Natural carbazole alkaloid murrayafoline A displays potent anti-neuroinflammatory effect by directly targeting transcription factor Sp1 in LPS-induced microglial cells.

Neuroinflammation is a leading cause for neurological disorders. Carbazole alkaloids, isolated from the medicinal plants of Murraya species (Rutaceae), have exhibited wide pharmacological activities particularly for neuroinflammation. However, its underlying cellular targets and molecular mechanisms still remain unclear. In current study, we found that murrayafoline A (MA), a carbazole alkaloid obtained from Murraya tetramera, potently inhibited the production of neuroinflammation mediators, such as nitric oxide (NO), TNF-α, IL-6 and IL-1ß in LPS-induced BV-2 microglial cells. Then, we performed thermal proteome profiling (TPP) strategy to identify Specificity protein 1 (Sp1) as a potential cellular target of MA. Moreover, we performed surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DRATS) assays to confirm the direct interaction between MA and Sp1. Furthermore, we downregulated Sp1 expression in BV2 cells using siRNA transfection, and observed that Sp1 knockdown significantly antagonized MA-mediated inhibition of neuroinflammation mediator production. Meanwhile, Sp1 knockdown also markedly reversed MA-mediated inactivation of IKKß/NF-κB and p38/JNK MAPKs pathways. Finally, in vivo studies revealed that MA significantly suppressed the expression of Iba-1, TNF-α, and IL-6, while increased the number of Nissl bodies in the brains of LPS-induced mice. Taken together, our study demonstrated that MA exerted obvious anti-neuroinflammation effect by directly targeting Sp1, thereby inhibiting NF-κB and MAPK signaling pathways. Our findings also provided a promising direction of pharmacological targeting Sp1 for anti-neuroinflammation therapeutics as well as novel agent development.

Exploration on the gap of single- and double-loop learning of balanced scorecard and organizational performance in a health organization.

This paper addresses and interprets learning styles, namely, single- and double-loop learning, of BSC implementation in the background of healthcare organizaiton/industry, through which barriers and facilitators are inducted for the BSC for the healthcare industry. Samples of this study are from a community hospital with 290 beds was probed with samples of 34 BSC members interviewed. Based on the qualitative research's grounded theory, the transcript data of this study were analyzed using open, axial, and selective coding through NVIVO 10.0. By using single- and double-loop learning, this study distinguishes between adding and changing a health organization's specific capabilities, routines or abilities. Findings of this study indicated that BSC learning is more likely to improve the efficiency of the strategic management and strengthen the company's existing capabilities and routines; but it is not possible for single-loop learning to develop new capabilities. This study contributes to indicate that single-loop learning can be useful facilitators for organizational learning via affecting the positive performance of the organization, because employees are in favor of following existing routines and rules and allowing the employees to see the meaning of this balanced scorecard. However, employees still do not have the power to make changes they expect, because they do not have the power and right to change. The purpose of this research is to evaluate organizational learning performance via the implementation of the balanced scorecard in order to understand the mechanism's impact on organizational development. In short, this paper contributes practically to depict the process of executing BSC in learning organization in detail, and theoretically to understand the mechanism in optimizing organizational learning effect via BSC implementation through discussion of (1) downward penetration of single-loop learning from organization vision and goals, and upward following and promotion of double-loop learning of sub-units in the form of routines, norms, action plans and others; (2) ways of eliminating the gap by linking organizational member's values with the organization's vision in the form of giving individuals opportunities to make their own interpretation of learning results in the workplace.

[Clinical studies of pedicle screw-rod fixation of thoracolumbar burst fractures through posterior unilateral approach after vertebrae corpectomy fusion].

OBJECTIVE: To compare the clinical curative effect of thoracolumbar burst fracture treated by the posterior unilateral approach corpectomy fusion screw-rod fixation and anterior corpectomy bone fusion screw plate fixation. METHODS: From January 2008 to May 2014,36 cases of thoracolumbar burst fracture underwent operation of decompression, fusion, and internal fixation was retrospective analyzed. Among them, 16 patients were treated through posterior approach as posterior group, including 13 males and 3 females aged from 37 to 62 years old; 9 cases caused by falling injury, 3 cases by traffic accident injury,4 cases by heavy aboved;the injury segment was on T12 in 2 cases, L1 in 5 cases, L2 in 7 cases, L3 in 2 cases; according ASIA grade, 3 cases were grade A, 2 cases were grade B, 2 cases were grade C, 5 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 5 to 15 days. Other 20 patients were treated through anterior-lateral approach as anterior-lateral group, including 15 males and 5 females with age from 27 to 62 years old; 12 cases caused by falling injury, 4 cases by traffic accident injury, 4 cases by heavy aboved; the injury segment was on T12 in 2 cases, L1, in 7 cases, L2 in 9 cases, L3 in 2 cases; for ASIA grade: 4 cases were grade A, 2 cases were grade B, 4 cases were grade C, 6 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 4 to 12 days. The operation time, bleeding during operation and postoperative drainage volume were observed in two groups,and the changes of nerve function of ASIA grade, clinical efficacy,improved degree of thoracic and lumbar lordosis,and bony fusion were compared between two groups. RESULTS: All patients were followed up from 12 to 24 months with an average of (15.8 ± 3.3) months. The operation time, bleeding during operation, and postoperative drainage volume had no significant different between two groups (P > 0.05). As compared with preoperative, ASIA grade of two groups at last follow-up had statistically significantly different (P < 0.01), the neural function of two groups after operation was recovered for different extent. The JOA score of two groups was compared between last follow-up and preoperative, the difference had statistically significant (P < 0.01), the two groups showed good clinical effect. The clinical results of ASIA grade, JOA score and RIS had no significant differences between two groups. All patients of two groups were obtained fusion. Thoracic and lumbar lordosis angle improvement degree had no significant difference between two groups ,it bad significant difference had statistical significance compared with preoperative, the two approaches could effectively restore the spinal sequence. CONCLUSION: For patients with thoracolumbar burst fracture just treated by anterior decompression and reconstruction of anterior column, according to the degree of operation performer' skill proficiency and the patient' condition to choose, but for patients must performed the spinal canal decompression anterior and posterior, the three column-reconstruction to required anterior-posterior approach, the posterior unilateral approach corpectomy fusion screw-rod fixation obviously shorten operation time, reduce the operation wound, it is worth the clinical promotion.

Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling.

AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47,296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a low- and a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.

Mediating effect of cooperative norm in predicting organizational citizenship behaviors from procedural justice climate.

Although the relationships between procedural justice climate and organizational citizenship behaviors have been examined in recent years, little research has explored the mechanism by which procedural justice climate shapes individual employee prosocial behaviors in the workplace. The purpose of this study was to examine the mediating role of a group-level cooperative norm on the relationships between the group-level procedural justice climate and individual-level organizational citizenship behaviors. The survey involved 45 work groups in four different industry fields in Taiwan, including manufacturing, technology, banking, and insurance, and each of the groups was composed of one supervisor and three subordinates. Cross-level analyses using hierarchical linear modeling (HLM) indicated that the cooperative norm fully mediated the relationship between procedural justice climate and individual helping behaviors. Procedural justice climate indirectly affects individual helping behaviors through their effects on the cooperative norm.