Dose-Response最新文献

Objectives: The intestine exhibits high radiosensitivity and is susceptible to damage during radiotherapy for abdominal or pelvic tumors, especially at radiation doses exceeding 5 Gy, which can lead to severe gastrointestinal complications. This study aims to elucidate the mechanisms of DNA repair and immune responses in radiation-induced intestinal injury, with the goal of enhancing radiotherapy efficacy.

Methods: We employed weighted correlation network analysis (WGCNA) to analyze RNA sequencing data from intestinal tissues collected at various time points following irradiation, as well as from mice with targeted disruption of the NFE2-like bZIP transcription factor 2 (Nrf2) gene and their wild-type counterparts.

Results: Our analysis revealed enhanced DNA repair capacity and attenuated immune response 3.5 days after irradiation. Histone variants and ribosomal proteins were identified as potential contributors to DNA repair processes. We also constructed a competing endogenous RNAs (ceRNA) network including genes from both the DNA repair and immune modules and identified Akr1b8, Gsta3, and Nqo1 as radiation-effect genes regulated by Nrf2.

Conclusions: These findings provide valuable insights into the molecular mechanisms of radiation-induced intestinal injury and suggest potential targets for protecting normal intestinal tissue during radiotherapy. This knowledge may contribute to improved treatment outcomes and enhanced patient well-being.

NCRP Commentary-27 reaffirmed Linear No Threshold (LNT) as the basis for radiation protection and listed six studies with "strong support" for LNT. This paper looks critically at these six studies and shows that they do not support LNT in the dose range of 0-100 mGy. These studies typically admit to no increase in cancer risk at significant dose levels. More importantly this paper shows that these studies assume LNT from the outset, underestimate uncertainty, ignore confounding factors, have biased control groups, and underestimate dose.

Purpose: Application of energy-spectrum computed tomography (CT) to assess specific efficacy of and response to carbon ion radiotherapy (CIRT) of C6 gliomas in rats.

Methods: After establishing C6 glioma rat models, 3 tumor-bearing rats were randomly selected as controls. The remaining were divided into 0 Gy, 1 Gy, and 2 Gy groups for CIRT. Energy-spectrum CT scans were performed, and brain tissues were collected for histopathology and western blot Test. Survival rates in each group were compared.

Results: The results demonstrated that tumors in the 1 Gy and 2 Gy groups decreased at different rates up to 14 days post-CIRT (P < 0.05). Furthermore, compared to pre-CIRT measurements, the energy-spectrum parameters gradually increased in the 0 Gy group, while they decreased in the 2 Gy group. Post-CIRT, the Ki-67 proliferation index and the expression levels of vascu-larassociated proteins in tumor tissues were significantly reduced in the 1 and 2 Gy groups. Additionally, the survival times of tumor-bearing rats were prolonged after CIRT.

Conclusions: CIRT effectively restricts tumor cell growth and proliferation, leading to improved survival rates in rats with C6 gliomas. The use of energy-spectrum CT with immunohistochemistry for quantitative detection can actively support the effectiveness of carbon ion radiotherapy in inhibiting tumor proliferation.

This study constructed a predictive model for occurrence of radiation esophagitis during breast-cancer radiotherapy. 308 breast-cancer patients were analyzed. Lasso regression identified crucial variables that were further integrated into a radiation esophagitis risk score, which was used to segregate patients into high- and low-risk groups. A nomogram model was designed for clinical applicability. Training and validations were performed to assess robustness and generalizability of proposed models, employing C-index, AUCs, calibration curves, and decision curves. SHAP algorithm was used for model interpretation, offering insights into the major contributory factors. Seven significant variables were identified by Lasso regression. C-indexes of nomograms of individual clinical variables and risk score were 0.795 and 0.784, respectively, exhibiting strong predictive ability. In internal validation, AUCs for risk score, nomogram, and logistic models were 0.784, 0.795, and 0.812, respectively. Calibration curves showed a close fit between predicted and observed outcomes across models. Decision curve analysis indicated logistic model's superior clinical utility when the risk threshold was above 0.2. SHAP interpretation emphasized radiation dose, pruritus, molecular type, and hepatic dysfunction as top contributory factors for radiation esophagitis. Models based on interpretable machine learning offer an intuitive tool to assess risk of radiation esophagitis in breast-cancer radiotherapy.

Background: We are exposed to natural ionizing radiation and other genomic stressors throughout life and radiophobia has caused much harm to society. The main basis for radiophobia is the invalid linear no-threshold (LNT) hypothesis for cancer induction, which the System of Radiological Protection (SRP) is linked to. Largely unknown to the public, evolution-associated genomic stress adaptation (gensadaptation) over many previous generations now provides protection to all lifeforms from low radiation doses. Objective: To help bring about an improved SRP not linked to the invalid LNT hypothesis for radiation-caused health detriment and to promote low-dose radiation therapy for different diseases. Methods: All-solid-cancer mortality risk dose-response relationships for A-bomb survivors were generated based on published LNT-modeling-related results. Dose-response relationships for lung cancer prevention by low-dose radiation were generated by linear interpolation based on published data from a study using > 15,000 mice. Uncertainty characterization was based on Monte Carlo calculations for binomial and Poisson distributions. New dose characterization tools were used for threshold dose-response relationships for radiation-caused cancer mortality. Results: The all-solid-cancer mortality risk for A-bomb survivors transitioned from LNT to threshold-linear when adjusted for key missing uncertainty at low doses. The prevention of lung cancer in mice by low radiation doses depends on the radiation absorbed dose and type. Conclusions: The SRP should be linked to population dose thresholds rather than the invalid LNT hypothesis and small likely harmless radiation doses could possibly be used in treating different diseases.

Background: Abrupt inflammation and alveolar epithelial membrane damage, which may cause the alveolar membrane's malfunction, are related to acute lung injury (ALI). This could eventually lead to pulmonary fibrosis. While lung injury can happen in many ways, the current study will concentrate on the changes in lung pathology mediated by paraquat (PQ). Paraquat, a widely used herbicide, targets lung toxicity through inflammation and oxidative stress, which significantly contribute to lung damage.

Objective: The current research was to ascertain whether low-dose gamma radiation (R) and misoprostol (MP) could lessen the lung inflammatory cascade started by PQ injection in rats.

Methods: The ALI model was induced by I.P. injection of PQ (20 mg/kg once), and then treatment was done by MP and/or R for 14 days, and finally, the biochemical and histological parameters were measured in the lung tissues.

Results: Our data suggest that PQ can promote ALI through TGF-β/smad, Notch, NF-κB, and ET-1 signaling pathways, resulting in EMT. These suggestions were supported by increased levels of TGF-β, inflammatory cytokines, α-SMA, NF-κB, ET-1, CTGF protein, and LPA, whereas PPAR-γ decreased. The aforementioned results have been confirmed by lung histopathology.

Conclusion: We suggest that the pulmonary inflammatory cascade was hindered and all the previously described gauges improved with R and/or MP therapy.

Purpose: The aim is to investigate the response of peripheral blood lymphocytes to a low-dose neutron-gamma field. Methods: The human peripheral blood was exposed to low-dose neutron-gamma radiation ex vivo. Flow cytometry was utilized to evaluate the changes in cell cycle and protein levels of p21, CDK2, and γH2AX. qPCR analysis was conducted to investigate the mRNA transcription of p21 and CDK2. The chromosomes aberration and micronucleus rate in peripheral blood lymphocytes were observed by microscope. Results: Within the radiation dose range of 0-5976 μGy, compared to the "0" dose group, there was an increase in the proportion of cells in G1 phase and a decrease in the proportion of cells in G2 phase. Additionally, there was an upregulation of p21 and γH2AX protein expression, a downregulation of CDK2 protein expression, and an increase in transcription levels of p21 and CDK2 mRNA. Furthermore, there was an elevation in the rate of chromosome aberrations in peripheral blood lymphocytes; however, no significant change of micronuclei rate was observed. Conclusions: The response of human lymphocytes to low dose neutron gamma irradiation can be reflected by the changes of cell cycle, chromosome aberration and RPS18 expression.

Objectives: Melatonin has been documented as an antioxidant agent. Numerous investigations have documented melatonin's radioprotective impact; however, investigation of its role post-irradiation requires further studies. Thus, the present study investigated melatonin's mitigating effect against radiation-induced alteration in the ovaries and reproductive hormones in female albino rats. Methods: Melatonin (10 mg/kg body weight, i. p.) was administered to the animals for 7, 11, and 15 days after whole-body exposure to 4 Gy γ-radiation. Results: The results demonstrated that melatonin has significantly attenuated the radiation-induced oxidative stress in the ovary, manifested by a decrease in protein carbonyl and malondialdehyde in conjunction with an increase in total antioxidant capacity. In addition, melatonin has alleviated the radiation-induced increase of the pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin-6, interleukin-1 beta) and caspase-3 levels in the serum. These results were accompanied by a noticeable improvement in serum E2-estradiol, testosterone, progesterone, follicle-stimulating hormone, and luteinizing hormone compared to their respective levels in the irradiated group. Conclusion: It could be concluded that melatonin is an effective agent for minimizing the deleterious impacts of radiation on the ovaries and reproductive hormones through synergistic interdependence between anti-inflammatory, antioxidant, and anti-apoptotic activities.

The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) had demonstrated a synergistic therapeutic effect, albeit with the occurrence of overlapping pulmonary toxicities. We established a mouse model using programmed cell death protein-1 (PD-1) antibody at different time points after thoracic radiotherapy. Hematoxylin and eosin (HE) staining, as well as TUNEL staining, were utilized for the morphological assessment of lung tissue damage. Inflammatory cells and cytokines present in bronchoalveolar lavage fluid (BALF) were analyzed using flow cytometry and cytometric bead array immunoassay (CBA). Additionally, immunohistochemistry (IHC) and immunofluorescence (IF) staining were conducted to observe the infiltration of inflammatory cells in lung tissue. Immediate administration of PD-1 antibody after thoracic radiotherapy resulted in more severe lung tissue injury compared to delayed administration. Concurrent treatment led to an increase in lymphocytes and neutrophils in BALF, as well as higher levels of inflammatory cytokines. IHC and IF analysis revealed that neutrophils, macrophages, and lymphocytes were more prominent in the concurrent treatment group. A more severe lung injury occurred when PD-1 antibody was given simultaneously with thoracic radiotherapy, possibly due to increased inflammation caused by the combination treatment.