Enhanced sensitivity of celecoxib in human glioblastoma cells: Induction of DNA damage leading to p53-dependent G1 cell cycle arrest and autophagy

<p>Abstract</p> <p>Background</p> <p>Selective cyclooxygenase (COX)-2 inhibitors elicit anti-proliferative responses in various tumours, however the underlying anti-tumour mechanisms are unclear. Mutational inactivation of the tumour suppressor p53 gene is frequent in malignant gliomas. The role of p53 mutation in the anti-tumour responses of the selective COX-2 inhibitor celecoxib in human glioblastoma cells is unknown. In this study, we used human glioblastoma cells with various p53 status; U87MG (with high and low p53 functional levels), LN229 (functional p53) and U373MG (mutant p53) cells. Inhibition of p53 was achieved in U87MG cells transfected with E6 oncoprotein (U87MG-E6) and treated with pifithrin-α, a reversible inhibitor of p53 (U87MG-PFT). We investigated whether the anti-glioblastoma responses of celecoxib were p53-dependent, and whether celecoxib induced DNA damage leading to p53-dependent G₁cell cycle arrest, followed by autophagy or apoptosis.</p> <p>Results</p> <p>Our findings demonstrated that celecoxib concentration-dependently reduced glioblastoma cell viability, following 24 and 72 hours of treatment. Inhibition of functional p53 in glioblastoma cells significantly reduced the anti-proliferative effect of celecoxib. In U87MG cells, celecoxib (8 and 30 μM) significantly induced DNA damage and inhibited DNA synthesis, corresponding with p53 activation. Celecoxib induced G₁-phase cell cycle arrest, accompanied with p21 activation in U87MG cells. Cell cycle progression of U87MG-E6 and U87MG-PFT cells was not affected by celecoxib. In parallel, celecoxib induced G₁cell cycle arrest in LN229 cells, but not in U373MG cells. Autophagy was induced by celecoxib in U87MG and LN229 cells, as shown by the significantly greater population of acridine orange-stained cells and increased levels of LC3-II protein (in comparison with non-treated controls). Celecoxib did not induce significant autophagy in U87MG-PFT, U87MG-E6 and U373MG cells, which lack functional p53. Regardless of p53 status, celecoxib caused no significant difference in apoptosis level of U87MG, U87MG-PFT, U87MG-E6 and U373MG cells.</p> <p>Conclusion</p> <p>Our findings reveal that p53 increases human glioblastoma sensitivity to celecoxib. Celecoxib inhibits glioblastoma cell viability by induction of DNA damage, leading to p53-dependent G₁cell cycle arrest and p53-dependent autophagy, but not apoptosis.</p

Gut Microbiome of a Multiethnic Community Possessed No Predominant Microbiota

With increasing globalisation, various diets from around the world are readily available in global cities. This study aimed to verify if multiethnic dietary habits destabilised the gut microbiome in response to frequent changes, leading to readily colonisation of exogenous microbes. This may have health implications. We profiled Singapore young adults of different ethnicities for dietary habits, faecal type, gut microbiome and cytokine levels. Subjects were challenged with Lactobacillus casei, and corresponding changes in microbiome and cytokines were evaluated. Here, we found that the majority of young adults had normal stool types (73% Bristol Scale Types 3 and 4) and faecal microbiome categorised into three clusters, irrespective of race and gender. Cluster 1 was dominated by Bacteroides, Cluster 2 by Prevotella, while Cluster 3 showed a marginal increase in Blautia, Ruminococaceae and Ruminococcus, without a predominant microbiota. These youngsters in the three faecal microbiome clusters preferred Western high sugary beverages, Southeast Asian plant-rich diet and Asian/Western diets in rotation, respectively. Multiethnic dietary habits (Cluster 3) led to a gut microbiome without predominant microbiota yet demonstrated colonisation resistance to Lactobacillus. Although Bacteroides and Prevotella are reported to be health-promoting but also risk factors for some illnesses, Singapore-style dietary rotation habits may alleviate Bacteroides and Prevotella associated ill effects. Different immunological outcome was observed during consumption of the lactobacilli among the three microbiome clusters.</p

Comparative Research on Ventilation Characteristics of Scattering and Sample Room from Chinese Spallation Neutron Source

Ventilation design of the scattering room and sample room in the Chinese Spallation Neutron Source (CSNS) is of great significance to maintain good indoor air quality and ensure the health of radiation workers. Based on the computational fluid dynamics (CFD) theory, the three-dimensional models of the scattering and sample rooms were established and fourteen layout schemes were simulated. Subsequently, the best schemes were selected among three typical layout schemes. On this basis, the paper presents research about the influence of changing the height of the outlet on the ventilation quality. The results show that the trend of numerical simulation is consistent with experimental data, which verifies the reliability of the numerical method. The change of the exhaust port position has an apparent influence on indoor ventilation, which reduces the air age by 4&ndash;27%. When the position of the outlet descends 0.5 m, the air age decreases by 2&ndash;11%, and this study provides guidance and suggestions for the design of the scattering and sample rooms

Comparative Research on Ventilation Characteristics of Scattering and Sample Room from Chinese Spallation Neutron Source

Ventilation design of the scattering room and sample room in the Chinese Spallation Neutron Source (CSNS) is of great significance to maintain good indoor air quality and ensure the health of radiation workers. Based on the computational fluid dynamics (CFD) theory, the three-dimensional models of the scattering and sample rooms were established and fourteen layout schemes were simulated. Subsequently, the best schemes were selected among three typical layout schemes. On this basis, the paper presents research about the influence of changing the height of the outlet on the ventilation quality. The results show that the trend of numerical simulation is consistent with experimental data, which verifies the reliability of the numerical method. The change of the exhaust port position has an apparent influence on indoor ventilation, which reduces the air age by 4–27%. When the position of the outlet descends 0.5 m, the air age decreases by 2–11%, and this study provides guidance and suggestions for the design of the scattering and sample rooms

<i>In Situ</i> Active Poling of Nanofiber Networks for Gigantically Enhanced Particulate Filtration

Enhancing the filtration efficiency of air filtering material without increasing its airflow resistance is a major challenge and of great significance. In this work, we report a type of active-poled nanofiber onto which <i>in situ</i> active poling is applied. It results in significantly enhanced filtration efficiency as well as dust holding capacity while keeping the airflow resistance constant. Owing to the <i>in situ</i> applied electric field, the nanofibers as well as the particulates are polarized. As a result, at a poling voltage of 2 kV, the removal efficiency and the quality factor for PM_2.5 are enhanced by 17% and 130%, respectively. More importantly, the dust holding capacity represents a 3.5-fold enhancement over normal nanofibers. The approach reported in this work has the potential of being practically utilized in air purification purposes because it can bring about not only promoted filtration performance but also lowered noise and reduced power consumption

Gut microbiome of a multiethnic community possessed no predominant microbiota

10.3390/microorganisms9040702Microorganisms9470