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Abstract While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage‐induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage‐induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.

Purpose: Recent studies indicate that shift work may affect workers' eating habits and overall well-being. This study aimed to assess differences in eating patterns, sleep quality, and mental health between Italian shift and non-shift workers, with a focus on individual chronotype and the type of shift work (day vs. night shift). Methods: The cross-sectional study involved 322 subjects (166 shift and 156 non-shift workers). Eating habits were evaluated using a 7-day diary and the Medi-Lite questionnaire. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and mental health with the Depression Anxiety Stress Scales (DASS). Individual chronotype was defined using the Morningness-Eveningness Questionnaire. Results: No significant differences in daily energy, macronutrient, and micronutrient intake between the two groups, nor in the temporal pattern of eating. However, shift workers had significantly (p < 0.05) lower adherence to the Mediterranean diet (MD) (7.6 ± 2.3 vs 8.1 ± 2.2) compared to non-shift workers. Shift workers also reported significantly poorer sleep quality (mean PSQI score 7.6 ± 3.7 vs. 5.8 ± 3.0) and higher levels of anxiety and stress symptoms. Among shift workers, those with an evening chronotype had significantly lower MD adherence than those with a morning chronotypes. Additionally, night shift workers experienced more sleep disturbances compared to day ones. Conclusion: Shift workers reported lower MD adherence, poorer sleep quality, and a higher prevalence of anxiety and stress symptoms compared to a similar group of non-shift workers. Evening chronotypes and night shift work were associated with worse eating habits and sleep quality. [ABSTRACT FROM AUTHOR]

Background: Previous studies employing polymeric micelles and molecular imaging for in vivo nanosystem characterization have led to the development of radionanoprobes (RNPs) designed for diagnosing and monitoring therapeutic interventions in preclinical oncology research, specifically within breast and colon cancer models. These models exhibit high GLUT1 expression on tumor cells and VEGFR expression on the tumor vasculature. We aimed to enhance the tumor-targeting specificity of these RNPs by functionalizing micelles with glucose and bevacizumab. The choice of 99mTc to label the nanoprobes is based on its availability and that direct labeling method is a widespread strategy to prepare radiopharmaceuticals using cold reagents and a 99Mo/99mTc generator. Soluplus® is an attractive polymer for synthesizing micelles that also allows their functionalization. With all the above, the objective of this work was to design, develop and characterize nanoprobes based on polymeric micelles and radiolabeled with 99mTc for the characterization of biological processes associated to the diagnosis, prognosis and monitoring of animal models of breast and colon cancer in preclinical research using molecular images. Results: Four RNPs ([99mTc]Tc-Soluplus®, [99mTc]Tc-Soluplus®+TPGS, [99mTc]Tc-Soluplus®+glucose and [99mTc]Tc-Soluplus®+bevacizumab) were produced with high radiochemical purity (> 95% in all cases) and stability in murine serum for up to 3 h. The RNPs maintained the 100 nm size of the Soluplus® polymeric micelles even when they were functionalized and labeled with 99mTc. The image acquisition protocol enabled the visualization of tumor uptake in two cancer experimental models using the assigned RNPs. In vivo biological characterization showed signal-to-background ratios of 1.7 ± 0.03 for [99mTc]Tc-Soluplus®+TPGS, 1.8 ± 0.02 for [99mTc]Tc-Soluplus®, and 2.3 ± 0.02 for [99mTc]Tc-Soluplus®+glucose in the breast cancer model, and 1.8 ± 0.04 for [99mTc]Tc-Soluplus® and 3.7 ± 0.07 for [99mTc]Tc-Soluplus®+bevacizumab in the colon cancer model. Ex vivo biodistribution, showed that the uptake of the tumors, regardless of the model, is < 2% IA/g while the blood activity concentration is higher, suggesting that the enhanced permeability and retention effect (EPR) would be one of the mechanisms involved in imaging tumors in addition to the active targeting of RNPs. Conclusions: Soluplus®-based polymeric micelles provide a promising nanotechnological platform for the development of RNPs. The functionalization with glucose and bevacizumab enhances tumor specificity enabling effective imaging and monitoring of cancer in animal models. [ABSTRACT FROM AUTHOR]

While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage‐induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage‐induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor. Synopsis: Genetic screens, proteomics, and metabolomics are performed to investigate the crosstalk between metabolism and the DNA damage response. Integrative analyses identify Peroxiredoxin‐1 (PRDX1) as a DNA damage surveillance factor. Systematic approaches following DNA damage induction by etoposide reveal the aspects of metabolism that are crucial for maintaining genome integrity.Loss of electron transport chain enzymes is synthetically viable with etoposide, and some of these enzymes are partially located on chromatin 24 h after etoposide release.The metabolic enzyme PRDX1 contributes to DNA repair and translocates to the nucleus where it reduces DNA damage‐induced nuclear ROS.Loss of PRDX1 lowers aspartate availability and perturbs de novo nucleotide synthesis, which induces replication stress and limits the DNA repair capacities of the cells. [ABSTRACT FROM AUTHOR]

Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, the efficiency of PE varies widely and depends not only on the genomic region targeted, but also on the genetic background of the edited cell. Here, to determine which cellular factors affect PE efficiency, we carry out a focused genetic screen targeting 32 DNA repair factors, spanning all reported repair pathways. We show that, depending on cell line and type of edit, ablation of mismatch repair (MMR) affords a 2–17 fold increase in PE efficiency, across several human cell lines, types of edits and genomic loci. The accumulation of the key MMR factors MLH1 and MSH2 at PE sites argues for direct involvement of MMR in PE control. Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised. Prime Editing is a versatile genome engineering tool. Here, the authors identify the DNA repair pathway known as mismatch repair as inhibitory for Prime Editing, thus, loss of mismatch repair enhances the efficiency of Prime Editing. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are bioactive molecules that have potential therapeutic interest and their derived salts are used in several pharmaceutical systems. BAs have been associated with tumorigenesis of several tissues including the mammary tissue. Therefore, it is crucial to characterize their effects on cancer cells. The objective of this work was to analyse the molecular and cellular effects of the bile salts sodium cholate and sodium deoxycholate on epithelial breast cancer cell lines. Bile salts (BSs) effects over breast cancer cells viability and proliferation were assessed by MTS and BrdU assays, respectively. Activation of cell signaling mediators was determined by immunobloting. Microscopy was used to analyze cell migration, and cellular and nuclear morphology. Interference of membrane fluidity was studied by generalized polarization and fluorescence anisotropy. BSs preparations were characterized by transmission electron microscopy and dynamic light scattering. Sodium cholate and sodium deoxycholate had dual effects on cell viability, increasing it at the lower concentrations assessed and decreasing it at the highest ones. The increase of cell viability was associated with the promotion of AKT phosphorylation and cyclin D1 expression. High concentrations of bile salts induced apoptosis as well as sustained activation of p38 and AKT. In addition, they affected cell membrane fluidity but not significant effects on cell migration were observed. In conclusion, bile salts have concentration-dependent effects on breast cancer cells, promoting cell proliferation at physiological levels and being cytotoxic at supraphysiological ones. Their effects were associated with the activation of kinases involved in cell signalling. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the genotoxic potential of surface waters located in a rural area in the north east of Buenos Aires province (Argentina) using the Allium cepa test. Water samples were collected at four sites located in a drainage channel and two sites on the Burgos stream that receives water from the channel, taking into account the sowing and harvesting months and rainfall periods. Analytical determinations revealed high total concentrations of Cd, Cu, Pb, and Zn (maximum values: 0.030, 0.252, 0.176, and 0.960 mg L−1, respectively), and concentrations of glyphosate and its metabolite aminomethylphosphonic acid (AMPA), with maximum values of 13.6 and 9.75 μg L−1, respectively. Statistically positive correlations were observed between the total metal concentrations and precipitation. No cytotoxicity (mitotic index MI) was observed in A. cepa. However, several water samples showed significant increases in micronucleus (MN) frequencies with respect to the controls. No correlations were observed between MN and the abiotic variables or precipitation. These results showed a state of deterioration in the water quality at the rural area studied in Buenos Aires province, and heavy metal contamination may contribute to the genotoxic activity. A. cepa was shown to be a useful tool for the detection of genotoxicity in water samples from areas with agricultural and livestock activities. [ABSTRACT FROM AUTHOR]

The toxicity of chlortetracycline (CTC), oxytetracycline (OTC) and enrofloxacin (ENF) was tested on two green algal species: the international standard Pseudokirchneriella subcapitata and the native Argentine species Ankistrodesmus fusiformis. All three antibiotics inhibited the algal growth. The most sensitive species was P. subcapitata, for which the EC for CTC, OTC and ENF were 1.19 ± 0.53, 0.92 ± 0.30 and 5.18 ± 3.80 mg L, respectively. The EC for A. fusiformis, were 3.23 ± 0.53, 7.15 ± 2.69 and 10.6 ± 1.28 mg L, respectively. The genotoxicity of these veterinary antibiotics was also assessed using chromosome aberration (CA) and micronuclei (MN) induction in Allium cepa roots. Three concentrations were tested (0.1, 1 and 10 mg L). Only ENF at 1 and 10 mg L showed any significant MN induction. These data revealed that CTC, OTC and ENF could cause toxicity on green algae, whereas ENF could cause genotoxicity on A. cepa plants. [ABSTRACT FROM AUTHOR]

The discharge of sewage effluents into low-order streams has negative effects on water quality. Macrophytes can be efficient in the treatment of this wastewater due to the removal of the main pollutants. The genotoxicity of sewage-polluted water discharging into La Choza stream was evaluated by testing with Allium cepa. Also, a phytoremediation assay with continuous recirculation of the residual water was conducted for 12 days. Three treatments were carried out. One treatment (Hr) was performed with a macrophyte ( Hydrocotyle ranunculoides), and two treatments were conducted without macrophytes: with lighting (Ai) and without lighting (Ao). The wastewater was toxic according to all the evaluated indexes (mitotic index, frequency of chromosomal aberrations and micronucleus). High concentrations of ammonium, dissolved inorganic nitrogen (DIN), total (TP) and soluble reactive phosphorous (SRP) and indicators of faecal contamination were determined in the wastewater. The ammonium, DIN, SRP and TP loads at the end of the assay were significantly lower in the treatments with light (Hr and Ai). So, the nutrient removal was due to their absorption and adsorption by the periphyton and H. ranunculoides. Our results lead us to recommend the maintenance and planting of macrophytes in lowland streams subject to sewage pollution. [ABSTRACT FROM AUTHOR]

The imazethapyr herbicide (formulation Verosil) was evaluated for phytotoxicity and genotoxicity using a battery of bioassays: (1) the growth inhibition of the green alga Pseudokirchneriella subcapitata, (2) the root growth and germination of the higher plant Lactuca sativa, (3) the genetic damage using the Salmonella/microsome test, and (4) the aneugenic and clastogenic effects on Allium cepa. The Verosil formulation was highly toxic to the non-target green alga (median effective concentration (EC50) = 1.05 ± 0.05 mg active ingredient (a.i.) L), and concentrations above 10 mg a.i. L inhibited root elongation in lettuce: relative growth index (RGI) between 0.28 ± 0.01 and 0.66 ± 0.10. No genotoxic effect was observed in S almonella typhimurium at 100 mg a.i. L, either with or without the microsomal fraction. However, significant differences in the frequency of chromosomal aberrations in anaphases and telophases (bridges, chromosome fragments, and vagrants) were observed in A. cepa at concentrations between 0.01 and 1 mg a.i. L with respect to the control. The frequencies of micronuclei showed significant differences with respect to the control at concentrations between 0.001 and 0.1 mg a.i. L. A very high mitotic index (MI = 93.8 ± 5.8) was observed associated with a high number of cells in the prophase stage at 100 mg a.i. L, indicating cytotoxicity. These results showed that imazethapyr is toxic to the non-target populations in both aquatic and terrestrial ecosystems. This herbicide might also exert clastogenic and aneugenic mitotic damage in higher plants. Therefore, the imazethapyr formulation may constitute an environmental risk to plants. [ABSTRACT FROM AUTHOR]

Abstract  Functional micro- and nanosized metal oxide thin film structures are very promising candidate for future gas-sensors. Their reduced size offers an increased surface to volume ratio thus improving sensitivity and sensor performance. Whilst most experimental nanostructures are produced using a bottom-up approach, a top-down sputtering technique for structuring nano-sized gas sensitive metal oxide areas is presented in this letter. Oxidised silicon wafers were used as substrates. The silicon dioxide film of 1 μm thickness was prepared by thermal oxidation in order to insulate the gas sensing elements from the substrate. The sensor chips had an overall size of (1.5 × 1.5) mm2 onto which a Ta/Pt film (20/200 nm thickness) was deposited and patterned to act as electrodes, heater and temperature sensor. In a second step micro-scaled tin dioxide layers (60 nm thick, 5 μm width) were deposited by sputtering techniques and photolithographical patterning between the platinum micro-electrodes (4 μm gap). Finally, the width of the stripes was reduced using focused ion beam technology to obtain the desired size and structure. This enables the control of the dimensions of the structures down to the resolution limit of the FIB-system which is about 10 nm. The structural and electrical characterisation of the sensors and their responses during exposure to several test gases including O2, CO, NO2 and H2O are presented as well. [ABSTRACT FROM AUTHOR]

The article cites a study conducted to determine the mutagenicity of samples of antineoplastic agents before and after autoclaving treatment was tested with the Salmonella mutagenicity assay. The antineoplastic drugs assayed were selected between the most widely used in cancer therapy. The lack of in-depth information on effects of different hospital waste treatments on antitumor agents points to an obvious need for research to develop this important baseline set of data. Results obtained when 5-fluorouracil, doxorubicin, cisplatin, carboplatin did not show any variation in mutagenic activity after autoclaving. The same concentration-response curves were found before and after treatment.

This article presents information related to water pollution in the Urban Argentine River. Chemical stress in aquatic ecosystems is increasing. Water pollution assessment and its possible effects upon river biotic communities, is required for development of control and management strategies. The Matanza-Riachuelo, a temperate lowland river, is one of the most polluted rivers of Latin America, representing a risk for human health. Its mixed pollution derives from farming, grazing, and wastewater from domestic sewage and thousands of industries.

The article examines the interference of sterilized river water samples on the genotoxicity detection of environmental mutagen called potassium dichromate from a river in Buenos Aires, Argentina. The researcher had chosen chromium as an environmental genotoxic pollutant because of its toxic and mutagenic properties that were easy to understand. The results demonstrated that there were interference in the genotoxic activity of potassium dichromate because of compounds found in the soluble fraction of the river water.

The article presents a study on the concentrates of polluted water through genetic alteration induction in Saccharomyces cerevisiae D7 strain. It states the reverse point mutation and mitotic gene conversion are the effects which viewed as gentotoxicity indicator. It also mentions that the water samples were examined by the XAD2 resin column. Result shows that the Saccharomyces cerevisiae D7 strain genotoxicity were positive when the study frequencies surpass the controls.

The article presents a study on the detection of genotoxicants in waste waters through a yeast system. The study used a strain of Saccharomyces cerevisiae that allows to detect mutation and genetic recombination as well as incubation of yeast cells. Results showed that there were variations in the genotoxic response of the samples and that a two-fold dilution of raw water led to a ten-fold reduction in the gene conversion frequencies induced.

Tuberculosis (TB) remains as the second most-deadly infection right behind the HIV/AIDS. Actually, in 2016, TB incidence was estimated in 10.4 million cases. Although an efficient and low-cost TB pharmacotherapy has been available for the last 50 years, the development of multi- and extra-drug-resistant Mycobacterium tuberculosis (Mtb) strains has put on the spot the necessity of improved TB regimens. In this framework, this review article presents the main relevant research outcomes of nanotechnology in TB. The novel delivery systems for antituberculosis drugs have been discussed. Moreover, the active-targeted nanomedicines to the Mtb reservoirs enlighten the possibility to eradicate low-replicant mycobacteria and diminish latent TB. Finally, we present an overview of the TB socio-economic impact and the cost-related features of TB regimens associated with the use of nanoformulations. [ABSTRACT FROM AUTHOR]