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

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

Surviving extreme radiation.

Tiny animals known as tardigrades use a combination of DNA repair machinery and a novel protein to mend their genome after intense ionizing radiation.

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

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

50 Hz magnetic field influences caspase-3 activity and cell cycle distribution in ionizing radiation exposed SH-SY5Y neuroblastoma cells.

PURPOSE: Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation. MATERIALS AND METHODS: Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis. RESULTS: Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT. CONCLUSIONS: Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.

Changes in Telomere Length in Leukocytes and Leukemic Cells after Ultrashort Electron Beam Radiation.

Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.

Observation Safely Reduces the Use of the Computerized Tomography in Medium-to-Low-Risk Patients with Suspected Acute Appendicitis: Results of a Randomized Controlled Trial.

Objectives-The objective was to compare the effectiveness of observation in standard-of-care computed tomography (CT) in adult patients with suspected acute appendicitis (AA). Methods-Patients with clinically suspected AA and inconclusive diagnosis after primary clinical examination, laboratory examination, and transabdominal ultrasound (TUS) were eligible for the study, and they were randomized (1:1) to parallel groups: observation-group patients were observed for 8-12 h and then, repeated clinical and laboratory examinations and TUS were performed; CT group (control group) patients underwent abdominopelvic CT scan. The study utilized Statistical Analysis System 9.2 for data analysis, including tests, logistic regression, ROC analysis, and significance evaluation. Patients were enrolled in the study at Vilnius University Hospital Santaros Klinikos in Lithuania between December 2018 and June 2021. Results-A total of 160 patients (59 men, 101 women), with a mean age of 33.7 ± 14.71, were included, with 80 patients in each group. Observation resulted in a reduced likelihood of a CT scan compared with the CT group (36.3% vs. 100% p < 0.05). One diagnostic laparoscopy was performed in the observation group; there were no cases of negative appendectomy (NA) in the CT group. Both conditional CT and observation pathways resulted in high sensitivity and specificity (97.7% and 94.6% vs. 96.7% and 95.8%). Conclusions-Observation including the repeated evaluation of laboratory results and TUS significantly reduces the number of CT scans without increasing NA numbers or the number of complicated cases.

Recent discoveries on the historical foundations of cancer risk assessment: Shedding light on the limits of LNT.

Within the past three years there has been a spate of historical discoveries by our research team on various different facets of the historical foundations of cancer risk assessment. This series of discoveries was stimulated by the creation of a 22-episode documentary of the historical foundations of cancer risk assessment by the US Health Physics Society and the need to provide documentation. This process yielded nearly two dozen distinct historical findings which have been published in numerous papers in the peer-reviewed literature. These discoveries are itemized and summarized in the present paper, along with the significance of each discovery within the historical context of ionizing radiation research and cancer risk assessment.

Ferroptosis Inhibition with Deferoxamine Alleviates Radiation-Induced Fibrosis.

Background: Radiation-induced fibrosis (RIF) is a debilitating sequelae of radiation therapy that has been shown to improve with topical treatment with the iron chelator deferoxamine (DFO). We investigated whether DFO exerts this effect through attenuation of ferroptosis, a recently described iron-dependent pathway of cell death. Methods: Adult C57BL/6J mice were treated with topical DFO or ferrostastin-1 (Fer-1) and irradiated with 30 Grays of ionizing radiation to the dorsal skin to promote development of chronic RIF. Immunofluorescent staining with 4-hydroxynonenal (4-HNE) antibody was carried out directly following irradiation to assess ferroptosis activity. Perfusion testing with laser Doppler was performed throughout the healing interval. Eight weeks following radiation, dorsal skin was harvested and analyzed histologically and biomechanically. Results: Immunohistochemical staining demonstrated lower presence of 4-HNE in non-irradiated skin, DFO-treated skin, and Fer-1-treated skin compared to irradiated, untreated skin. DFO resulted in histological measurements (dermal thickness and collagen content) that resembled normal skin, while Fer-1 treatment yielded less significant improvements. These results were mirrored by analysis of extracellular matrix ultrastructure and biomechanical testing, which recapitulated the ability of topical DFO treatment to alleviate RIF across these parameters while Fer-1 resulted in less notable improvement. Finally, perfusion levels in DFO treated irradiated skin were similar to measurements in normal skin, while Fer-1 treatment did not impact this feature. Conclusions: Ferroptosis contributes to the development of RIF and attenuation of this process leads to reduced skin injury. DFO further improves RIF through additional enhancement of perfusion not seen with Fer-1.

The effects of radiofrequency exposure on male fertility: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for research and evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews have been undertaken by a network of topic experts and methodologists to collect, assess and synthesise data relevant to these guidelines. Following the WHO handbook for guideline development and the COSTER conduct guidelines, we systematically reviewed the evidence on the potential effects of RF-EMF exposure on male fertility in human observational studies. METHODS: We conducted a broad and sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; Web of Science and EMF Portal. We also conducted searches of grey literature through relevant databases including OpenGrey, and organisational websites and consulted RF-EMF experts. We hand searched reference lists of included study records and for citations of these studies. We included quantitative human observational studies on the effect of RF-EMF exposure in adult male participants on infertility: sperm concentration; sperm morphology; sperm total motility; sperm progressive motility; total sperm count; and time to pregnancy. Titles and abstracts followed by full texts were screened in blinded duplicate against pre-set eligibility criteria with consensus input from a third reviewer as required. Data extraction from included studies was completed by two reviewers, as was risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. We conducted a dose-response meta-analysis as possible and appropriate. Certainty of the evidence was assessed by two reviewers using the OHAT GRADE tool with input from a third reviewer as required. RESULTS: We identified nine studies in this review; seven were general public studies (with the general public as the population of interest) and two were occupational studies (with specific workers/workforces as the population of interest). General public studies. Duration of phone use: The evidence is very uncertain surrounding the effects of RF-EMF on sperm concentration (10/6 mL) (MD (mean difference) per hour of daily phone use 1.6 106/mL, 95 % CI -1.7 to 4.9; 3 studies), sperm morphology (MD 0.15 percentage points of deviation of normal forms per hour, 95 % CI -0.21 to 0.51; 3 studies), sperm progressive motility (MD -0.46 percentage points per hour, 95 % CI -1.04 to 0.13; 2 studies) and total sperm count (MD per hour -0.44 106/ejaculate, 95 % CI -2.59 to 1.7; 2 studies) due to very low-certainty evidence. Four additional studies reported on the effect of mobile phone use on sperm motility but were unsuitable for pooling; only one of these studies identified a statistically significant effect. All four studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used an inappropriate statistical method. Position of phone: There may be no or little effect of carrying a mobile phone in the front pocket on sperm concentration, total count, morphology, progressive motility or on time to pregnancy. Of three studies reporting on the effect of mobile phone location on sperm total motility and, or, total motile count, one showed a statistically significant effect. All three studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used inappropriate statistical method. RF-EMF Source: One study indicates there may be little or no effect of computer or other electric device use on sperm concentration, total motility or total count. This study is at probably high risk of exposure characterisation bias and outcome assessment bias. Occupational studies. With only two studies of occupational exposure to RF-EMF and heterogeneity in the population and exposure source (technicians exposed to microwaves or seamen exposed to radar equipment), it was not plausible to statistically pool findings. One study was at probably or definitely high risk of bias across all domains, the other across domains for exposure characterisation bias, outcome assessment bias and confounding. DISCUSSION: The majority of evidence identified was assessing localised RF-EMF exposure from mobile phone use on male fertility with few studies assessing the impact of phone position. Overall, the evidence identified is very uncertain about the effect of RF-EMF exposure from mobile phones on sperm outcomes. One study assessed the impact of other RF-EMF sources on male fertility amongst the general public and two studies assessed the impact of RF-EMF exposure in occupational cohorts from different sources (radar or microwave) on male fertility. Further prospective studies conducted with greater rigour (in particular, improved accuracy of exposure measurement and appropriate statistical method use) would build the existing evidence base and are required to have greater certainty in any potential effects of RF-EMF on male reproductive outcomes. Prospero Registration: CRD42021265401 (SR3A).

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: To inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. METHODS: We conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults' preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers' data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose-response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. RESULTS: We identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces). General public studies. From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97-1.34, 95% prediction interval (PI): 0.83-1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96-1.36, 95% PI: 0.84-1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02-1.24, 95% PI: 0.99-1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth. Occupational studies. In occupational studies, based on dose-response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94-1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DISCUSSION: Most of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes. Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

A sperm-activating trypsin-like protease from the male reproductive tract of Spodoptera litura: Proteomic identification, sequence characterization, gene expression profile, RNAi and the effects of ionizing radiation.

Like other lepidopteran insects, males of the tobacco cutworm moth, Spodoptera litura produce two kinds of spermatozoa, eupyrene (nucleate) and apyrene (anucleate) sperm. Formed in the testis, both kinds of sperm are released into the male reproductive tract in an immature form and are stored in the duplex region of the tract. Neither type of sperm is motile at this stage. When stored apyrene sperm from the duplex are treated in vitro with an extract of the prostatic region of the male tract, or with mammalian trypsin, they become motile; activation is greater and achieved more rapidly with increasing concentration of extract or enzyme. The activating effect of prostatic extract is blocked by soybean trypsin inhibitor (SBTI), also in a dose-dependent way. These results suggest that the normal sperm-activating process is due to an endogenous trypsin-like protease produced in the prostatic region. Proteomic analysis of S. litura prostatic extracts revealed a Trypsin-Like Serine Protease, TLSP, molecular weight 27 kDa, whose 199-residue amino acid sequence is identical to that of a predicted protein from the S. litura genome and is highly similar to predicted proteins encoded by genes in the genomes of several other noctuid moth species. Surprisingly, TLSP is only distantly related to Serine Protease 2 (initiatorin) of the silkmoth, Bombyx mori, the only identified lepidopteran protein so far shown to activate sperm. TLSP has features typical of secreted proteins, probably being synthesized as an inactive precursor zymogen, which is later activated by proteolytic cleavage. cDNA was synthesized from total RNA extracted from the prostatic region and was used to examine TLSP expression using qPCR. tlsp mRNA was expressed in both the prostatic region and the accessory glands of the male tract. Injection of TLSP-specific dsRNA into adult males caused a significant reduction after 24 h in tlsp mRNA levels in both locations. The number of eggs laid by females mated to adult males that were given TLSP dsRNA in 10 % honey solution, and the fertility (% hatched) of the eggs were reduced. Injecting pupae with TLSP dsRNA caused the later activation of apyrene sperm motility by adult male prostatic extracts to be significantly reduced compared to controls. Exposure of S. litura pupae to ionizing radiation significantly reduced expression of tlsp mRNA in the prostatic part and accessory gland of irradiated males in both the irradiated generation and also in their (unirradiated) F1 progeny. The implications of these findings for the use of the inherited sterility technique for the control of S. litura and other pest Lepidoptera are discussed.

Radiation-induced eCIRP impairs macrophage bacterial phagocytosis.

Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection following radiation injury remains poorly examined. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that dysregulates host immune system responses such as phagocytosis. We hypothesized that radiation-induced eCIRP release impairs macrophage phagocytosis of bacteria. Adult healthy mice were exposed to 6.5-Gy total body irradiation (TBI). Primary peritoneal macrophages isolated from adult healthy mice were exposed to 6.5-Gy radiation. eCIRP-neutralizing monoclonal antibody (mAb) was added to the cell culture prior to irradiation. Bacterial phagocytosis by peritoneal macrophages was assessed using pHrodo Green-labeled E. coli 7 days after irradiation ex vivo and in vitro. Bacterial phagocytosis was also assessed after treatment with recombinant murine CIRP (rmCIRP). Rac1 and ARP2 protein expression in cell lysates and eCIRP levels in the peritoneal lavage were assessed by Western blotting. Bacterial phagocytosis by peritoneal macrophages was significantly decreased after irradiation compared to controls ex vivo and in vitro. Rac1 and ARP2 expression in the peritoneal macrophages were downregulated after TBI. TBI significantly increased eCIRP levels in the peritoneal cavity. rmCIRP significantly decreased bacterial phagocytosis in a dose-dependent manner. eCIRP mAb restored bacterial phagocytosis by peritoneal macrophages after irradiation. Ionizing radiation exposure impairs bacterial phagocytosis by macrophages after irradiation. Neutralization of eCIRP restores the phagocytic ability of macrophages after irradiation. Our findings elucidate a novel mechanism of immune dysfunction and provide a potential new therapeutic approach for limiting infection after radiation injury.

Physicochemical methods for disinfection of contaminated surfaces - a way to control infectious diseases.

This paper represents the reviews of recent advancements in different physicochemical methods for disinfecting contaminated surfaces, which are considered to be responsible for transmitting different bacterial, viral, and fungal infectious diseases. Surface disinfection can be achieved by applying chemicals, UV-based processes, ionization radiation (gamma-ray, X-ray and electron beam), application of self-disinfecting surfaces, no-touch room disinfection methods, and robotic disinfection methods for built-in settings. Application of different chemicals, such as alcohols, hydrogen peroxide, peracetic acid, quaternary ammonium salts, phenol, and iodine solution, are common and economical. However, the process is time-consuming and less efficient. The use of UVC light (wavelength: 200-280 nm, generated by low vapor mercury lamps or pulse xenon light) has gained much attention for disinfecting fomites worldwide. In recent times, the combination of UV and H2O2, based on the principle of the advanced oxidation process, has been applied for disinfecting inanimate surfaces. The process is very efficient and faster than chemical and UV processes. Heavy metals like copper, silver, zinc, and other metals can inactivate microbes and are used for surface modification to produce self-disinfecting surfaces and used in healthcare facilities. In combination with UVB (280-315 nm) and UVA (315-400 nm), titanium oxide has been utilized for disinfecting contaminated surfaces. Ionization radiation, one of the advanced methods, can be used in disinfecting medical devices and drugs. Post-COVID-19 pandemic, the no-touch and robotic disinfection methods utilizing chemicals or UVC lights have received much importance in built-in settings. Among these methods, surface disinfection by applying chemicals by fogging/vaporization and UV radiation methods has been widely reported in the literature compared to other methods. Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-024-00893-2.

Effective Radiosensitization of HNSCC Cell Lines by DNA-PKcs Inhibitor AZD7648 and PARP Inhibitors Talazoparib and Niraparib.

(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects of radiotherapy. We compared the effects of the PARP inhibitors talazoparib and niraparib and that of the DNA-PKcs inhibitor AZD7648, combined with ionizing radiation. (2) Seven HNSCC cell lines, including Cal33, CLS-354, Detroit 562, HSC4, RPMI2650 (HPV-negative), UD-SCC-2 and UM-SCC-47 (HPV-positive), and two healthy fibroblast cell lines, SBLF8 and SBLF9, were studied. Flow cytometry was used to analyze apoptosis and necrosis induction (AnnexinV/7AAD) and cell cycle distribution (Hoechst). Cell inactivation was studied by the colony-forming assay. (3) AZD7648 had the strongest effects, radiosensitizing all HNSCC cell lines, almost always in a supra-additive manner. Talazoparib and niraparib were effective in both HPV-positive cell lines but only consistently in one and two HPV-negative cell lines, respectively. Healthy fibroblasts were not affected by any combined treatment in apoptosis and necrosis induction or G2/M-phase arrest. AZD7648 alone was not toxic to healthy fibroblasts, while the combination with ionizing radiation reduced clonogenicity. (4) In conclusion, talazoparib, niraparib and, most potently, AZD7648 could improve radiation therapy in HNSCC. Healthy fibroblasts tolerated AZD7648 alone extremely well, but irradiation-induced effects might occur. Our results justify in vivo studies.

Epidemiological exploration of the impact of bluetooth headset usage on thyroid nodules using Shapley additive explanations method.

With an increasing prevalence of thyroid nodules globally, this study investigates the potential correlation between the use of Bluetooth headsets and the incidence of thyroid nodules, considering the cumulative effects of non-ionizing radiation (NIR) emitted by these devices. In this study, we analyzed 600 valid questionnaires from the WenJuanXing platform using Propensity Score Matching (PSM) and the XGBOOST model, supplemented by SHAP analysis, to assess the risk of thyroid nodules. PSM was utilized to balance baseline characteristic differences, thereby reducing bias. The XGBOOST model was then employed to predict risk factors, with model efficacy measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC). SHAP analysis helped quantify and explain the impact of each feature on the prediction outcomes, identifying key risk factors. Initially, 600 valid questionnaires from the WenJuanXing platform underwent PSM processing, resulting in a matched dataset of 96 cases for modeling analysis. The AUC value of the XGBOOST model reached 0.95, demonstrating high accuracy in differentiating thyroid nodule risks. SHAP analysis revealed age and daily Bluetooth headset usage duration as the two most significant factors affecting thyroid nodule risk. Specifically, longer daily usage durations of Bluetooth headsets were strongly linked to an increased risk of developing thyroid nodules, as indicated by the SHAP analysis outcomes. Our study highlighted a significant impact relationship between prolonged Bluetooth headset use and increased thyroid nodule risk, emphasizing the importance of considering health impacts in the use of modern technology, especially for devices like Bluetooth headsets that are frequently used daily. Through precise model predictions and variable importance analysis, our research provides a scientific basis for the formulation of public health policies and personal health habit choices, suggesting that attention should be paid to the duration of Bluetooth headset use in daily life to reduce the potential risk of thyroid nodules. Future research should further investigate the biological mechanisms of this relationship and consider additional potential influencing factors to offer more comprehensive health guidance and preventive measures.

Newly discovered letter: why Muller failed to cite the negative mouse mutation findings of Snell, preserving his chances to receive the Nobel Prize.

A recently acquired letter between Hermann Muller and his wife (March 21, 1933) reveals that Muller had learned that he had been nominated for the Nobel Prize in 1932 with about 1/3 of the total votes being supportive. Muller was hopeful that over time sufficient votes would lead to receiving the award. The knowledge of Muller on this matter and its timing provide a likely explanation why Muller never cited the negative mouse mutation findings of George Snell, performed under Muller's direction during that time period. This action of Muller, along with the failure of Snell to promote his discovery, greatly reduced the chances that those findings would complicate his attempt to garner support for his LNT single-hit model and its application to hereditary and cancer risk assessment. It also helped Muller achieve the Nobel Prize, allowing him the necessary international visibility to promote his ideologically driven ionizing radiation-related LNT-based paradigm.

Quantitative morphological analysis of Deinococcus radiodurans elucidates complex dose-dependent nucleoid condensation during recovery from ionizing radiation.

The extremophile Deinococcus radiodurans maintains a highly organized and condensed nucleoid as its default state, possibly contributing to its high tolerance to ionizing radiation (IR). Previous studies of the D. radiodurans nucleoid were limited by reliance on manual image annotation and qualitative metrics. Here, we introduce a high-throughput approach to quantify the geometric properties of cells and nucleoids using confocal microscopy, digital reconstructions of cells, and computational modeling. We utilize this novel approach to investigate the dynamic process of nucleoid condensation in response to IR stress. Our quantitative analysis reveals that at the population level, exposure to IR induced nucleoid compaction and decreased the size of D. radiodurans cells. Morphological analysis and clustering identified six distinct sub-populations across all tested experimental conditions. Results indicate that exposure to IR induced fractional redistributions of cells across sub-populations to exhibit morphologies associated with greater nucleoid condensation and decreased the abundance of sub-populations associated with cell division. Nucleoid-associated proteins (NAPs) may link nucleoid compaction and stress tolerance, but their roles in regulating compaction in D. radiodurans are unknown. Imaging of genomic mutants of known and suspected NAPs that contribute to nucleoid condensation found that deletion of nucleic acid-binding proteins, not previously described as NAPs, can remodel the nucleoid by driving condensation or decondensation in the absence of stress and that IR increased the abundance of these morphological states. Thus, our integrated analysis introduces a new methodology for studying environmental influences on bacterial nucleoids and provides an opportunity to further investigate potential regulators of nucleoid condensation.IMPORTANCEDeinococcus radiodurans, an extremophile known for its stress tolerance, constitutively maintains a highly condensed nucleoid. Qualitative studies have described nucleoid behavior under a variety of conditions. However, a lack of quantitative data regarding nucleoid organization and dynamics has limited our understanding of the regulatory mechanisms controlling nucleoid organization in D. radiodurans. Here, we introduce a quantitative approach that enables high-throughput quantitative measurements of subcellular spatial characteristics in bacterial cells. Applying this to wild-type or single-protein-deficient populations of D. radiodurans subjected to ionizing radiation, we identified significant stress-responsive changes in cell shape, nucleoid organization, and morphology. These findings highlight this methodology's adaptability and capacity for quantitatively analyzing the cellular response to stressors for screening cellular proteins involved in bacterial nucleoid organization.

The Potential Radioprotective Effect of Piperine against Radiation-Induced Lung Injury in Mice: Histopathological and Biochemical Evaluations.

INTRODUCTION: It has been hypothesized that piperine, the main alkaloid component of black pepper, possesses a unique radioprotective effect. This study aimed to investigate the protective effect of piperine against Radiation-Induced Lung Injury (RILI) in mice. METHOD: Firstly, eighty male mice were divided into eight groups; the control group did not receive any dosage of piperine and radiation (6 Gy), and the other groups received piperine alone at doses 10, 25, and 50 mg/kg, radiation, and radiation-piperine combination (6 Gy + 10, 25, and 50 mg/kg). Animals received piperine by gavage for 7 consecutive days. To investigate the effect of piperine pretreatment in mice that were exposed to radiation, histopathological and biochemical evaluations (markers of oxidative stress) were performed. Irradiation led to an increase in oxidative stress (increase in MDA and PC). Pretreatment of piperine in all three doses in irradiated mice was able to reduce oxidative stress compared to mice that were only exposed to radiation. RESULTS: Piperine at a dose of 25 mg/kg exhibited the highest protective effect as compared to other doses. Also, in the histopathological examination, it was seen that pretreatment with piperine was able to improve the infiltration of inflammatory cells and reduce the thickness of the alveolar septum and air sac damage. CONCLUSION: The outcomes completely proved significant lung protection by piperine in mice through reducing oxidative stress. This natural compound could be considered a protective agent against lung injury induced by ionizing radiation.

Monte Carlo modelling of cyclotron and radioisotope center (CYRIC) at Tohoku University: a radiation protection study.

Protection against ionizing radiations is important in laboratories with radioactive materials and high energy cyclotron beams. The Cyclotron and Radioisotope Center (CYRIC) located in Tohoku University in Miyagi prefecture, Japan and is a well-known nuclear science laboratory with cyclotron beams and substantial number of high activity radioactive materials. Considering this, it is important to perform complete radiation transport computations to ensure the safety of non-occupational and occupational workers. In the present work, we have developed a complete 3-dimensional model of the main cyclotron building and radiation labs using Monte Carlo method. We have found that the dispersed photons and neutrons inside and in the surrounding of the CYRIC building pose no significant risk to occupational and non-occupational workers. The present work and the developed models would be useful in the field of radiation protection.