.Methods. We evaluated the effects of emodin on CIA mice in vivo.Results. The pathological processes of RA are mediated by a number of cytokines and MMPs. Expression of these proinflammatory mediators is controlled by nuclear factor-κB (NF-κB). This study was performed to explore the effect of emodin on control of the NF-κB activation pathway and to investigate whether emodin has anti-inflammatory effects in CIA mice in vivo. Emodin inhibited the nuclear translocation and DNA binding of NF-κB subunits, which were correlated with its inhibitory effect on cytoplasmic IκBα degradation in CIA mice. These events further suppressed chemokine production and MMP expression. In addition, emodin inhibited the osteoclast differentiation induced by M-CSF and receptor activation of NF-κB ligand in bone marrow macrophages.Conclusion. These findings suggest that emodin exerts anti-inflammatory effects in CIA mice through inhibition of the NF-κB pathway and therefore may have therapeutic value for the treatment of RA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated. Patients and methods: From March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500mg/m2 over a 10-min intravenous infusion and carboplatin at an AUC 5mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed. Results: There were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1–2 peripheral neuropathy developed in 13 patients (40.6%). Conclusion: The combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC. [Copyright &y& Elsevier]

Case An 88-year-old woman visited us with a complaint of total urinary leak, and was diagnosed as having vesicovaginal fistula after pessary insertion. A part of pessary was seen in the bladder and it was removed by cutting pessary in the vagina. And then she was managed by antibiotics, local estrogen cream and Foley catheter indwelling. Outcome Vesicovaginal fistula was healed completely. This is the first successful case of conservative treatment of vesicovaginal fistula caused by vaginal pessary without surgical repair. Conclusion The conservative approach could be an option of treatments of vesicovaginal fistula caused by neglected vaginal pessary. [ABSTRACT FROM AUTHOR]

Traditional Chinese/Korean medicine suggests " blood stasis (瘀血)", " stagnation of vital energy (气滯)" and " dampness and Phlegm (湿痰)" as the main etiologies of liver disorders, and multiherbal formulas are generally believed to exert synergistic action. The present study aimed to investigate the synergistic hepatoprotective effects of CGplus (a mixture of Salviae miltiorrhiza , Artemisia iwayomogi and Ammomum xanthioides) compared to those of the individual herbs. A total of fifty-six male Balb/C mice were randomly divided into eight groups and were administered water (normal and CCl 4 groups), 100 mg/kg S. miltiorrhiza , A. iwayomogi , or A. xanthioides , 50 or 100 mg/kg CGPlus or dimethyl dimethoxybiphenyl dicarboxylate (DDB) as a positive control for 4 consecutive days. After a single CCl 4 injection (i.p., 10 mL/kg of 0.2% CCl 4 in olive oil), blood and liver tissues were collected after 18 h of fasting for serum biochemistry, histopathological examination and molecular analyses. CCl 4 injection induced drastic hepatic injury characterized by a more than 30-fold increase in the release of AST and ALT into the serum. These alterations were significantly attenuated by pretreatment with each of the three herbs, while the effects of the individual herbs were synergistically augmented by CGPlus pretreatment. The synergistic hepatoprotective actions of CGPlus were demonstrated consistently by analyses of oxidative stress (oxidative stressors, oxidation products and antioxidant enzymes), pro-/anti-inflammatory cytokines (TNF-ɑ, IL-1β, IL-6, IL-10), and apoptosis (caspase-3, p53 and BAX) and histopathology. These data suggest that CGPlus exerts its hepatoprotective effects in a synergistic manner, and further studies are required for clinical application using other chronic models. Image 1 [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CGA) is a major component of green coffee beans. Surfactin, a cyclic lipopeptide, is produced and secreted by Bacillus subtilis strains. In this study, bioactivities of fermented green coffee bean extract (FGCBE) and the individual compounds, CGA and surfactin. were compared in HepG2 cells. The concentration of surfactin and CGA in the FGCBE and non-fermented green coffee bean extract (NFGCBE) were determined to be 9.2 and 7.33 and 0.72 and 0.53 mg·mL−1, respectively. The FGCBE contained about 20% and 26% more CGA and surfactin than the NFGCBE. Although CGA and surfactin exhibited cytotoxicity at concentrations more than 100 and 20 μg respectively, the FGCBE 50 containing CGA (460 μg·mL−1) and surfactin (720 μg·mL−1) effectively prevented cell death by oxidative stress and also strongly activated the proliferation of cells incubated with under 50 μM H2O2. The CGA and surfactin in FGCBE were 9.2 and 72 times higher than the CGA and surfactin compounds (50 and 10 μg·mL−1). The relative proliferation of the FGCBE-treated cells also was 3.3 and 8.8 times higher than the CGA and surfactin compounds treated the oxidative stressed cells with 50 μM H2O2. These results suggest that the single compounds such as CGA and surfactin generally have cytotoxicity at low concentration of them but FGCBE contained them acted as strong antioxidants, activators of cell proliferation, inhibitors of cell apoptosis. Various bioactive compounds in fermented coffee bean also seem to help cell proliferation and decreasing of cytotoxicity by CGA and surfactin in coffee bean. [ABSTRACT FROM AUTHOR]

We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway. [ABSTRACT FROM AUTHOR]

Background Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7- O -xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. Methods We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. Results The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-β, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. Conclusion Thus, these results imply that PCE17 has protective effects against hot flushes. [ABSTRACT FROM AUTHOR]

Background The blood-brain barrier (BBB) presents a significant challenge to the therapeutic efficacy of stem cells in chronic stroke. Various methods have been developed to increase BBB permeability, but these are associated with adverse effects and are, therefore, not clinically applicable. We recently identified that combination drug treatment of mannitol and temozolomide improved BBB permeability in vitro . Here, we investigated whether this combination could increase the effectiveness of stem cell treatment in an animal model of chronic ischemic stroke. Methods Chronic stroke was induced in rats by middle cerebral artery occlusion (MCAo). After then, rats were administered human umbilical cord–derived mesenchymal stromal cells (hUC-MSCs) by intravenous injection with or without combination drug treatment of mannitol and temozolomide. To evaluate the therapeutic efficacy, behavioral and immunohistochemical tests were performed, and the differences among control, stem cell only, combination drug only and stem cell with combination drug treatment were analyzed. Results Although no hUC-MSCs were detected in any group, treatment with stem cells and combination drug of mannitol and temozolomide increased the intracerebral delivery of hCD63-positive microvesicles compared with stem cell only treatment. Furthermore, treatment with stem cells and drug combination ameliorated behavioral deficits and increased bromodeoxyuridine-, doublecortin- and Reca-1–positive cells in the perilesional area as compared with other groups. Discussion The combination drug treatment of mannitol and temozolomide allowed for the efficient delivery of hUC-MSC–derived microvesicles into the brain in a chronic stroke rat model. This attenuated behavioral deficits, likely by improving neural regeneration and angiogenesis. Thus, combination drug treatment of mannitol and temozolomide could be a novel therapeutic option for patients with chronic ischemic stroke. [ABSTRACT FROM AUTHOR]

The blood−brain barrier (BBB) is major obstacle in drug or stem cell treatment in chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a practically applicable method for resolving the low efficacy of intravenous mannitol therapy. In this study, we investigated whether BBB permeability could be increased by this combined treatment. First, we established a chronic ischemic stroke rat model and examined changes in leakage of Evans blue dye within a lesion site, and in expression of tight junction proteins (TJPs), by this combined treatment. Additionally, in an in vitro BBB model using trans -wells, we analyzed changes in diffusion of a fluorescent tracer and in expression of TJPs. Mannitol-TMZ combined treatment not only increased the amount of Evans blue dye within the stroke lesion site, but also reduced occludin expression in rat brain microvessels. The in vitro study also showed that combined treatment increased the permeability for two different-sized fluorescent tracers, especially large size, and decreased expression of TJPs, such as occludin and ZO-1. Increased BBB permeability effects were more prominent with combined than with single treatments. Mannitol-TMZ combined treatment induced a decrease of TJPs with a consequent increase in BBB permeability. This combined treatment is clinically useful and might provide new therapeutic options by enabling efficient intracerebral delivery of various drugs that could not otherwise be used to treat many CNS diseases due to their inability to penetrate the BBB. [ABSTRACT FROM AUTHOR]

There is great interest in the development of cardiac stem cells (CSCs) cell-based therapeutics; thus, clinical translation requires an efficient method for attaining therapeutic quantities of these cells. Furthermore, an in vitro model to investigate the mechanisms regulating the cardiac homeostasis is crucial. We sought to develop a simple myocardial culture method for enabling both the recapitulation of myocardial homeostasis and the simultaneous isolation of CSCs. The intact myocardial fragments were encapsulated 3-dimensionally into the fibrin and cultured under dynamic conditions. The fibrin provided secure physical support and substratum to the myocardium, which mediated integrin-mediated cell signaling that allowed in situ renewal, outgrowth and cardiomyogenic differentiation of CSCs, mimicking myocardial homeostasis. Since our culture maintained the myocardial CSCs niches, it was possible to define the identity of in vitro renewed CSCs that situated in the interstitium between cardiomyocytes and microvessels. Lastly, the use of matrix-restricted fibrinolysis enabled the selective isolation of outgrown CSCs that retained the clonogenicity, long-term growth competency and cardiovascular commitment potential. Collectively, this myocardial culture might be used as an alternative tool for studying cardiac biology and developing cell-based therapeutics. [ABSTRACT FROM AUTHOR]

Purpose To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m 2 on day 1 and S1 at 40 mg/m 2 twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m 2 on days 1 and 21 and S1 30 mg/m 2 twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P =.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P =.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate. [ABSTRACT FROM AUTHOR]