Mechanisms of piperonyl butoxide cytotoxicity and its enhancement with imidacloprid and metals in Chinese hamster ovary cells.

The widespread use of chemicals and the presence of chemical and metal residues in various foods, beverages, and other consumables have raised concerns about the potential for enhanced toxicity. This study assessed the cytotoxic effects of Piperonyl butoxide (PBO) and its enhancement by combination with major contamination chemicals including Imidacloprid and metals, using different cytotoxic and genotoxic assays in Chinese hamster ovary (CHO) cells. PBO exhibited elevated cytotoxic effects in poly (ADP-ribose) polymerase (PARP) deficient CHO mutants but not in Glutathione S-transferase deficient CHO mutants. PBO cytotoxicity was enhanced by PARP inhibitor, Olaparib. PBO cytotoxicity was also enhanced with co-exposure to Imidacloprid, Lead Chloride, or Sodium Selenite. PBO induces γH2AX foci formation and apoptosis. The induction of DNA damage markers was elevated with PARP deficiency and co-exposure to Imidacloprid, Lead Chloride, or Sodium Selenite. Moreover, PBO triggers to form etch pits on plastic surfaces. These results revealed novel mechanisms of PBO cytotoxicity associated with PARP and synergistic effects with other environmental pollutants. The toxicological mechanisms underlying exposure to various combinations at different concentrations, including concentrations below the permitted limit of intake or the level of concern, require further study.

The contribution of high-LET track to DNA damage formation and cell death for Monoenergy and SOBP carbon ion irradiation.

Carbon ion radiotherapy (CIRT) is a heavy ion charge particle therapy with 29 years of prominent use. Despite advantages like high relative biological effectiveness (RBE), improved quality of life, and reduced treatment time, challenges persist, especially regarding heavy nuclear fragments. Our research addresses these challenges in horizontal irradiation, aiming to comprehend Monoenergetic and Spread-Out Bragg peak (SOBP) carbon ion beam trajectories using cell survival analysis and visualizing biological effects through DNA damage (γ-H2AX). This reveals repair-related protein foci near the Bragg peak. CR-39, a plastic nuclear track detector, was explored to understand high-linear energy transfer (LET) tracks and radiation quality near the Bragg peak. Findings unveil high-LET DNA damage signatures through aligned γ-H2AX foci, correlating with LET values in SOBP. CR-39 visualized high-LET particle exposure, indicating comet-type etch-pits at the Bragg peak and suggesting carbon ion fragmentation. Unexpectedly, dot-type etch-pits in irradiated and post-Bragg peak regions indicated high-LET neutron production. This investigation highlights the intricate interplay of carbon ion beams, stressing the importance of understanding LET variations, DNA damage patterns, and undesired secondary exposure.

Predictive Role of Pretreatment Circulating miR-221 in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Aberrantly expressed circulating microRNAs (miRNAs) have been demonstrated to have a crucial role in the diagnosis and prognostication of various cancers, including hepatocellular carcinoma (HCC). This research aimed to examine the role of specific miRNAs in predicting the outcomes for individuals with hepatitis B virus (HBV)-related HCC treated with transarterial chemoembolization (TACE). Stored serum specimens collected prior to the first TACE procedure were employed to determine the expression of serum miR-122, miR-221, and miR-224 using quantitative real-time PCR analysis. The study included 100 HCC patients (84% males, with an average age of 60 years) who were treated with TACE. Throughout the median follow-up spanning 18.5 months (within a range of 3 to 60 months), 42 (42.0%) patients met the criteria of TACE refractoriness. Through multivariate analysis, elevated expressed miR-221 (≥4.0 log10 copies) and advanced HCC staging were identified as independent factors related to TACE refractoriness and short overall survival. However, serum miR-122 and miR-224 levels were not linked to treatment response or overall survival. These findings underscored the potential of incorporating pretreatment levels of serum miR-221 into the established tumor staging to enhance the accurate assessment of TACE responsiveness and prognostic outcome of patients with HCC.

From Basic Radiobiology to Translational Radiotherapy.

The Special Issue, entitled "From basic radiobiology to translational radiotherapy", highlights recent advances in basic radiobiology and the potential to improve radiotherapy in translational research [...].

Prognostic significance of uPA and uPAR expression in patients with cervical cancer undergoing radiotherapy.

Cervical cancer remains a major health threat. Urokinase serves as a marker of metastatic tumors. The present study aimed to determine whether the expression levels of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR), before and during the course of radiotherapy, serve as prognostic markers for patients with cervical cancer. Cervical tumor tissue biopsies were collected from 72 patients before radiotherapy and after the completion of external beam radiotherapy (EBRT) before intracavitary brachytherapy. The levels of uPA and uPAR were determined using ELISA assays. The significance of the associations between the protein expression levels and the clinical outcomes of patients was determined. Although irradiation enhanced uPA and uPAR expression in cervical cancer cell lines, average uPA levels significantly decreased in tumors, and uPAR levels significantly increased after EBRT. The levels of uPA increased in 12 patients and decreased in 26 patients; and those of uPAR increased in 13 patients and decreased in two patients. Cox regression analysis revealed that increased expression of uPAR was significantly associated with 5-year overall survival rate [hazard ratio (HR), 3.65; 95% confidence interval (CI), 1.18-11.30]. However, the levels of both proteins before radiotherapy failed to predict clinical outcomes. Other significant predictive factors were partial response (HR 7.22; 95% CI 1.17-44.73) and disease progression (HR, 13.41; 95% CI, 1.17-153.07). These findings indicated that increased expression of uPAR in cervical tumor tissue during radiotherapy may serve as a prognostic marker for patients with cervical cancer.