In vivo assessment of the toxic impact of exposure to magnetic iron oxide nanoparticles (IONPs) using Drosophila melanogaster.

Iron oxide nanoparticles (IONPs) have useful properties, such as strong magnetism and compatibility with living organisms which is preferable for medical applications such as drug delivery and imaging. However, increasing use of these materials, especially in medicine, has raised concerns regarding potential risks to human health. In this study, IONPs were coated with silicon dioxide (SiO2), citric acid (CA), and polyethylenimine (PEI) to enhance their dispersion and biocompatibility. Both coated and uncoated IONPs were assessed for genotoxic effects on Drosophila melanogaster. Results showed that uncoated IONPs induced genotoxic effects, including mutations and recombinations, while the coated IONPs demonstrated reduced or negligible genotoxicity. Additionally, bioinformatic analyses highlighted potential implications of induced recombination in various cancer types, underscoring the importance of understanding nanoparticle-induced genomic instability. This study highlights the importance of nanoparticle coatings in reducing potential genotoxic effects and emphasizes the necessity for comprehensive toxicity assessments in nanomaterial research.

Alcohol-free synthesis, biological assessment, in vivo toxicological evaluation, and in silico analysis of novel silane quaternary ammonium compounds differing in structure and chain length as promising disinfectants.

Quaternary ammonium compounds (QACs) are commonly used as disinfectants for industrial, medical, and residential applications. However, adverse health outcomes have been reported. Therefore, biocompatible disinfectants must be developed to reduce these adverse effects. In this context, QACs with various alkyl chain lengths (C12-C18) were synthesized by reacting QACs with the counterion silane. The antimicrobial activities of the novel compounds against four strains of microorganisms were assessed. Several in vivo assays were conducted on Drosophila melanogaster to determine the toxicological outcomes of Si-QACs, followed by computational analyses (molecular docking, simulation, and prediction of skin sensitization). The in vivo results were combined using a cheminformatics approach to understand the descriptors responsible for the safety of Si-QAC. Si-QAC-2 was active against all tested bacteria, with minimal inhibitory concentrations ranging from 13.65 to 436.74 ppm. Drosophila exposed to Si-QAC-2 have moderate-to-low toxicological outcomes. The molecular weight, hydrophobicity/lipophilicity, and electron diffraction properties were identified as crucial descriptors for ensuring the safety of the Si-QACs. Furthermore, Si-QAC-2 exhibited good stability and notable antiviral potential with no signs of skin sensitization. Overall, Si-QAC-2 (C14) has the potential to be a novel disinfectant.

Dose Volume and Liver Function Test Relationship following Radiotheraphy for Right Breast Cancer: A Multicenter Study.

OBJECTIVE: The liver is a critical organ at risk during right breast radiotherapy (RT). Liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) serve as biochemical markers for hepatobiliary damage. In this multicenter cross-sectional study, the effects of liver dose-volume on changes in LFTs pre- and post-RT in patients treated for right breast cancer were evaluated. MATERIALS AND METHODS: Between January 2019 and November 2022, data from 100 patients who underwent adjuvant right breast RT across three centers were retrospectively assessed. Target volumes and normal structures were contoured per the RTOG atlas. Patients were treated with a total dose of 50 Gy in 25 fractions to the CTV, followed by a boost to the tumor bed where indicated. The percentage change in LFT values in the first two weeks post-RT was calculated. Statistics were analyzed with SPSS version 22 software, with significance set at p < 0.05. Statistical correlation between liver doses (in cGy) and the volume receiving specific doses (Vx in cc) on the change in LFTs were analyzed using Kolmogorov-Smirnov, Mann-Whitney U test. RESULTS: The median age among the 100 patients was 56 (range: 29-79). Breast-conserving surgery was performed on 75% of the patients. The most common T and N stages were T1 (53%) and N0 (53%), respectively. None of the patients had distant metastasis or simultaneous systemic treatment with RT. A total of 67% of the treatments utilized the IMRT technique and 33% VMAT. The median CTV volume was 802 cc (range: 214-2724 cc). A median boost dose of 10 Gy (range: 10-16 Gy) was applied to 28% of the patients with electrons and 51% with IMRT/VMAT. The median liver volume was 1423 cc (range: 825-2312 cc). Statistical analyses were conducted on a subset of 57 patients for whom all three LFT values were available both pre- and post-RT. In this group, the median values for AST, ALT, and GGT increased up to 15% post-RT compared to pre-RT, and a median liver Dmean below 208 cGy was found significant. While many factors can influence LFT values, during RT planning, attention to liver doses and subsequent regular LFT checks are crucial. CONCLUSION: Due to factors such as anatomical positioning, planning technique, and breast posture, the liver can receive varying doses during right breast irradiation. Protecting patients from liver toxicity secondary to RT is valuable, especially in breast cancer patients with a long-life expectancy. Our study found that, even in the absence of any systemic treatment or risk factors, there was an average increase of nearly 15% in enzymes, indicating acute liver damage post-RT compared with pre-RT. Attention to liver doses during RT planning and regular follow-up with LFTs is essential.

Morphologically different hydroxyapatite nanoparticles exert differential genotoxic effects in Drosophila.

Hydroxyapatite (HAP) occurs naturally in sedimentary and metamorphic rocks and constitutes the hard structures in many organisms. Since synthetic nano-sized HAP (HAP-NPs) are used in orthopedic applications and for heavy metal remediation in aquatic and terrestrial media, both environment and humans are exposed to them. Due to the concerns about their potential hazards, the genotoxic effects that round/rod forms of HAP-NPs were investigated in Drosophila using the wing-spot and the comet assays. Furthermore, caspase activities were evaluated to examine the activation of cell death pathways. As a novelty, the expression of 36 genes involved in DNA repair was investigated, as a tool to indirectly determine DNA damage induction. Obtained sizes were 35-60 nm (roundHAP-NPs) and 45-90 nm (rodHAP-NPs) with a low Zeta-potential (-1.65 and 0.37 mV, respectively). Genotoxicity was detected in the wing-spot (round form), and in the comet assay (round and rod-like HA-NPs). In addition, increased expression of Caspases 3/7, 8, and 9 activities were observed. For both HAP forms, increased changes in the expression were observed for mismatch repair genes, while decreased expression was observed for genes involved in ATM, ATR, and cell cycle pathways. The observed changes in the repair pathways would reinforce the view that HAP-NPs have genotoxic potential, although more markedly in the round form. Thus, the environmental presence of engineered nanoparticles, including HAPs, raises concerns about potential effects on human health. It is essential that the effects of their use are carefully assessed and monitored to ensure safety and to mitigate any potential adverse effects.

Comparative evaluation of natural and artificial sweeteners from DNA damage, oxidative stress, apoptosis, to development using Drosophila melanogaster.

The overconsumption of added sugars makes people vulnerable to a myriad of diseases. Several biochemical and developmental assays were performed in the current study to assess the effect of fructose on Drosophila melanogaster and to find substitutes for fructose by comparing it to well-known sweeteners. Drosophila was exposed separately to the same ratio of sugar 9.21% (w/v) of several types of sweeteners (sucrose, fructose, glucose syrup, high-fructose corn syrup and stevia). Results revealed that fructose might induce recombination, whereas stevia lacks genotoxic potential. No developmental delay, growth defects, or neurotoxic effects were recorded for any of the sweeteners. We also observed no striking differences in reactive oxygen species levels. Thus, stevia seems to be an alternative sweetener to fructose that can be consumed to reduce fructose-induced anomalies.

Computational assessment of the biological response of curcumin to type 2 diabetes mellitus induced by metal exposure.

The current study aimed to identify the molecular mechanisms of a metal mixture (cadmium, nickel, and lead) involved in type 2 diabetes mellitus (T2DM) development and the therapeutic effect of curcumin in this metal mixture-induced T2DM. To accomplish this, SwissADME assessed the physicochemical and pharmacokinetic properties of curcumin and the Prediction of Activity Spectra for Substances evaluates its biological activities. The Comparative Toxicogenomics Database, Cytoscape, AutoDock Vina, and MicroRNA ENrichment TURned NETwork were used as tools to perform data-mining approaches and molecular docking. Curcumin properties were fitted within the acceptable range to be a promising drug candidate. The mixed metal altered 23 genes linked to T2DM development and targeted by curcumin. Curcumin had a dual-natured effect or antagonistic effect for most of the involved genes in T2DM and metal mixture. The most prominent biological processes were identified as ''response to external stimulus'', ''regulation of programmed cell death'', ''programmed cell death'', ''cell death'', and ''response to stress''. Three highly interacted miRNAs related to metal mixture-induced T2DM and targeted by curcumin (hsa-miR-98-5p, hsa-miR-34a-5p, and hsa-miR-155-5p) were identified. These findings could pave the way for further studies to evaluate the link between these genes and T2DM.

Genotoxic and genoprotective effects of phytoestrogens: a systematic review.

Phytoestrogens are xenoestrogens found in plants with a myriad of health benefits. However, various studies reported the genotoxic effects of these substances. Thus, we reviewed in vitro and in vivo studies published in PubMed, Scopus, and Web of Science to evaluate the genotoxic and the genoprotective potential of phytoestrogens. Only studies written in English and intended to study commercially available phytoestrogens were included. The screening was performed manually. Moreover, the underlying mechanism of action of phytoestrogens was described. Around half of those studies (43%) reported genoprotective results. However, several studies revealed positive results for genotoxicity with specific model organisms and with dose/concentration dependence. The assessment of the selected articles showed substantial differences in the used concentrations and a biphasic response was recorded in some phytoestrogens. As far as we know, this is the first study to assess the genotoxic and genoprotective effects of phytoestrogens systematically.

Genotoxic potential of different nano-silver halides in cultured human lymphocyte cells.

Most antibacterial applications in nanotechnology are carried out using silver nanoparticles (AgNPs). However, there is a dearth of information on the biological effects of AgNPs on human blood cells. In this study, the cytotoxic and genotoxic potentials of ionic silver (Ag+), AgNP, silver bromide (AgBr), silver chloride (AgCl), and silver iodide (AgI) were evaluated through chromosome aberration (CA) test and cytokinesis-blocked micronucleus (CBMN) test in human cultured lymphocytes in vitro. Furthermore, the potential damages that can cause to DNA were evaluated through alkaline single cell gel electrophoresis (Comet) assay on isolated lymphocytes. The results showed that AgNPs exerted cytotoxic effects by reducing the cytokinesis-block proliferation index and mitotic index at 24 and 48 h. AgNPs also increased micronucleus (MN) formation at both exposure times in the cultured cells. Meanwhile, AgCl had no genotoxic effects on the human lymphocyte cultured cells but had a cytotoxic effect at high doses. AgNP, Ag+, AgBr, and AgI caused substantial DNA damage by forming DNA strand breaks. They may also have clastogenic, genotoxic and cytotoxic effects on human lymphocyte cells. Based on the foregoing findings, silver nanomaterials may have genotoxic and cytotoxic potentials on human peripheral lymphocytes in vitro.

Genotoxic hazard assessment of cerium oxide and magnesium oxide nanoparticles in Drosophila.

The use of metal oxide nanoparticles (NPs) is steadily spreading, leading to increased environmental exposures to many organisms, including humans. To improve our knowledge of this potential hazard, we have evaluated the genotoxic risk of cerium oxide (CeO2NPs) and magnesium oxide (MgONPs) nanoparticle exposures using Drosophila as an in vivo assay model. In this study, two well-known assays, such as the wing somatic mutation and recombination test (wing-spot assay) and the single-cell gel electrophoresis test (comet assay) were used. As a novelty, and for the first time, changes in the expression levels of a wide panel of DNA repair genes were also evaluated. Our results indicate that none of the concentrations of CeO2NPs increased the total spot frequency in the wing-spot assay, while induction was observed at the highest dose of MgONPs. Regarding the comet assay, both tested NPs were unable to induce single DNA strand breaks or oxidative damage in DNA bases. Nevertheless, exposure to CeO2NPs induced significant increases in the expression levels of the Mlh1 and Brca2 genes, which are involved in the double-strand break repair pathway, together with a decrease in the expression levels of the MCPH1 and Rad51D genes. Regarding the effects of MgONPs exposure, the expression levels of the Ercc1, Brca2, Rad1, mu2, and stg genes were significantly increased, while Mlh1 and MCPH1 genes were decreased. Our results show the usefulness of our approach in detecting mild genotoxic effects by evaluating changes in the expression of a panel of genes involved in DNA repair pathways.

Genotoxic assessment of cerium and magnesium nanoparticles and their ionic forms in Eisenia hortensis coelomocytes by alkaline comet assay.

The present study aimed to evaluate the genotoxic potential of cerium oxide (CeO2 ), magnesium oxide (MgO) nanoparticles and their ionic forms by alkaline comet assay. Eisenia hortensis were exposed to different series of concentrations (25, 50, 100, 200, and 400 µg/ml) of chemicals for 48 h to find LC50 . The LC50 for MgO and CeO2 NPs were 70 and 80 µg/ml. Whereas, the LC50 for their ionic forms were 50 and 70 µg/ml. To assess the potential DNA damage caused by the chosen chemicals, E. hortensis was further exposed for 48 h to the following concentrations, based on their respective LC50s : LC50/2 , LC50 , and 2xLC50 . Comet scores demonstrated the significant increase (p < 0.05) in DNA damage at all concentrations, both for NPs and ionic forms in a concentration-dependent manner. Findings of the present study revealed the genotoxic effects of CeO2 NPs, MgO NPs and their ionic forms on E. hortensis. RESEARCH HIGHLIGHTS: Genotoxic assessment of CeO2 and MgO NPs and their ionic forms was conducted. Characterization of NPs through electron microscopy and alkaline comet assay was performed on E. Hortensis. Highest DNA damage of CeO2 and MgO NPs was observed on earthworm.

Comparison of pre-PICU and per-PICU interventions, clinical features and neurologic outcomes of motor vehicle collision trauma and other mechanisms of trauma in children.

BACKGROUND: Motor vehicle collisions (MVCs) are the number one cause of death in the pediatric age group. The aim of this study was to determine the differences between MVCs and other trauma mechanisms (OTMs) in patients who were followed up at a pediatric intensive care unit (PICU). METHODS: Data were retrospectively collected for pediatric trauma patients hospitalized at a third level PICU between 2014 and 2018. Patients have been divided into two groups as MVC and OTM. Demographic data, pre-PICU interventions (cardiopulmonary resuscitation, intubation, injury severity scores, time period before intensive care), intensive care interventions (invasive mechanical ventilation, non-invasive mechanical ventilation, need for surgery, type of surgery, need for transfusion, and inotrope therapy) were compared between two groups. Outcomes were evaluated by survival, discharge from hospital, Pediatric Cerebral Performance Cate-gory (PCPC) at discharge, tracheotomy presence, and amputation performed. RESULTS: During the 5-year study period, 135 patients were hospitalized for trauma. The injured body regions were the head and neck (61.5%), abdomen and lumbar spine (39.4%), and extremities and pelvis (36.3%). Multiple trauma was mostly seen in the MVC trauma group (p=0.001). The need for invasive mechanical ventilation and inotrope therapy was greater in the MVC group (p=0.002, 0.001 respectively). One hundred and twenty-three patients (91.1%) survived. The mortality rate was higher in the MVC group (p=0.026). The PCPC results were better in the OTM group (p=0.017). CONCLUSION: MVCs lead to more multiple trauma cases than OTMs. Invasive mechanical ventilation, inotropes, and other inten-sive care interventions were necessary much more often in MVC victims than in OTM patients.

An Evaluation of the Genotoxic Effects of Electromagnetic Radiation at 900 MHz, 1800 MHz, and 2100 MHz Frequencies with a SMART Assay in Drosophila melanogaster.

With the development of today's technology, the electromagnetic radiation spread by mobile phones and base stations is also rapidly increasing, and this causes serious concerns about the environment and human health. The Drosophila model organism is widely used in genetic toxicology studies because its genome is highly similar to the genes identified in human diseases. In this study, the genotoxic effects of radiofrequency electromagnetic radiation were evaluated by the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster at 900 MHz, 1800 MHz, and 2100 MHz. The SMART method is based on the observation of genetic changes occurring in the trichomes of the Drosophila wings appearing as mutant clones under the microscope. Throughout the study, total clone parameters were evaluated by exposing the Drosophila larvae to electromagnetic fields for two, four, and six hours per day for two days. As a result of the study, it was observed that the number of mutant clones was statistically increased according to the negative control group in all applications except for the six-hour application at 1800 MHz.

Demographic characteristics and delayed neurological sequelae risk factors in carbon monoxide poisoning.

AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240 days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43 ±â€¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.

Ameliorative effects of melatonin against nano and ionic cobalt induced genotoxicity in two in vivo Drosophila assays.

The aim of this study is to evaluate the ameliorative effect of melatonin (MEL) against induced genotoxicity by cobalt (II) chloride (CoCl2) and cobalt nanoparticles (CoNPs) (50 nm). Genotoxicity of CoCl2 and CoNPs were investigated using single cell gel electrophoresis (COMET) in Drosophila melanogaster hemocytes, which are blood cells of the Drosophila, and the somatic mutation and recombination test (SMART) was used to investigate mutant effects on the Drosophila wings. Three concentrations (0.1, 1, and 10 mM) of CoNPs and CoCl2 were applied to demonstrate their genotoxic potential. Both CoNPs and CoCl2 have mutagenic potential for the three concentrations tested in the COMET assay; however, only the 10 mM concentration of the ionic form and two high concentrations (1 and 10 mM) of CoNPs induced genotoxicity in the Drosophila SMART assay. Three different concentrations of MEL (0.1, 0.5 and 2.5 mM) were used against cobalt at highest concentration (10 mM) of both CoCl2 and CoNPs in both the SMART and COMET assays. MEL ameliorated the genotoxicity induced by CoCl2 and CoNPs in vivo Drosophila COMET and SMART assays.

In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles.

Triticum aestivum plant extracts are often used as a natural healer in traditional medicine but which particles mainly have role in these processes are not scientifically proven. In other words, no attempts have been made to investigate the effects of wheat exosomes in regenerative medicine applications or drug development up to now. The current study was first time performed to demonstrate the activity of wheat exosomes in wound healing process using in vitro approaches. Although its fundamental wound healing process remains a mystery, in the current study, the efficiency of wheat grass juice-derived exosomes on cell viability and migration was examined. Increasing concentrations up to 200 µg/mL of the wheat exosome have yielded astonishing proliferative and migratory effects on endothelial, epithelial, and dermal fibroblast cells. RT-PCR analysis also showed collagen type I; mRNA levels were approximately twofold higher in expression after treating with 200 µg/mL wheat exosome. Additionally, Annexin V staining of apoptotic cells accompanied with the cell cycle analysis resulted with the reduction of the apoptotic cell number with no dispersion to the cell cycle analysis while plant exosomes have also increased tube-like structure formation of the endothelial cells. All in all, this research suggests a brand-new opening for skin wound healing therapy strategy by using wheat-derived exosomes due to its proliferative and migratory characteristics. Plant exosomes require a further research both clinically and in in vivo for wound healing drug development. Moreover, plant exosome therapy strategies would be safer and economical alternative for clinical wound healing.

Screening Effects of Methanol Extracts of Diplotaxis tenuifolia and Reseda lutea on Enzymatic Antioxidant Defense Systems and Aldose Reductase Activity.

OBJECTIVES: The aim of the study was to investigate the effects of methanol extracts from the flowers and leaves of Diplotaxis tenuifolia and Reseda lutea on the activity of AR, CAT, GST, and GPx. MATERIALS AND METHODS: Total phenolic and flavonoid contents of the plant samples were evaluated using Folin-Ciocalteu reagent and aluminum chloride colorimetric methods. Also, the effects of extracts on CAT, GST, GPx, and AR enzyme activities were investigated using kinetic assays. RESULTS: The highest phenolic and flavonoid contents were detected in the methanol extract of D. tenuifolia leaves with 144.49±0.29 mg gallic acid equivalent/L and 250.485±0.002 quercetin equivalent/L, respectively. The best activity profile for GST and GPx were observed in the extract of leaves belonging to D. tenuifolia with IC50 values of 121±0.05 and 140±0.001 ng/mL, respectively. According to the results, methanol extracts from leaves of R. lutea and D. tenuifolia showed no significant activity potential on AR. Moreover, none of the studied extracts demonstrated any reasonable CAT activation potential. CONCLUSION: The results indicated that leaves of D. tenuifolia had good effect on the antioxidant enzymatic defense system, which it makes it a good constituent of the daily diet.