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Cells Jun 2024UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such...
UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.
Topics: Humans; Oxidation-Reduction; Skin; Ultraviolet Rays; Cannabinoids; Signal Transduction; Cannabidiol; Fibroblasts; Keratinocytes; Inflammation; Oxidative Stress; Antioxidants; Reactive Oxygen Species; NF-E2-Related Factor 2; Lipid Peroxidation
PubMed: 38891097
DOI: 10.3390/cells13110965 -
Cells May 2024Apolipoprotein E (ApoE) is a lipid carrier in both the peripheral and the central nervous systems (CNSs). Lipid-loaded ApoE lipoprotein particles bind to several cell...
Apolipoprotein E (ApoE) is a lipid carrier in both the peripheral and the central nervous systems (CNSs). Lipid-loaded ApoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and brain injury repair. In the brain, ApoE is produced predominantly by astrocytes, but it is also abundantly expressed in most neurons of the CNS. In this study, we addressed the role of ApoE in the hippocampus in mice, focusing on its role in response to radiation injury. To this aim, 8-week-old, wild-type, and ApoE-deficient (ApoE) female mice were acutely whole-body irradiated with 3 Gy of X-rays (0.89 Gy/min), then sacrificed 150 days post-irradiation. In addition, age-matching ApoE females were chronically whole-body irradiated (20 mGy/d, cumulative dose of 3 Gy) for 150 days at the low dose-rate facility at the Institute of Environmental Sciences (IES), Rokkasho, Japan. To seek for ApoE-dependent modification during lineage progression from neural stem cells to neurons, we have evaluated the cellular composition of the dentate gyrus in unexposed and irradiated mice using stage-specific markers of adult neurogenesis. Our findings indicate that ApoE genetic inactivation markedly perturbs adult hippocampal neurogenesis in unexposed and irradiated mice. The effect of ApoE inactivation on the expression of a panel of miRNAs with an established role in hippocampal neurogenesis, as well as its transcriptional consequences in their target genes regulating neurogenic program, have also been analyzed. Our data show that the absence of ApoE also influences synaptic functionality and integration by interfering with the regulation of mir-34a, mir-29b, and mir-128b, leading to the downregulation of synaptic markers PSD95 and synaptophysin mRNA. Finally, compared to acute irradiation, chronic exposure of ApoE null mice yields fewer consequences except for the increased microglia-mediated neuroinflammation. Exploring the function of ApoE in the hippocampus could have implications for developing therapeutic approaches to alleviate radiation-induced brain injury.
Topics: Animals; Apolipoproteins E; Hippocampus; Mice; Radiation, Ionizing; Female; MicroRNAs; Mice, Inbred C57BL; Neurons; Neurogenesis; Whole-Body Irradiation; Radiation Exposure; Dentate Gyrus
PubMed: 38891031
DOI: 10.3390/cells13110899 -
Reviews on Environmental Health Jun 2024The fifth generation, 5G, for wireless communication is currently deployed in Sweden since 2019/2020, as well as in many other countries. We have previously published... (Review)
Review
The fifth generation, 5G, for wireless communication is currently deployed in Sweden since 2019/2020, as well as in many other countries. We have previously published seven case reports that include a total of 16 persons aged between 4 and 83 years that developed the microwave syndrome within short time after being exposed to 5G base stations close to their dwellings. In all cases high radiofrequency (RF) radiation from 4G/5G was measured with a broadband meter. RF radiation reached >2,500,000 to >3,180,000 μW/m in peak maximum value in three of the studies. In total 41 different health issues were assessed for each person graded 0 (no complaint) to 10 (worst symptoms). Most prevalent and severe were sleeping difficultly (insomnia, waking night time, early wake-up), headache, fatique, irritability, concentration problems, loss of immediate memory, emotional distress, depression tendency, anxiety/panic, dysesthesia (unusual touched based sensations), burning and lancinating skin, cardiovascular symptoms (transitory high or irregular pulse), dyspnea, and pain in muscles and joints. Balance disorder and tinnitus were less prevalent. All these symptoms are included in the microwave syndrome. In most cases the symptoms declined and disappeared within a short time period after the studied persons had moved to a place with no 5G. These case histories are classical examples of provocation studies. They reinforce the urgency to inhibit the deployment of 5G until more safety studies have been performed.
PubMed: 38889394
DOI: 10.1515/reveh-2024-0017 -
Radiotherapy and Oncology : Journal of... Jun 2024Synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) can serve as a substitute for planning CT in radiation therapy (RT), thereby removing... (Review)
Review
Challenges and opportunities in the development and clinical implementation of artificial intelligence based synthetic computed tomography for magnetic resonance only radiotherapy.
Synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) can serve as a substitute for planning CT in radiation therapy (RT), thereby removing registration uncertainties associated with multi-modality imaging pairing, reducing costs and patient radiation exposure. CE/FDA-approved sCT solutions are nowadays available for pelvis, brain, and head and neck, while more complex deep learning (DL) algorithms are under investigation for other anatomic sites. The main challenge in achieving a widespread clinical implementation of sCT lies in the absence of consensus on sCT commissioning and quality assurance (QA), resulting in variation of sCT approaches across different hospitals. To address this issue, a group of experts gathered at the ESTRO Physics Workshop 2022 to discuss the integration of sCT solutions into clinics and report the process and its outcomes. This position paper focuses on aspects of sCT development and commissioning, outlining key elements crucial for the safe implementation of an MRI-only RT workflow.
PubMed: 38885905
DOI: 10.1016/j.radonc.2024.110387 -
The Canadian Journal of Cardiology Jun 2024The potential of artificial intelligence (AI) in medicine lies in its ability to enhance clinicians' capacity to analyze medical images, thereby improving diagnostic... (Review)
Review
The potential of artificial intelligence (AI) in medicine lies in its ability to enhance clinicians' capacity to analyze medical images, thereby improving diagnostic precision and accuracy, thus enhancing current tests. However, the integration of AI within healthcare is fraught with difficulties. Heterogeneity among healthcare system applications, reliance on proprietary closed-source software, and rising cyber-security threats pose significant challenges. Moreover, prior to their deployment in clinical settings, AI models must demonstrate their effectiveness across a wide range of scenarios and must be validated by prospective studies, but doing so requires testing in an environment mirroring the clinical workflow which is difficult to achieve without dedicated software. Finally, the use of AI techniques in healthcare raises significant legal and ethical issues, such as the protection of patient privacy, the prevention of bias, and the monitoring of the device's safety and effectiveness for regulatory compliance. This review describes challenges to AI integration in healthcare and provides guidelines on how to move forward. We describe an open-source solution that we developed which integrates AI models into the Picture Archives Communication System (PACS), called PACS-AI. This approach aims to increase the evaluation of AI models by facilitating their integration and validation with existing medical imaging databases. PACS-AI may overcome many current barriers to AI deployment and offers a pathway towards responsible, fair, and effective deployment of AI models in healthcare. Additionally, we propose a list of criteria and guidelines that AI researchers should adopt when publishing a medical AI model, to enhance standardization and reproducibility.
PubMed: 38885787
DOI: 10.1016/j.cjca.2024.05.025 -
Schizophrenia Research Jun 2024Environment and genes both contribute to schizophrenia. However, the impact of different natural environments surrounding residential addresses on schizophrenia in urban...
BACKGROUND
Environment and genes both contribute to schizophrenia. However, the impact of different natural environments surrounding residential addresses on schizophrenia in urban settings remains unknown. This study aimed to investigate the association of urbanisation, measured by residential environments, with late-onset schizophrenia and explore whether genetic risk for schizophrenia modified the associations.
METHODS
We examined the associations between residential environments and late-onset schizophrenia and its interaction with genetic risk factors in UK Biobank, followed from 2006 to 2010 (baseline) to Dec 2021. Residential environments, including greenspace, domestic garden, blue space, and total natural environment, were evaluated using land use coverage percentage. The polygenic risk score (PRS) of schizophrenia was derived using a Bayesian approach and adjusted it against ancestry. Cox proportional hazard regression model was used to assess the associations between per interquartile (IQR) increase of each type of residential environments and late-onset schizophrenia. Interactive effects of PRS and residential environments on late-onset schizophrenia were assessed on both additive and multiplicative scales.
RESULTS
A total of 393,680 participants were included in the analysis, with 844 cases of late-onset schizophrenia being observed after 12.8 years of follow-up. Within 300 m buffer surrounding the residential addresses, per interquartile increase in greenspace (31.5 %) and total natural environment (34.4 %) were both associated with an 11 % (HR = 0.89, 95 % CI 0.80, 0.99) lower risk of late-onset schizophrenia. Domestic garden and blue space did not show significant protective effects on late-onset schizophrenia. A strong dose-response relationship between schizophrenia PRS and schizophrenia was found, while no additive or multiplicative interaction effects were present between residential environments and PRS on late-onset schizophrenia.
CONCLUSION
Residential greenspace and total natural environment may protect against late-onset schizophrenia in older people regardless of genetic risk. These findings shed light on the prevention of schizophrenia and urban planning to optimise ecosystem benefits linked to schizophrenia.
PubMed: 38885569
DOI: 10.1016/j.schres.2024.06.008 -
Translational Cancer Research May 2024Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase...
BACKGROUND
Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents.
METHODS
CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle.
RESULTS
The IC value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX).
CONCLUSIONS
The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.
PubMed: 38881946
DOI: 10.21037/tcr-23-2169 -
Scientific Reports Jun 2024From the useless municipal solid waste (MSW) ashes, CeO, GdO and CeO + GdO doped borosilicate glasses were organized via melting-quenching procedure. Various...
From the useless municipal solid waste (MSW) ashes, CeO, GdO and CeO + GdO doped borosilicate glasses were organized via melting-quenching procedure. Various optical, structural, physical and radiation shielding parameters were examined towards the influence of 100 kGy of γ-radiation. UV-visible NIR spectra revealed UV peaks at 351, 348 and 370 nm corresponding to the trivalent states of Ce and Gd ions, while, photoluminescence (PL) spectra displayed asymmetric broad excitations of Ce and Gd ions due to 4f → 5d transitions, and emission intense bands at 412, 434, and 417 nm. CIE chromaticity shows that Gd ions increase the luminescence of Ce. FTIR absorption bands revealed an overlapping between tetrahedral groups of silicate (SiO), with trigonal (BO) and tetrahedral (BO) units of borate. The influence of 100 kGy obtains quite reduction in UV-visible NIR and PL peaks, large stability in FTIR and ESR spectra, and stability of thermal expansion coefficient (CTE) as well. The whole data revealed optical, structural and physical stability of glasses after irradiation besides an enhancement in microhardness owing to more structural compactness and high bonding connectivity. Radiation shielding parameters from PhyX/PSD program showed higher values of mass (MAC) and linear attenuation coefficients (LAC), and effective atomic number (Z) in the order of; glass > glass > glass . Ce + Gd doped glass revealed also the lowest half value layer (HVL) comparing to other shielding commercial concretes. The study recommends the beneficial and economical use of the useless MSW ash to produce CeO and/or GdO borosilicate glasses with hopeful radiation shielding features.
PubMed: 38871825
DOI: 10.1038/s41598-024-63207-4