Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The transcription factor NF-κB is overexpressed in human MB and is a critical factor for MB tumor growth. NF-κB is known to regulate the expression of interleukin-8 (IL-8), the chemokine that enhances cancer cell growth and resistance to chemotherapy. We have recently shown that thymoquinone (TQ) suppresses growth of hepatocellular carcinoma cells in part by inhibiting NF-κB signaling. Here we sought to extend these studies in MB cells and show that TQ suppresses growth of MB cells in a dose- and time-dependent manner, causes G2M cell cycle arrest, and induces apoptosis. TQ significantly increased generation of reactive oxygen species (ROS), while pretreatment of MB cells with the ROS scavenger N-acetylcysteine (NAC) abrogated TQ-induced cell death and apoptosis, suggesting that TQ-induced cell death and apoptosis are oxidative stress-mediated. TQ inhibitory effects were associated with inhibition of NF-κB and altered expression of its downstream effectors IL-8 and its receptors, the anti-apoptotic Bcl-2, Bcl-xL, X-IAP, and FLIP, as well as the pro-apoptotic TRAIL-R1, caspase-8, caspase-9, Bcl-xS, and cytochrome c. TQ-triggered apoptosis was substantiated by up-regulation of the executioner caspase-3 and caspase-7, as well as cleavage of the death substrate poly(ADP-ribose)polymerase. Interestingly, pretreatment of MB cells with NAC or the pan-caspase inhibitor zVAD-fmk abrogated TQ-induced apoptosis, loss of cyclin B1 and NF-κB activity, suggesting that these TQ-mediated effects are oxidative stress- and caspase-dependent. These findings reveal that TQ induces both extrinsic and intrinsic pathways of apoptosis in MB cells, and suggest its potential usefulness in the treatment of MB

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets

Influence of aluminum oxide nanoparticles addition with diesel fuel on emissions and performance of engine generator set using response surface methodology

The present study investigates the effect of small-sized aluminum oxide nanoparticle concentration and engine load on the emissions and performance parameters of a single-cylinder diesel engine connected to an AC generator. Response surface methodology (RSM) based on central composite design (CCD) was employed to simulate the design of the experiment. The ultrasonication-assisted preparation method has been used to mix the diesel (D) with two different concentrations of aluminum oxide, namely 50 ppm and 100 ppm. The tested fuels are called D, (D + 50AL2O3), and (D + 100AL2O3) accordingly. The tests were carried out at various engine loads of 0.9, 1.8, and 2.7 kW at a rated speed of 3000 rpm without engine modification. The evaluated characteristics were nitrogen oxide (NOx), hydrocarbons (HC), carbon dioxide (CO2), carbon monoxide (CO), brake-specific fuel consumption (BSFC), brake thermal efficiency (BTE), and exhaust gas temperature (EGT). According to the analysis of variance (ANOVA) results, the experimental outputs were found to be in good agreement with that of the predicted. Furthermore, the results revealed that the tested fuel D + 50Al2O3 favorably reduced the harmful emissions at all loads investigated. For instance, NOx, HC, and CO emissions decreased by 32.28%, 21.74%, and 20%, respectively. In addition, the BTE improved by 4.91% at 2.7 kW compared to pure diesel. The aforementioned potential results revealed that aluminum oxide nanoparticles could effectively reduce emissions parameters and enhance engine performance. Furthermore, the small nanoparticle size of 11 nm and low concentration of only 50 ppm (mixed with diesel) revealed positive technical, environmental, and economic perspectives on the applicability of the proposed nanofuel

Investigating the Combined Impact of Water–Diesel Emulsion and Al₂O₃ Nanoparticles on the Performance and the Emissions from a Diesel Engine via the Design of Experiment

This study aims to assess the impact of the water ratio and nanoparticle concentration of neat diesel fuel on the performance characteristics of and exhaust gas emissions from diesel engines. The experimental tests were conducted in two stages. In the first stage, the effects of adding water to neat diesel fuel in ratios of 2.5% and 5% on engine performance and emissions characteristics were examined and compared to those of neat diesel at a constant engine speed of 3000 rpm under three different engine loads. A response surface methodology (RSM) based on a central composite design (CCD) was utilized to simulate the design of the experiment. According to the test results, adding water to neat diesel fuel increased the brake-specific fuel consumption and reduced the brake thermal efficiency compared to neat diesel fuel. In the examination of exhaust emissions, hydrocarbons (HC), carbon monoxide (CO), and nitrogen oxides (NOx) in the tested fuel containing 2.5% of water were decreased in comparison to pure diesel fuel by 16.62%, 21.56%, and 60.18%, respectively, on average, through engine loading. In the second stage, due to the trade-off between emissions and performance, the emulsion fuel containing 2.5% of water is chosen as the best emulsion from the previous stage and mixed with aluminum oxide nanoparticles at two dose levels (50 and 100 ppm). With the same engine conditions, the emulsion fuel mixed with 50 ppm of aluminum oxide nanoparticles exhibited the best performance and the lowest emissions compared to the other evaluated fuels. The outcomes of the investigations showed that a low concentration of 50 ppm with a small amount of 11 nm of aluminum oxide nanoparticles combined with a water diesel emulsion is a successful method for improving diesel engine performance while lowering emissions. Additionally, it was found that the mathematical model could accurately predict engine performance parameters and pollution characteristics

Early Avastin management in acute retinal vein occlusion

AbstractPurposeTo evaluate the safety, functional and anatomical effects of intravitreal Avastin (bevacizumab) in treatment of recent retinal venous occlusion.DesignProspective interventional series non-comparative study.SettingDepartment of Ophthalmology, Faculty of Medicine, El-Minia University, Egypt.MethodsThe study included 30 eyes of 30 patients with recent retinal venous occlusion of less than 3months duration 12 eyes (40%) of patients with central retinal vein occlusion (CRVO) and 18 eyes (60%) with branch retinal vein occlusion (BRVO) were injected with intravitreal bevacizumab 1.25mg (0.05ml) of commercially available bevacizumab [Avastin; Genentech, Inc., San Francisco, CA] at a concentration of 25mg/ml as a primary treatment. The mean number of injections was 2.7 (range, 1–6 injections) 6–8weeks intervals and follow-up for 12months (range, 9–13months). Patients underwent visual acuity testing (VA) as functional assessment. Anatomically, optical coherence tomography (OCT) is used for measurement of central retinal thickness (CRT) to detect macular edema (ME), fundus photography and fluorescein angiography (FA) to detect venous tortuosity, optic disc edema and surface wrinkling rather than ME. All finding at baseline and each follow-up visit were reported.ResultsThe mean age of all patients was 65.3years±8.5 (range, 55–82years), 20 males and 10 females patients. The mean baseline VA was 20/240 (logMAR 1.08±0.52) and improved to 20/60 (logMAR 0.48±0.32) with statistically significance difference change (P<0.001). The mean baseline CRT was 455μm±126 (range, 386–510), decreased to 356μm±118 (range, 296–416) after 1month with statistically significance difference change (P<0.02) and to 402μm±170 (range, 338–468) after 6months (P<0.067) and to 250μm±48 (range, 200–298) at last follow-up with statistically significance difference change from the baseline (P<0.001). There were great proportional decrease in venous tortuosity, optic disc edema and surface wrinkling after 1month of injection. Neither systemic nor intraocular adverse events were reported.ConclusionsIntravitreal Avastin (IVA) is safe well tolerated, effectively improve VA, fundus picture and stabilize anterior segment neo-vascular activity in patients with recent retinal venous occlusion