Search Results (171)

Background/Objectives: Allophylus edulis, known as “vacum”, is popularly used in Brazil for treating inflammatory diseases, though no scientific evidence supports the anti-inflammatory activity of its leaf infusion. This study aimed to assess the chemical composition, antioxidant and anti-inflammatory properties of the lyophilized infusion (ILAE) of A. edulis leaves, as well as the pharmacological effects of its hydromethanolic fraction (HMf) and the isolated compound vitexin 2″-O-rhamnoside (AE-1). Histochemical analyses of the leaves and in silico toxicity prediction of AE-1 were also performed. Methods: Fresh leaves were used for histochemical analysis and preparation of ILAE. The infusion was fractionated into n-hexane (Hf), ethyl acetate (EAf), and HMf fractions. Total phenols, flavonoids, flavonols, tannins, and antioxidant activity were determined by spectrophotometric methods. AE-1 was obtained from HMf through chromatographic methods and was evaluated by the ProTox model in relation to toxicity predictions (in silico). Anti-inflammatory effects of ILAE (3, 30, 100 mg/kg), HMf (3, 30 mg/kg), and AE-1 (3 mg/kg) were evaluated in carrageenan-induced paw edema, pleurisy, and CFA-induced inflammation in mice. Results: ILAE and its fractions were rich in total phenols (≤177 mg GAE/g) and showed potent antioxidant activity. Histochemical analysis revealed leaf secretory structures. AE-1 showed no hepatotoxic, carcinogenic, mutagenic, or cytotoxic effects in silico. All doses of ILAE and HMf reduced edema, hyperalgesia, and leukocyte migration. ILAE (30 mg/kg), HMf (30 mg/kg), and AE-1 (3 mg/kg) reduced CFA-induced inflammatory responses. Conclusions: ILAE contains polyphenolic compounds with antioxidant, anti-inflammatory, and antihyperalgesic properties, supporting the traditional use of A. edulis and its potential in inflammation-related therapies. Full article

Plants from the Brassicaceae family are characterized by their high content of glucosinolates (GSLs), whose hydrolysis products, isothiocyanates (ITC) or indole compounds, have been found to have anti-inflammatory, antioxidant and metabolic regulatory functions. In this work, we used a model of transformation using the MCF10A cell line, a non-tumorigenic breast fibrocystic disease cell line, treated with benzo(a)pyrene (B(a)P), a potent carcinogen known to induce the production of reactive oxygen species (ROS) and DNA damage. Broccoli sprout (BSE) or red cabbage aqueous (RCA) extracts were rich in ITC and indole compounds. Their use decreased B(a)P induced cellular proliferation and ROS production. in addition, RCA extract induced autophagy in MCF10A cells. Our results indicate a potential use of BSE or RCA for the prevention of carcinogen-induced transformation and of RCA as a method for autophagy, a tumor suppressor pathway, induction. Full article

Vanadium is a transition metal whose environmental presence has increased due to human activities such as fossil fuel combustion and industrial processes. A central mechanism of its toxicity involves mitochondrial dysfunction, as vanadium exposure disrupts energy metabolism, enhances reactive oxygen species (ROS) generation, and triggers oxidative stress, ultimately leading to genetic damage and alterations in cellular signaling. These mitochondrial alterations contribute to its potential carcinogenic, immunotoxic, and neurotoxic properties, affecting multiple systems, including the neurological, renal, immune, and reproductive systems. Since there are no specific treatments for vanadium intoxication, natural compounds—particularly plant-derived metabolites with antioxidant, mitochondrial-targeted, and chelating properties—have been investigated as potential therapeutic agents to counteract its toxicity. In this context, simple models such as the nematode Caenorhabditis elegans (C. elegans), the fruit fly (Drosophila melanogaster), and the zebrafish (Danio rerio) have emerged as valuable experimental systems for studying vanadium-induced mitochondrial dysfunction and evaluating protective strategies. These organisms offer key advantages, including a short life cycle, ease of handling, and conservation of essential biological pathways with mammals, making them effective tools in environmental toxicology. The aim of this review is to outline the mitochondrial-related toxic effects of vanadium across different biological models and to explore plant-based therapeutic approaches capable of mitigating its harmful health impacts. We also propose the use of simple models, such as D. melanogaster, D. rerio, and, most notably, C. elegans, as versatile and complementary experimental platforms to advance research in this field. Full article

Per- and polyfluoroalkyl substances (PFASs), called forever chemicals, persist in the environment and bioaccumulate, posing significant health risks. While epidemiological studies have linked exposure to specific PFAS types, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), to an increased incidence of various cancers, specific tumorigenesis mechanisms are unknown. Here, we investigated the potential molecular markers and signatures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) tumorigenesis. We performed a comprehensive transcriptomic analysis across multiple species and tissue types (N = 529) using PFOS and PFOA-exposed RNA-Seq samples. Conserved signatures demonstrate significant disruptions in seven key carcinogenic characteristics including metabolic reprogramming, epigenetic modifications, immune suppression, oxidative stress, and genomic instability. Tumorigenic markers such as SERPINE1, FN1, PLIN2, ALDOA, TRIB3, and TSC22D3 and their associated pathways may act independently or synergistically to promote a pro-tumorigenic environment. Additionally, PPARα, LARP1, ACOX1, MYC, and MYCN were identified as key upstream regulators supporting disruptions in lipid metabolism, oxidative stress, and uncontrolled cell proliferation. In liver samples, low concentrations of PFOS and PFOA were sufficient to exhibit tumorigenic signatures associated with tumorigenesis initiation and development. Inferred mechanisms of ccRCC initiation and development were linked to lipid metabolism dysregulation and immunosuppressive signaling. In prostate and testicular xenograft tumor models, carcinogenic mechanisms for tumor progression and promotion were hypothesized. Receptor-mediated signaling and protein synthesis was disrupted in prostate cancer and epigenetic alterations and ECM remodeling observed in testicular cancer. We also explored potential therapeutic rescue strategies, including chemopreventive agents for early intervention. All our findings provide hypotheses for PFOS/PFOA-induced tumorigenesis; however, experimental studies are required to establish translational relevance. All the R codes developed in this study are publicly available. Full article

Objectives: Tobacco has been associated with the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). This study aimed to evaluate the in vitro and in vivo changes caused by carcinogen 4-nitroquinoline 1-oxide (4NQO), simulating smoking conditions. Materials and Methods: In the in vitro study, normal keratinocytes were exposed to 1.3 µM and 2.6 µM concentrations of 4NQO to induce dysplastic transformation (H-DISP) and malignant transformation (H-SCC), respectively. The cells were collected and subjected to hematoxylin and eosin (H&E) staining and immunocytochemistry with Ki-67. For the in vivo study, female C57BL/6J mice were divided into a pure control (PC) group and experimental groups exposed to 50 µg/mL (NQ) and 100 µg/mL (CM) of 4NQO in autoclaved drinking water. Each group was euthanized after 8, 12, 16, and 20 weeks of exposure. The tongues were collected, processed, stained with H&E, and analyzed using conventional light microscopy. Results: In vitro, significant morphological changes were observed in the H-DISP and H-SCC groups, with a cell proliferation index exceeding 30% in the H-DISP group. In vivo, the CM group showed greater progression to severe dysplasia/carcinoma within a shorter treatment period compared to the NQ group. Conclusions: We established critical doses and exposure durations for 4NQO, both in vitro and in vivo, to induce cellular changes and the formation of OL and OSCC, providing a standardized model for studies related to oral carcinogenesis. Full article

Arsenic, a naturally occurring metalloid, poses a significant global public health threat due to widespread environmental contamination. Despite its well-documented carcinogenicity, critical gaps remain in understanding the health impacts of chronic low-level airborne exposure and the multi-modal mechanisms driving inorganic arsenic toxicity. This narrative review synthesizes recent molecular research and population health data to explain how airborne inorganic arsenic causes harm through multiple biological pathways. Key novel insights include (1) a comprehensive analysis of inorganic arsenic-induced oxidative stress and epigenetic dysregulation, revealing transgenerational effects via germline epigenetic markers; (2) a critical evaluation of the linear no-threshold (LNT) model, demonstrating its overestimation of low-dose risks by 2–3× compared to threshold-based evidence; and (3) descriptions of mechanistic links between inorganic arsenic speciation, organ-specific pathologies (e.g., neurodevelopmental impairments, cardiovascular diseases), and pollution mitigation strategies. This study connects molecular mechanisms with public health strategies to improve arsenic risk assessment. It focuses on how inorganic arsenic alters gene regulation (epigenetics) and combines exposure from multiple sources, while also clarifying uncertainties about low-dose effects and refining safety standards. Full article

Ionizing radiation can damage DNA, leading to mutations, and is a risk factor for cancer. Based on the assumption that all radiation exposure poses a risk in linear proportion to its dose, ionizing radiation is considered a non-threshold carcinogen. However, most epidemiological studies have had insufficient statistical power to detect excess cancer risks from low-dose radiation exposure. Therefore, research is needed to identify radiation signatures that distinguish radiation-induced cancers from spontaneously developed cancers. In rodent cancer models, interstitial chromosomal deletions of specific tumor-suppressor gene loci are characteristically found in cancers from irradiated animals. In humans, a high frequency of small deletions and chromosome rearrangements, such as large deletions, inversions, and translocations, has also been reported in second cancers that develop in patients who received radiotherapy and in thyroid cancers diagnosed in residents after the Chornobyl accident. These genomic alterations are likely to be generated as a consequence of the processing of radiation-induced DNA double-strand breaks. Particularly, chromosome rearrangements that occur at loci directly linked to tumor formation after ionizing-radiation exposure are potentially useful as biomarkers and as therapeutic targets for radiation-induced cancer. Here we provide an overview of the radiation-induced mutational signatures observed in animal and human cancers. Full article

Despite increasing evidence that cigarette smoke is a significant source of indoor fine particulate matter (PM_2.5), quantitative emission factors (EFs) for PM_2.5 and its toxic chemical composition in mainstream (MS) and sidestream (SS) smoke are still not well defined. In this study, we employed a custom-designed chamber to separately collect MS (intermittent puff) and SS (continuous sampling) smoke from eleven cigarette models, representing six brands and two product types, under controlled conditions. PM_2.5 was collected on quartz-fiber filters and analyzed for carbon fractions (using the thermal–optical IMPROVE-A protocol), nine water-soluble inorganic ions (by ion chromatography), and twelve trace elements (via ICP-MS). SS smoke exhibited significantly higher mass fractions of total analyzed species (84.7% vs. 65.9%), carbon components (50.6% vs. 44.2%), water-soluble ions (17.1% vs. 13.7%), and elements (17.0% vs. 7.0%) compared to MS smoke. MS smoke is characterized by a high proportion of pyrolytic organic carbon fractions (OC₁–OC₃) and specific elements such as vanadium (V) and arsenic (As), while SS smoke shows elevated levels of elemental carbon (EC1), water-soluble ions (NH₄⁺, NO₃⁻), and certain elements like zinc (Zn) and cadmium (Cd). The toxicity-weighted distribution indicates that MS smoke primarily induces membrane disruption and pulmonary inflammation through semi-volatile organics and elements, whereas SS smoke enhances oxidative stress and cardiopulmonary impairment via EC-mediated reactions and secondary aerosol formation. The mean OC/EC ratio of 132.4 in SS smoke is an order of magnitude higher than values reported for biomass or fossil-fuel combustion, indicative of extensive incomplete combustion unique to cigarettes and suggesting a high potential for oxidative stress generation. Emission factors (µg/g cigarette) revealed marked differences: MS delivered higher absolute EFs for PM_2.5 (422.1), OC (8.8), EC (5.0), Na⁺ (32.6), and V (29.2), while SS emitted greater proportions of NH₄⁺, NO₃⁻, Cl⁻, and carcinogenic metals (As, Cd, Zn). These findings provide quantitative source profiles suitable for receptor-oriented indoor source-apportionment models and offer toxicological evidence to support the prioritization of comprehensive smoke-free regulations. Full article

Plastics have become integral to modern life; however, their widespread use and persistent nature have resulted in significant environmental contamination, especially by microplastics (MPs < 5 mm) and nanoplastics (NPs < 100 nm). These plastic particles can enter the human body via ingestion, inhalation, or dermal absorption, raising substantial concerns about their potential health impacts. Recent studies using zebrafish, rodent models, and human cell lines have begun to elucidate the mechanisms underlying micro- and nanoplastics (MNPs)-induced toxicity. These mechanisms include oxidative stress, inflammation, disruption of metabolic processes, neurotoxicity, reproductive dysfunction, and carcinogenicity. Despite these advances, significant knowledge gaps remain. There remains a lack of comprehensive reviews that systematically evaluate these effects across major human organ systems and address how MNPs cross biological barriers in the human body. This review addresses these gaps by summarizing the available evidence on MNPs’ toxicity, critically discussing their absorption, distribution, metabolism, and the associated cellular and molecular mechanisms of action. Furthermore, it outlines urgent research priorities, emphasizing the need for standardized analytical protocols, realistic exposure models, and extended epidemiological research to evaluate human health risks posed by MNPs accurately. In addition, the adoption of precautionary regulatory actions is recommended to mitigate exposure and safeguard public health. Full article

Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article

Volatile organic compounds (VOCs) are highly volatile chemicals in natural and anthropogenic environments, significantly affecting indoor air quality. Major sources of indoor VOCs include emissions from building materials, furnishings, and consumer products. Natural wood products release VOCs, including terpenes and aldehydes, which exert diverse health effects ranging from mild respiratory irritation to severe outcomes, such as formaldehyde-induced carcinogenicity. The temporal dynamics of VOC emissions were investigated, and the toxicological and physiological effects of the VOCs emitted by two types of natural wood, Korean Red Pine (Pinus densiflora) and Japanese Cypress (Chamaecyparis obtusa), were evaluated. Using female C57BL/6 mice as an animal model, the exposure setups included phytoncides, formaldehyde, and intact wood samples over short- and long-term durations. The exposure effects were assessed using oxidative stress markers, antioxidant enzyme activity, hepatic and renal biomarkers, and inflammatory cytokine profiles. Long-term exposure to Korean Red Pine and Japanese Cypress wood VOCs did not induce significant pathological changes. Japanese Cypress exhibited more distinct benefits, including enhanced oxidative stress mitigation, reduced systemic toxicity, and lower pro-inflammatory cytokine levels compared to the negative control group, attributable to its more favorable VOC emission profile. These findings highlight the potential health and environmental benefits of natural wood VOCs and offer valuable insights for optimizing timber use, improving indoor air quality, and informing public health policies. Full article

Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article

Bioactive peptides from black soldier fly larvae (BSFL) protein hydrolysates have gained attention for their health-promoting properties. Our previous study demonstrated the chemopreventive potential of BSFL hydrolysates prepared with Alcalase (ASBP-AH) in colon cancer cells; their in vivo efficacy has not been fully elucidated. This study evaluated the chemopreventive effects of ASBP-AH, processed by spray-drying (ASBP-AHS) or freeze-drying (ASBP-AHF), in a diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH)-induced rat model of early-stage colorectal carcinogenesis. Oral administration of ASBP-AHS or ASBP-AHF significantly reduced aberrant crypt foci (ACF) and downregulated PCNA, COX-2, and NF-κB expression, without affecting apoptosis. Furthermore, both treatments restored microbial species richness and shifted gut microbial diversity disrupted by carcinogen exposure. ASBP-AHS specifically enriched short-chain fatty acid (SCFA)-producing bacteria, while ASBP-AHF favored anti-inflammatory microbial signatures. Likewise, correlation analysis revealed positive associations between microbial changes and SCFA levels, particularly with ASBP-AHS. Peptidomic profiling identified identical peptides in both hydrolysates, including stable pyroglutamyl-containing sequences with potential anti-inflammatory and microbiota-modulating effects. These findings support the in vivo chemopreventive potential of ASBP-AH and its promise as a functional food ingredient for promoting gut health and reducing colorectal cancer risk. Full article

In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article

Breast cancer (BC) is among the most common neoplasms globally and is the leading cause of cancer-related mortality in women. Despite significant advancements in prevention, early diagnosis, and treatment strategies made over the past two decades, breast cancer continues to pose a significant global health challenge. One of the major obstacles in the clinical management of breast cancer patients is the high intertumoral and intratumoral heterogeneity that influences disease progression and therapeutic outcomes. The inability of preclinical experimental models to replicate this diversity has hindered the comprehensive understanding of BC pathogenesis and the development of new therapeutic strategies. An ideal experimental model must recapitulate every aspect of human BC to maintain the highest predictive validity. Therefore, a thorough understanding of each model’s inherent characteristics and limitations is essential to bridging the gap between basic research and translational medicine. In this context, omics technologies serve as powerful tools for establishing comparisons between experimental models and human tumors, which may help address BC heterogeneity and vulnerabilities. This review examines the BC models currently used in preclinical research, including cell lines, patient-derived organoids (PDOs), organ-on-chip technologies, carcinogen-induced mouse models, genetically engineered mouse models (GEMMs), and xenograft mouse models. We emphasize the advantages and disadvantages of each model and outline the most important applications of omics techniques to aid researchers in selecting the most relevant model to address their specific research questions. Full article