Genotoxicity responses of single and mixed exposure to heavy metals (cadmium, silver, and copper) as environmental pollutants in Drosophila melanogaster.

Heavy metals are now persistently present in living things' environments, in addition to their potential toxicity. Therefore, the aim of this study was to utilize D. melanogaster to determine the biological effects induced by different heavy metals including cadmium chloride (CdCl2), copper (II) sulfate pentahydrate (CuSO 4.5 H2O), and silver nitrate (AgNO3). In vivo experiments were conducted utilizing three low and environmentally relevant concentrations from 0.01 to 0.5 mM under single and combined exposure scenarios on D. melanogaster larvae. The endpoints measured included viability, reactive oxygen species (ROS) generation and genotoxic effects using Comet assay and the wing-spot test. Results indicated that tested heavy metals were not toxic in the egg-to adult viability. However, combined exposure (CdCl2+AgNO3 and CdCl2+AgNO3+CuSO 4.5 H2O) resulted in significant genotoxic and unfavorable consequences, as well as antagonistic and/or synergistic effects on oxidative damage and genetic damage.

Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.

Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets. Here, we created G47Δ-KR, clinical oncolytic herpes simplex virus G47Δ that expresses photosensitizer protein KillerRed (KR). Optical properties and cytotoxic effects of G47Δ-KR infection followed by amber LED illumination (peak wavelength: 585-595 nm) were examined in human glioblastoma (GBM) and malignant meningioma (MM) models in vitro. G47Δ-KR infection of tumor cells mediated KR expression that was activated by LED and produced reactive oxygen species, leading to cell death that was more robust than G47Δ-KR without light. In vivo, we tested photodynamic-oncolytic virus (PD-OV) therapy employing intratumoral injection of G47Δ-KR followed by laser light tumor irradiation (wavelength: 585 nm) in GBM and MM xenografts. PD-OV therapy was feasible in these models and resulted in potent anti-tumor effects that were superior to G47Δ-KR alone (without laser light) or laser light alone. RNA sequencing analysis of post-treatment tumor samples revealed PD-OV therapy-induced increases in TME infiltration of variable immune cell types. This study thus demonstrated the proof-of-concept that G47Δ-KR enables PD-OV therapy for neuro-oncological malignancies and warrants further research to advance potential clinical translation.

Interactions of Ingested Polystyrene Microplastics with Heavy Metals (Cadmium or Silver) as Environmental Pollutants: A Comprehensive In Vivo Study Using Drosophila melanogaster.

Living organisms are now constantly exposed to microplastics and nanoplastics (MNPLs), and besides their toxic potential, they can also act as carriers of various hazardous elements such as heavy metals. Therefore, this study explored possible interactions between polystyrene microplastics (PSMPLs) and two metal pollutants: cadmium chloride (CdCl2) and silver nitrate (AgNO3). To better understand the extent of biological effects caused by different sizes of PSMPLs, we conducted in vivo experiments with five doses (from 0.01 to 10 mM) that contained polystyrene particles measuring 4, 10, and 20 µm in size on Drosophila larvae. Additional experiments were performed by exposing larvae to two individual metals, CdCl2 (0.5 mM) and AgNO3 (0.5 mM), as well as combined exposure to PSMPLs (0.01 and 10 mM) and these metals, in an attempt to gain new insight into health risks of such co-exposure. Using transmission electron microscopy imaging, we managed to visualize the biodistribution of ingested PSMPLs throughout the fly's body, observing the interactions of such plastics with Drosophila intestinal lumen, cellular uptake by gut enterocytes, the passage of plastic particles through the intestinal barrier to leak into the hemolymph, and cellular uptake by hemocytes. Observations detected size and shape changes in the ingested PSMPLs. Egg-to-adult viability screening revealed no significant toxicity upon exposure to individual doses of tested materials; however, the combined exposure to plastic and metal particles induced aggravated genotoxic effects, including intestinal damage, genetic damage, and intracellular oxidative stress (ROS generation), with smaller sized plastic particles + metals (cadmium and silver) causing greater damage.