Guessing nonstate terrorism throughout the world

The mitochondria are the major source of reactive species in the mammalian cells. Hydrogen peroxide (H2O2) is a potent inducer of redox impairment by a mechanism, at least in part, dependent on its ability to impair mitochondrial function. H2O2 plays an important role in several pathological conditions, including neurodegeneration and cardiovascular diseases. Astaxanthin (AST) is a xanthophyll that may be found in microalgae, crustaceans, and salmon and exhibits antioxidant and anti-inflammatory effects in different cell types. Even though there is evidence pointing to a role for AST as mitochondrial protectant agent, it was not clearly demonstrated how this xanthophyll attenuates mitochondrial stress. Therefore, we investigated here whether and how AST would be able to prevent the H2O2-induced mitochondrial dysfunction in the human neuroblastoma SH-SY5Y cells. We found that AST (20 μM) prevented the H2O2-induced loss of mitochondrial membrane potential (MMP) and decrease in the activity of the Complexes I and V. AST pretreatment blocked the mitochondria-related pro-apoptotic effects elicited by H2O2. AST upregulated the enzyme heme oxygenase-1 (HO-1) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by a mechanism dependent on the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathway. Inhibition of the PI3K/Akt or of the HO-1 enzyme abolished the AST-induced mitochondrial protection in cells challenged with H2O2. Silencing of Nrf2 caused similar effects. Thus, we suggest that AST promotes mitochondrial protection by a mechanism dependent on the PI3K/Akt/Nrf2/HO-1 signaling pathway in SH-SY5Y cells exposed to H2O2.Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted.
Radioresistance is a major barrier to the successful treatment of head and neck squamous cell carcinoma (HNSCC).
We took advantage of different types of data, including single-cell sequencing data, bulk tissue sequencing data and deconvolution data, to conduct a comprehensive analysis of HNSCC radiosensitivity at the cellular, patient, and cell type levels. Single-cell transcriptomes for 1388 primary cancer cells from a previous study were analysed. The TCGA HNSCC dataset including 499 primary HNSCC samples with RNA-seq data, DNA methylation data and clinical information were used for bulk tissue sequencing analyses and deconvolution.
We found that radiosensitivity clustering of HNSCC cells was highly consistent with molecular typing, where cancer cells of the atypical subtype exhibited a higher sensitivity than those of the classical and basal subtypes. The common radioresistant gene modules of the classical and basal subtypes were mainly associated with cell division and cell cycle regulation; the clapy and immune checkpoint blockade, and proposed new targets for the treatment of radioresistant HNSCC.
This study comprehensively discussed the radioresistance of HNSCC, identified a group of HNSCCs that were likely to benefit from combined radiotherapy and immune checkpoint blockade, and proposed new targets for the treatment of radioresistant HNSCC.
This study compared MRI to CBCT for the identification and registration of lymph nodes (LN) in patients with locally advanced (LA)-NSCLC, to assess the suitability of targeting LNs in future MR-image guided radiotherapy (MRgRT) workflows.
Radiotherapy radiographers carried out Visual Grading Analysis (VGA) assessment of image quality, LN registration and graded their confidence in registration for each of the 24 LNs on CBCT and two MR sequences, MR1 (T2w Turbo Spin Echo) and MR2 (T1w DIXON water only image).
Pre-registration image quality assessment revealed MR1 and MR2 as significantly superior to CBCT in terms of image quality (p≤0.01). No significant differences were noted in interobserver variability for LN registration between CBCT, MR1 and MR2. Observers were more confident in their MR registrations compared to their CBCT based LN registrations (p≤0.02).
Interobserver setup correction variability was not found to be significantly different between CBCT and MR. Image quality and registration confidence were found to be superior for MRI sequences. This is a promising step towards MR-guided radiotherapy for the treatment of LA-NSCLC.
Interobserver setup correction variability was not found to be significantly different between CBCT and MR. Image quality and registration confidence were found to be superior for MRI sequences. This is a promising step towards MR-guided radiotherapy for the treatment of LA-NSCLC.
To assess radiation response using γH2AX assay in surgical specimens from glioblastoma (GB) patients and their corresponding primary gliosphere culture. To test the hypothesis that gliospheres (stem cell enriched) are more resistant than specimens (bulky cell dominated) but that the interpatient heterogeneity is similar.
Ten pairs of specimens and corresponding gliospheres derived from patients with IDH-wildtype GB were studied. Asunaprevir concentration Specimens and gliospheres were irradiated with graded doses and after 24h the number of residual γH2AX foci was counted.
Gliospheres showed a higher Nestin expression than specimens and exhibited two different phenotypes free floating (n=7) and attached (n=3). Slope analysis revealed an interpatient heterogeneity with values between 0.15 and 1.30 residual γH2AX foci/Gy. Free-floating spheres were more resistant than their parental specimens (median slope 0.13 foci/Gy versus 0.53) as well as than the attached spheres (2.14). The slopes of free floating spheres did not correlate with their corresponding specimens while a trend for a positive correlation was found for the attached spheres and the respective specimens.