Oxidative DNA Damage Research Articles

Protection against oxidative DNA damage: Green tea polyphenols in Hsd:ICR mice exposed to hexavalent chromium

Protection against oxidative DNA damage: Green tea polyphenols in Hsd:ICR mice exposed to hexavalent chromium

Review article: The Role of Probiotic Strains in Cancer Prevention

Probiotics are living microorganisms that confer health benefits when administered in adequate amounts. One main way that probiotics may help fight cancer is by changing bacteria in the gut. Some types of probiotics have been shown to stop the growth of harmful bacteria, make chemicals that stop cancer cells from spreading, and boost the production of short-chain fatty acids that fight inflammation and cell growth. Probiotics may also strengthen the intestinal epithelial barrier, stopping the movement of compounds that can cause cancer and stopping chronic inflammation, which is known to increase the risk of cancer. Probiotics can also change the way your immune system works. For example, some types can make natural killer cells, dendritic cells, and T cells work harder, which is very important for finding and killing cancer. Some probiotics have also been shown to lower oxidative stress and DNA damage. This makes it less likely that genetic changes that can cause cancer will occur. Although more research needs to be done on how probiotics can help prevent cancer, several clinical studies have shown encouraging results, especially when it comes to colorectal cancer. The burgeoning field of probiotics and cancer prevention holds potential for transforming our understanding of the role of the gut microbiome in cancer development and progression. Continued research is essential to optimize the use of probiotics as a complementary approach to cancer prevention and treatment.

Aqueous sage leave extract attenuates inflammation and oxidant-induced genotoxicity in human peripheral blood mononuclear cells.

Traditional medicine has used sage (Salvia officinalis L.) preparations for centuries to prevent and treat various inflammatory and oxidative stress-induced conditions. The aim of this in vitro study was to determine the bioactive properties of a sage leave extract obtained with environmentally friendly aqueous extraction and lyophilisation in primary human peripheral blood cells. To that end we measured the total phenolic and flavonoid content (TPC and TFC, respectively) with gas chromatography-mass spectrometry (GC-MS). Non-cytotoxic concentrations determined with the trypan blue assay were used to assess the antioxidant (DPPH, ABTS, and PAB assay), antigenotoxic (CBMN assay), immunomodulatory (IL-1β and TNF-α), and neuroprotective effects (AChE inhibition). The extract contained high TPC (162 mg GAE/g of dry extract) and TFC (39.47 mg QE/g of dry extract) concentrations, while β-thujone content was unexpectedly low (below 0.9 %). Strong radical-scavenging activity combined with glutathione reductase activation led to a decrease in basal and H2O2-induced oxidative stress and DNA damage. A decrease in TNF-α and increase in IL-1β levels suggest complex immunomodulatory response that could contribute to antioxidant and, together with mild AChE inhibition, neuroprotective effects. Overall, this study has demonstrated that aqueous sage leave extract reduces the levels of thujone, 1,8-cineole, pinene, and terpene ketones that could be toxic in high concentrations, while maintaining high concentrations of biologically active protective compounds which have a potential to prevent and/or treat inflammatory and oxidative stress-related conditions.

An ultrasensitive aptasensor for 8-hydroxy-2′-deoxyguanosine of human urine detection based on COFTAPB-DMTP@MWCNT-COOH nanocomposites and CeFeOx-C@Au@Apt nanoprobe

An ultrasensitive electrochemical aptasensor was proposed for quantitative detection of 8-hydroxy-2′-deoxyguanosine (8-OHdG). Covalent organic framework (COFTAPB-DMTP) and carboxylated multi-walled carbon nanotubes (MWCNT-COOH) were used to prepare COFTAPB-DMTP@MWCNT-COOH (TAPB, 1,3,5-tris(4-aminopheny) benzene; DMTP, 5-dimethoxybenzene-1,4-dicarboxaldehyde) nanocomposites as the electrode sensing platform. COFTAPB-DMTP@MWCNT-COOH displayed excellent biocompatibility, a large specific surface area, and efficient conductivity, facilitating accelerated electron transfer rates. Furthermore, the cerium iron oxide–carbon nanocomposites (CeFeOx-C) derived from UiO-66-CeFe bimetallic organic framework showed outstanding peroxidase-like activity. Gold nanoparticles-modified CeFeOx-C effectively loads 8-OHdG-aptamer, yielding novel CeFeOx-C@Au@Apt nanoprobes. CeFeOx-C@Au@Apt nanoprobes were immobilized on the electrode via base pairing to thiolated cDNA and the signal change was detected in the environment of hydroquinone and H2O2. In the presence of 8-OHdG, Apt-cDNA unwound, leading to CeFeOx-C@Au@Apt to fall off the electrode, thereby causing distinguishable electrochemical variations. The optimized aptasensor for 8-OHdG showed a wide linear range from 10 fg/mL to 50 ng/mL, with a low detection limit of 1.06 fg/mL. The reliability of this aptasensor was confirmed using human urine samples, yielding satisfactory results, highlighting its potential in evaluating the extent of oxidative DNA damage. Crucially, the aptasensor’s ideal performance position it as a promising approach for detecting various biomolecules through modifications the aptamers sequence modifications.

STING1-accelerated vascular smooth muscle cell senescence-associated vascular calcification in diabetes is ameliorated by oleoylethanolamide via improved mitochondrial DNA oxidative damage

Vascular calcification is a prevalent hallmark of cardiovascular risk in elderly and diabetic individuals. Senescent vascular smooth muscle cells (VSMCs) participate in calcification; however, the associated underlying mechanisms remain unknown. Aberrant activation of the cytosolic DNA sensing adaptor stimulator of interferon gene 1 (STING1) caused by cytosolic DNA, particularly that leaked from damaged mitochondria, is a catalyst for aging-related diseases. Although oleoylethanolamide (OEA) is an endogenous bioactive lipid mediator with lipid overload-associated vasoprotective effects, its benefit in diabetic vascular calcification remains uncharacterized. This study focused on the role of STING1 in mitochondrial dysfunction-mediated calcification and premature VMSC senescence in diabetes and the effects of OEA on these pathological processes. In diabetic in vivo rat/mouse aorta calcification models and an in vitro VSMC calcification model induced by Nε-carboxymethyl-lysine (CML), senescence levels, STING1 signaling activation, and mitochondrial damage markers were significantly augmented; however, these alterations were markedly alleviated by OEA, partially in a nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent manner, and similar anti-calcification and senescence effects were observed in STING1-knockout mice and STING1-knockdown VSMCs. Mechanistically, mitochondrial DNA (mtDNA) damage was aggravated by CML in a reactive oxygen species-dependent manner, followed by mtDNA leakage into the cytosol, contributing to VSMC senescence-associated calcification via STING1 pathway activation. OEA treatment significantly attenuated the aforementioned cytotoxic effects of CML by enhancing cellular antioxidant capacity through the maintenance of Nrf2 translocation to the nucleus. Collectively, targeting STING1, a newly defined VSMC senescence regulator, contributes to anti-vascular calcification effects.

Molecular Mechanisms of N-Acetylcysteine in RSV Infections and Air Pollution-Induced Alterations: A Scoping Review.

N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.

Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells.

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondrial RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor or mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells.

Turmeric: from spice to cure. A review of the anti-cancer, radioprotective and anti-inflammatory effects of turmeric sourced compounds.

Turmeric (Curcuma longa) has been extensively studied for its diverse pharmacological properties, including its potential role as an anticancer agent, antioxidant, and radioprotector. This review provides an overview of the chemical composition of turmeric, focusing on its main bioactive compounds, such as curcuminoids and volatile oils. Curcumin, the most abundant curcuminoid in turmeric, has been widely investigated for its various biological activities, including anti-inflammatory, antioxidant, and anticancer effects. Numerous in vitro and in vivo studies have demonstrated the ability of curcumin to modulate multiple signaling pathways involved in carcinogenesis, leading to inhibition of cancer cell proliferation, induction of apoptosis, and suppression of metastasis. Furthermore, curcumin has shown promising potential as a radioprotective agent by mitigating radiation-induced oxidative stress and DNA damage. Additionally, turmeric extracts containing curcuminoids have been reported to exhibit potent antioxidant activity, scavenging free radicals and protecting cells from oxidative damage. The multifaceted pharmacological properties of turmeric make it a promising candidate for the development of novel therapeutic strategies for cancer prevention and treatment, as well as for the management of oxidative stress-related disorders. However, further research is warranted to elucidate the underlying mechanisms of action and to evaluate the clinical efficacy and safety of turmeric and its bioactive constituents in cancer therapy and radioprotection. This review consolidates the most recent relevant data on turmeric's chemical composition and its therapeutic applications, providing a comprehensive overview of its potential in cancer prevention and treatment, as well as in radioprotection.

Pathological Changes and Metabolic Adaptation in the Myocardium of Rats in Response to Chronic Variable Mild Stress.

Chronic variable mild stress (CVS) in rats is a well-established paradigm for inducing depressive-like behaviors and has been utilized extensively to explore potential therapeutic interventions for depression. While the behavioral and neurobiological effects of CVS have been extensively studied, its impact on myocardial function remains largely unexplored. To induce the CVS model, rats were exposed to various stressors over 40 days. Behavioral assessments confirmed depressive-like behavior. Biochemical analyses revealed alterations in myocardial metabolism, including changes in NAD+ and NADP+, and NADPH concentrations. Free amino acid analysis indicated disturbances in myocardial amino acid metabolism. Evaluation of oxidative DNA damage demonstrated an increased number of abasic sites in the DNA of rats exposed to CVS. Molecular analysis showed significant changes in gene expression associated with glucose metabolism, oxidative stress, and cardiac remodeling pathways. Histological staining revealed minor morphological changes in the myocardium of CVS-exposed rats, including increased acidophilicity of cells, collagen deposition surrounding blood vessels, and glycogen accumulation. This study provides novel insights into the impact of chronic stress on myocardial function and metabolism, highlighting potential mechanisms linking depression and cardiovascular diseases. Understanding these mechanisms may aid in the development of targeted therapeutic strategies to mitigate the adverse cardiovascular effects of depression.

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization.

Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells' clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation.

Lack of cytotoxic and genotoxic effects of mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium despite cellular uptake in cancerous and noncancerous lung cells

Cytotoxic and genotoxic effects of novel mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) have been investigated on human adenocarcinomic alveolar basal epithelial (A549) and human normal bronchial epithelial (BEAS-2B) cells. In the studies several molecular and cellular targets addressing to cell membrane, cytoplasm organelles and nucleus components were served as toxicological endpoints. The as-synthesized nanoparticles were found to be stable in the cell culture media and were examined for different concentration and exposure times. No cytotoxicity of the tested nanoparticles was found although these nanoparticles slightly increased reactive oxygen species in both cell types studied. Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles did not produce any DNA strand breaks and oxidative DNA damages in A549 and BEAS-2B cells. Different concentration of Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles and different incubation time did not affect cell migration. The lung cancer cells' uptake of the nanoparticles was more effective than in normal lung cells. Altogether, the results evidence that mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium do not elucidate any deleterious effects on human normal and cancerous lung cells despite cellular uptake of these nanoparticles. Therefore, it seems reasonable to conclude that these novel biocompatible nanoparticles are promising candidates for further development towards medical applications.

Mitotic MTH1 inhibitor TH1579 induces PD-L1 expression and inflammatory response through the cGAS-STING pathway

The mitotic MTH1 inhibitor TH1579 is a dual inhibitor that inhibits mitosis and incorporation of oxidative DNA damage and leads to cancer-specific cell death. The response to immune checkpoint inhibitor (ICI) treatment is often augmented by DNA damaging agents through the cGAS-STING pathway. This study investigates whether TH1579 can improve the efficacy of immune checkpoint blockades through its immunomodulatory properties. Various human and murine cancer cell lines were treated with mitotic MTH1i TH1579, and the expression of PD-L1 and T-cell infiltration-related chemokines was analysed by flow cytometry and real-time qPCR. Syngeneic mouse models were established to examine the combined effect of TH1579 and PD-L1 blockade. In our investigation, we found that TH1579 upregulates PD-L1 expression at both the protein and mRNA levels in human cancer cell lines. However, in murine cell lines, the increase was less pronounced. An in vivo experiment in a syngeneic mouse melanoma model showed that TH1579 treatment significantly increased the efficacy of atezolizumab, an anti-PD-L1 antibody, compared to vehicle or atezolizumab monotherapy. Furthermore, TH1579 exhibited immune-modulatory properties, elevating cytokines such as IFN-β and chemokines including CCL5 and CXCL10, in a cGAS-STING pathway-dependent manner. In conclusion, TH1579 has the potential to improve ICI treatment by modulating immune checkpoint-related proteins and pathways.

Quantifying the Level of 8-oxo-dG Using ELISA Assay to Evaluate Oxidative DNA Damage in MCF-7 Cells

Quantifying the Level of 8-oxo-dG Using ELISA Assay to Evaluate Oxidative DNA Damage in MCF-7 Cells

Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic-Inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces.

The escalating threat of antimicrobial resistance has become a global health crisis. Therefore, there is a rising momentum in developing biomaterials with self-sanitizing capabilities and inherent antibacterial properties. Despite their promising antimicrobial properties, metal nanoparticles (MNPs) have several disadvantages, including increased toxicity as the particle size decreases, leading to oxidative stress and DNA damage that need consideration. One solution is surface functionalization with biocompatible organic ligands, which can improve nanoparticle dispersibility, reduce aggregation, and enable targeted delivery to microbial cells. The existing research predominantly concentrates on the advancement of peptide-based hydrogels for coating materials to prevent bacterial infection, with limited exploration of developing surface coatings using organogels. Herein, we have synthesized organogel-based coatings doped with MNPs that can offer superior hydrophobicity, oleophobicity, and high stability that are not easily achievable with hydrogels. The self-assembled gels displayed distinct morphologies, as revealed by scanning electron microscopy and atomic force microscopy. The cross-linked matrix helps in the controlled and sustained release of MNPs at the site of bacterial infection. The synthesized self-assembled gel@MNPs exhibited excellent antibacterial properties against harmful bacteria such as Escherichia coli and Staphylococcus aureus and reduced bacterial viability up to 95% within 4 h. Cytotoxicity testing against metazoan cells demonstrated that the gels doped with MNPs were nontoxic (IC50 > 100 μM) to mammalian cells. Furthermore, in this study, we coated the organogel@MNPs on cotton fabric and tested it against Gram +ve and Gram -ve bacteria. Additionally, the developed cotton fabric exhibited superhydrophobic properties and developed a barrier that limits the interaction between bacteria and the surface, making it difficult for bacteria to adhere and colonize, which holds potential as a valuable resource for self-cleaning coatings.

Deciphering the Effects of Different Types of Sunlight Radiation on Skin Function: A Review

Sunlight radiation is a fundamental component of our daily lives. Specifically, blue light as well as UV light appear to play a role in the development of oxidative stress, DNA damage, photoaging, and pigmentation through the chromophores in skin tissues. However, several skin problems like psoriasis, eczema, and atopic dermatitis can be avoided with short-duration exposures to low-energy blue light radiation or UV radiation. In addition, exploring the effects of blue light as well as UV radiation on skin is quite essential for the development of minimally invasive antiaging strategies and for the design of innovative cosmetic formulations in modern aesthetics and cosmetology. Thus, in this review, we present the advantages as well as the disadvantages of light radiation, with a special focus on blue light and UV radiation activity on the human skin. We also discuss the molecular action of blue light and UV radiation on human skin. Other types of light radiation are included to holistically approach the effect of light on human skin.

Revealing an adverse outcome pathway network for reproductive toxicity induced by atrazine, via oxidative stress

Adverse outcome pathway AOPs are conceptual frameworks that organize scientific knowledge about how stressors disrupt specific biological targets, pathways. AOP network consists of two or more AOPs that share common key events (KEs), including crucial events like molecular initiating events (MIEs) and adverse outcomes (AOs), which offer the opportunity to link toxicological pathways. Thus, to better understand the sequential series of KEs involved in the AOP 492 (https://aopwiki.org/aops/492), which is triggered by atrazine (ATZ), we first generated a Reproductive Toxicity via Oxidative Stress (RTOS) AOP network from individual AOPs published in the AOP-Wiki database, using this AOP as a seed. The KEs “Increased, Reactive oxygen species” and “Apoptosis” were considered the most common/highly connected KE within this network and an important point of divergence. Furthermore, “Increased, DNA damage and mutations” is a critical KE within the network, as it is highly connected and central, and represents a point of divergence. This suggests that these three KEs have a high predictive value and could, for example, serve as a basis for the development/selection of in vitro assays to assess reproductive toxicity. The in silico analyses revealed that the pivotal target proteins for ATZ-induced infertility via oxidative stress in humans are Tp53, Bcl2, Esr1, and Nos3, which interact indirectly with ATZ via intermediary factors such as Mapk3, Mapk1, and Cyp19a1. Further, the gene enrichment analyses indicate that these entities are involved in several biological processes and pathways directly associated with oxidative stress, DNA damage and apoptosis, further reinforcing the developed network.

P04 How fibroblasts and azathioprine prepare the soil for cutaneous squamous cell carcinoma

Abstract Introduction and aims DNA damage-inducing immunosuppressive drugs such as azathioprine (AZA) act synergistically with ultraviolet (UV)A radiation and photosensitize the skin of immunosuppressed individuals, such as organ transplant recipients. These individuals have an increased risk of developing cutaneous squamous cell carcinoma (cSCC). The specific combination of AZA and UVA causes oxidative DNA damage that leaves behind a characteristic mutational signature in tumour keratinocytes of patients treated with AZA. However, as UVA radiation can penetrate the dermis, the impact of AZA/UVA on cells of the tumour microenvironment, such as fibroblasts, also need to be addressed. Fibroblasts are crucial for cSCC development and progression as they can switch to a protumourigenic phenotype. Methods Cell viability and senescence assays were performed to investigate the impact of AZA in combination with or without UVA on neonatal (nonsun-exposed) and adult (sun-exposed) human dermal fibroblasts. In addition, the impact of AZA/UVA-treated fibroblasts on the clonal growth properties of different cSCC cell models was investigated using three-dimensional (co)culture models. Results We found that AZA and UVA synergistically reduce the viability of both UV-naïve neonatal and sun-exposed adult dermal fibroblasts. In addition, combined AZA and UVA treatments lead to an increased percentage of senescent fibroblasts. We hypothesize that the aberrant secretome of these senescent fibroblasts can impact the growth behaviour of tumour cells. In a soft agar assay, the more malignant cSCC cells (MET-1) formed more and larger clonal spheroids and were less dependent on growth factors compared with spheroids formed by premalignant (PM-1) keratinocytes. Conclusions AZA and UVA act synergistically and potentiate a UVA-induced senescent fibroblast phenotype. The changed characteristics of these fibroblasts can impact the stem cell-like properties from premalignant and malignant keratinocytes. Combining keratinocyte and fibroblast culture models enables us to study how AZA/UVA promote the initiation and progression of cSCC.

Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain

Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia. This study utilized post-mortem brain tissue from rhesus monkeys that died after decades on a 30 % reduced calorie diet. We found that CR subjects had significantly fewer cells with oxidative damage within the corpus callosum and the cingulum bundle. Oligodendrocytes specifically showed the greatest response to CR with a robust reduction in DNA damage. Additionally, we observed alterations in microglia morphology with CR subjects having a higher proportion of ramified, homeostatic microglia and fewer pro-inflammatory, hypertrophic microglia relative to controls. Furthermore, we determined that the observed attenuation in damaged DNA occurs primarily within mitochondria. Overall, these data suggest that long-term CR can reduce oxidative DNA damage and offer a neuroprotective effect in a cell-type-specific manner in the aging monkey brain.

Hormonal, liver, and renal function associated with electronic waste (e-waste) exposure in Dhaka, Bangladesh

Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63 µg/dL), similar blood cadmium (Cd) (1.04 vs 0.99 µg/L) and lower total mercury (Hg) in hair (0.38 vs 0.57 ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT3), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p≤0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p≥0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.002, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p≥0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from e-waste exposure.

Cytotoxicity of green synthesized zinc oxide nanoparticles using Musa acuminata on Vero cells

Zinc oxide nanoparticles (ZnO NPs) have become a highly regarded substance in various industries especially biologically synthesized ZnO NPs due to their adherence to the principles of green chemistry. However, concerns have been raised regarding the potential cytotoxic effects of ZnO NPs on biological systems. This study aimed to investigate and compare the cytotoxicity of ZnO NPs that were synthesized through chemical (C–ZnO NPs) and green approach using Musa acuminata leaf aqueous extract (Ma-ZnO NPs) on Vero cells.Characterization of ZnO NPs through Uv–Vis, FESEM, EDX, XRD, FTIR and XPS confirmed the successful synthesis of C- and Ma-ZnO NPs. MTT and ROS assays revealed that C- and Ma-ZnO NPs induced a concentration- and time-dependent cytotoxic effect on Vero cells. Remarkably, Ma-ZnO NPs showed significantly higher cell viability compared to C–ZnO NPs. The corelation of ROS and vell viability suggest that elevated ROS levels can lead to cell damage and even cell death. Flow cytometry analysis indicated that Ma-ZnO NPs exposed cells had more viable cells and a smaller cell population in the late and early apoptotic stage. Furthermore, more cells were arrested in the G1 phase upon exposure to C–ZnO NPs, which is associated with oxidative stress and DNA damage caused by ROS generation, proving its higher cytotoxicity than Ma-ZnO NPs. Similarly, time-dependent cytotoxicity and morphological alterations were observed in C- and Ma-ZnO NPs treated cells, indicating cellular damage. Furthermore, fluorescence microscopy also demonstrated a time-dependent increase in ROS formation in cells exposed to C- and Ma-ZnO NPs.In conclusion, the findings suggest that green ZnO NPs possess a favourable biocompatibility profile, exhibiting reduced cytotoxicity compared to chemically synthesized ZnO NPs on Vero cells. These results emphasize the potential of green synthesis methods for the development of safer and environmentally friendly ZnO NPs.