CSC-3436 sensitizes triple negative breast cancer cells to TRAIL-induced apoptosis through ROS-mediated p38/CHOP/death receptor 5 signaling pathways.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) shows little or no toxicity in most normal cells and preferentially induces apoptosis in a variety of malignant cells. However, patients develop resistance to TRAIL, therefore, sensitizing agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are necessary. In this study, we investigated the effect of 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), an useful flavonoid, to overcome the TRAIL-resistant triple negative breast cancer (TNBC) cells. We found that CSC-3436 potentiated TRAIL-induced apoptosis in TRAIL-resistant TNBC cells and this correlated with the upregulation of death receptors (DR)-5 and down-regulation of decreased decoy receptor (DcR)-1 expression. When examined for its mechanism, we found that the decreased expression of anti-apoptotic proteins c-FLIPS/L, Bcl-Xl, Bcl-2, Survivin, and XIAP. CSC-3436 would increase the expression of Bax and promoted the cleavage of bid. In addition, the induction of DR5 by CSC-3436 was found to be dependent on the modulation of reactive oxygen species (ROS)/p38/C/EBP-homologous protein (CHOP) signaling pathways. Overall, our results indicated that CSC-3436 could potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and upregulation of DR5 via the ROS-mediated upregulation of CHOP protein.

Anti-Inflammatory and Anti-Oxidative Effects of Polysaccharides Extracted from Unripe Carica papaya L. Fruit.

This study evaluated the antioxidative and anti-inflammatory activities of polysaccharides extracted from unripe Carica papaya L. (papaya) fruit. Three papaya polysaccharide (PP) fractions, namely PP-1, PP-2, and PP-3, with molecular weights of 2252, 2448, and 3741 kDa, containing abundant xylose, galacturonic acid, and mannose constituents, respectively, were obtained using diethylaminoethyl-Sepharose™ anion exchange chromatography. The antioxidant capacity of the PPs, hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay revealed that the PP-3 fraction had the highest antioxidant activity, with an EC50 (the concentration for 50% of the maximal effect) of 0.96 mg/mL, EC50 of 0.10 mg/mL, and Abs700 nm of 1.581 for the hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay, respectively. In addition, PP-3 significantly decreased reactive oxygen species production by 45.3%, NF-κB activation by 32.0%, and tumor necrosis factor-alpha and interleukin-6 generation by 33.5% and 34.4%, respectively, in H2O2-induced human epidermal keratinocytes. PP-3 exerts potent antioxidative and anti-inflammatory effects; thus, it is a potential biofunctional ingredient in the cosmetic industry.

A multidimensional analysis of ethical climate, job satisfaction, organizational commitment, and organizational citizenship behaviors.

The high turnover of nurses has become a global problem. Several studies have proposed that nurses' perceptions of the ethical climate of their organization are related to higher job satisfaction and organizational commitment and thus lead to higher organizational citizenship behaviors. This study uses hierarchical regression to understand which types of ethical climate, facets of job satisfaction, and the three components of organizational commitment influence different dimensions of organizational citizenship behaviors. Questionnaires were distributed to 450 nurses, and 352 usable questionnaires were returned. The findings of the article suggest that hospitals can increase organizational citizenship behaviors by influencing an organization's ethical climate, job satisfaction, and organizational commitment. Hospital administrators can foster within organizations, the climate types of caring, law and code and rules climate, satisfaction with coworkers, and affective commitment and normative commitment that increase organizational citizenship behavior, while preventing organizations from developing the type of instrumental climate and continuance commitment that decreases it.

Sinonasal teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive neoplasm characterized by the combination of malignant teratoma and carcinosarcoma. Sinonasal teratocarcinosarcoma usually is found mainly among adults, and the common original sites of SNTCS were nasal cavities and paranasal sinuses. There are fewer than 50 reported SNTCS cases in the literature. The most common cause of treatment failure is local recurrence. Distant metastasis of SNTCS is seldom described because of the invasive character of the cancer. We report on a 52-year-old man with SNTCS involving the left sinonasal cavity. Recurrent cervical metastasis developed in the 18th, 23rd, and 28th month after initial sinonasal surgery. Despite multiple aggressive neck surgeries and postoperative adjuvant radiotherapy, the patient died of lung metastasis 43 months after the initial surgery. Our patient was younger than other reported patients with SNTCS; besides, good locoregional control and lung metastasis have not been reported previously. An aggressive elective neck dissection should be performed in the early disease stage, and more attention should be given to the soft tissue surrounding any possible lymphadenopathy. This may decrease the risk of lower cervical lymph node or distant metastasis in patients with SNTCS.

Operative treatment of displaced lateral malleolar fractures: the Knowles pin technique.

OBJECTIVES: To assess the use of Knowles pin fixation for isolated displaced lateral malleolar fractures and to present our surgical experience using this method. DESIGN: Retrospective evaluation. SETTING: The study was carried out at a municipal teaching hospital. The senior surgeons were all orthopedic trauma subspecialists. PATIENTS: A total of 168 patients meeting our inclusion criteria, an isolated displaced lateral malleolar fracture surgically treated by a Knowles pin between 1995 and 2000, were studied. All the patients had a stable syndesmosis, less than 50% comminution, and had no other operations in the same extremity. Patients were assigned into 4 groups according to the Orthopedic Trauma Association classification of ankle fractures. INTERVENTION: Open reduction and internal fixation with a Knowles pin fixation of the lateral malleolus. MAIN OUTCOME MEASUREMENTS: Functional results were evaluated using the Baird and Jackson ankle scoring system. RESULTS: There was a 100% union rate. The average satisfactory outcome of the 4 groups was 88.1%. No instrumentation problems were encountered. Three complications occurred, but resolved with nonoperative therapy. CONCLUSIONS: Knowles pin fixation for displaced lateral malleolar fractures is a useful and effective method. This implant offers several advantages, including easy application, less soft tissue dissection, less palpable instrumentation, stable fixation, and a short operating time.

Association between single nucleotide polymorphisms of the estrogen receptor 1 and receptor activator of nuclear factor kappa B ligand genes and bone mineral density in postmenopausal Taiwanese.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of the genes encoding the estrogen receptor 1 (ESR1) and the receptor activator of nuclear factor kappa B ligand (RANKL) and bone mineral density (BMD) in postmenopausal Taiwanese. MATERIALS AND METHODS: Five ESR1 SNPs and three RANKL SNPs in 467 women were genotyped. Results of genotyping were correlated with BMD that had been adjusted for body mass index (BMI), age, and years after menopause. RESULTS: Those with the ESR1 Crs1884054 allele were found to have a lower BMD at LS2-4/Lateral view (p = 0.005 and permutated p = 0.046), and those with the ESR1 haplotype Trs2234693-Ars922996 had a higher risk for low BMD also at LS2-4/Lat (OR = 1.8, 95% CI = 1.1-2.9). In addition, women without the RANKL haplotype Grs2148072-Crs2200287-Grs922996 had a higher risk for low BMD at LS1-4/AP (OR = 2.09, 95% CI = 1.21 ∼ 3.64). Stratification analyses revealed that those with ESR1 AArs1884054 and RANKL Ars2148072 (p = 0.032) or RANKL Trs2200287 (p = 0.007) had a lower BMD at LS1-4/AP. CONCLUSION: Genotypes of these SNPs of ESR1 and RANKL may help us predict the osteoporosis risk in menopausal women.