Propofol affects the biological behavior of ovarian cancer SKOV3 cells via ERK1/2-MMP-2/9 signaling pathway

Purpose: To investigate the effect of propofol on the biological behavior of ovarian cancer SKOV3 cells, and the mechanism of action involved. Methods: SKOV3 cells cultured in vitro were randomly divided into control group, fat emulsion group, low-dose propofol group (LDPG, 25 μmol/L), medium-dose propofol group (MDPG) (50 μmol/L) and high-dose propofol group (HDPG) (100 μmol/L). Apoptosis was determined by flow cytometry, while Transwell assay was used to measure the migration and invasion abilities of the cells. The protein levels of ERK1/2, MMP-2, MMP-9 were assayed with Western blotting. Moreover, the cells were transfected with siERK, and the regulatory effect of propofol on ERK1/2-MMP-2/9 signaling pathway was determined. Results: Apoptosis in HDPG was significantly reduced, relative to MDPG, while migration and invasion were enhanced, relative to MDPG (p < 0.05). Moreover, MMP-2, ERK1/2, and MMP-9 proteins were significantly higher in MDPG and HDPG than in control, fat emulsion and LDPGs (p < 0.05), and were upregulated in HDPGs, relative to MDPG (p < 0.05). In contrast, propofol did not up-regulate these proteins in siRNA-treated cells. Conclusion: Propofol enhances the migration, proliferation, and invasive ability SKOV3 cells, and upregulates the expressions of MMP-2, ERK1/2, and MMP-9 in these cells, via a mechanism related to the activation of ERK1/2-MMP-2/9 signaling route. These properties provide novel leads for the development of new drugs for ovarian cancer Keywords: Propofol, ERK1/2-MMP-2/9 signal route, Ovarian cancer, Biological behavio

Eucalyptus essential oil exerted a sedative-hypnotic effect by influencing brain neurotransmitters and gut microbes via the gut microbiota-brain axis

Sleep disorders are becoming more and more common, leading to many health problems. However, most of current available medications to treat sleep disorders are addictive and even impair cognitive abilities. Therefore, it is important to find a natural and safe alternative to treat sleep disorders. In this study, twenty-four 8-week-old male ICR mice (25 ± 2 g) were equally divided into three groups: the control group (gavage of 0.9% saline), the eucalyptus essential oil (EEO) group (10 mg/kg B.W.), and the diazepam group (1 mg/kg B.W.). Firstly, open field test and sleep induction test were used to determine the sedative-hypnotic effect of EEO. Secondly, the effect of EEO on neurotransmitters in the mice brain was determined. Finally, based on the gut microbiota-brain axis (GMBA), the effect of EEO on the intestinal flora of mice was explored. It was found that EEO significantly reduce the activity and prolong the sleep duration of mice, exhibiting a good sedative-hypnotic effect. In the brain, EEO could increase the levels of sleep-promoting neurotransmitters, such as glutamine, Gamma-aminobutyric acid (GABA), glycine, tryptophan, N-acetylserotonin, and 5-hydroxyindoleacetic acid (5-HIAA). In the intestine, EEO was found to increase the diversity of gut microbes, the abundance of short chain fatty acid (SCFA) producing flora, and the abundance of functional flora synthesizing GABA and glycine neurotransmitters. These studies suggested that EEO exerted a sedative-hypnotic effect by acting on gut microbes and neurotransmitters in the brain. EEO has the potential to become a natural and safe alternative to traditional hypnotic sedative drugs

Benzo[a]pyrene exacerbates allergen-induced airway inflammation through NLRP3-dependent dendritic cell activation and pathogenic T helper cell polarization

BackgroundEnvironmental pollutants are known to aggravate allergic diseases, but the molecular mechanisms by which polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) potentiate allergic airway inflammation remain poorly understood.ObjectiveWe investigated how BaP co-exposure modifies house dust mite (HDM)–driven allergic airway responses, focusing on the role of the NLRP3 inflammasome in dendritic cells (DCs).MethodsMice were sensitized and challenged intranasally with HDM with or without BaP. Airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL) cell counts, lung histopathology, and serum HDM-specific IgE were assessed. Cytokine production and epithelial alarmins were measured by ELISA. The role of NLRP3 was evaluated using Nlrp3−/− mice, in vitro bone marrow–derived DC (BMDC) cultures, and adoptive transfer of lung DCs. T helper cell polarization was analyzed in OT-II co-culture assays.ResultsCo-exposure to BaP and HDM markedly exacerbated airway inflammation, with enhanced AHR, increased eosinophil and neutrophil infiltration, severe goblet cell hyperplasia, and elevated HDM-specific IgE. Cytokine analysis revealed synergistic induction of Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) responses, alongside increased epithelial alarmins (TSLP, IL-33). This exacerbated phenotype was abolished in Nlrp3−/− mice, which failed to produce IL-1β/IL-18 and exhibited attenuated inflammation. In vitro, BaP synergized with HDM to activate NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1β release, and enhanced CD80/CD86 expression. Adoptive transfer of BaP/HDM-exposed WT lung DCs, but not Nlrp3−/− DCs, was sufficient to drive allergic airway inflammation in naïve recipients. Finally, BaP–conditioned WT DCs skewed naïve CD4+ T cells toward Th2 and Th17 lineages, an effect absent in Nlrp3−/− DCs.ConclusionBaP amplifies allergic airway disease by activating the NLRP3 inflammasome in DCs, thereby enhancing DC maturation, cytokine release, and pathogenic Th2/Th17 polarization. These findings identify a critical mechanism linking environmental pollutants to exacerbated allergic asthma and highlight the NLRP3 inflammasome as a potential therapeutic target

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Analysis on the Characteristics of Ordinary and More Serious Accidents in Building Projects in China from 2005 to 2016

In China, the frequent safety accidents in building projects seriously affect the sustainable development of construction projects. The paper makes a statistical analysis on the characteristics of ordinary and more serious accidents in building projects from the types of accidents, the trends of development and the characteristics of geographical distribution from 2005 to 2016 in China by using the histogram, trend chart, pie chart and table. It can be concluded that in the recent 12 years, the security situation of construction projects generally fluctuates in a big way and is still not optimistic. Among the five major types of accidents, the electric shock and the lifting accidents have been maintained at a relatively stable and low incidence, and the sloughing accidents have accounted for more than half of the proportion. Accidents concentrated in East China, Central China, North China and Southwest China. The economic development in all provinces and cities in China is positively related to the accident. The greater the total regional economy, the rate of economic growth and the demand for infrastructure construction, the more deaths and accidents in construction projects in the corresponding regions

Impact of migration on the multi-strategy selection in finite group-structured populations

AbstractFor large quantities of spatial models, the multi-strategy selection under weak selection is the sum of two competition terms: the pairwise competition and the competition of multiple strategies with equal frequency. Two parameters σ1 and σ2 quantify the dependence of the multi-strategy selection on these two terms, respectively. Unlike previous studies, we here do not require large populations for calculating σ1 and σ2, and perform the first quantitative analysis of the effect of migration on them in group-structured populations of any finite sizes. The Moran and the Wright-Fisher process have the following common findings. Compared with well-mixed populations, migration causes σ1 to change with the mutation probability from a decreasing curve to an inverted U-shaped curve and maintains the increase of σ2. Migration (probability and range) leads to a significant change of σ1 but a negligible one of σ2. The way that migration changes σ1 is qualitatively similar to its influence on the single parameter characterizing the two-strategy selection. The Moran process is more effective in increasing σ1 for most migration probabilities and the Wright-Fisher process is always more effective in increasing σ2. Finally, our findings are used to study the evolution of cooperation under direct reciprocity.</jats:p

Analysis on the Characteristics of Ordinary and More Serious Accidents in Building Projects in China from 2005 to 2016

In China, the frequent safety accidents in building projects seriously affect the sustainable development of construction projects. The paper makes a statistical analysis on the characteristics of ordinary and more serious accidents in building projects from the types of accidents, the trends of development and the characteristics of geographical distribution from 2005 to 2016 in China by using the histogram, trend chart, pie chart and table. It can be concluded that in the recent 12 years, the security situation of construction projects generally fluctuates in a big way and is still not optimistic. Among the five major types of accidents, the electric shock and the lifting accidents have been maintained at a relatively stable and low incidence, and the sloughing accidents have accounted for more than half of the proportion. Accidents concentrated in East China, Central China, North China and Southwest China. The economic development in all provinces and cities in China is positively related to the accident. The greater the total regional economy, the rate of economic growth and the demand for infrastructure construction, the more deaths and accidents in construction projects in the corresponding regions