Baby Foods: 9 Out of 62 Exceed the Reference Limits for Acrylamide.

Acrylamide (AA) is a contaminant resulting from the Maillard reaction and classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen in Group 2A, with proven neurotoxic effects on humans. European Union (EU) Regulation No. 2017/2158 is currently in force, which establishes measures meant to reduce AA levels in food and sets reference values, but not legal limits, equal to 40 and 150 µg/kg AA in processed cereal-based foods intended for infants and young children and in biscuits and rusks, respectively. For this reason, sixty-two baby foods were analyzed using ultra-high performance liquid chromatography with diode array detector and quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF/MS) to check whether industries were complying with these values, even though AA control is not legally mandatory. In total, 14.5% of the samples exceeded the reference values; these were homogenized chicken products (211.84 ± 16.53, 154.32 ± 12.71, 194.88 ± 7.40 µg/kg), three biscuits (276.36 ± 0.03, 242.06 ± 0.78, 234.78 ± 4.53 µg/kg), a wheat semolina (46.07 ± 0.23 µg/kg), a homogenized product with plaice and potatoes (45.52 ± 0.28 µg/kg), and a children's snack with milk and cocoa (40.95 ± 0.32 µg/kg). Subsequently, the daily intake of AA was estimated, considering the worst-case scenario, as provided by the consumption of homogenized chicken products and biscuits. The results are associated with margins of exposure (MOEs) that are not concerning for neurotoxic effects but are alarming for the probable carcinogenic effects of AA.

Unlocking the potential of AI: Machine learning and deep learning models for predicting carcinogenicity of chemicals.

The escalating apprehension surrounding the carcinogenic potential of chemicals emphasizes the imperative need for efficient methods of assessing carcinogenicity. Conventional experimental approaches such as in vitro and in vivo assays, albeit effective, suffer from being costly and time-consuming. In response to this challenge, new alternative methodologies, notably machine learning and deep learning techniques, have attracted attention for their potential in developing carcinogenicity prediction models. This article reviews the progress in predicting carcinogenicity using various machine learning and deep learning algorithms. A comparative analysis on these developed models reveals that support vector machine, random forest, and ensemble learning are commonly preferred for their robustness and effectiveness in predicting chemical carcinogenicity. Conversely, models based on deep learning algorithms, such as feedforward neural network, convolutional neural network, graph convolutional neural network, capsule neural network, and hybrid neural networks, exhibit promising capabilities but are limited by the size of available carcinogenicity datasets. This review provides a comprehensive analysis of current machine learning and deep learning models for carcinogenicity prediction, underscoring the importance of high-quality and large datasets. These observations are anticipated to catalyze future advancements in developing effective and generalizable machine learning and deep learning models for predicting chemical carcinogenicity.

Colorimetric Detection of Aqueous N-Nitrosodimethylamine via Photonitrosation of a Naphtholsulfonate Indicator.

N-Nitrosamines are contaminants found throughout the environment, including in drinking water, and many nitrosamines are likely potent carcinogens. Correspondingly, there is a need for rapid and cost-effective in-field detection methods that can provide timely information about their contamination levels in water. This study details a colorimetric assay for detecting aqueous N-nitrosodimethylamine (NDMA) by photochemical nitrosation of a commercial naphtholsulfonate, to offer an attractive alternative to traditional laboratory-based analysis. The resulting naphthoquinone-oxime coordinates to aqueous iron(II) ions to form a green complex, allowing for direct visual detection. Characterization via Mössbauer and electron paramagnetic resonance (EPR) spectroscopy, alongside single-crystal structure determination, provides comprehensive structure information on the iron indicator complex. Optimization of detection conditions, including UV irradiation and response times, led to an improved colorimetric detection method with a limit of detection of 0.66 ppm for NDMA. The practical applicability and selectivity of this colorimetric detection scheme make it a promising candidate for the development of field-deployable sensors for NDMA in environmental water samples.

Overrepresentation of New Workers in Jobs with Multiple Carcinogen Exposures in Canada.

Background. In Canada, understanding the demographic and job-related factors influencing the prevalence of new workers and their exposure to potential carcinogens is crucial for improving workplace safety and guiding policy interventions. Methods. Logistic regression was performed on the 2017 Labour Force Survey (LFS), to estimate the likelihood of being a new worker based on age, industry, occupation, season, and immigration status. Participants were categorized by sector and occupation using the North American Industry Classification System (NAICS) 2017 Version 1.0 and National Occupational Classification (NOC) system 2016 Version 1.0. Finally, an exposures-per-worker metric was used to highlight the hazardous exposures new workers encounter in their jobs and industries. Results. Individuals younger than 25 years had 3.24 times the odds of being new workers compared to those in the 25-39 age group (adjusted odds ratios (OR) = 3.24, 95% confidence interval (95% CI) = 3.18, 3.31). Recent immigrants (less than 10 years in the country) were more likely to be new workers than those with Canadian citizenship (OR 1.36, 95% CI: 1.32, 1.41). The total workforce exposures-per-worker metric using CAREX Canada data was 0.56. By occupation, new workers were the most overrepresented in jobs in natural resources and agriculture (20.5% new workers), where they also experienced a high exposures-per-worker metric (1.57). Conclusions. Younger workers (under 25 years) and recent immigrants who had arrived 10 or fewer years prior were more likely to be new workers, and were overrepresented in jobs with more frequent hazardous exposures (Construction, Agriculture, and Trades).

Confirmation of Di(2-ethylhexyl) phthalate-induced micronuclei by repeated dose liver micronucleus assay: focus on evaluation of liver micronucleus assay in young rats.

BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment. RESULTS: We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats. CONCLUSION: The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens.

An evidence based comprehensive review on thiacloprid, a pesticide residue, induced toxicity: Unveiling hazard to human health.

Thiacloprid, a hazardous neonicotinoid insecticide, prevalent in daily agricultural practices, raises concerns due to the harmful effects of its residues on food items, and on unintended organisms poses a significant threat to human health. Introduced in 1990, Thiacloprid have gained popularity for its perceived effectiveness and reduced risks to non-target animals. However, emerging research in recent years reports significant toxic effects of Thiacloprid on non-target species, spanning neurotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, and reproductive issues. Mammalian studies, particularly involving rodents, reveal cognitive impairment, hippocampal damage, and hepatic abnormalities upon Thiacloprid exposure. Reproductive toxicity and DNA damage are imminent concerns, disrupting gestational epigenetic reprogramming and suggesting persistent effects on future generations. Genotoxic effects, Embryotoxic, and observed reproductive toxicity accentuate the need for caution in the utilization of Thiacloprid. This review highlights reported toxic effects produced by Thiacloprid in recent years, challenging the initial belief in its lower toxicity for vertebrates.

CarD-T: Interpreting Carcinomic Lexicon via Transformers.

The identification and classification of carcinogens is critical in cancer epidemiology, necessitating updated methodologies to manage the burgeoning biomedical literature. Current systems, like those run by the International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP), face challenges due to manual vetting and disparities in carcinogen classification spurred by the volume of emerging data. To address these issues, we introduced the Carcinogen Detection via Transformers (CarD-T) framework, a text analytics approach that combines transformer-based machine learning with probabilistic statistical analysis to efficiently nominate carcinogens from scientific texts. CarD-T uses Named Entity Recognition (NER) trained on PubMed abstracts featuring known carcinogens from IARC groups and includes a context classifier to enhance accuracy and manage computational demands. Using this method, journal publication data indexed with carcinogenicity & carcinogenesis Medical Subject Headings (MeSH) terms from the last 25 years was analyzed, identifying potential carcinogens. Training CarD-T on 60% of established carcinogens (Group 1 and 2A carcinogens, IARC designation), CarD-T correctly to identifies all of the remaining Group 1 and 2A designated carcinogens from the analyzed text. In addition, CarD-T nominates roughly 1500 more entities as potential carcinogens that have at least two publications citing evidence of carcinogenicity. Comparative assessment of CarD-T against GPT-4 model reveals a high recall (0.857 vs 0.705) and F1 score (0.875 vs 0.792), and comparable precision (0.894 vs 0.903). Additionally, CarD-T highlights 554 entities that show disputing evidence for carcinogenicity. These are further analyzed using Bayesian temporal Probabilistic Carcinogenic Denomination (PCarD) to provide probabilistic evaluations of their carcinogenic status based on evolving evidence. Our findings underscore that the CarD-T framework is not only robust and effective in identifying and nominating potential carcinogens within vast biomedical literature but also efficient on consumer GPUs. This integration of advanced NLP capabilities with vital epidemiological analysis significantly enhances the agility of public health responses to carcinogen identification, thereby setting a new benchmark for automated, scalable toxicological investigations.

CarcSeq detection of lorcaserin-induced clonal expansion of Pik3ca H1047R mutants in rat mammary tissue.

Lorcaserin is a 5-hydroxytryptamine 2C (serotonin) receptor agonist and a nongenotoxic rat carcinogen, which induced mammary tumors in male and female rats in a 2-yr bioassay. Female Sprague Dawley rats were treated by gavage daily with 0, 30, or 100 mg/kg lorcaserin, replicating bioassay dosing but for shorter duration, 12 or 24 wk. To characterize exposure and eliminate possible confounding by a potentially genotoxic degradation product, lorcaserin and N-nitroso-lorcaserin were quantified in dosing solutions, terminal plasma, mammary, and liver samples using ultra-high-performance liquid chromatography-electrospray tandem mass spectrometry. N-nitroso-lorcaserin was not detected, supporting lorcaserin classification as nongenotoxic carcinogen. Mammary DNA samples (n = 6/dose/timepoint) were used to synthesize PCR products from gene segments encompassing hotspot cancer driver mutations, namely regions of Apc, Braf, Egfr, Hras, Kras, Nfe2l2, Pik3ca, Setbp1, Stk11, and Tp53. Mutant fractions (MFs) in the amplicons were quantified by CarcSeq, an error-corrected next-generation sequencing approach. Considering all recovered mutants, no significant differences between lorcaserin dose groups were observed. However, significant dose-responsive increases in Pik3ca H1047R mutation were observed at both timepoints (ANOVA, P < 0.05), with greater numbers of mutants and mutants with greater MFs observed at 24 wk as compared with 12 wk. These observations suggest lorcaserin promotes outgrowth of spontaneously occurring Pik3ca H1047R mutant clones leading to mammary carcinogenesis. Importantly, this work reports approaches to analyze clonal expansion and demonstrates CarcSeq detection of the carcinogenic impact (selective Pik3ca H0147R mutant expansion) of a nongenotoxic carcinogen using a treatment duration as short as 3 months.

Oral squamous cell carcinoma: Effect of tobacco and alcohol on cancer location.

INTRODUCTION: The underlying factors of oral squamous cell cancers (OSCC) have been elucidated, but studies have focused little on etiological differences in affected oral cavity sites. The aim of this retrospective study was to clarify the role of carcinogen exposure in OSCC of different oral cavity areas. METHODS: A cross-sectional study of patients with primary OSCC was conducted retrospectively, based on patient records from Helsinki University Hospital, Finland, between January 2016 and December 2020. The patients' self-reported history of tobacco smoking and alcohol use was explained by tumor site, age, sex, tumor size, and lymph node status in a logistic regression model. The information on smoking and alcohol use was compiled from a patient background form. RESULTS: In 519 patients, tumors occurred most often in the tongue (51%), gingiva (21%), or floor of the mouth (FOM; 15%). FOM had 26-fold greater odds for a history of smoking and alcohol use than other tumor sites (OR=25.78; 95% CI: 8.02-82.95; p<0.001). Gingival and buccal sites were associated significantly less with smoking and alcohol use (OR=0.43, 95% CI: 0.28-0.67; p<0.001 and OR=0.47; 95% CI: 0.25-0.92; p<0.026, respectively). Patients of older age were less likely to have a history of smoking and alcohol use (AOR=0.95; 95% CI: 0.94-0.97; p<0.001) than younger patients. Tumor size (T3-4) and FOM increased the odds for history of smoking and alcohol use (AOR=1.73; 95% CI: 1.15-2.60; p=0.009 and AOR=26.15; 95% CI: 8.01-84.84; p<0.001, respectively). CONCLUSIONS: OSCC of oral cavity sites has notable differences in etiology. FOM seems to be related almost exclusively to conventional smoking and heavy alcohol use.

The carcinogenic PAHs in breads, amount, analytical method and mitigation strategy, a systematic review study.

Bread is one of the most consumed foods all over the world. Several contaminants are identified in bread. Polycyclic aromatic hydrocarbons (PAHs) is one of these contaminants. This systematic study evaluates the amount of four carcinogenic PAHs (PAH4) in various types of breads. To conduct this study, a comprehensive search was carried out using keywords of polycyclic aromatic hydrocarbons, PAHs, PAH4, and bread, with no time limitations. 17 articles were selected and fully evaluated. The observed range of PAH4 concentrations in bread varied from non-detected (ND) to 20.66 µg/kg. In the sample preparation process for analysis, an ultrasonic bath was predominantly utilized. Most chromatographic methods are able to measure PAHs in food, but the GC-MS method has been used more. To mitigate PAH levels in bread, it is suggested to incorporate antioxidants during the bread-making process. Furthermore, the type of bread, the type of fuel used to bake the bread, the temperature and the cooking time were some of the factors affecting the amount of PAH. Restricting these factors could significantly reduce PAH content. Regarding the risk assessment conducted in the manuscript, it was determined that industrial breads are usually considered safe. However, some traditional breads may pose risks in terms of their potential PAH content.

Topographic modification of the extracellular matrix precedes the onset of bladder cancer.

Background: Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment. Objective: Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to bona fide tumor) and whether those changes favour the development of NMIBC. Design Setting and Participants: Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC. Findings: Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor. Conclusions: The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.

Potential impact of controlling opium use prevalence on future cancer incidence in Iran.

Background: The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential reduction in incident cancers by 2035 in Iran, which accounts for 42% of global opium consumption, through decreasing opium use prevalence. Methods: The population attributable fraction (PAF) of opium-related cancers was projected using national cancer incidence, age- and gender-specific opium use prevalence, relative cancer risks associated with opium use, and annual percentage changes in cancer incidence rates in Iran. Opium-related cancers were defined based on IARC monographs as cancers of lung, larynx, bladder, esophagus, stomach, pancreas, and pharynx. The number of preventable cancer cases under different opium prevalence scenarios was determined by subtracting attributable cases in each year based on current prevalence from those in alternative scenarios. Findings: By 2035, an estimated 3,001,421 new cancer cases are expected in Iran, with 904,013 (30.1%) occurring in opium-related sites. Maintaining the current opium prevalence (5.6%) is projected to cause 111,130 new cancer cases (3.7% of all cancers, 12.3% of opium-related). A 10%, 30%, and 50% reduction in opium prevalence could prevent 9,016, 28,161, and 49,006 total incident cancers by 2035 in Iran, respectively. Reducing opium use prevalence by 10%-50% is projected to have the highest impact on lung cancer (prevention of 2,946-15,831 cases), stomach cancer (prevention of 2,404-12,593 cases), and bladder cancer (prevention of 1,725-9,520 cases). Interpretation: Our results highlight the significant benefits that can be achieved through effective cancer prevention policies targeting opium use in Iran. Neglecting this risk factor is estimated to pose a significant burden on cancer incidence in the next decade in this population. Funding: None.

Ultraviolet Filters: Dissecting Current Facts and Myths.

Skin cancer is a global and increasingly prevalent issue, causing significant individual and economic damage. UV filters in sunscreens play a major role in mitigating the risks that solar ultraviolet ra-diation poses to the human organism. While empirically effective, multiple adverse effects of these compounds are discussed in the media and in scientific research. UV filters are blamed for the dis-ruption of endocrine processes and vitamin D synthesis, damaging effects on the environment, induction of acne and neurotoxic and carcinogenic effects. Some of these allegations are based on scientific facts while others are simply arbitrary. This is especially dangerous considering the risks of exposing unprotected skin to the sun. In summary, UV filters approved by the respective governing bodies are safe for human use and their proven skin cancer-preventing properties make them in-dispensable for sensible sun protection habits. Nonetheless, compounds like octocrylene and ben-zophenone-3 that are linked to the harming of marine ecosystems could be omitted from skin care regimens in favor of the myriad of non-toxic UV filters.

Exploring novel insights into the molecular mechanisms underlying Bisphenol A-induced toxicity: A persistent threat to human health.

Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.

Characterization of fire investigators' polyaromatic hydrocarbon exposures using silicone wristbands.

BACKGROUND: Exposures to polyaromatic hydrocarbons (PAHs) contribute to cancer in the fire service. Fire investigators are involved in evaluations of post-fire scenes. In the US, it is estimated that there are up to 9000 fire investigators, compared to approximately 1.1 million total firefighting personnel. This exploratory study contributes initial evidence of PAH exposures sustained by this understudied group using worn silicone passive samplers. OBJECTIVES: Evaluate PAH exposures sustained by fire investigators at post-fire scenes using worn silicone passive samplers. Assess explanatory factors and health risks of PAH exposure at post-fire scenes. METHODS: As part of a cross-sectional study design, silicone wristbands were distributed to 16 North Carolina fire investigators, including eight public, seven private, and one public and private. Wristbands were worn during 46 post-fire scene investigations. Fire investigators completed pre- and post-surveys providing sociodemographic, occupational, and post-fire scene characteristics. Solvent extracts from wristbands were analyzed via gas chromatography-mass spectrometry (GC-MS). Results were used to estimate vapor-phase PAH concentration in the air at post-fire scenes. RESULTS: Fire investigations lasted an average of 148 minutes, standard deviation ± 93 minutes. A significant positive correlation (r=0.455, p<.001) was found between investigation duration and PAH concentrations on wristbands. Significantly greater time-normalized PAH exposures (p=0.039) were observed for investigations of newer post-fire scenes compared to older post-fire scenes. Regulatory airborne PAH exposure limits were exceeded in six investigations, based on exposure to estimated vapor-phase PAH concentrations in the air at post-fire scenes. DISCUSSION: Higher levels of off-gassing and suspended particulates at younger post-fire scenes may explain greater PAH exposure. Weaker correlations are found between wristband PAH concentration and investigation duration at older post-fire scenes, suggesting reduction of off-gassing PAHs over time. Exceedances of regulatory PAH limits indicate a need for protection against vapor-phase contaminants, especially at more recent post-fire scenes.

Electrochemical detection of 4(5)-methylimidazole in aqueous solutions.

4(5)-methylimidazole (4-MeI) is a potential carcinogen widely used in food colours. EU regulations specify a maximum allowable concentration of 200 ppm for 4-MeI in caramel colours. This study reports an electrochemical determination technique for 4-MeI in caramel colours for the first time. The effect of pH and interference from air were studied to optimize the detection conditions on a glassy carbon electrode in aqueous alkaline solutions using square wave voltammetry (SWV) technique. The concentration of 4-MeI was quantitatively measured down to 10 µM (∼0.8 ppm). Traditional methods such as HPLC, GC, spectrometry and immunoassays involve either expensive instrumentation and reagents or time consuming preparation and detection processes. This study demonstrates the possibility of rapid and simple electrochemical determination of (4-MeI) in food colours with minimum workup using a portable potentiostat.

Possible contribution of 8-hydroxydeoxyguanosine to gene mutations in the kidney DNA of gpt delta rats following potassium bromate treatment.

8-Hydroxydeoxyguanosine (8-OHdG) is well known not only as an effective biomarker of oxidative stress but also as a mutagenic DNA modification. Incorporation of dAMP at the opposite site of 8-OHdG induces G>T or A>C transversions. However, in vivo analyses of gene mutations caused by potassium bromate (KBrO3), which can induce 8-OHdG at carcinogenic target sites, showed that G>T was prominent in the small intestines of mice, but not in the kidneys of rats. Because KBrO3 was a much clearer carcinogen in the kidneys of rats, detailed analyses of gene mutations in the kidney DNA of rats treated with KBrO3 could improve our understanding of oxidative stress-mediated carcinogenesis. In the current study, site-specific reporter gene mutation assays were performed in the kidneys of gpt delta rats treated with KBrO3. Groups of 5 gpt delta rats were treated with KBrO3 at concentrations of 0, 125, 250, or 500 ppm in the drinking water for 9 weeks. At necropsy, the kidneys were macroscopically divided into the cortex and medulla. 8-OHdG levels in DNA extracted from the cortex were dramatically elevated at concentrations of 250 ppm and higher compared with those from the medulla. Cortex-specific increases in mutant frequencies in gpt and red/gam genes were found at 500 ppm. Mutation spectrum and sequence analyses of their mutants demonstrated significant elevations in A>T transversions in the gpt gene and single base deletions at guanine or adenine in the gpt or red/gam genes. While A>T transversions and single base deletions of adenine may result from the oxidized modification of adenine, the contribution of 8-OHdG to gene mutations was limited despite possible participation of the 8-OHdG repair process in guanine deletion.

Integrated In-Silico and In Vitro analysis to Decipher the contribution of bisphenol-A in cervical cancer.

Bisphenol A (BPA) is a synthetic chemical widely used as a monomer for producing polycarbonate plastics. The present investigation employed an in-silico approach to identify BPA-responsive genes and comprehend the biological functions affected using in vitro studies. A Comparative Toxicogenomics Database search identified 29 BPA-responsive genes in cervical cancer (CC). Twenty-nine genes were screened using published datasets, and thirteen of those showed differential expression between normal and CC samples. Protein-Protein Interaction Networks (PPIN) analysis identified BIRC5, CASP8, CCND1, EGFR, FGFR3, MTOR, VEGFA, DOC2B, WNT5A, and YY1 as hub genes. KM-based survival analysis identified that CCND, EGFR, VEGFA, FGFR3, DOC2B, and YY1 might affect CC patient survival. SiHa and CaSki cell proliferation, migration, and invasion were all considerably accelerated by BPA exposure. Changes in cell morphology, remodeling of the actin cytoskeleton, increased number and length of filopodia, elevated intracellular reactive oxygen species and calcium, and lipid droplet accumulation were noted upon BPA exposure. BPA treatment upregulated the expression of epithelial to mesenchymal transition pathway members and enhanced the nuclear translocation of CTNNB1. We showed that the enhanced migration and nuclear translocation of CTNNB1 upon BPA exposure is a calcium-dependent process. The present study identified potential BPA-responsive genes and provided novel insights into the biological effects and mechanisms affected by BPA in CC. Our study raises concern over the use of BPA.

Sporadic Kaposi Sarcoma Following a COVID-19 Vaccine: Mere Coincidence or Something More?

In this case report, we present a distinctive occurrence of classic Kaposi sarcoma (KS) in an individual of Latin origin, emerging seven days following the administration of the third dose of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine. The progression of KS continued over two months, culminating in the development of a tumor. Given the absence of prior reports on KS development post-COVID-19 vaccination, the primary aim of this report is to explore the potential relationship between the ChAdOx1 nCoV-19 vaccine, reactivation of Kaposi sarcoma-associated herpes virus, and the subsequent onset of KS.