Ga complexes of 8-hydroxyquinoline-2-carboxylic acid: Chemical speciation and biological activity.

The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga3+ has been investigated by ISEH+ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl(aq) at I = 0.2 mol dm-3 and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]+, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)2]- and [Ga(8-HQA)2]- species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]- and [Ga(EDTA)(OH)]2- in the above conditions. Due to the relevance of Ga3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm-3 ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization - Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga3+/8-HQA complexes were also performed, identifying [Ga(8-HQA)2]- as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga3+/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga3+/8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga3+/8-HQA complex. Nevertheless, Ga3+/8-HQA complex highlighted potential anti-inflammatory properties.

Studies on Human Cultured Fibroblasts and Cutaneous Squamous Cell Carcinomas Suggest That Overexpression of Histone Variant H2A.J Promotes Radioresistance and Oncogenic Transformation.

Background: Cellular senescence in response to ionizing radiation (IR) limits the replication of damaged cells by causing permanent cell cycle arrest. However, IR can induce pro-survival signaling pathways that reduce the extent of radiation-induced cytotoxicity and promote the development of radioresistance. The differential incorporation of histone variant H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of radiation-induced senescence. However, the precise epigenetic mechanism and function of H2A.J overexpression in response to IR exposure still needs to be elucidated. Methods: Primary (no target, NT) and genetically modified fibroblasts overexpressing H2A.J (H2A.J-OE) were exposed to 20 Gy and analyzed 2 weeks post-IR for radiation-induced senescence by immunohistochemistry and immunofluorescence microscopy. Transcriptome signatures were analyzed in (non-)irradiated NT and H2A.J-OE fibroblasts by RNA sequencing. Since H2A.J plays an important role in the epidermal homeostasis of human skin, the oncogenic potential of H2A.J was investigated in cutaneous squamous cell carcinoma (cSCC). The tissue microarrays of cSCC were analyzed for H2A.J protein expression pattern by automated image analysis. Results: In response to radiation-induced DNA damage, the overexpression of H2A.J impairs the formation of senescence-associated heterochromatin foci (SAHF), thereby inhibiting the SAHF-mediated silencing of proliferation-promoting genes. The dysregulated activation of cyclins and cyclin-dependent kinases disturbs cell cycle arrest in irradiated H2A.J-OE fibroblasts, thereby overcoming radiation-induced senescence. Comparative transcriptome analysis revealed significantly increased WNT16 signaling in H2A.J OE fibroblasts after IR exposure, promoting the fundamental mechanisms of tumor development and progression, including the activation of the epithelial-mesenchymal transition. The quantitative analysis of cSCCs revealed that undifferentiated tumors are associated with high nuclear H2A.J expression, related with greater oncogenic potential. Conclusion: H2A.J overexpression induces radioresistance and promotes oncogenic transformation through the activation of WNT16 signaling pathway functions. H2A.J-associated signatures may improve risk stratification by identifying patients with more aggressive cSCC who may require radiotherapy with increased doses.

Recent insights into trends of thyroid cancer incidence in Lithuanian population exposed to Chernobyl fallout early in life.

In the last three decades, an increase in thyroid cancer incidence has been observed worldwide, as well as in Lithuania. Although the rise was linked to overdiagnosis, the role of lifestyle and environmental factors, including exposure to ionizing radiation, cannot be excluded. In our retrospective study, we aimed to assess the association between the average age-specific thyroid dose due to the radioactive iodine uptake during childhood and adolescence from the Chernobyl fallout in Lithuania, and the trends of incidence of thyroid cancer from 1991 to 2015 in different regions. Averaged age-dependent thyroid doses were estimated for every municipality based on radioiodine activity in milk, reconstructed from available 131I activity measurements in the grass. Thyroid cancer incidence rates were calculated for the entire population and for two age at the time of exposure groups: 0-19 years and 0-9 years. Thyroid cancer relative risk (RR) was estimated for three municipality-specific thyroid dose (for 0-year-old babies) categories: less than 100 mGy (reference group), 100-199 mGy, and ≥200 mGy. Over the study period (1991-2015), a total of 5664 cases of thyroid cancer were registered in the entire Lithuanian population; 817 cases in the age group from 0 to 19 years at the time of the Chernobyl accident, and 266 cases in the age group from 0 to 9 years. Age-standardized thyroid cancer incidence rates have notably increased since 2000, peaked in 2009 (especially in females), and then slightly decreased and stabilized. The estimated average municipality-specific age-dependent thyroid doses ranged from 270 mGy in western Lithuania to 1.5 mGy in central and northern Lithuania. For the age group of 0-19 years at the time of the accident, in the period 1991-1995, the thyroid cancer relative risk was significantly increased (RR 3.91; 95 % CI: 1.27-10.29, p=0.01) in the highest dose category, compared to the lowest (although based on a small number of cases). For the age group 0-9 years at the time of the accident, a tendency of increased RR in the highest dose category appeared in the most recent period, 2011-2015. Our observations need to be confirmed by further following trends of thyroid cancer incidence in the cohort of 0-19-year-old Lithuanians at the time of the Chernobyl accident.

Cosmic Ionizing Radiation: A DNA Damaging Agent That May Underly Excess Cancer in Flight Crews.

In the United States, the Federal Aviation Administration has officially classified flight crews (FC) consisting of commercial pilots, cabin crew, or flight attendants as "radiation workers" since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to the dosimetry of CIR, the role of other genotoxic exposures among FC, and whether possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to exposure to CIR in FC. We aimed to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate the risks for those who travel by air.

Ergonomics, Health, and Perceptions about Remote Domestic Workposts: Study in Areas of City of João Pessoa, Paraíba, Brazil.

Home office (HO) stands out as one of the most promising and popular forms of teleworking, especially after the COVID-19 pandemic. Therefore, many companies want to implement or maintain this working method, given its numerous advantages. However, there are adverse effects that are mainly related to physical and mental health. This article presents ergonomic analyses of HOs in neighborhoods considered heat islands. Temperature levels, extreme low-frequency non-ionizing radiation (ELF-NIR), illuminance, physical layout characteristics, and physiological parameters of teleworkers were measured. The results reveal that 92% of these professionals work 6 to 8 h daily with an ambient temperature between 25 and 30 °C, illumination levels in the range 11.20-290 Lux, and ELF-NIR > 0.4 µT. The majority of teleworkers are overweight (BMI > 24.9), and some of them have blood pressure higher than average values (129 mmHg for systolic and 84 mmHg for diastolic) in addition to a reduction in the number of red blood cells and hematocrits. Symptoms such as burning sensation, dryness, tired eyes, redness, itching, and photophobia (light sensitivity) show a 68.95% similarity. These HOs do not meet the required ergonomic and health standards.

Low-Dose Ionizing Radiation Exposure on Human Male Gametes: Damage or Benefit.

With the improvement of medical devices for diagnosis and radiotherapy, concerns about the effects of low doses of ionizing radiation are also growing. There is no consensus among scientists on whether they might have beneficial effects on humans in certain cases or pose more risks, making the exposure unreasonable. While the damaging consequences of high-dose radiation have been known since the discovery of radioactivity, low-dose effects present a much bigger investigative challenge. They are highly specific and include radio-adaptive responses, bystander effects, and genomic instability. Current data regarding the consequences of exposure to low-dose radiation on the quality of male gametes and fertility potential are contradictory. The reports suggest two directions: indirect impact on male gametes-through spermatogenesis-or direct effects at low doses on already mature spermatozoa. Although mature gametes are used for observation in both models, they are fundamentally different, leading to varied results. Due to their unique physiological characteristics, in certain cases, exposure of spermatozoa to low-dose ionizing radiation could have positive effects. Despite the findings indicating no beneficial effects of low-dose exposure on male fertility, it is essential to research its impact on mature spermatozoa, as well.

Research on Food Preservation Based on Antibacterial Technology: Progress and Future Prospects.

The nutrients present in food are not only prone to a series of physicochemical reactions but also provide conditions for the growth and reproduction of foodborne microorganisms. In recent years, many innovative methods from different fields have been introduced into food preservation, which extends the shelf life while maximizing the preservation of the original ingredients and properties of food. In this field, there is a lack of a systematic summary of new technologies emerging. In view of this, we overview the innovative methods applied to the field of food preservation in recent 3 years, focusing on a variety of technological approaches such as antimicrobial photodynamic therapy based on nanotechnology, electromagnetic radiation sterilization based on radiation technology, and antimicrobial peptides based on biomolecules. We also discuss the preservation mechanism and the application of the different methods to specific categories of products. We evaluated their advantages and limitations in the food industry, describing their development prospects. In addition, as microorganisms are the main causes of food spoilage, our review also has reference significance for clinical antibacterial treatment.

Radio-miRs: a comprehensive view of radioresistance-related microRNAs.

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.

Comparative transcriptomics reveal a novel tardigrade-specific DNA-binding protein induced in response to ionizing radiation.

Tardigrades are microscopic animals renowned for their ability to withstand extreme conditions, including high doses of ionizing radiation (IR). To better understand their radio-resistance, we first characterized induction and repair of DNA double- and single-strand breaks after exposure to IR in the model species Hypsibius exemplaris. Importantly, we found that the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in tardigrades' radio-resistance. To identify novel tardigrade-specific genes involved, we next conducted a comparative transcriptomics analysis across three different species. In all three species, many DNA repair genes were among the most strongly overexpressed genes alongside a novel tardigrade-specific gene, which we named Tardigrade DNA damage Response 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and preserve chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade-specific gene conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping cope with high levels of DNA damage inflicted by IR.

WHO to build neglect of RF-EMF exposure hazards on flawed EHC reviews? Case study demonstrates how "no hazards" conclusion is drawn from data showing hazards.

We examined one of the first published of the several systematic reviews being part of WHO's renewed initiative to assess the evidence of associations between man-made radiofrequency electromagnetic radiation (RF-EMF) and adverse health effects in humans. The examined review addresses experimental studies of pregnancy and birth outcomes in non-human mammals. The review claims that the analyzed data did not provide conclusions certain enough to inform decisions at a regulatory level. Our objective was to assess the quality of this systematic review and evaluate the relevance of its conclusions to pregnant women and their offspring. The quality and relevance were checked on the review's own premises: e.g., we did not question the selection of papers, nor the chosen statistical methods. While the WHO systematic review presents itself as thorough, scientific, and relevant to human health, we identified numerous issues rendering the WHO review irrelevant and severely flawed. All flaws found skew the results in support of the review's conclusion that there is no conclusive evidence for nonthermal effects. We show that the underlying data, when relevant studies are cited correctly, support the opposite conclusion: There are clear indications of detrimental nonthermal effects from RF-EMF exposure. The many identified flaws uncover a pattern of systematic skewedness aiming for uncertainty hidden behind complex scientific rigor. The skewed methodology and low quality of this review is highly concerning, as it threatens to undermine the trustworthiness and professionalism of the WHO in the area of human health hazards from man-made RF-EMF.

Reproductive Capacity, but not Food Consumption, is Reduced by Continuous Exposure to Typical Genotoxic Stressor γ-Rays in the sentinel species Gammarus fossarum.

The long-term impacts of radiocontaminants (and the associated risks) for ecosystems are still subject to vast societal and scientific debate while wildlife is chronically exposed to various sources and levels of either environmental or anthropogenic ionizing radiation from the use of nuclear energy. The present study aimed to assess induced phenotypical responses in both male and female gammarids after short-term continuous γ-irradiation, acting as a typical well-characterized genotoxic stressor that can interact directly with living matter. In particular, we started characterizing the effects using standardized measurements for biological effects on few biological functions for this species, especially feeding inhibition tests, molting, and reproductive ability, which have already been proven for chemical substances and are likely to be disturbed by ionizing radiation. The results show no significant differences in terms of the survival of organisms (males and females), of their short-term food consumption which is linked to the general health status (males and females), and of the molting cycle (females). In contrast, exposure significantly affected fecundity (number of embryos produced) at the highest dose rates for irradiated females (51 mGy h-1) and males (5 and 51 mGy h-1). These results showed that, in gammarids, reproduction, which is a critical endpoint for population dynamics, is the most radiosensitive phenotypic endpoint, with significant effects recorded on male reproductive capacity, which is more sensitive than in females. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC.

Environmental factors related to the origin and evolution of differentiated thyroid cancer: a narrative review.

INTRODUCTION: The global incidence of thyroid cancer (TC) has increased in the last decades. While improvements in diagnosis may contribute, overdiagnosis is also a possibility. This review focuses on the epidemiology, risk factors, and immune microenvironment associated with differentiated TC (DTC). AREAS COVERED: A search was conducted in Scielo, Scopus, and EMBASE databases, involving 72 articles. TC is the most common endocrine neoplasm, with DTC form being predominant. Its incidence has globally risen, particularly among women aged over 45. Endogenous risk factors for DTC include genetic disorders, race, age, female gender, obesity, and type 2 diabetes mellitus. Environmental risks involve ionizing radiation, whether through therapeutic treatment or environmental contamination from nuclear accidents, iodine deficiency, endocrine disruptors, residence in volcanic areas, environmental pollution, and stress. The use of anti-obesity medications remains controversial. The tumor's immune microenvironment is the histological space where tumor cells interact with host cells, crucial for understanding aggressiveness. Immunotherapy emerges as a promising intervention. EXPERT OPINION: Recent advances in DTC management offer transformative potential, requiring collaborative efforts for implementation. Emerging areas like precision medicine, molecular profiling, and immunotherapy present exciting prospects for future exploration, shaping the next era of diagnostic and therapeutic strategies in thyroid cancer research.

The global incidence of thyroid cancer (TC) has significantly increased, attributed partly to improved diagnosis and potentially to overdiagnosis. This review focuses on the epidemiology, risk factors, and immune microenvironment associated with differentiated TC (DTC). DTC is the most common endocrine neoplasm, and predominantly affects women over 45 years old. Endogenous risk factors include genetic disorders, race, age, female gender, obesity, and type 2 diabetes mellitus (T2DM). Environmental risks encompass ionizing radiation, iodine deficiency, endocrine disruptors, volcanic residence, pollution, and stress. The use of glucagon-like peptide 1 agonists remains controversial. The tumor's immune microenvironment is crucial for understanding aggressiveness, with immunotherapy showing promise. Understanding both macro and microenvironmental factors is crucial for devising effective prevention and treatment strategies for DTC.

Health literacy in medical imaging: a scoping review of current evidence and future directions.

OBJECTIVE: The importance of health literacy in medical imaging is well recognized, yet the current landscape remains inadequately understood. This study aims to explore the extent of health literacy studies contextualized to medical imaging. STUDY DESIGN: Scoping review. METHODS: A scoping review was conducted using three online bibliographic databases namely, PubMed, ScienceDirect, and CINAHL. We have adopted the concept of health literacy, as a clinical risk and personal asset, to guide this review. RESULTS: Of 311 unique articles, 39 met our selection criteria. Five themes (categories) were identified by the authors: appropriate communication with patients who receive medical imaging test results, appropriate usage of medical imaging, classes and characteristics of eHealth literacy, disease/deterioration prevention, and patient education. Additionally, 17 health literacy assessment tools were identified, including 11 original creations. Finally, 11 recommendations have emerged from this scoping review, offering valuable insights into methods, considerations, and strategies for promoting health literacy. CONCLUSIONS: Health literacy studies in medical imaging cover both clinical and public health perspectives, benefiting diverse populations, regardless of underlying medical conditions. Notably, the majority of assessment tools used in these studies were author-generated, hindering cross-study comparisons. Given the innate capacity of medical images to convey intuitive information, those images do not solely benefit the patients who are given medical imaging examinations, but they also hold significant potential to enhance public health literacy. Health literacy and medical imaging are closely associated and mutually reinforce each other.

Radiolytic Effects on Biological and Abiotic Amino Acids in Shallow Subsurface Ices on Europa and Enceladus.

Europa and Enceladus are key targets to search for evidence of life in our solar system. However, the surface and shallow subsurface of both airless icy moons are constantly bombarded by ionizing radiation that could degrade chemical biosignatures. Therefore, sampling of icy surfaces in future life detection missions to Europa and Enceladus requires a clear understanding of the necessary ice depth where unaltered organic biomolecules might be present. We conducted radiolysis experiments by exposing individual amino acids in ices and amino acids from dead microorganisms in ices to gamma radiation to simulate conditions on these icy worlds. In the pure amino acid samples, glycine did not show a detectable decrease in abundance, whereas the abundance of isovaline decreased by 40% after 4 MGy of exposure. Amino acids in dead Escherichia coli (E. coli) organic matter exhibited a gradual decline in abundances with the increase of exposure dosage, although at much slower rates than individual amino acids. The majority of amino acids in dead A. woodii samples demonstrated a step function decline as opposed to a gradual decline. After the initial drop in abundance with 1 MGy of exposure, those amino acids did not display further decreases in abundance after exposure up to 4 MGy. New radiolysis constants for isolated amino acids and amino acids in dead E. coli material for Europa/Enceladus-like conditions have been derived. Slow rates of amino acid destruction in biological samples under Europa and Enceladus-like surface conditions bolster the case for future life detection measurements by Europa and Enceladus lander missions. Based on our measurements, the "safe" sampling depth on Europa is ∼20 cm at high latitudes of the trailing hemisphere in the area of little impact gardening. Subsurface sampling is not required for the detection of amino acids on Enceladus-these molecules will survive radiolysis at any location on the Enceladus surface. If the stability of amino acids observed in A. woodii organic materials is confirmed in other microorganisms, then the survival of amino acids from a potential biosphere in Europa ice would be significantly increased.

Study of Radiosensitivity and Induction of Radiation Adaptive Response in Peripheral Blood Lymphocytes of Patients with Oncological Diseases Using the Micronuclear Test.

Radiosensitivity to low and medium doses of X-ray radiation and the ability to induce a radiation adaptive response (RAR) of lymphocytes during in vitro irradiation of peripheral blood of patients with cancer were studied. The criterion for cytogenetic damage was the frequency of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes in culture. It was found that the spontaneous level of cytogenetic damage in the lymphocytes of patients was 2.6 times higher than in healthy volunteers, and there was also significant interindividual variability in values compared to the control cohort. There were no differences in mean values for radiosensitivity to low and medium doses of X-ray between the study groups. There was no correlation between the spontaneous level of MN in lymphocytes and the radiosensitivity of individuals in both groups. RAR was induced with the same frequency and to the same extent in lymphocytes from both patients and healthy individuals.

Cerium Vanadate Nanozyme with pH-Dependent Dual Enzymatic Activity for Glioblastoma Targeted Therapy and Postradiotherapy Damage Protection.

Nanocatalytic therapy is an emerging technology that uses synthetic nanoscale enzyme mimics for biomedical treatment. However, in the field of neuroscience, achieving neurological protection while simultaneously killing tumor cells is a technical challenge. Herein, we synthesized a biomimic and translational cerium vanadate (CeVO4) nanozyme for glioblastoma (GBM) therapy and the repair of brain damage after GBM ionizing radiation (IR). This system exhibited pH dependence: it showed potent Superoxide dismutase (SOD) enzyme activity in a neutral environment and Peroxidase (POD) enzyme activity in an acidic environment. In GBM cells, this system acted in lysosomes, causing cellular damage and reactive oxygen species (ROS) accumulation; in neuronal cells, this nanozyme could undergo lysosomal escape and nanozyme aggregation with mitochondria, reversing the mitochondrial damage caused by IR and restoring the expression level of the antiapoptotic BCL-2 protein. Mechanistically, we believe that this distribution difference is related to the specific uptake internalization mechanism and lysosomal repair pathway in neurons, and ultimately led to the dual effect of tumor killing and nerve repair in the in vivo model. In summary, this study provides insight into the repair of brain damage after GBM radiation therapy.

Voltage-dependent anion channel 1 mediates mitochondrial fission and glucose metabolic reprogramming in response to ionizing radiation.

The ionizing radiation (IR) represents a formidable challenge as an environmental factor to mitochondria, leading to disrupt cellular energy metabolism and posing health risks. Although the deleterious impacts of IR on mitochondrial function are recognized, the specific molecular targets remain incompletely elucidated. In this study, HeLa cells subjected to γ-rays exhibited concomitant oxidative stress, mitochondrial structural alterations, and diminished ATP production capacity. The γ-rays induced a dose-dependent induction of mitochondrial fission, simultaneously manifested by an elevated S616/S637 phosphorylation ratio of the dynamin-related protein 1 (DRP1) and a reduction in the expression of the mitochondrial fusion protein mitofusin 2 (MFN2). Knockdown of DRP1 effectively mitigated γ-rays-induced mitochondrial network damage, implying that DRP1 phosphorylation may act as an effector of radiation-induced mitochondrial damage. The mitochondrial outer membrane protein voltage-dependent anion channel 1 (VDAC1) was identified as a crucial player in IR-induced mitochondrial damage. The VDAC1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), counteracts the excessive mitochondrial fission induced by γ-rays, consequently rebalancing the glycolytic and oxidative phosphorylation equilibrium. This metabolic shift was uncovered to enhance glycolytic capacity, thus fortifying cellular resilience and elevating the radiosensitivity of cancer cells. These findings elucidate the intricate regulatory mechanisms governing mitochondrial morphology under radiation response. It is anticipated that the development of targeted drugs directed against VDAC1 may hold promise in augmenting the sensitivity of tumor cells to radiotherapy and chemotherapy.

Reparative effects after low-dose radiation exposure: Inhibition of atherosclerosis by reducing NETs release.

OBJECTIVE: The cardiovascular system effects of environmental low-dose radiation exposure on radiation practitioners remain uncertain and require further investigation. The aim of this study was to initially investigate and explore the mechanisms by which low-dose radiation may contribute to atherosclerosis through a multi-omics joint comprehensive basic experiment. METHODS: We used WGCNA and differential analyses to identify shared genes and potential pathways between radiation injury and atherosclerosis sequencing datasets, as well as tissue transcriptome immune infiltration level extrapolation and single-cell transcriptome data correction using the CIBERSORT deconvolution algorithm. Animal models were constructed by combining a high-fat diet with 5 Gy γ-ray whole-body low-dose ionizing radiation. The detection of NETs release was validated by enzyme-linked immunosorbent assay. RESULTS: Analysis reveals shared genes in both datasets of post-irradiation and atherosclerosis, suggesting that immune system neutrophils may be a key node connecting radiation to atherosclerosis. NETs released by neutrophil death can influence the development of atherosclerosis. Animal experiments showed that the number of neutrophils decreased (P < 0.05) and the concentration of NETs reduced after low-dose radiation compared with the control group, and the concentration of NETs significantly increased (P < 0.05) in the HF group. Endothelial plaques were significantly increased in the high-fat feed group and significantly decreased in the low-dose radiation group compared with the control group. CONCLUSIONS: Long-term low-dose ionizing radiation exposure stimulates neutrophils and inhibits their production of NETs, resulting in inhibition of atherosclerosis.

Ionizing Radiation-Induced Oxidative Stress in Computed Tomography-Effect of Vitamin C on Prevention of DNA Damage: PREVIR-C Randomized Controlled Trial Study Protocol.

Exposure to ionizing radiation (IR) is inevitable in various X-ray imaging examinations, with computed tomography (CT) being a major contributor to increased human radiation exposure. Ionizing radiation may cause structural damage to macromolecules, particularly DNA, mostly through an indirect pathway in diagnostic imaging. The indirect pathway primarily involves the generation of reactive oxygen species (ROS) due to water radiolysis induced by IR, leading to DNA damage, including double-strand breaks (DSB), which are highly cytotoxic. Antioxidants, substances that prevent oxidative damage, are proposed as potential radioprotective agents. This Study Protocol article presents the rationale for selecting vitamin C as a preventive measure against CT-associated IR-induced DNA damage, to be investigated in a randomized placebo-controlled trial, with a full in vivo design, using an oral easy-to-use schedule administration in the outpatient setting, for the single CT examination with the highest total global IR dose burden (contrast-enhanced abdomen and pelvis CT). The study also aims to explore the mediating role of oxidative stress, and it has been written in adherence to the Standard Protocol Items recommendations.