Pyrrolizidine alkaloids (PAs) form a family of toxic and carcinogenic phytochemicals found in plants worldwide. The metabolism of toxic PAs, both and , generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5-pyrrolizine (DHP)-derived DNA adducts, namely, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, as documented in previous research. We have proposed that these DHP-DNA adducts play a pivotal role in the induction of liver tumor by PAs in rats and mice, serving as potential common biological biomarkers for PA exposure and carcinogenesis. In this study, we found that the metabolism of PAs and PA -oxides by human liver microsomes, in the presence of calf thymus DNA, results in the formation of DNA adducts. This process serves as a convenient and biologically significant platform for investigating the structure-carcinogenicity relationships of PAs.

Monosodium glutamate (MSG) is a food additive that enhances the palatability of foods, thus its frequent use both domestically and industrially. Based on the dose-factor, frequency, and duration of exposure, MSG may provoke adverse health outcomes both in animals and humans. The present report aims at providing a comprehensive analysis of the scientifically proven untoward health effects of MSG. To achieve our aim, we adopted the PRISMA guidelines and checklist and searched four databases (Scopus, Web of Science, PubMed, and Google Scholar) from 2014 to 2024. Retrieved research papers were critically appraised for quality using the ARRIVE and Joanna Briggs (JB) checklists and data analysis was conducted the narrative synthesis method. Our analysis reveals that though MSG is generally considered safe at low doses; however, high doses and repeated exposure to MSG are associated with embryotoxicity and teratogenicity, obesity, cardiotoxicity, hepatotoxicity, kidney toxicity, neurotoxicity, endothelial dysfunction, reproductive toxicities, alteration of lipid, and glucose metabolism. Thus, chronic exposure to MSG may be of human pathological importance. The findings of the present narrative synthesis provide a rationale for informed decisions on the use and labeling of this widely used food additive.

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.

Since usnic acid was first isolated in 1844 as a prominent secondary lichen metabolite, it has been used for various purposes worldwide. Usnic acid has been claimed to possess numerous therapeutic properties, including antimicrobial, anti-inflammatory, antiviral, anti-proliferative, and antipyretic activities. Approximately two decades ago, crude extracts of usnic acid or pure usnic acid were marketed in the United States as dietary supplements for aiding in weight loss as a "fat-burner" and gained popularity in the bodybuilding community; however, hepatotoxicity was documented for some usnic acid containing products. The US Food and Drug Administration (FDA) received numerous reports of liver toxicity associated with the use of dietary supplements containing usnic acid, leading the FDA to issue a warning letter in 2001 on a product, LipoKinetix. The FDA also sent a recommendation letter to the manufacturer of LipoKinetix, resulting in the withdrawal of LipoKinetix from the market. These events triggered investigations into the hepatotoxicity of usnic acid and its mechanisms. In 2008, we published a review article titled "Usnic Acid and Usnea Barbata Toxicity". This review is an updated version of our previous review article and incorporates additional data published since 2008. The purpose of this review is to provide a comprehensive summary of the understanding of the liver toxicity associated with usnic acid, with a particular focus on the current understanding of the putative mechanisms of usnic acid-related hepatotoxicity.

Hexavalent chromium (Cr(VI)) is a well-known occupational and environmental human carcinogen. The cellular effect of Cr(VI) is complex and often nonspecific due to its ability to modulate multiple cellular targets. The toxicity of Cr(VI) is strongly linked to the generation of reactive oxygen species (ROS) during its reduction process. ROS can cause oxidation of cellular macromolecules, such as proteins, lipids, and DNA, thereby altering their functions. A major genotoxic effect of Cr(VI) that contributes to carcinogenesis is the formation of DNA adducts, which can lead to DNA damage. Modulations of cellular signaling pathways and epigenetics may also contribute to the carcinogenic effects of Cr(VI). Cr(VI) has a major impact on many aspects of mitochondrial biology, including oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. These effects have the potential to alter the trajectory of Cr(VI)-induced carcinogenic process. This perspective article summarizes current understandings of the effect of Cr(VI) on mitochondria and discusses the future directions of research in this area, particularly with regard to carcinogenesis.

The escalation of technological advancements, coupled with the increased use of hazardous chemicals, has emerged as a significant concern for human health. Exposure to environmental pollutants like heavy metals and pesticides (insecticides, herbicides and fungicides) is known to significantly contribute to various health problems, particularly affecting reproductive health. Disturbances in reproductive potential and reproductive toxicity in males are particularly worrisome. Existing literature suggests that exposure to these environmental pollutants significantly alters male reproductive parameters. Thus, it is imperative to thoroughly analyze, comprehend, and evaluate their impact on male reproductive toxicity. Oxidative stress and disruptions in redox equilibrium are major factors through which these pollutants induce changes in sperm parameters and affect the reproductive system. Insecticides, fungicides, and herbicides act as endocrine disruptors, interfering with the secretion and function of reproductive hormones such as testosterone and luteinizing hormone (LH), consequently impacting spermatogenesis. Additionally, heavy metals are reported to bio-accumulate in reproductive organs, acting as endocrine disruptors and triggering oxidative stress. The co-operative association of these pollutants can lead to severe damage. In this comprehensive review, we have conducted an in-depth analysis of the impact of these environmental pollutants on the male reproductive system, shedding light on the underlying mechanisms of action.

The Cancer Genome Atlas (TCGA) and its patient-derived multi-omics datasets have been the backbone of cancer research, and with novel approaches, it continues to shed new insight into the disease. In this study, we delved into a method of multi-omics integration of patient datasets and the association of biological pathways related to the disease. First, across thirty-three types of cancer present in TCGA, we merged genomic mutations and drug response datasets and filtered for the viable variant-drug response combinations available in TCGA, containing more than three samples for each drug response label with RNA sequencing (RNA-seq) and genomic methylation data available for each patient. We identified two distinct combinations in TCGA, one being pancreatic adenocarcinoma patients with/without rs121913529 variant in gene treated with gemcitabine, and the other low-grade glioma with/without rs121913500 variant in gene administered with temozolomide. In these two groups, different patterns of gene expression were observed in the pathways often associated with cancer progression, such as mTOR and PDGF between the patients with complete response and progressive disease. Our result will provide yet another example of the relevance of these biological pathways in cancer drug response and a way for multi-omics integration in cancer datasets.

Public health concerns on surface and groundwater contamination worldwide have increased. Sachet water contamination has also raised serious concerns across many developing countries. While previous studies attempted to address this issue, this review takes a different approach by utilizing a comprehensive analysis of physicochemical parameters, heavy metals, and microbial loads tested in sachet water across Nigeria's six geopolitical zones, within the period of 2020-2023. In this review study, over 50 articles were carefully analyzed. Collected data unveiled regional variations in the quality of sachet water across Nigeria. Noteworthy concerns revolve around levels of pH, total hardness, magnesium, calcium, nickel, iron, lead, mercury, arsenic, and cadmium. Fecal contamination was also identified as a significant issue, with the prevalence of several pathogens like , , , , and . The manufacturing, delivery, storage, and final sale of sachet water, as well as poor environmental hygiene, were identified as potential contamination sources. The intake of contaminated sachet water exposes the citizens to waterborne and carcinogenic diseases. While the sachet water industry keeps growing and making profits, it is apparent that improvement calls made by previous studies, regarding the quality of water produced, have not been paid serious attention.

Elevated radon concentrations in drinking water pose an increased risk of cancer among nonsmokers. A Monte-Carlo Simulation was employed to assess the effective dose and cancer risk associated with radon exposure in humans, utilizing a systematic review and meta-analysis of related studies. These studies were sourced from databases including PubMed, Web of Science, Scopus, Science Direct, and Google Scholar, focusing on drinking water from Nigeria's six geopolitical zones. The random effects models revealed a Rn concentration in drinking water of Nigeria at 25.01, with 95% confidence intervals (CI) of 7.62 and 82.09, indicating significant heterogeneity of (I = 100%;  < 0.001). The probabilistic risk of effective dose revealed a best-scenario (P 5%) at Kundiga and Magiro that exceeded the World Health Organization's (WHO) recommended effective dose limit of 200 µSv/y. Conversely, the worst-case scenario (P 95%) indicated concentrations surpassing the recommended limit at Kundiga, Edbe, Magiro, Ekiti, and Abeokuta. Excess Life Cancer Risk for infants, children, and adults attributed to the ingestion and inhalation of radon from various drinking water sources exceeded the recommended values of 0.2 x 10 established by the International Commission on Radiological Protection (ICRP) and the United Nations Scientific Committee on the Effect of Atomic Radiation (UNSCEAR). It underscores the necessity for treating radon-polluted water, employing methos such as aeration and granular activated carbon (GAC) processes.

Nanotechnology has attained significant attention from researchers in past decades due to its numerous advantages, such as biocompatibility, biodegradability, and improved stability over conventional drug delivery systems. The fabrication of engineered nanoparticles (ENPs), including carbon nanotubes (CNTs), fullerenes, metallic and metal oxide-based NPs, has been steadily increasing day due to their wide range of applications from household to industrial applications. Fabricated ENPs can release different materials into the environment during their fabrication process. The effect of such materials on the environment is the primary concern with due diligence on the safety and efficacy of prepared NPs. In addition, an understanding of chemistry, reactivity, fabrication process, and viable mechanism of NPs involved in the interaction with the environment is very important. To date, only a limited number of techniques are available to assess ENPs in the natural environment which makes it difficult to ascertain the impact of ENPs in natural settings. This review extensively examines the environmental effects of ENPs and briefly discusses useful tools for determining NP size, surface charge, surface area, and external appearance. In conclusion, the review highlights the potential risks associated with ENPs and suggests possible solutions.

In the rapidly evolving field of artificial intelligence (AI), explainability has been traditionally assessed in a post-modeling process and is often subjective. In contrary, many quantitative metrics have been routinely used to assess a model's performance. We proposed a unified formular named PERForm, by incorporating explainability as a weight into the existing statistical metrics to provide an integrated and quantitative measure of both predictivity and explainability to guide model selection, application, and evaluation. PERForm was designed as a generic formula and can be applied to any data types. We applied PERForm on a range of diverse datasets, including DILIst, Tox21, and three MAQC-II benchmark datasets, using various modeling algorithms to predict a total of 73 distinct endpoints. For example, AdaBoost algorithms exhibited superior performance (PERForm AUC for AdaBoost is 0.129 where Linear regression is 0) in DILIst prediction, where linear regression outperformed other models in the majority of Tox21 endpoints (PERForm AUC for linear regression is 0.301 where AdaBoost is 0.283 in average). This research marks a significant step toward comprehensively evaluating the utility of an AI model to advance transparency and interpretability, where the tradeoff between a model's performance and its interpretability can have profound implications.

Increasing public interest has resulted in the widespread use of non-pharmaceutical cannabidiol (CBD) products. The sales of CBD products continue to rise, accompanied by concerns regarding unsubstantiated benefits, lack of product quality control, and potential health risks. Both animal and human studies have revealed a spectrum of toxicological effects linked to the use of CBD. Adverse effects related to exposure of humans to CBD include changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes. Animal studies reported changes in organ weight, reproduction, liver function, and the immune system. This review centers on human-derived data, including clinical studies and investigations. Animal studies are also included when human data is not available. The objective is to offer an overview of CBD-related hepatotoxicity, metabolism, and potential CBD-drug interactions, thereby providing insights into the current understanding of CBD's impact on human health. It's important to note that this review does not serve as a risk assessment but seeks to summarize available information to contribute to the broader understanding of potential toxicological effects of CBD on the liver.

Recent discoveries of microplastics in cities, suburbs, and even remote locations, far from microplastic source regions, have raised the possibility of long-distance transmission of microplastics in many ecosystems. A little is known scientifically about the threat that it posed to the environment by microplastics. The problem's apparent size necessitates the rapid development of reliable scientific advice regarding the ecological risks of microplastics. These concerns are brought on by the lack of consistent sample and identification techniques, as well as the limited physical analysis and understanding of microplastic pollution. This review provides insight regarding some unaddressed issues about the occurrence, fate, movement, and impact of microplastics, in general, with special emphasis on primary microplastics. The approaches taken in the earlier investigations have been analyzed and different recommendations for future research have been suggested.

Disinfecting swimming pool water plays a crucial role in preventing the spread of harmful bacteria. However, the interaction between disinfectants and precursors can lead to the formation of potentially disinfection by-products (DBPs). Prolonged exposure to these DBPs may pose health risks. This review study investigates recent research advancements concerning the formation, exposure, and regulation of DBPs within swimming pools. It also provides an overview of existing models that predict DBPs generation in pools, highlighting their limitations. The review explores the mechanisms behind DBPs formation under different disinfectant and precursor conditions. It specifically discusses two types of models that simulate the production of these by-products. Compared to drinking water, swimming pool water presents unique challenges for model development due to its complex mix of external substances, human activities, and environmental factors. Existing models can be categorized as empirical or mechanistic. Empirical models focus on water quality parameters and operational practices, while mechanistic models delve deeper into the kinetics of DBPs generation and the dynamic nature of these compounds. By employing these models, it becomes possible to minimize DBPs production, optimize equipment design, enhance operational efficiency, and manage mechanical ventilation systems effectively.

The rapidly increasing incidence of nonalcoholic fatty liver disease (NAFLD) is a growing health crisis worldwide. If not detected early, NAFLD progression can lead to irreversible pathological states, including liver fibrosis and cirrhosis. Using models to understand the molecular pathogenesis has been extremely beneficial; however, most studies have utilized only short-term exposures, highlighting a limitation in current research to model extended fat-induced liver injury. We treated Hep3B cells continuously with a low dose of oleic and palmitic free fatty acids (FFAs) for 7 or 28 days. Transcriptomic analysis identified dysregulated molecular pathways and differential expression of 984 and 917 genes after FFA treatment for 7 and 28 days respectively. DNA methylation analysis of altered DNA methylated regions (DMRs) found 7 DMRs in common. Pathway analysis of differentially expressed genes (DEGs) revealed transcriptomic changes primarily involved in lipid metabolism, small molecule biochemistry, and molecular transport. Western blot analysis revealed changes in PDK4 and CPT1A protein levels, indicative of mitochondrial stress. In line with this, there was mitochondrial morphological change demonstrating breakdown of the mitochondrial network. This model of human NAFL mimics results observed in human patients and may be used as a pre-clinical model for drug intervention.

Due to their simplicity, eco-friendliness, availability and non-toxicity, the greener fabrication of metal and metal oxide nanoparticles has been a highly attractive research area over the last decade. This study aimed to assess the antioxidant and antimicrobial activities of the green synthesized zinc oxide nanoparticles (ZnO-NPs) using an aqueous leaf extract of . The antioxidant property of ZnO-NPs was analyzed by the α, α-diphenyl-β-picrylhydrazyl (DPPH) and hydrogen peroxide (HO). Additionally, the diffusion agar method assessed the antimicrobial activities against bacteria and fungi. ZnO-NPs synthesized by had shown promising HO and DPPH free radical scavenging actions compared to vitamin C. The ZnO-NPs exhibited significant antibacterial activity against the tested bacteria with various susceptibility as a concentration-dependent effect. The largest zone of inhibition for was observed (36 ± 2 mm) compared to (15 ± 2 mm) by the same concentration of ZnO-NPs. The ZnO-NPs showed remarkable antifungal activity against . It can be concluded that, ZnO-NP have been imposed as suitable antimicrobial agent being able to combat both and .

There has been growing interest in the use of human-derived metabolically competent cells for genotoxicity testing. The HepaRG cell line is considered one of the most promising cell models because it is TP53-proficient and retains many characteristics of primary human hepatocytes. In recent years, HepaRG cells, cultured in both a traditional two-dimensional (2D) format and as more advanced in-vivo-like 3D spheroids, have been employed in assays that measure different types of genetic toxicity endpoints, including DNA damage, mutations, and chromosomal damage. This review summarizes published studies that have used HepaRG cells for genotoxicity assessment, including cell model evaluation studies and risk assessment for various compounds. Both 2D and 3D HepaRG models can be adapted to several high-throughput genotoxicity assays, generating a large number of data points that facilitate quantitative benchmark concentration modeling. With further validation, HepaRG cells could serve as a unique, human-based new alternative methodology for genotoxicity testing.

Polychlorinated biphenyls (PCBs) are a class of ubiquitous and significant synthetic organic chemicals that pose deleterious threats to the environment and human health. This study examined the concentration, indoor-outdoor and seasonal change, sources, and health effects of PCBs in particulate-bound dust near a scrap iron recycling plant. PCBs levels were determined in samples using gas chromatograph mass spectrometer. The results indicated that 5 Cl atoms PCB constituted the majority of PCBs (41% overall), contributing 43% during the rainy season and 39% during the dry season. Dioxin-like PCBs (DLPCBs) contributed 38% during the rainy season and 33% during the dry season. In addition, DLPCB accounted for 26% and 40% of indoor and outdoor PCB emissions, respectively. Iron and steel production were identified as the highest identified contributing sources, accounting for 76% of PCB emissions in the rainy season, while plastic combustion had the highest contribution in the dry season, accounting for 44% of PCB emissions. Incremental Lifetime Cancer Risk assessment showed ingestion as the main exposure pathway for children and adults during the two seasons (74.42% and 58.24%, respectively), followed by dermal exposure, while inhalation had the least contribution. A multifaced approach involving relevant agencies, the industry, and the community is required to reduce exposure.

The mode of action (MOA) underlying perfluorooctanoic acid (PFOA)-induced liver tumors in rats is proposed to involve peroxisome proliferator-activated receptor α (PPARα) agonism. Despite clear PPARα activation evidence in rodent livers, the mechanisms driving cell growth remain elusive. Herein, we used dose-responsive apical endpoints and transcriptomic data to examine the proposed MOA. Male Sprague-Dawley rats were treated with 0, 1, 5, and 15 mg/kg PFOA for 7, 14, and 28 days oral gavage. We showed PFOA induced hepatomegaly along with hepatocellular hypertrophy in rats. PPARα was activated in a dose-dependent manner. Toxicogenomic analysis revealed six early biomarkers (, , , , , and ) in response to PPARα activation. A transient rise in hepatocellular DNA synthesis was demonstrated while Ki-67 labeling index showed no change. Transcriptomic analysis indicated no significant enrichment in pathways related to DNA synthesis, apoptosis, or the cell cycle. Key cyclins including , , , and were dose-dependently suppressed by PFOA. Oxidative stress and the nuclear factor-κB signaling pathway were unaffected. Overall, evidence for PFOA-induced hepatocellular proliferation was transient within the studied timeframe. Our findings underscore the importance of considering inter-species differences and chemical-specific effects when evaluating the carcinogenic risk of PFOA in humans.

The changes in dietary habit around the world have led to an increased use of additives in the food. The safety of food additives has been a main focus of research for many years due to the ongoing debate on their potential effects on health. In this study, the genotoxic effects of mannitol and lactitol, polyols used as sweetener food additives, were evaluated using chromosomal aberrations (CAs) and micronucleus (MN) assays in human peripheral lymphocytes. Additionally, the effects of these sweeteners on the mitotic index (MI) and nuclear division index (NDI) were investigated. Concentrations of 500, 1000, 2000, 4000, and 8000 μg/mL for mannitol and 250, 500, 1000, 2000, and 4000 μg/mL for lactitol were used. The results indicated that both polyols did not affect CA and MN frequency, and did not cause a significant change in NDI at all treatment concentratoins. However, mannitol (except at concentrations of 500 and 1000 μg/mL) and lactitol (except at 250 μg/mL) significantly decreased the MI compared to the control at almost all concentrations and treatment times. In conclusion, it was observed that mannitol and lactitol did not have a significant genotoxic effect at the concentrations used in human lymphocytes .

has grown in popularity due to its broad therapeutic benefits. Despite its popularity, comprehensive safety evaluations for three medicinal species are limited. In this study, female Sprague-Dawley rats received oral doses (0, 25, 50, 100, 200 mg/kg/d) of 75% (v/v) ethanol extract from the aerial parts of 9 samples of three species - , , and - over a 7-day period. Blood and serum samples, collected twenty-four hours post the final dose, were analyzed for hematology and clinical chemistry parameters. The results revealed varied effects across the tested samples, with many parameters showing no discernible impacts at administered doses. Subtle alterations were observed in parameters such as relative liver weight, alkaline phosphatase (ALP), and platelet count. Parameters like relative spleen weight, alanine transaminase (ALT), glucose, urea, hematocrit, hemoglobin, and RBC count exhibited effects in only one out of the nine samples tested. These findings emphasize the heterogeneity in the effects of . While the results suggest that samples might be considered relatively safe, potential clinical implications warrant caution and underscore the importance of extended testing. A comprehensive toxicity profile assessment remains paramount to conclusively ascertain the safety of three species.