Search Results (1,006)

Among existing radiobiological models, the MKM and its extensions (SMK and OSMK) have demonstrated strong predictive capabilities but remain computationally demanding. To address this, we present pyMKM v0.1.0, an open-source Python package for the generation of microdosimetric tables and radiobiological quantities based on these models. The package includes modules for track structure integration, saturation and stochastic corrections, oxygen modulation, and survival fraction computation. Validation was conducted against multiple published datasets across various ion species, LET values, and cell lines under both normoxic and hypoxic conditions. Quantitative comparisons showed high agreement with reference data, with average log errors typically below 0.06 and symmetric mean absolute percentage errors under 2%. The software achieved full unit test coverage and successful execution across multiple Python versions through continuous integration workflows. These results confirm the numerical accuracy, structural robustness, and reproducibility of pyMKM. The package provides a transparent, modular, and extensible tool for microdosimetric modeling in support of radiobiological studies, Monte Carlo-based dose calculation, and biologically guided treatment planning. Full article

The complex bidirectional relationship between diabetes mellitus (DM) and oral cancer (OC) denotes that metabolic dysfunction and malignancy intersect at molecular, cellular, and systemic levels. This state-of-the-art review analyzes the most recent literature data on the multiple interconnected pathways linking DM and OC, including hyperinsulinemia/IGF-1 signaling, chronic hyperglycemia-induced cellular damage, persistent inflammation, immune dysfunction, and oral microbiota dysbiosis. These mechanisms create a permissive environment for oral carcinogenesis while simultaneously impairing the body’s natural tumor surveillance systems. Key molecular networks explored include the PI3K/AKT/mTOR pathway, AGE-RAGE interactions, NF-κB signaling, the p53 tumor suppressor pathway, and HIF-mediated responses. Clinical evidence demonstrates that patients with diabetes have higher OC prevalence (250 per 100,000 patients) and significantly increased mortality (HR of 2.09) compared to non-diabetics. The review highlights metformin as the most promising anti-diabetic agent for OC management, showing anti-tumor effects through mTOR inhibition. Novel therapeutics, such as GLP-1 agonists, particularly semaglutide, may be helpful but require further clinical validation. Understanding the shared molecular pathways enables the development of integrated therapeutic strategies that target both conditions simultaneously, and it supports effective screening programs, personalized prevention strategies, and optimized multidisciplinary management approaches for this high-risk patient population. Full article

The complexity of adverse responses from radiation injury (RI) followed by physical trauma, namely, radiation combined injury (RCI), is unique and more pronounced than either insult alone due to a poor understanding of the integration of these insults at the molecular/cellular/tissue and/or organ levels. It was shown that mice receiving ⁶⁰Co γ-photon RCI with wounding had a lower LD_50/30 than RI alone. This survival synergism was observed in bone marrow and the gastrointestinal system, as evidenced by an increase in γ-H2AX expression in bone marrow cell DNA, loss of circulatory blood cells, elevation of serum cytokine concentration, and activation of nuclear factor-κB/inducible nitric oxide synthase, and an earlier onset of bacterial infection and sepsis after RCI than after RI was detected. Dysbiosis (imbalance of the gut microbiota) was observed. There remains a pressing need for both prophylactic countermeasures and therapeutic remedies to deal with RCI threats. Investigations of how RCI can affect this important network of communication between the gut microbiota and other organs, including the brain, lung, heart, liver, kidney, and skin, could lead to new and critical interventions and prevention strategies. This review provides an update on new RCI animal models, dynamic changes in cytokine expression, dysbiosis, as well as links between the gut microbiome and other organs after RCI. Full article

Laser-accelerated electron beams, in the so-called Very High-Energy Electron (VHEE) energy range, are of great interest for biomedical applications. For instance, laser-driven VHEE beams are envisaged to offer suitable compact accelerators for the promising field of FLASH radiotherapy. Radiobiology experiments carried out using laser-driven beams require the real-time knowledge of the dose delivered to the sample. We have developed an online dose monitoring procedure, using an Integrating Current Transformer (ICT) coupled to a suitable collimator, that allows the estimation of the delivered dose on a shot-to-shot basis under suitable assumptions. The cross-calibration of the measured charge with standard offline dosimetry measurements carried out with RadioChromic Films (RCFs) is discussed, demonstrating excellent correlation between the two measurements. Full article

Residential exposure to radon and environmental gamma radiation poses a significant public health concern in uranium-rich regions. The Akmola Region of Kazakhstan, home to one of the world’s largest uranium tailings sites, lacks localized data on seasonal exposure variations and associated health risks. This study assessed indoor radon progeny concentrations and gamma dose rates in 62 dwellings across two settlements—Aqsu and Zavodskoy—in the Akmola Region during autumn 2023 through summer 2024. Using RAMON-02 and Alpharad Plus detectors, seasonal equivalent equilibrium volumetric activity (EEVA) of radon progeny and effective doses were calculated, stratified by presence of a cellar. In Aqsu, ambient dose equivalent rates reached up to 0.55 µSv/h, and winter median EEVA levels exceeded 130 Bq/m³ in some non-cellar homes. Seasonal effective doses peaked in spring (up to 8.82 mSv) in cellar dwellings, with annual doses reaching 23.5 mSv—substantially higher than in Zavodskoy. Although mitigation efforts have reduced exposure in some homes, several cellar dwellings in Aqsu exhibited persistently elevated EEVA, suggesting potential structural vulnerabilities or residual contamination. These findings underscore significant seasonal and structural disparities in radiation exposure and highlight the need for targeted, site-specific interventions to reduce long-term health risks in affected communities. Full article

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death. Full article

In many cancers, tumorigenesis is determined in part by the cell type in the tissue that transforms, which has been called the cell of origin. In intestinal cancer, previous observations suggested that transformation can occur from both stem cells and more differentiated cells; in the latter case, this is provided that NF-kB is activated and apoptosis is blocked. However, whether these distinct transformation trajectories yield similar types of cancer remains unresolved. In this study the effect of APC loss within different cellular backgrounds was analyzed. Transformation of either stem-like cells or secretory-like cells, as defined by CD24 or c-KIT expression, by deleting the APC function in organoids in vitro, led to WNT-independent growth of organoids in both cellular populations. Importantly, transformed cultures derived from secretory-like cells had significantly distinct gene expression profiles as compared to the more stem cell-derived (CD44^high cells) APC mutant cultures and in fact preserved a level of gene expression that relates back to their original cell lineage. Our data highlights the influence of different cellular backgrounds on the initiation of intestinal cancer and suggests that the cell of origin could be a defining factor in colorectal cancer heterogeneity. Full article

Background/Objectives: Polymeric barrier membranes (BMs) are usually used in guided bone regeneration to isolate the bone defect from the surrounding tissue, favoring bone apposition. This study proposes a third-generation BM made of polycaprolactone (PCL), loaded with different concentrations of nano-hidroxyapatite (nHAP) and gentamicin (GEN), and fabricated by electrospinning. Methods: The mechanical properties of the polymer, together with the fabrication procedure, offer porosity with interconnectivity to permit cell adhesion and proliferation. Bacterial contamination of the BM can induce infection at the bone level, leading to unfavorable clinical outcomes of the regeneration procedure. Results: Therefore, BMs have been proposed as carriers for local GEN antibiotic therapy, demonstrating antibacterial properties against S. aureus, S. mutans, and P. aeruginosa, depending on the drug concentration, while being negligibly affected by the nHAP content. X-ray diffraction, FTIR-ATR, and SEM allowed for BM structural characterization, demonstrating the presence of GEN/nHAP and establishing the fiber diameter, which influences the mechanical properties in dry and wet conditions and the drug release behaviorA BM cytotoxicity assessment, performed over 1 and 5 days, revealed that a high nHAP concentration provided protection against cytotoxicity, in contrast to GEN, and that cell proliferation and cell adhesion increased in the presence of nHAP. The BM’s bioactivity was demonstrated by mineralization after 21 days in simulated body fluid in an SEM/EDX analysis. Conclusions: The electrospun 15 wt.% nHAP and 2 wt.% GEN-loaded third-generation BM could be a promising alternative for guided bone regeneration. Full article

Background: Steroidal glucocorticoid and gestagenic drugs and cold plasma-treated solutions (PTSs) are known to exert anti-inflammatory effects by influencing the production of a number of cytokines. The aim of this work was to test their independent and combined effects exerted on the production of cytokines IL-1, IL-6, TNF-α, TGF-β, and IL-10 and reactive oxygen and nitrogen species (RONS) by leukocytes in women of a reproductive age and postmenopausal women. Methods: ELISA and chemiluminescence methods were used for this purpose. Results: PTS reduced IL-6 and RONS production by 50% and increased IL-10 production 2-fold in postmenopausal women, and it reduced IL-6 production by 80% and RONS production by 50% in women of reproductive age. When PTS and steroid hormonal drugs are used together, there is a general suppression of cytokine and oxidant activity. Conclusions: PTS reduces the production of inflammatory factors by leukocytes and stimulates the production of anti-inflammatory factors, more so in postmenopausal women. Progestins showed greater suppression of pro-inflammatory cytokine and RONS formation and stimulation of anti-inflammatory cytokines for women of reproductive age and dexamethasone showed such results for postmenopausal women. Full article

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, due to its efficacy and good local tumour control, as well as its precision to spare surrounding ocular structures. PBT is an effective alternative to surgical enucleation and other non-precision-targeted radiotherapies. Despite this, the radiobiology of UM in response to PBT is still not fully understood. This enhanced knowledge would help to further optimise UM treatment and improve patient outcomes through reducing radiation dosage to ocular structures, treating larger tumours that would otherwise require enucleation, or even offering a treatment strategy for the otherwise fatal liver metastases. In this review, we explore current knowledge of the treatment of UM with PBT, evaluating the biological responses to the therapy. Molecular factors, such as tumour size, oxygen tension levels, DNA damage proficiency, and autophagy, are known to influence the cellular response to radiotherapy, and these will be discussed. Furthermore, we examine innovative strategies to enhance radiotherapy outcomes, such as combination therapies with DNA damage repair and autophagy modulators, as well as advancements in PBT planning and delivery. By integrating current research and emerging technologies, we aim to provide opportunities to improve the therapeutic effectiveness of PBT in UM management. Full article

Herpes simplex virus-1 (HSV-1) is a neurotropic virus that can infect the brain, and an uncontrolled infection can lead to severe encephalitis. NO can exert both antiviral as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration and site of infection. In this study, we report that treatment of an intranasal murine HSV-1 infection with aminoguanidine (AMG) decreases both neuroinflammation and neurodegeneration markers, but its positive effect depends on the time of treatment. Specifically, early treatment with AMG impaired the activation of microglia/monocytes, leading to decreased virus-specific antiviral response and higher viral titers in the brain. However, AMG treatment during the peak of brain infection significantly improved antiviral response, reduced inflammation and improved general clinical score. We also found that treatment with AMG decreased beta amyloid levels during both primary and latent infections and protected from the accumulation of phosphorylated Tau protein during early infection. Our findings position inducible nitric oxide synthetase (iNOS) as a potential therapeutic target for mitigating virus-induced neuroinflammation and neurodegeneration. Full article

A three-year-old male bearded dragon (Pogona vitticeps) exhibited acute anorexia. Biochemistry revealed mild hyperproteinemia (88 g/L) and elevated liver enzymes (ALT 60 U/L, AST 272 U/L), while the hematology report showed marked lymphocytosis. The animal had been clinically normal at a routine examination 10 months earlier. Based on the clinical and laboratory findings, acute lymphoblastic leukemia was suspected. Treatment was initiated with methylprednisolone (1 mg/kg PO q24h), marbofloxacin (10 mg/kg IM q24h), and lomustine (80 mg/m² PO q14d), calculated according to reptile-specific body surface area formulas. A transient stabilization was followed by sudden deterioration on day 3, characterized by hematemesis and severe respiratory distress, leading to spontaneous death. A complete necropsy including histopathology and anti-CD3 immunohistochemistry revealed disseminated infiltration of neoplastic T-lymphocytes throughout all major visceral organs and confirmed the diagnosis of T-cell lymphoblastic lymphoma/leukemia (L/L). This case represents a rare report of systemic acute lymphoblastic L/L in a bearded dragon and underlies the importance of comprehensive diagnostics in reptiles with non-specific clinical signs and the challenges in the treatment of neoplastic diseases in exotic species. Full article

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood–brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2–5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases. Full article

Background and objective: In Boron Neutron Capture Therapy, treatment planning is based on a weighted dose in which dose components are weighted with different biological effectiveness (RBE) factors. The most important one for the tumor dose is the compound dependent biological effectiveness (CBE) factor which weighs the boron dose. This was established for brain tumors from radiobiological experiments and has been extrapolated to the more recent application of BNCT to head and neck cancers. The purpose of this work is to study the validity of this assumption. Methods: Two cell lines, CAL-33 (head and neck squamous cell carcinoma) and A172 (Glioblastoma Multiforme), were irradiated with a very pure thermal-equivalent neutron beam after BPA incubation, and the surviving fraction of cells after irradiation was determined by clonogenicity assays. Results: The Compound Biological Effectiveness of both cell lines is similar, although for head and neck carcinoma, 10% higher values are systematically found. In addition to this, radiobiological coefficients for the different dose components (photon, neutron and boron) of BNCT in both cell lines are provided. Full article