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Background: Boron neutron capture therapy (BNCT) is a targeted radiotherapy that relies on the 10 B (n, α) 7 Li reaction, which produces secondary particles with high linear energy transfer (LET), leading to a high relative biological effectiveness (RBE) in tumors. The biological effectiveness of BNCT is influenced by factors such as boron distribution and concentration, necessitating improved methods for assessing its radiobiological effects and clarifying the sensitivity of the differences in different factors to the biological effects., Purpose: This paper introduces a method to evaluate the biological effects of BNCT using the cellular repair model. This method aims to overcome some of the limitations of current evaluation approaches. The primary goal is to provide guidance for clinical treatments and the development of boron drugs, as well as to investigate the impact of the synergistic effects of mixed radiation fields in BNCT on treatment outcomes., Methods: The approach involves three key steps: first, extending the radial energy deposition distribution of BNCT secondary particles using Geant4-DNA. This allows for the calculation of initial DNA double-strand breaks (DSBs) distributions for a given absorbed dose. Next, the obtained initial DSB distributions are used for DNA damage repair simulations to generate cell survival curves, then thereby quantifying RBE and compound biological effectiveness (CBE). The study also explores the synergistic effects of the mixed radiation fields in BNCT on assessing biological effects were also explored in depth., Results: The results showed that the RBE of boronophenylalanine (BPA) and sodium borocaptate (BSH) drugs at cell survival fraction 0.01 was 2.50 and 2.15, respectively. The CBE of the boron dose component was 3.60 and 0.73, respectively, and the RBE of the proton component was 3.21, demonstrating that BPA has a significantly higher biological impact than BSH due to superior cellular permeability. The proton dose significance in BNCT treatment is also underscored, necessitating consideration in both experimental and clinical contexts. The study demonstrates that synergistic effects between disparate radiation fields lead to increased misrepairs and enhanced biological impact. Additionally, the biological effect diminishes with rising boron concentration, emphasizing the need to account for intercellular DNA damage heterogeneity., Conclusions: This methodology offers valuable insights for the development of new boron compounds and precise assessment of bio-weighted doses in clinical settings and can be adapted to other therapeutic modalities., (© 2024 American Association of Physicists in Medicine.)

Background: Studies show that photobiomodulation therapy (PBMT) boosts cellular ATP production and cell growth and reduces inflammation. Additionally, mechanical tension affects gene expression, impacting cellular functions like proliferation and migration. Objective: We investigated the impact of PBMT on OCCM-30 cementoblast cells under tensile stress, focusing on cell survival, differentiation, and inflammatory responses, particularly relating to orthodontic tooth movement and root resorption. Methods: Cultured OCCM-30 cells under negative pressure received PBMT with a 10.6 μm wavelength in continuous mode at 1.0 W power for 3, 5, or 10 sec, corresponding to energy densities of 3, 5, or 10 J/cm 2 . We assessed cell viability with the Presto Blue assay and inflammatory markers Interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) through western blots at 1, 12, 24 h, and 7 days post-irradiation. Results: PBMT improved cell viability over time while maintaining levels of inflammatory markers. alkaline phosphatase levels dropped initially but increased after 7 days, suggesting enhanced cementoblast differentiation. IL-6 levels rose gradually, with 3J and 5J treatments showing significantly higher levels than the control. iNOS levels spiked within the first 24 h, then declined by day 7. COX-2 levels consistently rose, with the 5J treatment showing greater increases. Conclusions: PBMT appears to support cementoblast survival and differentiation while managing inflammation, potentially aiding root repair during orthodontic treatments and reducing inflammatory root resorption.

The efficacy of radiation treatment (RT) of head and neck squamous cell carcinoma (HNSCC) is limited by radioresistance and the toxicity of FDA approved radiosensitizers. In extension to our previous research where we demonstrated that telaglenastat (CB839) increased efficacy of RT in in vitro and in vivo HNSCC models, here, we examine the radiosensitizing effects of telaglenastat in comparison to cisplatin's, as cisplatin is currently the standard of care for concurrent therapy. Combination of telaglenastat with RT reduced tumor volume in a HNSCC patient derived xenograft mouse model. The efficacy of telaglenastat with RT in reducing cell survival and increasing apoptosis was similar if not greater than that of cisplatin with RT in Cal27 and HN5 HNSCC cells. The addition of telaglenastat increased reactive oxygen species and reduced the antioxidant glutathione in both Cal27 and HN5 cells. Reverse Phase Protein Array analyses revealed alterations in cell death and DNA damage response proteins. This study provides the scientific underpinnings for the use of telaglenastat as a radiosensitizer in the treatment of HNSCC either as an alternative to cisplatin or in cisplatin-ineligible patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Recently, the use of natural products as skin photoprotective agents has been in increasing demand. This study investigated the bioactivity of phycocyanin (PC) extracted from Spirulina sp. on human skin fibroblast cell line (CCD-966SK), specifically focusing on apoptosis, necrosis, anti-inflammatory effects, and enzymatic reactions., Methods: The first step of this study was cyanobacterial cell culture and the extraction and purification of PC. After that, CCD-966SK cell line was cultivated under normal and UV irradiation. The bioassays included the cytotoxicity measurement, cell viability assay, morphology determination, tumour necrosis factor-α and Interleukin 6 release assays, enzyme activity for superoxide dismutase and glutathione peroxidase as well as malondialdehyde content and the cell-free extract of cyanobacterial stains were assessed., Results: The cell viability results showed that as the concentration of the PC increased, the viability of CCD-966SK cell line was reduced, which suggested that the effect of PC on the growth of fibroblast cells was dose dependent. The morphological results indicated that presence of PC in the fibroblast cell culture medium led to a transformation in cell morphology from spindle-shaped to spherical. PC released anti-inflammatory IL-6 and TNF-a cytokines, indicating high inflammation resistance. Furthermore, the findings revealed that PC dramatically reduced the release of superoxide dismutase, glutathione peroxidase, and malondialdehyde from inflammatory cells, with the reduction being more apparent at increasing doses., Conclusions: In conclusion, the results indicated that PC inhibit the CCD-966SK cell line by membrane destructor, which led to the increase the leakage of cell constituent and increase enzymes activities.

Objective: Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo., Methods: Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm 2 in vitro and 3 W/cm 2 in vivo) in conjunction with DVDMS also being examined., Results: The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy., Conclusion: DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electromagnetic fields create potential negative implications on biological systems, including modifications to DNA structure, nuclear condensation, cellular ion transport, and intracellular Ca 2+ accumulation. To explore these effects on cancer cells, we exposed prostate, glioblastoma and cervix cancer cell lines to electromagnetic fields of wireless and assessed its anti-proliferative effects. PC3, A172, and HeLa cancer cells were cultured and exposed to electromagnetic fields for 24, 48, and 72 h. We used the MTT assay to detect cell viability and proliferation, Annexin V staining to determine apoptotic cells, and confocal microscopy to measure apoptosis-mediated intracellular calcium signals. Additionally, we performed profiling for apoptosis-related miRNAs. The results indicated that the electromagnetic field triggers apoptosis in the glioblastoma cell line A172 by increasing level of miR-129-5p, a known tumor suppressor. In contrast, the cervix cancer cell line and the prostate cancer cell line remained largely unaffected. In summary, our investigation underscores that electromagnetic fields at a 2.4 GHz frequency may adversely affect certain cancer cell lines, notably triggering apoptosis in the glioblastoma cancer cell line., Competing Interests: Compliance with Ethical Standards Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p -AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Iodine has an anti-proliferative effect on cancer cells; however, its effects have not been explored adequately. The aim of this study was to evaluate the therapeutic potential of iodine and radioiodine by assessing their effects on the viability of various breast cancer cell lines: MCF7, SKBR3, and MDA-MB231. The viability of cells was measured in treated cells exposed to six doses of iodine (5, 10, 20, 40, 60, 80 µM) and two doses of radioiodine (3.7 × 10 4 and 3.7 × 10 5 Bq). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and modified clonogenic assays were used to assess cell viability. Exposure to 80 µM of iodine significantly reduced the viability of all cell types. The cells were then exposed to a 50% inhibitory concentration (IC 50 ) dose. When the cells were exposed to the IC 50 dose of iodine, the MCF7 cell viability was reduced by 42.6 ± 0.14% (IC 50 dose 12.88 µM), 40.2 ± 0.08% for SKBR3 (IC 50 dose 11.03 µM) and 47.0 ± 0.02% for MDA-MB231 (IC 50 dose 14.09 µM). All cells were also exposed to 3.7 × 10 4 Bq and 3.7 × 10 5 Bq radioiodine. Both doses significantly reduced the cell viability of MCF7 and SKBR3 cells compared to the unexposed control cells (all had p  < 0.05), while MDA-MB231 cell viability only reduced significantly after 3.7 × 10 5 Bq of radioiodine exposure compared to the unexposed control cells ( p  < 0.05). This study highlighted that iodine had a toxic effect on breast cancer cells, and radioiodine enhanced the toxicity to breast cancer cells. The types of cancer cells and doses of iodine and radioiodine influenced the effect. These findings suggest that iodine and radioiodine hold promise as therapeutic agents for breast cancer, similar to their established use in thyroid disease treatment. However, further in vivo studies are important to provide more evidence., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (© 2024 The Author(s).)

Aim: Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD., Methods: Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661 W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components., Results: Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661 W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 h of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group., Conclusion: CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661 W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sonoporation has long been known to disrupt intracellular signaling, yet the involved molecules and pathways have not been identified with clarity. In this study, we employed whole transcriptome shotgun sequencing (RNA-seq) to profile sonoporation-induced gene responses after membrane resealing has taken place. Sonoporation was achieved by microbubble-mediated ultrasound (MB-US) exposure in the form of 1 MHz ultrasound pulsing (0.50 MPa peak negative pressure, 10 % duty cycle, 30 s exposure period) in the presence of microbubbles (1:1 cell-to-bubble ratio). Using propidium iodide (PI) and calcein respectively as cell viability and cytoplasmic uptake labels, post-exposure flow cytometry was performed to identify three viable cell populations: 1) unsonoporated cells, 2) sonoporated cells with low uptake, and 3) sonoporated cells with high uptake. Fluorescence-activated cell sorting was then conducted to separate the different groups followed by RNA-seq analysis of the gene expressions in each group of cells. We found that sonoporated cells with low or high calcein uptake showed high similarity in the gene responses, including the activation of multiple heat shock protein (HSP) genes and immediate early response genes mediating apoptosis and transcriptional regulation. In contrast, unsonoporated cells exhibited a more extensive gene expression alteration that included the activation of more HSP genes and the upregulation of diverse apoptotic mediators. Four oxidative stress-related and three immune-related genes were also differentially expressed in unsonoporated cells. Our results provided new information for understanding the intracellular mobilization in response to sonoporation at the molecular level, including the identification of new molecules in the sonoporation-induced apoptosis regulatory network. Our data also shed light on the innovative therapeutic strategy which could potentially leverage the responses of viable unsonoporated cells as a synergistic effector in the microenvironment to favor tumor treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation., Competing Interests: Declaration of Conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Peter Sykora is the CSO and director of Amelia Technologies LLC. None of the entities involved in this research have any commercial interest now or in the future regarding UV-emitting nail devices.

Background: The management of non-small cell lung cancer (NSCLC) often includes the use of radiotherapy, with individual outcomes being impacted by the tumor's response to this treatment modality. Cephalomannine (CPM), a taxane diterpenoid found in Taxus spp, has been found to have anti-tumor activity. This study was aim to the explore the role and mechanism by which CPM affects radiotherapy resistance in NSCLC., Methods: H460 cells were pretreated with different doses of CPM. H460 cells were transfected with β-catenin overexpression plasmids. The cell viability, colony-forming ability, migration ability, and sphere-forming ability and apoptosis of the cells were measured by using CCK-8, colony-forming, transwell, and sphere-forming assay and flow cytometry. Western blot assay was employed to detect the expression of β-catenin and BMP2., Results: The cell viability, proliferation, migration and sphere-forming ability of cells in the radiotherapy-resistant (RR) group were significantly higher than those in the radiotherapy-sensitivity (RS) group. Conversely, the apoptosis rate of cells in the RR group was lower than that in the RS group. However, after CPM pretreatment of RR group cells, the above phenomena were reversed in a CPM dose-dependent manner. Subsequently, pretreatment with CPM resulted in a decrease in the expression levels of β-catenin and BMP2 in the RR group. In addition, overexpression of β-catenin mitigated the inhibitory effects of CPM on radiotherapy-resistant NSCLC cells., Conclusion: CPM has the potential to decrease radiotherapy resistance in NSCLC cells by inhibiting the β-catenin-BMP2 signaling pathway, promoting apoptosis, and ultimately impeding cell growth., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Targeted radiotherapies with low-energy ions show interesting possibilities for the selective irradiation of tumor cells, a strategy particularly appropriate for the treatment of disseminated cancer. Two promising examples are boron neutron capture therapy (BNCT) and targeted radionuclide therapy with α $\alpha$ -particle emitters (TAT). The successful clinical translation of these radiotherapies requires the implementation of accurate radiation dosimetry approaches able to take into account the impact on treatments of the biological effectiveness of ions and the heterogeneity in the therapeutic agent distribution inside the tumor cells. To this end, biophysical models can be applied to translate the interactions of radiations with matter into biological endpoints, such as cell survival., Purpose: The NanOx model was initially developed for predicting the cell survival fractions resulting from irradiations with the high-energy ion beams encountered in hadrontherapy. We present in this work a new implementation of the model that extends its application to irradiations with low-energy ions, as the ones found in TAT and BNCT., Methods: The NanOx model was adapted to consider the energy loss of primary ions within the sensitive volume (i.e., the cell nucleus). Additional assumptions were introduced to simplify the practical implementation of the model and reduce computation time. In particular, for low-energy ions the narrow-track approximation allowed to neglect the energy deposited by secondary electrons outside the sensitive volume, increasing significantly the performance of simulations. Calculations were performed to compare the original hadrontherapy implementation of the NanOx model with the present one in terms of the inactivation cross sections of human salivary gland cells as a function of the kinetic energy of incident α $\alpha$ -particles., Results: The predictions of the previous and current versions of NanOx agreed for incident energies higher than 1 MeV/n. For lower energies, the new NanOx implementation predicted a decrease in the inactivation cross sections that depended on the length of the sensitive volume., Conclusions: We reported in this work an extension of the NanOx biophysical model to consider irradiations with low-energy ions, such as the ones found in TAT and BNCT. The excellent agreement observed at intermediate and high energies between the original hadrontherapy implementation and the present one showed that NanOx offers a consistent, self-integrated framework for describing the biological effects induced by ion irradiations. Future work will focus on the application of the latest version of NanOx to cases closer to the clinical setting., (© 2024 American Association of Physicists in Medicine.)

In radiation tumor therapy, irradiation, on one hand, should cause cell death to the tumor. On the other hand, the surrounding non-tumor tissue should be maintained unaffected. Therefore, methods of local dose enhancements are highly interesting. Gold nanoparticles, which are preferentially uptaken by very-fast-proliferating tumor cells, may enhance damaging. However, the results in the literature obtained from cell culture and animal tissue experiments are very contradictory, i.e., only some experiments reveal increased cell killing but others do not. Thus, a better understanding of cellular mechanisms is required. Using the breast cancer cell model SkBr3, the effects of gold nanoparticles in combination with ionizing radiation on chromatin network organization were investigated by Single-Molecule Localization Microscopy (SMLM) and applications of mathematical topology calculations (e.g., Persistent Homology, Principal Component Analysis, etc.). The data reveal a dose and nanoparticle dependent re-organization of chromatin, although colony forming assays do not show a significant reduction of cell survival after the application of gold nanoparticles to the cells. In addition, the spatial organization of γH2AX clusters was elucidated, and characteristic changes were obtained depending on dose and gold nanoparticle application. The results indicate a complex response of ALU-related chromatin and heterochromatin organization correlating to ionizing radiation and gold nanoparticle incorporation. Such complex whole chromatin re-organization is usually associated with changes in genome function and supports the hypothesis that, with the application of gold nanoparticles, not only is DNA damage increasing but also the efficiency of DNA repair may be increased. The understanding of complex chromatin responses might help to improve the gold nanoparticle efficiency in radiation treatment.

Graphene oxide-mediated photothermal therapy using femtosecond lasers has recently shown promise in treating hepatocellular carcinoma. However, significant work remains to optimize irradiation parameters for specific nanoparticle types and cancer cells to improve nanomaterial-mediated photothermal anticancer therapy. This study investigated the photothermal potential of nGO and nGO-PEG nanoparticles (NPs) combined with femtosecond laser irradiation at 515 nm and 1030 nm wavelengths, with varying power (0.1 and 0.2 W/cm 2 ) and duration (5 and 10 min), to optimize photothermal therapy for hepatocellular carcinoma. Conversion efficiency of NPs, morphology and viability of HepG2 and normal MDCK cells after treatments were evaluated using an electronic thermometer, phase-contrast microscopy, and WST-1 assay. The results revealed that nGO-PEG NPs exhibited better photothermal efficiency than nGO, with 515 nm of irradiation inducing a temperature increase up to 19.1 °C compared to 4.7 °C with 1030 nm of light. Laser exposure to 515 nm significantly reduced HepG2 cell viability, with the most intense conditions (10 min at 0.2 W/cm 2 ) causing a decrease of up to 58.2% with nGO and 43.51% with nGO-PEG. Normal MDCK cells showed minimal impact or a slight viability increase, especially with nGO-PEG. Combined treatment with laser irradiation and NPs induced significant morphological changes in HepG2 cells, including cell detachment and apoptotic-like characteristics, particularly with 1030 nm of irradiation. MDCK cells exhibited minimal morphological changes, with some recovery observed under lower energy conditions. These findings suggest that low-energy lasers and engineered nanomaterials could provide a minimally invasive approach to photothermal cancer therapy with reduced side effects.

Reactive oxygen species (ROS) play a pivotal role in apoptosis. We reported that Blue Light (BL) induced oxidative stress in human retinal pigment epithelial (RPE) cells in vitro and increased drusen deposition and RPE cell apoptosis in human eyes. Here, we investigated the mechanisms underlying BL-induced damage to RPE cells. Cells were exposed to BL with or without the antioxidant N-acetylcysteine. Cells were analyzed for levels of ROS, proliferation, viability, and mitochondria membrane potential (ΔΨ M ) fluctuation. We performed proteomic analyses to search for differentially expressed proteins. ROS levels increased following RPE cell exposure to BL. While ROS production did not affect RPE cell proliferation, it was accompanied by decreased ΔΨ M and increased cell apoptosis due to the caspase cascade activation in a ROS-dependent manner. Proteomic analyses revealed that BL decreased the levels of ROS detoxifying enzymes in exposed cells. We conclude that BL-induced oxidative stress is cytotoxic to RPE cells. These findings bring new insights into the involvement of BL on RPE cell damage and its role in the progression of age-related macular degeneration. The use of antioxidants is an avenue to block or delay BL-mediated RPE cell apoptosis to counteract the disease progression.

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O 2 , 48 h) p53 null H358 NSCLC cells after X-ray exposure. We used the colony-forming ability assay to determine cell survival, γH2AX immunofluorescence microscopy to quantify DNA double-strand breaks (DSBs), flow cytometry of DAPI-stained cells to measure cell cycle distribution, ELISAs to quantify IL-6 and IL-8 secretion in cell culture supernatants, and RNA sequencing to determine gene expression. Chronic hypoxia increased the colony-forming ability and radioresistance of H358 cells. It did not affect the formation or resolution of X-ray-induced DSBs. It reduced the fraction of cells undergoing G2 arrest after X-ray exposure and delayed the onset of G2 arrest. Hypoxia led to an earlier enhancement in cytokines secretion rate after X-irradiation compared to normoxic controls. Gene expression changes were most pronounced after the combined exposure to hypoxia and X-rays and pertained to senescence and different cell death pathways. In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.

UVB radiation induces DNA damage generating several thymine photo-adducts (TDPs), which can lead to mutations and cellular transformation. The DNA repair pathways preserve genomic stability by recognizing and removing photodamage. These DNA repair side products may affect cellular processes. We previously synthesized novel thymine biomimetic thymine dimers (BTDs) bearing different alkane spacers between nucleobases. Thus, the present study investigates whether novel BTDs and their TDPs can modulate DNA damage safeguard pathways of primary keratinocytes and fibroblasts using 2D and 3D models. We found that the p53/p21 waf1 pathway is activated by BTDs and TDPs in primary cells similar to UVB exposure. Compound 1b can also induce the p53/p21 waf1 pathway in a 3D skin model. However, BTDs and TDPs exhibit distinct effects on cell survival. They have a protective action in keratinocytes, which maintain their clonogenic ability following treatments. Conversely, compounds induce pro-apoptotic pathways in fibroblasts that exhibit reduced clonogenicity. Moreover, compounds induce inflammatory cytokines mainly in keratinocytes rather than fibroblasts. Matrix metalloproteinase 1 is up-regulated in both cell types after treatments. Therefore, BTDs and TDPs can act in the short term as safeguard mechanisms helping DNA damage response. Furthermore, they have distinct biological effects depending on photodamage form and cell type.

The epidermis, the outer layer of the skin, relies on a delicate balance of cell growth and keratinocyte differentiation for its function and renewal. Recent research has shed light on exosomes' role in facilitating skin communication by transferring molecules like miRNAs, which regulate gene expression post-transcriptionally. Additionally, these factors lead to skin aging through oxidative stress caused by reactive oxygen species (ROS). In this research project, experiments were conducted to study the impact of Sun2000 solar simulator irradiation on exosomal miRNA profiles in HEKa cells. We hypothesized that acute oxidative stress induced by solar simulator irradiation would alter the expression profile of exosomal miRNAs in HEKa cells. The cells were exposed to different durations of irradiation to induce oxidative stress, and the levels of reactive ROS were measured using the CellROX Deep Red flow cytometry assay kit. Exosomes were isolated from both control and irradiated cells, characterized using DLS and SEM techniques, and their miRNAs were extracted and analyzed using qPCR. Solar simulator irradiation led to a time-dependent increase in intracellular ROS and a decrease in cell viability. Exosomal size increased in irradiated cells. Fifty-nine exosomal miRNAs were differentially expressed in irradiated HEKa cells, including hsa-miR-425-5p, hsa-miR-181b-5p, hsa-miR-196b-5p, hsa-miR-376c-3p, and hsa-miR-15a-5p. This study highlights the significant impact of solar radiation on exosomal miRNA expression in keratinocytes, suggesting their potential role in the cellular response to oxidative stress., Competing Interests: The authors declare no conflicts of interest.

The therapeutic application and dose of cisplatin are limited due to its toxicity to normal cells. Therefore, combination treatments might be the solution with a low dose of cisplatin. The combination effect of nanosecond pulsed high-power microwave (HPM) with cisplatin has not been investigated before. In this work, we aimed to investigate and assess the potential synergistic effects and most likely underlying mechanisms resulting from the combination of nanosecond pulsed HPM and cisplatin. Three cancer (SKOV3, H460, and MDA-MB231) and two normal (MRC5 and HGF) cell lines underwent separate treatments with HPM and cisplatin, as well as a combined treatment. A higher reduction of viability was observed in cancer cells using combination treatments following 24-h incubation. Cell death, membrane permeability, and intracellular reactive oxygen species (ROS) levels exhibit a noteworthy increase in response to combined 60 pulses of HPM (HPM60) and cisplatin (0.5 μM) treatments compared to control and individual treatments. Elevated γ-H2AX levels indicate DNA double-strand breaks in combined treatments. Additionally, upregulation of ATR/ATM, Chk1/Chk2, P53, and caspase 3/8, Bax, PARP, and Bcl2 confirms DNA damage and mitochondrial dysfunction, leading to apoptosis. Remarkably, half maximal inhibitory concentration (IC 50 ) results showed that HPM60 and cisplatin (0.5 μM) resulted in 16 times higher cell death in SKOV3 and H460 cells compared to cisplatin alone. Moreover, the efficacy of this combined treatment led to an over 50 % decrease in the viability of cancer cells. On the other hand, normal cells (MRC5 and HGF) exhibited only a minor 3-5 % decrease in viability under the same treatment conditions. The obtained results elucidate the cellular mechanisms driving cell apoptosis/death, offering insights for potential advancements in cancer therapy through the combined application of nanosecond pulses of HPM and cisplatin. This serves as a first step for future investigations in this domain., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer is a global concern worldwide. Prostate cancer has high prevalence and mortality rates among men. Photodynamic therapy (PDT) is an alternative treatment that is promising and effective with fewer side-effects than conventional therapies. However, some factors may limit its efficacy. For this, PDT can be combined with other modalities such as photobiomodulation (PBM) which is commonly used for increased cell proliferation/differentiation and wound healing. In this study, PBM pre-treatment at 655 nm of wavelength with 1, 3, and 5 J/cm 2 energy densities was applied to prostate cancer cells to investigate its role in indocyanine green (ICG)-mediated PDT applications. Following PBM treatment, various analyses were assessed including cell viability, cellular uptake of ICG, ATP production, nitric oxide release, reactive oxygen species generation, and the changes in mitochondrial membrane potential. Increased cell death was observed with the PBM pre-treatment at 1 and 3 J/cm 2 energy densities depending on ICG incubation time. Intracellular ROS generation and nitric oxide release by PBM had a significant impact on anticancer PDT action. An enhanced anticancer PDT effect was obtained with the PBM pre-treatment which may become a valuable modality to increase the sensitivity of the cancerous cells to PDT applications., Competing Interests: Declarations Conflict of interest The authors have no competing interest to declare that is relevant to the content of this article. Ethical approval This study does not involve any study with human participants or animals performed by any of the authors. Consent for publication All authors agreed with the content and all gave explicit consent to submit the manuscript for publication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Thermal neutrons generated in the body during proton beam therapy (PBT) can be used to cause boron neutron capture reactions and have recently been proposed as neutron capture enhanced PBT (NCEPBT). However, the cell killing effect of NCEPBT remains underexplored. Here, we show an increase in the cell killing effect of NCEPBT. Using Monte Carlo simulations, we showed that neutrons generated by proton beam irradiation are uniformly spread on tissue culture plates. Human salivary gland tumor cell line (HSG), human osteosarcoma cell line (MG63), human tongue squamous cell carcinoma cell line (SAS), and human malignant melanoma cell line (G-361) were irradiated with X-rays, proton beams, and proton beams with 10 B-enriched boronophenylalanine (boron concentration of 20 and 80 ppm). The relative biological effectiveness (RBE) values of proton beams alone, proton beams with 20 ppm boron, and proton beams with 80 ppm boron for HSG, MG63, SAS, and G-361 were 1.02, 1.07, and 1.23; 1.01, 1.08, and 1.44; 1.05, 1.09, and 1.46; and 1.04, 1.13, and 1.63, respectively. NCEPBT with high boron concentration showed high RBE and a high sensitizing effect. Our results confirm an increase in the cell killing effect of NCEPBT, should aid in its clinical use, and warrant its further investigation., Competing Interests: Declarations Competing interests Boronophenylalanine used in this study was provided by Stella Pharma Corporation (Japan). Tatsuya Ohno received research funding from Hitachi. All other authors declare no conflict of interest., (© 2024. The Author(s).)

In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting reactive oxygen species (ROS) production and apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/AKT pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and AKT/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced apoptosis and migration. Blocking AKT/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an AKT activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of AKT inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/AKT/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/AKT/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ye Shen reports financial support was provided by National Natural Science Foundation of China. Xiawei Wang reports financial support was provided by Traditional Chinese innovative talent support program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Senescence-like growth arrest (SLGA), which is a radiation-induced cell death pathway, is induced in immortalized normal human epithelial cell (hTERT-RPE1) by the daily fractionated X-irradiation with 1.5 Gy within 30 times. We here demonstrate that pre-treatment induces acquired radioresistance (ARR) that can survive from the lethal fractionated radiation. The parent cells were daily fractionated with 1.5 Gy for 5 d and then incubated for 7 d without fractionated radiation. After this, the daily fractionated radiation with 1.5 Gy was restarted. A small population of surviving cells appeared after 30 times of the daily fractionated radiation was completed and they were continuously growing up to 120 times of the daily fractionated radiation (RPE1-1.5Fr). We confirmed a higher basal expression level of p53, which functions in the activation of the SLGA pathway but fails to further accumulate after 1.5 Gy of single irradiation in RPE1-1.5Fr. It is the first report to induce ARR phenotype for fractionated radiation in normal human cells., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The radiation sensitivity of tumor cells is a critical determinant of their therapeutic response to radiotherapy. Histone deacetylase 6 (HDAC6), beyond its known role in modulating tubulin acetylation and influencing cell motility, is also involved in the DNA damage response, potentially enhancing tumor cell radiosensitivity. Targeted HDAC6 inhibitors have shown substantial promise in preclinical studies aimed at increasing radiosensitivity and inhibiting cellular migration., Methods: A new HDAC inhibitor, named OXHA, was designed by substituting the phenyl cap of SAHA with an N,5-diphenyloxazole-2-carboxamide group. The inhibitory activity of OXHA was evaluated via in vitro enzymatic assays. Its effects on tumor cell migration and radiosensitization potential were assessed using scratch wound healing assays, micronucleus formation, and clonogenic survival assays., Result: Enzymatic assays confirmed OXHA's selective inhibition of HDAC6. Compared to SAHA, OXHA significantly increased α-tubulin acetylation while minimally impacting histone H3 acetylation, indicating a high selectivity for HDAC6. In combination with X-ray irradiation, OXHA markedly impaired wound healing in A549 and HepG2 cells, enhanced micronucleus formation, and reduced clonogenic survival across multiple tumor lines., Conclusion: OXHA exhibits potent and selective HDAC6 inhibition, effectively impeding tumor cell migration and enhancing radiosensitivity across multiple cell lines. These findings suggest that OXHA has strong potential as a therapeutic strategy to improve radiotherapy efficacy., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval It is not applicable. Consent to participate It is not applicable. Consent for publication It is not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Radioprotectors help to protect the body or at least minimize the negative consequences of radiation exposure. The present study aimed to assess the radioprotective potential of Helianthus tuberosus L. polysaccharide (HTLP) in vitality and micronuclei tests. To assess the cytotoxic effects of HTLP, both vitality and MTT reductase assays were conducted., Materials and Methods: RAW 264.7 cells viability was assessed 24 h after adding 200 μg/ml HTLP solution by staining cell cultures with propidium iodide and bis-benzimide to detect the nuclei of dead cells and the total number of cells in culture. To assess cell viability via cellular metabolic activity MTT test was used. In this work outbred 24-30 g 5-months old SHK mice have been used. Irradiation was provided with proton beams with an energy of 660 MeV at a dose rate of 80 Gy with doses 1.5 Gy for micronuclei test and 8.5 Gy for survival test. Whole body X-ray irradiation was conducted using the RUT-15 therapeutic X-ray unit with doses of 1.5 Gy for MN test and 6.5 Gy for survival. The HTLP sterile solution in dose 100 μg/animal was injected into the tail vein 15 min before X-ray or proton irradiation., Results and Conclusion: s: Vitality test showed no significant differences between the control group and cells treated with 200 μl of 200 μg/ml HTLP solution, though a greater variability was noted. In contrast, the MTT assay indicated enhanced cell viability in the HTLP-treated cells. HTLP does not exert any toxic effects in cell culture. Moreover, results of MTT reductase assay shows, that HTLP may enhance the cells' metabolic activity. Animals pre-treated with HTLP displayed a significant reduction in micronuclei formation, showing five times fewer micronuclei in bone marrow cells compared to the non-treated group. This comparison highlights HTLP's potential protective effect against radiation-induced chromosomal damage. HTLP treatment demonstrates a significant reduction in hazard compared to the control, indicating its protective effects against irradiation. Thus, it can be concluded that the use of HTLP increases the likelihood of animal survival under the ionizing effects of X-rays and protons. The survival analysis reveals that the HTLP-treated groups exhibit a higher survival rate compared to both the control and Cysteamine-treated groups, suggesting a significant protective effect of HTLP against irradiation, regardless of the type of irradiation (proton or X-ray) with p < 0.0001., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study evaluates the safety and potential benefits of PBM on pancreatic beta cells and islets. PBM was applied to insulin-secreting cell lines (MIN6) and rat pancreatic islets using a 670 nm light source, continuous output, with a power density of 2.8 mW/cm², from 5 s to several 24 h. Measure of cell viability, insulin secretion, mitochondrial function, ATP content, and cellular respiration were assessed. Additionally, a diabetic rat model is used for islet transplantation (pre-conditioning with PBM or not) experiments. Short and long-term PBM exposure did not affect beta cell islets viability, insulin secretion nor ATP content. While short-term PBM (2 h) increases superoxide ion content, this was not observed for long exposure (24 h). Mitochondrial respirations were slightly decreased after PBM. In the islet transplantation model, both pre-illuminated and non-illuminated islets improved metabolic control in diabetic rats with a safety profile regarding the post-transplantation period. In summary, for the first time, long-term PBM exhibited safety in terms of cell viability, insulin secretion, energetic profiles in vitro, and post-transplantation period in vivo. Further investigation is warranted to explore PBM's protective effects under conditions of stress, aiding in the development of innovative approaches for cellular therapy., (© 2024. The Author(s).)

Radiotherapy combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only a few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. Oral squamous cell carcinoma is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of Croton tonkinensis and Curcuma longa on cell viability in OSCC cells. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used. The anticancer effect and the mechanism of action of Croton tonkinensis and Curcuma longa in OSCC cells were analyzed by using cell viability assays, Western blot analysis, and Tranwell migration assays. The results showed that Croton tonkinensis concentration-dependently reduced the viability of OML1 and OML1-R (radioresistant) cells by downregulating the levels of AKT/mTOR mediators, such as p110α, p85, pAKT (ser473), p-mTOR (ser2448), and p-S6 Ribosomal (ser235/236). We found that cotreatment of OML1 and OML1R cells with either zVAD-FMK (apoptosis inhibitor), Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), or chloroquine (CQ, an autophagy inhibitor) markedly reduced cell death. These results demonstrate that Croton tonkinensis exhibits anti-proliferation activity and highlight the therapeutic potential of small-molecule inhibitors against PI3K/mTOR signaling for radiosensitization in HNC treatment.

Exposure to artificial blue light, one of the most energetic forms of visible light, can increase oxidative stress in retinal cells, potentially enhancing the risk of macular degeneration. Retinal pigment epithelial (RPE) cells play a crucial role in this process; the loss of RPE cells is the primary pathway through which retinal degeneration occurs. In RPE cells, Kelch-like ECH-associated protein 1 (KEAP1) is located in both the nucleus and cytosol, where it binds to nuclear factor erythroid 2-related factor 2 (NRF2) and p62 (sequestosome-1), respectively. Blue light exposure activates the NRF2-heme oxygenase 1 (HMOX1) axis through both canonical and noncanonical p62 pathways thereby reducing oxidative damage, and initiates autophagy, which helps remove damaged proteins. These protective responses may support the survival of RPE cells. However, extended exposure to blue light drastically decreases the viability of RPE cells. This exposure diminishes the ability of KEAP1 to bind to p62 and reduces the level of KEAP1. Inhibition of autophagy does not prevent KEAP1 degradation, the NRF2-HMOX1 axis, or blue-light-induced cytotoxicity. However, proteasome inhibitor along with a transient increase in the amount of KEAP1 in RPE cells, partially restores the p62-KEAP1 complex and reduces blue-light-induced cytotoxicity. In vivo studies confirmed the downregulation of KEAP1 in damaged RPE cells. Mice subjected to periodic blue light exposure exhibited significant atrophy in the outer retina, particularly in the peripheral areas. Additionally, there was a significant decrease in c-wave electroretinography and pupillary light reflex, indicating functional impairments in both visual and nonvisual physiological processes. These data underscore the essential role of KEAP1 in managing oxidative defense and autophagy pathways triggered by blue light exposure in RPE cells., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prevalence of male infertility has become a significant clinical concern worldwide, with a noticeable upward trend in recent times. The rates of fertilization and subsequent development of embryos are dependent on many parameters associated with the quality and viability of sperm. Photobiomodulation (PBM) is a promising approach with a great potential for translational applications in the treatment of spermatozoa exhibiting low quality and motility. In this study, a comprehensive analysis of the existing literature, specifically examining the mechanisms of action of PBM has been presented. Our objective was to enhance knowledge in the field of laser light therapy in order to promote the usage of irradiation in clinical settings in a more effective way. Within the realm of reproductive science, the utilization of PBM has been employed to enhance the metabolic processes, motility, and viability of spermatozoa. This is attributed to its advantageous effects on mitochondria, resulting in the activation of the mitochondrial respiratory chain and subsequent synthesis of ATP. This therapeutic approach can be highly advantageous in circumventing the reliance on chemical substances within the culture medium for spermatozoa while also facilitating the viability and motility of spermatozoa, particularly in circumstances involving thawing or samples with significant immotility., (© 2024 American Society for Photobiology.)

Background/aim: Natural compounds such as propolis have gained wide popularity in the last decades. While its antibacterial, antiviral, and antifungal properties are well known, the anticancer properties of propolis are just beginning to be appreciated. Herein, we comparatively investigate the cytotoxic and radiosensitizing potential of four different ethanolic propolis extracts originating from three different countries (Germany, Ireland, South Africa) in human lung cancer cell models., Materials and Methods: Liquid chromatography-mass spectrometry (LC-MS/MS) was applied to characterize the four different propolis extracts. Cytotoxicity and radiation survival were determined by 3D matrix-based clonogenic assays and autophagy was examined by western blotting., Results: We found cytotoxicity in a propolis type-, time- and cell model- dependent manner. In the four ethanolic propolis extracts, Coumaric acid, Caffeic acid phenethyl ester, Pinocembrin and Chrysin presented the major compounds identified. Examining the induction of autophagy using the marker LC3B and autophagy inhibition with chloroquine suggested autophagy to be part of the survival mechanisms upon propolis treatment in a cell model-dependent manner. Combining propolis with X-ray irradiation showed the radiosensitizing potential of propolis in human lung cancer cell models, which clearly presented in a manner dependent on the incubation time of propolis and the cell model treated., Conclusion: Propolis treatment showed cytotoxic and radiosensitizing effects of propolis on human lung cancer cells. Since these effects differ greatly between the four propolis extracts studied and originating from different regions, further studies are urgently needed to differentiate propolis species and their anticancer properties in more detail., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The prognosis of osteosarcoma has not been improved for decades. As radioresistance is one of the major reasons, effective radiotherapy sensitization drugs need to be discovered. HOS and K7M2 osteosarcoma cell lines were treated with disulfiram (DSF) and radiation to assess cell viability, proliferation, migration ability, apoptosis level, ROS and Ca2+ level, and cell cycle in vitro. A HOS-derived subcutaneous tumor mouse model was constructed to evaluate tumor growth after DSF combined with radiation, and the Tunel assay and immunohistochemistry of Ki67 were conducted. Western blot was used to evaluate the protein expression level. The IC50 and working concentration of DSF in osteosarcoma cell lines were ascertained. When combined with radiation, DSF effectively suppressed cell viability, proliferation, and migration, while enhancing apoptosis in osteosarcoma cells. The cell cycle postirradiation exhibited a downward shift in the G1 phase, but the addition of DSF counteracted this trend. The combination of DSF and radiation exhibited inhibitory effects on tumor growth in vivo, which was corroborated by Ki67 staining and Tunel assay. Western blot analysis revealed that DSF upregulated the expression of P53, P21, CDKN2C, BAX, and cleaved Caspase-3 while downregulating BCL2, CDK4/6, and CyclinD1 after irradiation. Our results document that DSF exerts its radiosensitization effects in vivo and in vitro, and is a valuable radiosensitizing drug option for osteosarcoma. The radiosensitization effect is mainly achieved by activating the apoptotic pathway and promoting cell cycle arrest induced by P53/P21 and CDKN2C after irradiation., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background and Purpose: Radiotherapy (RT) is an integral treatment part for patients with head and neck squamous cell carcinoma (HNSCC), but radioresistance remains a major issue. Here, we use MitoTam, a mitochondrially targeted analogue of tamoxifen, which we aim to stimulate ferroptotic cell death with, and sensitize radioresistant cells to RT., Materials and Methods: We assessed viability, reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential, and lipid peroxidation in radiosensitive (UT-SCC-40) and radioresistant (UT-SCC-5) HNSCC cells following MitoTam treatment. To assess ferroptosis specificity, we used the ferroptosis inhibitor ferrostatin-1 (fer-1). Also, total antioxidant capacity and sensitivity to tert-butyl hydroperoxide were evaluated to assess ROS-responses. 53BP1 staining was used to assess radiosensitivity after MitoTam treatment., Results: Our data revealed increased ROS, cell death, disruption of mitochondrial membrane potential, and lipid peroxidation following MitoTam treatment in both cell lines. Adverse effects of MitoTam on cell death, membrane potential and lipid peroxidation were prevented by fer-1, indicating induction of ferroptosis. Radioresistant HNSCC cells were less sensitive to the effects of MitoTam due to intrinsic higher antioxidant capacity. MitoTam treatment prior to RT led to superadditive residual DNA damage expressed by 53BP1 foci compared to RT or MitoTam alone., Conclusion: MitoTam induced ferroptosis in HNSCC cells, which could be used to overcome the elevated antioxidant capacity of radioresistant cells and sensitize such cells to RT. Treatment with MitoTam followed by RT could therefore present a promising effective therapy of radioresistant cancers., Statement of Significance: Radiotherapy is applied in the treatment of a majority of cancer patients. Radioresistance due to elevated antioxidant levels can be overcome by promoting ferroptotic cell death combining ROS-inducing drug MitoTam with radiotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [J.N., J.S. and L.W. own part of MitoTam intellectual property]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The nucleotide excision repair (NER) system removes UV photoproducts from genomic DNA and is controlled by the circadian clock. Given that small-molecule compounds have been developed to target various clock proteins, we examined whether the cryptochrome inhibitor KS15 and REV-ERB antagonist SR8278 could modulate keratinocyte responses to UV radiation in vitro. We observed that though SR8278 promoted cell viability in UVB-irradiated cells, it had little effect on NER or on the expression of the clock-regulated NER factor XPA. Rather, we found that both KS15 and SR8278 absorb light within the UV spectrum to limit initial UV photoproduct formation in DNA. Moreover, SR8278 promoted UVB viability even in cells in which the core circadian clock protein BMAL1 was disrupted, which indicates that SR8278 is likely acting via other REV-ERB transcriptional targets. We further observed that SR8278 sensitized keratinocytes to light sources containing primarily UVA wavelengths of light likely due to the generation of toxic reactive oxygen species. Though other studies have demonstrated beneficial effects of SR8278 in other model systems, our results here suggest that SR8278 has limited utility for UV photoprotection in the skin and will likely cause phototoxicity in humans or mammals exposed to solar radiation., (© 2024 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)

Background: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer and is frequently resistant to therapy, ultimately resulting in treatment failure. Clinical trials have demonstrated the potential of sensitizing radiation therapy (RT)-resistant TNBC through the combination of chemotherapy and RT. This study sought to explore the potential of CD151 as a therapy response marker in the co-treatment strategy involving ionizing radiation (IR) and the repurposed antiviral drug 2-Thio-6-azauridine (TAU) for sensitizing RT-resistant TNBC (TNBC/RR)., Methods: The investigation encompassed a variety of assessments, including viability using MTT and LDH assays, cell proliferation through BrdU incorporation and clonogenic assays, cell cycle analysis via flow cytometry, cell migration using wound scratch and Boyden chamber invasion assays, DNA damage assessment through γH2AX analysis, apoptosis evaluation through acridine-orange and ethidium bromide double staining assays, as well as caspase 3 activity measurement using a colorimetric assay. CD151 expression was examined through ELISA, flow cytometry and RT-qPCR., Results: The results showed a significant reduction in TNBC/RR cell viability following co-treatment. Moreover, the co-treatment reduced cell migration, induced apoptosis, downregulated CD151 expression, and increased caspase 3 activity in TNBC/RR cells. Additionally, CD151 was predicted to serve as a therapy response marker for co-treatment with TAU and IR., Conclusion: These findings suggest the potential of combination treatment with IR and TAU as a promising strategy to overcome RT resistance in TNBC. Furthermore, CD151 emerges as a valuable therapy response marker for chemoradiotherapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective . We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity. Approach . The EUAD is defined as the uniform dose that, under well-oxygenated conditions, produces equal integrated survival of clonogenic cells in radiotherapy for heterogeneous hypoxic tumors with a non-uniform dose distribution. We define the dose nonuniformity effectiveness (DNE) in heterogeneous tumors as the ratio of the EUAD( D N ) for a non-uniform distribution D N and the reference EUAD( D U ) for the uniform dose distribution D U with equal integral tumor dose. The DNE concept is illustrated in a radiotherapy model problem for non-small cell lung cancer treated with hypoxia targeted dose escalation. A two-level cell population tumor model was used to consider the hypoxic and oxygenated tumor cells. Results . Theoretical analysis of the DNE shows that the entire region of the OER can be separated in two regions by a threshold OER th : (1) OER > OER th where DNE > 1 indicating higher effectiveness of nonuniform dose distributions and (2) OER < OER th where DNE < 1 indicating higher effectiveness of uniform dose distributions. Our simulations show that the value of the threshold OER th in radiotherapy with conventional fractionation is significant in the range of about 1.2-1.6 depending on selected radiotherapy parameters. In general, the OER th increases with reoxygenation rate, relative hypoxic volume and dose escalation factor. The threshold value of OER th is smaller of about 1.1 for hypofractionated radiotherapy. Significance . The analysis of dose distributions using the DNE shows that the uniform dose distributions may improve biological cell killing effect in heterogeneous tumors with intermediate oxygen levels compared to targeted nonuniform dose distribution., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: The present study aimed to investigate the effects of infrared diode laser irradiation on the proliferation and differentiation capacity of periodontal ligament stem cells (hPDLSCs), which are optimal cell sources for periodontal regeneration., Methods: hPDLSCs were isolated and characterized by flow cytometric analysis of mesenchymal stem cell markers, and their trilineage differentiation capacity was tested. hPDLSCs were then cultured and irradiated with infrared diode laser (970 nm) at a power of 200 mW and a fluence of 4 J/cm 2 for 3 s. MTT assay was performed to assess cellular proliferation. Cell cycle analysis was performed, and the impact of infrared diode laser irradiation on the stemness and osteogenic differentiation potential of hPDLSCs was evaluated via RT‒PCR., Results: Infrared diode laser application enhanced the stemness, viability, proliferation, and differentiation of PDLSCs. Stem cell markers (OCT4, SOX2, and NANOG) were significantly upregulated in hPDLSCs exposed to laser irradiation. There was significant overexpression of RUNX2, ALP, OPN, and OCN on day 14 after laser application., Conclusions: These findings provide valuable insights into the specific applications of infrared diode lasers to effectively regenerate periodontal tissues. The results can aid in the development of precise clinical protocols aimed at enhancing osseointegration and promoting tissue regeneration. Ultimately, the combination of infrared diode laser with hPDLSCs is promising for stimulating periodontal regeneration., (© 2024. The Author(s).)

Treating lung and prostate cancer cells is a major health problem that may be solved through the interactions of laser beams with nanoparticles. In the paper, Au-H 2 Ti 3 O 7 nanotubes (NTs) are proposed as a treatment agent and the interactions of different laser beams with the nanostructure are considered to solve the mentioned health problem. Also, the NTs are employed to treat the cancers in dark conditions. The results are motivating because Au-H 2 Ti 3 O 7 NPs do not affect healthy cells, while they strongly affect cancer cells, and the viability percentage of LNCap cells reaches 16% for incubation times of 48 h. Furthermore, treating LNCap cells using the irradiated Au-H 2 Ti 3 O 7 NTs by NIR beam at 808 nm has no cytotoxicity, while cytotoxicity of 92% is obtained using an irradiation laser beam at 532 nm. Also, applying the laser beam at 635 nm to the NTs leads to a cytotoxicity of ∼53% in lung cancer (A549 cells). In total, the Au-H 2 Ti 3 O 7 NTs have a selective effect on cancer cells and greatly reduce the viability in the given dark and irradiation conditions, leading to the introduction of them as a promising agent for the non-invasive treatment of prostate cancer and a moderate candidate for lung cancer therapy., (© 2024. The Author(s).)

To overcome chondrosarcoma's (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONP DOX ) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONP DOX . Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONP DOX compound. IONP DOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONP DOX -low-LET proton combination caused a more lethal effect compared to IONP DOX -high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS., Competing Interests: The authors declare no conflicts of interest.

Introduction: Radiobiological studies at low dose rates allow us to improve our knowledge of the mechanisms by which radiation exerts its effects on biological systems following chronic exposures. Moreover, these studies can complement available epidemiological data on the biological effects of low doses and dose rates of ionizing radiation. Very few studies have simultaneously compared the biological effects of low- and high-LET radiations at the same dose rate for chronic irradiation., Methods: We compared, for the first time in the same experiment, the effects of chronic (dose rates as low as ~18 and 5 mGy/h) and acute irradiations on clonogenicity and micronucleus formation in AG1522 normal human skin fibroblasts in the confluent state exposed to doses of low- and high-LET radiation (gamma rays and alpha particles) to investigate any differences due to the different radiation quality and different dose rate (in the dose range 0.006-0.9 Gy for alpha particles and 0.4-2.3 Gy for gamma rays)., Results: As expected, alpha particles were more effective than gamma rays at inducing cytogenetic damage and reduced clonogenic cell survival. For gamma rays, the cytogenetic damage and the reduction of clonogenic cell survival were greater when the dose was delivered acutely instead of chronically. Instead, for the alpha particles, at the same dose, we found equal cytogenetic damage and reduction of clonogenic cell survival for both chronic and acute exposure (except for the highest doses of 0.4 and 0.9 Gy, where cytogenetic damage is greater at a low dose rate)., Conclusion: The results of this study may have an impact on space and terrestrial radioprotection of humans at low doses and low dose rates, on biodosimetry, and on the use of ionizing radiation in medicine. These results also provide insights into understanding damage induction and cell reaction mechanisms following chronic exposure (at dose rates as low as 18 and 5 mGy/h) to low- and high-LET radiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Anello and Esposito.)

This study assessed the impact of low-level laser irradiation on the viability and proliferation of human periodontal ligament stem cells (hPDLSCs) cultivated on polylactic acid (PLA) scaffolds. hPDLSCs were obtained, characterized, and grown on the surface of PLA films produced via the solvent casting technique. The study involved two groups: the control group, which was not exposed to radiation, and the laser group, which was irradiated with a diode laser (InGaAIP) with a power of 30 mW, a wavelength of 660 nm, and a single dose of 1 J/cm² emitted continuously. Cell viability was assessed 24 and 48 hours after irradiation using the Alamar blue and Live/Dead assays. Flow cytometry was used to assess cell cycle events, and scanning electron microscopy (SEM) was used to evaluate the interaction between cells and the biomaterial. The results revealed a statistically significant increase in cell metabolic activity in the laser group compared with the control group at 24 hours (p <0.05) and 48 hours (p <0.001), as indicated by the Alamar blue assay. The Live/Dead assay also revealed a greater density of viable cells in the laser group. The cell cycle analysis revealed a significant increase in the number of cells in the proliferative phase (G2/M) in the laser group compared with the control group (p <0.001). The SEM images demonstrated that the irradiated group had a greater concentration of cells while still maintaining their cell shape and projections. This study demonstrated that photobiomodulation can increase the viability and proliferation of periodontal stem cells cultured on PLA scaffolds, suggesting the potential of this protocol for future studies on periodontal tissue engineering., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Rationale: 212 Pb, a promising in vivo alpha - particle generator of 212 Bi, has aroused much interest as a therapeutic radionuclide. For the development of targeted alpha therapy (TAT), it is important to determine the contribution of targeted effects in irradiated cells, and also of non-targeted effects in non-irradiated bystander cells. Currently, the critical roles of mitochondrial transfer in cellular crosstalk have garnered significant attention. However, the specific involvement of damaged mitochondrial transfer in orchestrating this alpha-particle radiation-induced bystander effect (RIBE) needs to be further explored. Methods: A novel alpha-emitting radiopharmaceutical, 212 Pb-hydrogel nanoparticles (HNPs), was synthesized and subsequently evaluated its theranostics effects. The impact of irradiated cell-conditioned media (ICCM), collected at different times post- 212 Bi irradiation, on bystander cancer cells regarding cell viability was also investigated. Additionally, damaged mitochondria were isolated and cultured with non-irradiated bystander cells to assess their role. Results: 212 Pb-HNPs exhibited efficient therapeutic antitumor effects in vitro , including increased GSH depletion, ROS accumulation, and mitochondrial damage in irradiated tumor cells. In vivo studies demonstrated its imaging potential through SPECT/CT, and RNA sequencing results indicated activation of oxidative stress-related pathways in irradiated tumors. Additionally, ICCM influenced the viability of non-irradiated bystander cells, suggesting a radiation-induced bystander effect by the alpha-particle 212 Bi. Interestingly, damaged mitochondria isolated from ICCM were observed to enter co-cultured non-irradiated bystander cells. Further experiments confirmed that the transfer of damaged mitochondria results in the death of non-irradiated bystander cells. Conclusion: The present study highlights the theranostic potential of the alpha-particle generator 212 Pb and, more importantly, elucidates the role of damaged mitochondrial transfer in alpha-particle RIBE. These findings provide a novel theoretical mechanism for the antitumor effects of alpha-particles and expand the clinical application prospects of TAT., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The influence of UV radiation on skin discoloration, skin aging and the development of skin cancer is widely known. As a part of this study, the effect of extracts from three varieties of Cornus mas L. ( C. mas L.) on skin cells exposed to UVA radiation was assessed. The analyses were performed on both normal and cancer skin cells. For this purpose, the potential photoprotective effects of the obtained extracts (aqueous and ethanolic) was assessed by performing two cytotoxicity tests (Alamar blue and Neutral red). Additionally, the antioxidant capacity was compared using three different assays. The 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA) probe was used to evaluate the intracellular level of free radicals in cells exposed to the simultaneous action of UVA radiation and dogwood extracts. Additionally, the ability to inhibit excessive pigmentation was determined by assessing the inhibition of melanin formation and tyrosinase activity. The obtained results confirmed the strong antioxidant properties of dogwood extracts and their photoprotective effect on normal skin cells. The ability to inhibit the viability of melanoma cells was also observed. Additionally, a reduction in oxidative stress in skin cells exposed to UVA radiation and a strong inhibition of melanin formation and tyrosinase activity have been demonstrated. This study shows that dogwood extract could be a valuable cosmetic raw material that can play both a photoprotective and antihyperpigmentation role in cosmetic preparations.

Adipose-derived mesenchymal stem cells (ADMSCs) possess the ability to transform into various cell types, including neurons. It has been proposed that the optimization of this transformation can be achieved by using photobiomodulation (PBM). The objective of this laboratory-based investigation was to induce the transformation of immortalized ADMSCs (iADMSCs) into neurons with chemical triggers and then evaluate the supportive effects of PBM at two different wavelengths, 525 nm and 825 nm, each administered at a dose of 5 J/cm 2 , as well as the combined application of these wavelengths. The results revealed that the treated cells retained their stem cell characteristics, although the cells exposed to the green laser exhibited a reduction in the CD44 marker. Furthermore, early, and late neuronal markers were identified using flow cytometry analysis. The biochemical analysis included the assessment of cell morphology, viability, cell proliferation, potential cytotoxicity, and the generation of reactive oxygen species (ROS). The findings of this study indicate that PBM does not harm the differentiation process and may even enhance it, but it necessitates a longer incubation period in the induction medium. These research findings contribute to the validation of stem cell technology for potential applications in in vivo, pre-clinical, and clinical research environments., (© 2024. The Author(s).)

Cold atmospheric plasma (CAP) has been extensively utilized in medical treatment, particularly in cancer therapy. However, the underlying mechanism of CAP in skin cancer treatment remains elusive. In this study, we established a skin cancer model using CAP treatment in vitro . Also, we established the Xenograft experiment model in vivo . The results demonstrated that treatment with CAP induced ferroptosis, resulting in a significant reduction in the viability, migration, and invasive capacities of A431 squamous cell carcinoma, a type of skin cancer. Mechanistically, the significant production of reactive oxygen species (ROS) by CAP induces DNA damage, which then activates Ataxia-telangiectasia mutated (ATM) and p53 through acetylation, while simultaneously suppressing the expression of Solute Carrier Family 7 Member 11 (SLC7A11). Consequently, this cascade led to the down-regulation of intracellular Glutathione peroxidase 4 (GPX4), ultimately resulting in ferroptosis. CAP exhibits a favorable impact on skin cancer treatment, suggesting its potential medical application in skin cancer therapy., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Hair loss is a prevalent issue worldwide, which, though not life-threatening, can result in psychological problems, low self-esteem, and social anxiety. Previous studies have shown that ultraviolet radiation can have negative effects on hair follicle cells, leading to hair loss, while the impact of blue light on hair and hair follicle has largely been overlooked. This study aimed to examine the effects of blue light on hair follicle stem cells (HFSCs) and primary dermal papilla cells (DPCs), which are essential components of hair follicles. Human HFSCs and primary DPCs were exposed to blue light (457 nm) at various intensities (1, 4, 8, and 16 mW/cm 2 ) for 3 days. Subsequently, cell viability, cell proliferation, and intracellular reactive oxygen species (ROS) were assessed. The results showed that blue light (457 nm) significantly reduced the cell viability and proliferation of HFSCs and DPCs in vitro, with the inhibition being intensity-dependent. Additionally, blue light triggered the overproduction of ROS in the DPCs. While the exact mechanisms by which blue light affects hair follicle cells remain unclear, these findings suggest that blue light could impede the growth of these cells. This insight may offer a new approach to protecting hair by avoiding exposure to high-intensity blue light., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Chrysin is a natural flavonoid with anti-cancer effects. Despite its beneficial effects, little information is available regarding its immunogenic cell death (ICD) properties. In this work, we hypothesized that chrysin can potentiate radiotherapy(RT)-induced immunogenicity in melanoma cell line (B16-F10). We examined the effects of chrysin alone and in combination with radiation on ICD induction in B16-F10 cells. Cell viability was assessed using an MTT assay. Cell apoptosis and calreticulin (CRT) exposure were determined using flow cytometry. Western blotting and ELISA assay were employed to examine changes in protein expression. Combination therapy exhibited a synergistic effect, with an optimum combination index of 0.66. The synergistic anti-cancer effect correlated with increased cell apoptosis in cancer cells. Compared to the untreated control, chrysin alone and in combination with RT induced higher levels of DAMPs, such as CRT, HSP70, HMGB1, and ATP. The protein expression of p-STAT3/STAT3 and PD-L1 was reduced in B16-F10 cells exposed to chrysin alone and in combination with RT. Conditioned media from B16-F10 cells exposed to mono-and combination treatments elicited IL-12 secretion in dendritic cells (DCs), inducing a Th1 response. Our findings revealed that chrysin could induce ICD and intensify the RT-induced immunogenicity., (© 2024. The Author(s).)

Objective. Relative biological effectiveness (RBE) differs between radiation qualities. However, an RBE of 1.0 has been established for photons regardless of the wide range of photon energies used clinically, the lack of reproducibility in radiobiological studies, and outdated reference energies used in the experimental literature. Moreover, due to intrinsic radiosensitivity, different cancer types have different responses to radiation. This study aimed to characterize the RBE of clinically relevant high and low photon energies in vitro for three human cancer cell lines: HCT116 (colon), HeLa (cervix), and PC3 (prostate). Approach. Experiments were conducted following dosimetry protocols provided by the American Association of Physicists in Medicine. Cells were irradiated with 6 MV x-rays, an 192 Ir brachytherapy source, 225 kVp and 50 kVp x-rays. Cell survival post-irradiation was assessed using the clonogenic assay. Survival fractions were fitted using the linear quadratic model, and survival curves were generated for RBE calculations. Main results. Cell killing was more efficient with decreasing photon energy. Using 225 kVp x-rays as the reference, the HCT116 RBE SF0.1 for 6 MV x-rays, 192 Ir, and 50 kVp x-rays were 0.89 ± 0.03, 0.95 ± 0.03, and 1.24 ± 0.04; the HeLa RBE SF0.1 were 0.95 ± 0.04, 0.97 ± 0.05, and 1.09 ± 0.03, and the PC3 RBE SF0.1 were 0.84 ± 0.01, 0.84 ± 0.01, and 1.13 ± 0.02, respectively. HeLa and PC3 cells had varying radiosensitivity when irradiated with 225 and 50 kVp x-rays. Significance. This difference supports the notion that RBE may not be 1.0 for all photons through experimental investigations that employed precise dosimetry. It highlights that different cancer types may not have identical responses to the same irradiation quality. Additionally, the RBE of clinically relevant photons was updated to the reference energy of 225 kVp x-rays., (Creative Commons Attribution license.)

Preclinical data have shown that 161 Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their 177 Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose-response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [ 161 Tb]Tb- and [ 177 Lu]Lu-DOTATATE (agonist) and with [ 161 Tb]Tb- and [ 177 Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β - particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [ 161 Tb]Tb-DOTATATE and [ 161 Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their 177 Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by 161 Tb. When activity concentrations were considered, both [ 161 Tb]Tb-DOTATATE and [ 161 Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with 177 Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose-response curves for [ 161 Tb]Tb- and [ 177 Lu]Lu-DOTATATE. [ 161 Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [ 161 Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by 161 Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [ 161 Tb]Tb-DOTATATE and [ 161 Tb]Tb-DOTA-LM3 than for the 177 Lu-labeled analogs. In contrast, [ 161 Tb]Tb-DOTATATE showed no higher dose response than [ 177 Lu]Lu-DOTATATE, whereas for [ 161 Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [ 161 Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [ 161 Tb]Tb-DOTATATE for labeling with 161 Tb., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To assess how laser light affects blood lymphocyte viability in vitro., Methods: The comparative study was conducted from November 2021 to April 2022 at the Department of Medical Physics, Mustansiriyah University, Baghdad, Iraq, and comprised blood samples collected from healthy adults with no medical history of major illnesses or history of taking medications for major diseases.Low-level laser 589nm and 532nm was used at 30 J/cm², 50 J/cm² and 70J/cm² energy intensities and three different post-exposure time; immediately, 1h and 2h after radiation exposure. The viability of normal human lymphocytic cells of the blood was noted. Data was analysed using SPSS 24., Results: The blood samples were drawn from 6 adult male voluteers. The percentage of cells that showed apoptosis post-exposure to 589nm laser was significantly lower than that following exposure to 532nm laser (p<0.05). However, the proportion of apoptotic cells was significantly higher following irradiation with 532nm at varying doses than after irradiation with 589nm (p<0.05)., Conclusions: A low-level laser could promote and prevent apoptosis in human peripheral blood cells in a dose- and time-dependent manner.