P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5.

Gliomas are the most common central nervous system tumors. They show malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the nuclear factor-κB signaling pathway by a downstream molecular mechanism that remains incompletely understood. In this study, we found that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68, using microarray analysis, and that p68 negatively regulates DUSP5. Upregulating DUSP5 in stably expressing cell lines (U87 and LN-229) suppressed proliferation, invasion, and migration in glioma cells in vitro, consistent with the downregulation of p68. Furthermore, upregulating DUSP5 inhibited ERK phosphorylation, whereas downregulating DUSP5 rescued the level of ERK phosphorylation, indicating that DUSP5 might negatively regulate ERK signaling. Additionally, we show that DUSP5 levels were lower in high-grade glioma than in low-grade glioma. These results suggest that the p68-induced negative regulation of DUSP5 promoted invasion by glioma cells and mediated the activation of the ERK signaling pathway.

Drag reduction effects facilitated by microridges inside the mouthparts of honeybee workers and drones.

The mouthpart of a honeybee is a natural well-designed micropump that uses a reciprocating glossa through a temporary tube comprising a pair of galeae and labial palpi for loading nectar. The shapes and sizes of mouthparts differ among castes of honeybees, but the diversities of the functional microstructures inside the mouthparts of honeybee workers and drones remain poorly understood. Through scanning electron microscopy, we found the dimensional difference of uniformly distributed microridges on the inner galeae walls of Apis mellifera ligustica workers and drones. Subsequently, we recorded the feeding process of live honeybees by using a specially designed high-speed camera system. Considering the microridges and kinematics of the glossa, we constructed a hydrodynamic model to calculate the friction coefficient of the mouthpart. In addition, we test the drag reduction through the dimensional variations of the microridges on the inner walls of mouthparts. Theoretical estimations of the friction coefficient with respect to dipping frequency show that inner microridges can reduce friction during the feeding process of honeybees. The effects of drag reduction regulated by specific microridges were then compared. The friction coefficients of the workers and drones were found to be 0.011±0.007 (mean±s.d.) and 0.045±0.010, respectively. These results indicate that the mouthparts of workers are more capable of drag reduction compared with those of drones. The difference was analyzed by comparing the foraging behavior of the workers and drones. Workers are equipped with well-developed hypopharyngeal, and their dipping frequency is higher than that of drones. Our research establishes a critical link between microridge dimensions and drag reduction capability during the nectar feeding of honeybees. Our results reveal that microridges inside the mouthparts of honeybee workers and drones reflect the caste-related life cycles of honeybees.

Long-Term Outcomes among Patients with Prolonged Disorders of Consciousness.

PURPOSE: To evaluate the long-term survival and functional outcomes of patients with prolonged disorders of consciousness (pDoC) 1-8 years after brain injuries. METHODS: Retrospective study to assess the long-term survival and functional outcomes of patients with pDoC was conducted. We performed Cox regression and multivariate logistic regression to calculate hazard ratios (HRs) for the outcome of survival and to identify risk factors of the functional outcome. RESULTS: We recruited 154 patients with pDoC. The duration of follow-up from disease onset was 1-8 years. The median age was 46 years (IQR, 32-59), and 65.6% (n = 101) of them were men. During the follow-up period, one hundred and ten patients (71.4%) survived; among them, 52 patients had a good outcome. From the overall survival curve, the 1-, 3-, and 8-year survival rates of patients were about 80.5%, 72.0%, and 69.7%, respectively. Cox regression analysis revealed a significant association between the lower APACHE II score (p = 0.005) (cut-off score ≥ 18) and the presence of sleep spindles (p = 0.001) with survival. Logistic regression analysis demonstrated a higher CRS-R score (cut-off score ≥ 7), and presence of sleep spindles were related to a favorable outcome among patients with pDoC. CONCLUSIONS: Sleep spindles are correlated with both long-term survival and long-term functional outcome in pDoC patients.

Antimalarial and Anticancer Activity Evaluation of Bridged Ozonides, Aminoperoxides, and Tetraoxanes.

Bridged aminoperoxides, for the first time, were investigated for the in vitro antimalarial activity against the chloroquine-resistant Plasmodium falciparum strain K1 and for their cytotoxic activities against immortalized human normal liver (LO2) and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer cell lines. Aminoperoxides exhibit good cytotoxicity against lung A549 cancer cell line. Synthetic ozonides were shown to have high activity against the chloroquine-resistant P. falciparum. A cyclic voltammetry study of peroxides was performed, and most of the compounds did not show a direct correlation in oxidative capacity-activity. Peroxides were analyzed for ROS production to understand their mechanism of action. However, none of the compounds has an impact on ROS generation, suggesting that ozonides induce apoptosis in HepG2 cells through ROS-independent dysfunction pathway.

Denuded human amniotic membrane seeding bone marrow stromal cells as an effective composite matrix stimulates axonal outgrowth of rat neural cortical cells in vitro.

BACKGROUND: Previous studies have shown that axonal outgrowth in the damaged central nervous system is closely related to the local microenvironment. Transplantation of bone marrow stromal cells (BMSC) or BMSC with some biomaterials has been used to treat various central nervous system diseases with some success. In the current study, we investigated if BMSC on denuded human amniotic membrane (DhAM) as a composite matrix could stimulate axonal outgrowth or not. METHOD: After completely removing the cells on the amniotic membrane with a tryptic and mechanical approach, we seeded BMSC on it. The MTS was applied to test the cytotoxicity of DhAM compared with PLGA and PLL. The morphology of the BMSC was observed by light, electronic and laser confocal microscopy. We also used four kinds of substance (PLL, DhAM, BMSC + PLL, BMSC + DhAM) to coculturing with the cortical neurons. Finally, the lengths of axons in each group were studied using the positive axon-specific marker NF-H. FINDINGS: The DhAM was devoid of cellular components and only its intact basement membrane was left. BMSC grew on the substrate and proliferated with a flat to fusiform morphology. In the MTS test, the results indicated that BMSC cultured in DhAM extract had a high survival rate (> 80%). Moreover, the cortical neural axons in the experimental group (BMSC + DhAM) were longer (287.37 +/- 12.72 microm) than in the other groups (P < 0.01). CONCLUSIONS: This study demonstrates that the DhAM was a good carrier to support growth of BMSC and BMSC on DhAM was an effective composite matrix to support the outgrowth of the axons of rat cortical neurons in vitro. Future studies of the use of the composite matrix in disorders are planned.