Objective To investigate the role of the O-6-methylguanine-DNA methyltransferase (MGMT) gene-3′ untranslated region (UTR) microRNA-associated single nucleotide polymorphism (miRSNP) (rs7896488 G>A) in affecting miR-4297-targeted modulation of MGMT in senescence of lung cells with polymorphic genotypes induced by fractionated low dose ionizing radiation (LDIR). Methods i) MiRSNPs were predicted and screened using bioinformatics, and DNA from two types of lung cells, A549 cells and human bronchial epithelioid cells (HBE cells), was extracted for target gene sequencing. After co-transfection of pGL3c-MGMT-3′UTR-rs7896488 G>A reporter gene recombinant plasmid, pRL-TK Vector with micrON mimic NC #22 or micrON hsa-miR-4297 mimic (set up as the mimic NC group and the miR-4297 mimic group) in these two types of lung cells, dual luciferase reporter gene assay was performed. The relative expression of MGMT mRNA was detected by real-time fluorescence quantitative polymerase chain reaction, and the relative expression of MGMT protein was detected by Western blotting. ii) These two types of lung cells were randomly divided into the control group and irradiation group, which received either 0 or 100 mGy X-rays irradiation seven times. After irradiation, the cells were transfected with either micrON mimic NC #22 or micrON hsa-miR-4297 mimic, resulting in mimic NC + control group, miR-4297 mimic + control group, mimic NC + irradiation group, and miR-4297 mimic + irradiation group. Cells were collected for senescence-associated-β-galactosidase (SA-β-Gal) staining, and the relative expression of matrix metalloproteinase-9 (MMP-9) and chemokine (C-X-C motif) ligand-1 (CXCL-1) proteins was detected via Western blotting. Results i) The rs7896488 G>A was the miRSNP located in the conserved binding region targeted by miR-4297 in the MGMT gene 3′UTR. A549 cells were the rs7896488 GG wild-type homozygous genotype, while HBE cells were the rs7896488 GA heterozygous mutant genotype. In the miR-4297 mimic group, A549 and HBE cells carrying the rs7896488 G allele showed significantly lower dual-luciferase activity compared with that in the mimic NC group (both P<0.01). However, there was no significant difference in dual-luciferase activity between the two groups in both A549 and HBE cells carrying the rs7896488 A allele (both P>0.05). The relative expression levels of MGMT mRNA and MGMT protein of A549 cells in the miR-4297 mimic group were lower than those in the mimic NC group (both P<0.05). However, there was no significant difference in MGMT mRNA and MGMT protein of HBE cells between these two groups (both P>0.05). ii) The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of A549 cells in the miR-4297 mimic+irradiation group were higher than those in the mimic NC + control group, the miR-4297 mimic + control group, and the mimic NC + irradiation group (all P<0.05). The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of HBE cells in the miR-4297 mimic + irradiation group were higher than those in the mimic NC + control group and the miR-4297 mimic + control group (all P<0.05), while there was no significant difference compared with those in the mimic NC + irradiation group (all P>0.05). Conclusion MGMT-3′UTR-miRSNP rs7896488 G>A plays a role in LDIR-induced senescence of lung cells with different polymorphic genotypes by affecting miR-4297-targeted regulation of MGMT.

Objective To investigate the effects of fractionated low-dose ionizing radiation (LDIR) on the ferroptosis in human bronchial epithelial (HBE) cells as well as the associated differentially expressed genes (DEGs), biological processes, and signaling pathways. Methods HBE cells were exposed to different single doses of X-ray irradiation (0, 25, 50, 75, and 100 mGy) for 24, 48, and 72 h, respectively. The change in cell viability was detected by MTT assay. Cells were irradiated with 0, 25, 50, and 100 mGy X-rays 5 times, with 48 h between each irradiation and a dose rate of 50 mGy/min. Cells were harvested 24 h after irradiation for the measurement of the expression of ferroptosis-related genes SLC7A11 and GPX4 at the mRNA and protein levels, cellular iron content, and the expression of FTH1 and FTL mRNAs. High-throughput sequencing was used to screen for the DEGs in each dose group, followed by Gene Ontology-Biological Process (GO-BP) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results Compared with the control group, single-dose LDIR significantly increased cell proliferation at 75 mGy after 24 h (P < 0.05), at 50, 75, and 100 mGy after 48 h (P < 0.05), and at 75 and 100 mGy after 72 h (P < 0.05). Compared with the control group, at the end of the fifth fractionated LDIR, SLC7A11 and GPX4 mRNAs decreased at all doses (P < 0.05), SLC7A11 protein decreased at all doses, GPX4 protein decreased at 25 and 100 mGy, iron content increased at all doses, and FTH1 and FTL mRNAs decreased at all doses (P< 0.05). Sequencing analysis identified 248, 30, and 291 DEGs and 10, 2, and 9 ferroptosis-associated genes at the three doses compared to the control. Gene Ontology-Biological Process analysis showed that DEGs were mainly enriched in biological processes such as response to lipids, cell death, and response to unfolded proteins. Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were mainly enriched in the JAK-STAT signaling pathway, lipids and atherosclerosis, ferroptosis, protein processing in the endoplasmic reticulum, and FoxO signaling pathway. Gene set enrichment analysis showed that DEGs were mainly enriched in ferroptosis, fatty acid degradation, and glutathione metabolism. Conclusion Fractionated low-dose radiation induced ferroptosis in HBE cells, and DEGs were predominantly enriched in biological processes and signaling pathways related to inflammation, ferroptosis, and endoplasmic reticulum stress.

Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

Objective To investigate the induction of senescence in L02 hepatocytes by low-dose fractionated X-ray radiation and its effects on oxidative stress, oxidative damage, and nuclear factor-κB (NF-κB) pathway protein levels. Methods L02 cells were subjected to fractionated X-ray irradiation at doses of 0.1, 0.2, and 0.5 Gy per fraction for a total of six fractions. Assays were performed 24 hours after the final irradiation. Measurements included SA-β-gal staining, the mRNAs of senescence-related genes p53 and p21 and their encoded proteins, mRNAs of genes encoding senescence-associated secretory phenotype factors (IL-6, IL-8, GM-CSF, MMP-15), reactive oxygen species, oxidative and anti-oxidative markers (malondialdehyde, glutathione, superoxide dismutase), DNA oxidative damage markers (8-OHdG and γ-H2AX), and NF-κB pathway protein levels. Results Compared with the control group, at 24 hours after the end of six irradiations, the number of cells positive in SA-β-gal staining was significantly increased in all dose groups. The mRNA and protein levels of p21 and p53 were significantly elevated in the 0.2 Gy × 6 and 0.5 Gy × 6 groups (P < 0.05). The mRNA levels of genes encoding IL-6, GM-CSF, and MMP-15 were significantly increased in all dose groups (P < 0.05). The mRNA levels of the gene encoding IL-8 were significantly increased in the 0.2 Gy × 6 and 0.5 Gy × 6 groups (P < 0.05). The levels of reactive oxygen species, malondialdehyde, and glutathione were significantly increased in all dose groups (P < 0.01). The level of superoxide dismutase was significantly increased in the 0.5 Gy × 6 group (P < 0.01). The levels of 8-OHdG were significantly increased in all dose groups (P < 0.05). In both the 0.2 Gy × 6 and 0.5 Gy × 6 groups, the expression levels of γ-H2AX and p-NF-κB p65 were significantly increased (P < 0.05), and the levels of IκBα were significantly decreased (P < 0.05). Conclusion Low-dose fractionated X-ray radiation can induce senescence and cause alterations in oxidative stress, oxidative damage, and the levels of NF-κB pathway proteins in L02 hepatocytes.

Objective To investigate the status of metabolically unhealthy status (MUS) and its influencing factors in male residents living around a uranium mine in Guangdong Province. Methods A total of 867 local male residents born and living around a uranium mine in Guangdong Province were selected as the study subjects using two-stage random sampling method. The residents were divided into 10 km- and 20 km- radius groups, according to their living distance <10 km or 10-20 km from the uranium mine. Blood pressure, fasting blood glucose, and blood lipid levels were tested among the study subjects. The influencing factors of MUS and its components were analyzed by multiple logistic regression. Results The detection rate of MUS was 42.2%. The detection rates of MUS component such as elevated diastolic blood pressure, elevated systolic blood pressure, elevated fasting blood glucose, elevated triglyceride and low high-density lipoprotein cholesterol (HDL-C) were 48.8%, 60.9%, 11.9%, 40.7% and 19.3%, respectively. The MUS detection rate in the 10 km group was lower than that in the 20 km group (38.5% vs 45.9%, P<0.05). The result of multivariate logistic regression analysis showed that subjects aged >50 years had a higher risk of MUS and elevated systolic blood pressure than those aged ≤ 50 years (all P<0.05). Drinkers had a higher risk of MUS, elevated systolic blood pressure, elevated diastolic blood pressure, elevated triglyceride, and low HDL-C than non-drinkers (all P<0.05). Those who ate fruit occasionally had a higher risk of MUS than those who ate fruit regularly (P<0.05). Overweight and obese individuals had a higher risk of MUS, elevated systolic blood pressure, elevated diastolic blood pressure, elevated triglyceride, and low HDL-C than those with normal body mass (all P<0.05). Individuals in the 20 km group had a higher risk of MUS and low HDL-C than the 10 km group (all P<0.05). Conclusion The risk factors of MUS detection among male residents living around the uranium mines are age > 50 years, drinking, occasional fruit intake, and being overweight or obese. Age > 50 years, drinking alcohol, overweight and obesity can affect the detection of MUS components in different degrees. Environmental radiation levels have not been identified as a risk factor for MUS in these study subjects.

Objective:To investigate the changes in liver injury and oxidative-antioxidant level in mice exposed to X-rays at varying doses.Methods:Fifty-four 8-week-old male C57BL/6J mice were divided into three groups, namely the control, 2 Gy irradiation, and 4 Gy irradiation groups. Then, each of the groups was further divided by days post-irradiation (i.e., 1, 3, and 7 d), and so nine sub-groups ( n = 6). After irradiation was performed as planned, all the mice were dissected and weighed, and their liver indexes were calculated to determine any histopathological changes in the liver. The peripheral blood cell count and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were detected. Furthermore, spectrophotometry was also used to determine the superoxide dismutase (SOD) activity, the malondialdehyde (MDA) concentration, and the reduced glutathione (GSH) concentration in liver tissues. Results:Compared to the control group, mice undergoing irradiation exhibited a significant reduction in body weight ( F = 84.03, 27.11, 25.50, P < 0.001), but significantly increased liver indexes ( F = 28.40, 17.75, P <0.001) at 1, 3, and 7 d post-irradiation. Pathological observations of these mice revealed liver injury, which proved related to dose and time course. The counts of leukocytes, neutrophils, and lymphocytes in peripheral blood decreased significantly ( F = 8.42-22.91, P < 0.05), trending downward with an increase in the radiation dose. For mice in the 4 Gy irradiation group, their AST and ALT levels increased significantly at 1 d post-irradiation ( H = 7.24, 7.82, P < 0.05), and their ALP levels rose notably at 1 and 3 d post-irradiation ( F = 11.86, 9.75, P < 0.05). Furthermore, their MDA and SOD levels initially rose and then dropped but their GSH levels exhibited an opposite trend at 1, 3, and 7 d post-irradiation. There was a positive correlation between their MDA levels in the liver and the degree of damage to histopathological lesions at 1, 3, and 7 d post-irradiation ( r = 0.30, P < 0.001). Conclusions:A model for radiation-induced liver injury of mice was preliminarily established in this study. It can be concluded that X-rays at varying doses affect the severity of liver injury, pathological grade, peripheral blood cell count, liver function index, and liver oxidative and antioxidant levels of mice, presenting a certain relationship between dose and time course effects.

Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.

Objective To investigate the mechanism of fractionated low-dose ionizing radiation (LDIR) in the induction of EA.hy926 cell senescence. Methods EA.hy926 cells were irradiated with X-ray at 0, 50, 100, and 200 mGy × 4, respectively, and cultured for 24, 48, and 72 h. Several indicators were measured, including the levels of cellular senescence-associated β-galactosidase (SA-β-gal) staining, mRNA levels of senescence-associated cell cycle protein-dependent kinase inhibitor genes CDKN1A and CDKN2A, reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and phosphorylated H2A histone family member X (γ-H2AX). Results After 4 fractionated LDIR, compared with the control group, the treatment groups showed increased nucleus area, blurred cell edge, and increased SA-β-gal positive area (P < 0.05) at 24, 48 and 72 h. After 4 fractionated LDIR, the mRNA level of CDKN1A increased in the 100 and 200 mGy × 4 groups at 24 and 48 h (P < 0.05), and CDKN2A mRNA level increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). The fluorescence intensity of ROS increased in treatment groups at 24, 48, and 72 h after 4 fractionated LDIR (P < 0.05). After 4 fractionated LDIR, the T-AOC level increased in the 100 and 200 mGy × 4 groups at 24 h (P < 0.05), and T-AOC level increased in all treatment groups at 48 and 72 h (P < 0.05). After 4 fractionated LDIR, γ-H2AX fluorescence intensity increased in all treatment groups at 24 h (P < 0.05), and the fluorescence intensity increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). Conclusion Fractionated LDIR can induce cellular senescence in EA.hy926 cells by impacting the cellular oxidation-antioxidation and oxidative damage levels, and the effects were relatively evident at 100 and 200 mGy.

Objective To investigate the effects of lowdose ionizing radiation (LDIR) on oxidative stress and damage repair in human bronchial epithelial (HBE) cells. Methods HBE cells were divided into 0, 50, 100, and 200 mGy groups, and cultured for 24 and 48 h after X-ray irradiation, respectively. The cell viability, levels of glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG), and transcriptional levels of DNA damage repair genes PPP2R2D and TP53 were measured. Results At 24 h after irradiation, there was no significant difference in the cell viability between the dose groups and the control group (P > 0.05); all dose groups had significantly increased MDA level, dose-dependently decreased GSH level, dose-dependently increased 8-OHdG level, and significantly increased mRNA level of PPP2R2D gene (all P < 0.05); the mRNA expression level of TP53 gene was significantly increased in the 50 mGy group (P < 0.05). At 48 h after irradiation, there were the highest cell viability, significantly decreased MDA and 8-OHdG levels, and significantly increased mRNA expression levels of PPP2R2D and TP53 genes in the 50 mGy group compared with the control group (all P < 0.05); the GSH level in the 100 mGy group was significantly increased (P < 0.05). Conclusion LDIR, especially radiation at 50 mGy, can affect the oxidative-antioxidant level in HBE cells and the transcript-level differential expression of DNA damage repair genes.

Objective:To analyze the serum lipid levels, and its influencing factors, of male residents around an uranium mine in order to provide a scientific basis for health risk assessment for such residents.Methods:With such a mine as the center, the surveyed subjects were divided into four groups as within 5, 10, 15 and 20 km of this mine, respectively. These male residents living around the mine were randomly selected as subjects. A health questionnaire survey was conducted among the subjects. The indicator such as height, weight and blood pressure were measured by means of the standard method. Peripheral venous blood was extracted from the subjects, and their venous blood glucose and serum lipid were detected. The levels of serum lipid and detectable rates of abnormal serum lipid were analyzed by using univariate analysis, and multivariate logistic regression analysis was used to analyze the influencing factors of dyslipidemia.Results:A total of 867 males at age 40 to 69 was included in the vicinity of the mine. The mean levels ( ± s) of TC, TG, LDL-C, and HDL-C were (5.46±1.11), (1.92±1.64), (3.19±1.02), and (1.39±0.43) mmol/L, respectively. 384 subjects with dyslipidemia were totally detected in the residents, and the detection rate was 44.29% (384/867). Of the residents with dyslipidemia, the majority was abnormal in two lipid related indexes (45.57%, 175/384). Univariate analysis result showed that there was statistically significant difference in TG level in different distance groups ( F=3.34, P<0.05). There were statistically significant differences in the abnormal detection rates of TG and HDL-C in subjects in different distance groups ( χ2=9.52, 10.18, P<0.05). The detection rates of dyslipidemia were significantly different in the groups of BMI, blood pressure and blood glucose ( χ2=45.91, 32.31, 11.42, P<0.05). Multivariate logistic regression analysis showed that excluding marital status and degree of education, the BMI, blood pressure and blood glucose all had an impact on dyslipidemia. The residents with overweight ( OR=2.08, 95% CI: 1.52-2.86) and obeseness ( OR=2.88, 95% CI: 1.58-5.24) had a higher risk for dyslipidemia than those with normal weight. The risks for dyslipidemia in the residents with hypertension ( OR=1.94, 95% CI: 1.45-2.60) and hyperglycemia ( OR= 2.17, 95% CI: 1.27-3.69) were higher than those with normal blood pressure and blood glucose, respectively. Conclusions:The detection rate of dyslipidemia is higher in male residents around the mine. The BMI, alcohol consumption, blood pressure, blood glucose and distance from the mine are influencing dyslipidemia and other relevant indexes. Overweight is an independent risk factor for dyslipidemia and its components. The distances from uranium mine has no significant effect on the dyslipidemia of male residents.