Search Results (161)

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

Benzo[a]pyrene (B[a]P) is a widespread and persistent organic pollutant that poses serious threats to human health. Although its carcinogenic properties have been extensively studied, its developmental toxicity and underlying mechanisms remain poorly understood. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effects of B[a]P exposure during early developmental stages. To comprehensively assess B[a]P-induced developmental toxicity, we employed high-throughput sequencing along with transgenic and mutant C. elegans strains. Exposure to B[a]P at concentrations exceeding 1 mg/L significantly reduced larval body size, decreased the number of adult worms, and delayed larval-to-adult development. Furthermore, we analyzed the expression of genes involved in cuticle collagen synthesis and key components of the insulin/insulin-like growth factor signaling (IIS) pathway, including daf-2 and daf-16. These findings suggest that B[a]P-induced developmental toxicity may be associated with dysregulation of the IIS pathway. Specifically, B[a]P appears to influence the activity of the downstream transcription factor daf-16, thereby altering the expression of collagen-related genes. This disruption in collagen synthesis may contribute to delayed larval development and impaired maturation. Our study provides new insights into the environmental hazards associated with B[a]P exposure and reveals a potential mechanism underlying its developmental toxicity. Moreover, our findings highlight the critical role of collagen gene regulation during early developmental stages. These genes may serve as potential biomarkers for environmental toxicant exposure, particularly in vulnerable populations such as children undergoing critical periods of development. Full article

The present study aimed to analyze the physicochemical properties and biological activity of an L-malic acid descaler. The treated water with L-malic acid descaler complies with EU Directive No. 2020/2184 for the quality of water intended for human consumption. The L-malic acid descaler contains L-malic acid as the active component, while polyethylene and activated charcoal function as structural and absorbent materials, respectively. The composition was analyzed in a licensed laboratory using Chemical Abstracts Service Number (CAS) and European List of Notified Chemical Substances (EINECS) standards. Fourier Transform Infrared (FT-IR) analysis confirmed the presence of hydroxyl (–OH), carbonyl (C=O), and carboxyl (–COOH) groups in L-malic acid descaler, which are connected with proton-donating ability, and redox activity. The biological activity was evaluated using Saccharomyces cerevisiae as a model system. The role of the YAP1 transcription factor, a key regulator of oxidative stress defense mechanisms, was also examined. The detrimental effects on a cellular level were induced by the well-known mutagen—methyl methanesulfonate (MMS). Our data revealed that yeast cells treated with such water decrease the MMS-induced superoxide anions (3.5-fold), total glutathione lipid peroxidation (1.5-fold), and total glutathione (3-fold) and increase cell survival (2-fold). In conclusion, water treated with L-malic acid descaler possesses antioxidant effects in yeast-cell-based tests, independent of YAP1 transcription factor activity. This study provides preliminary evidence that L-malic acid, when dissolved in water, significantly reduced MMS-induced superoxide anions, one of the biomarkers contributing to the genotoxic and carcinogenic effects of MMS. Full article

During the natural cooling process of magnesium slag stockpiles in the open air, the phase transformation of gamma-dicalcium silicate (γ-C₂S) induces a powdering phenomenon, resulting in the generation of a large amount of PM10 and PM2.5 dust. Based on the dust emission model of stockpiles and the Gaussian dispersion model, combined with the Monte Carlo simulation method, this study conducted a quantitative assessment of the environmental risk of heavy metals (Pb, Cd, Hg, As, Cr(VI)) in dust to the surrounding residential areas. The results show that the enrichment degree of heavy metals in PM2.5 is significantly higher than that in PM10. At a downwind distance of 1000 m, the exceedance multiples of Cr(VI), As, and Cd reach 131.5, 23.6, and 51.8 times, respectively. The total carcinogenic risk (9.2 × 10⁻⁷) and total non-carcinogenic hazard quotient (0.15) in the residential area are below the limits, but the contribution rates of As and Cd are relatively high. Sensitivity analysis further reveals that the moisture content of the stockpile, dust removal rate, and distance are the key control parameters affecting the environmental risk. Based on the research findings, it is recommended to increase sprinkling frequency, install windbreak nets, and promote magnesium slag utilization to effectively control dust risks. Full article

Introduction: Diethyl nitrosamine (DEN), a known carcinogen, has been used for validating the RasH2 and P53 transgenic models in chemical testing and has been shown to enhance primary liver tumor growth in the ATT-Myc transgenic mouse model of liver cancer. Material and Methods: to better understand the mechanism of hepatocellular carcinoma acceleration following DEN, BHT and vehicles treatments in ATT-Myc, transgenic and non-transgenic, mice. We employed an exon array, RT-PCR, Western blotting, and IHC to investigate the complex interplay between the c-Myc transgene and other growth factors in treated mice versus control transgenic and non-transgenic mice. Results: Notably, DEN treatment induced a 12-fold increase in c-Myc expression compared to non-transgenic mice. Furthermore, tumor growth in the DEN group was strongly associated with increased proliferation of transformed or carcinogenic hepatocytes, as evidenced by proliferative cell nuclear antigen and bromodeoxyuridine expression. Internally, the loss of c-Met signaling, enriched transcription factors, and the diminished expression of antioxidants, such as superoxide dismutase (SOD1) and NRF2, further enhanced c-Myc-induced liver tumor growth as early as four months post-DEN treatment. Discussion: Extensive tumor growth was observed at 8.5 months, coinciding with the downregulation of tumor suppressors such as p53. In contrast, at these time points, ATT-Myc transgenic mice exhibited only dysplastic hepatocytes without tumor formation. Additionally, the antioxidant butylated hydroxytoluene maintained c-Met expression and did not promote liver tumor formation. Conclusions: the persistent upregulation of c-Myc in the ATT-Myc liver cancer model, at both the gene and protein levels following DEN treatment inhibited the ETS1 transcription factor, further exacerbating the decline of c-Met signaling, SOD1, and NRF2. These changes led to increased reactive oxygen species production and promoted rapid liver tumor growth. Full article

Bioremediation induced by bacteria offers a promising alternative for the contamination of aromatic hydrocarbons due to their metabolic processes suitable for the removal of these pollutants, as many of them are carcinogenic molecules and dangerous to human health. Our research focused on isolating a bacterium from the rhizosphere of the tara tree with the ability to degrade polycyclic aromatic hydrocarbons, using draft genomic sequencing and computational analysis. Enterobacter sp. strain UNJFSC 003 possesses 4460 protein-coding genes, two rRNA genes, 77 tRNA genes, and a GC content of 54.38%. A taxonomic analysis of our strain revealed that it has an average nucleotide identity (ANI) of 87.8%, indicating that it is a new native Enterobacteria. Additionally, a pangenomic analysis with 15 strains demonstrated that our strain has a phylogenetic relationship with strain FDAARGOS 1428 (Enterobacter cancerogenus), with a total of 381 core genes and 4778 accessory genes. Orthologous methods predicted that strain UNJFSC 003 possesses genes with potential for use in hydrocarbon bioremediation. Genes were predicted in the sub-pathways for the degradation of homoprotocatechuate and phenylacetate, primarily located in the cytoplasm. Studies conducted through molecular modeling and docking revealed the affinity of the predicted proteins in the degradation of benzo[a]pyrene in the homoprotocatechuate sub-pathway, specifically hpcB, which has enzymatic activity as a dioxygenase, and hpcC, which functions as an aldehyde dehydrogenase. This study provides information on native strains from Lomas de Lachay with capabilities for the bioremediation of aromatic hydrocarbons and other compounds. Full article

The incidence of multiple-organ cancers has recently increased due to simultaneous exposure to various environmental carcinogens. Houttuynia cordata Thunb. (H. cordata) is recognized for its many health benefits, including its anti-cancer properties. The fermentation of its leaves has been shown to significantly enhance the bioflavonoid content and its bioactivities. This study aimed to evaluate the effectiveness of fermented H.cordata leaf (FHCL) extracts against combined carcinogens and investigate the underlying mechanisms. The crude ethanolic extract of FHCL was partitioned to obtain hexane- (HEX), dichloromethane- (DCM), ethyl acetate- (ETAC), butanol- (nBA), and residue fractions. The crude ethanolic extract (200–250 μg/mL) and the DCM fraction (50 μg/mL) significantly reduced NO production in RAW264.7 macrophages. In addition, the crude extract and the DCM and ETAC fractions showed anti-genotoxicity against aflatoxin B₁ and 2-amino-3,4-dimethylimidazo [4,5-f]quinoline (MeIQ) in Salmonella typhimurium assays (S9+). Despite demonstrating genotoxicity in the Salmonella mutation assay (with and without S9 activation), oral administration of the crude extract at 500 mg/kg of body weight (bw) for 40 days in rats did not induce micronucleated hepatocytes, indicating that the extract is non-genotoxic in vivo. Moreover, the crude extract significantly decreased Phase I but increased Phase II xenobiotic-metabolizing enzyme activities in the rats. Next, the anti-cancer effects of FHCL were evaluated in a dual-organ carcinogenesis model of the colon and liver in rats induced by 1,2-dimethylhydrazine (DMH) and diethylnitrosamine (DEN), respectively. The crude extract significantly reduced not only the number and size of glutathione S-transferase placental form positive foci in the liver (at doses of 100 and 500 mg/kg bw) but also the number of aberrant crypt foci in rat colons (at 500 mg/kg bw). Furthermore, FHCL significantly reduced the expression of proliferating cell nuclear antigen (PCNA) in the colon (at 100 and 500 mg/kg bw) and liver (at 500 mg/kg bw) of the treated rats. In conclusion, FHCL exhibits significant preventive properties against colon and liver cancers in this dual-organ carcinogenesis model. Its mechanisms of action may involve anti-inflammatory effects, the prevention of genotoxicity, the modulation of xenobiotic-metabolizing enzymes, and the inhibition of cancer cell proliferation. These findings support the use of FHCL as a natural supplement for preventing cancer. Full article

Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research. Full article

Alterations in cellular metabolism are vital for cancer cell growth and motility. Here, we focused on metabolic reprogramming and changes in tumor hallmarks in lung cancer by silencing the expression of the mitochondrial gatekeeper VDAC1. To better mimic the clinical situation of lung cancer, we induced lung cancer in A/J mice using the carcinogen urethane and examined the effectiveness of si-m/hVDAC1-B encapsulated in PLGA-PEI nanoparticles. si-m/hVDAC1-B, given intravenously, induced metabolism reprogramming and inhibited tumor growth as monitored using MRI. Mice treated with non-targeted (NT) PLGA-PEI-si-NT showed many large size tumors in the lungs, while in PLGA-PEI-si-m/hVDAC-B-treated mice, lung tumor number and area were markedly decreased. Immunofluorescence staining showed decreased expression of VDAC1 and metabolism-related proteins and altered expression of cancer stem cell markers. Morphological analysis showed two types of tumors differing in their morphology; cell size and organization within the tumor. Based on specific markers, the two tumor types were identified as small cell (SCLC) and non-small cell (NSCLC) lung cancer. These two types of tumors were found only in control tumors, suggesting that PLGA-PEI-si-m/hVDAC1-B also targeted SCLC. Indeed, using a xenograft mouse model of human-derived SCLC H69 cells, si-m/hVDAC1-B inhibited tumor growth and reduced the expression of VDAC1 and energy- and metabolism-related enzymes, and of cancer stem cells in the established xenograft. Additionally, intravenous treatment of urethane-induced lung cancer mice with the VDAC1-based peptide, Retro-Tf-D-LP4, showed inhibition of tumor growth, and decreased expression levels of metabolism- and cancer stem cells-related proteins. Thus, silencing VDAC1 targeting both NSCLC and SCLC points to si-VDAC1 as a possible therapeutic tool to treat these lung cancer types. This is important as target NSCLC tumors undergo transformation to SCLC. Full article

The potential connection between exposure to glyphosate and glyphosate-based herbicides (GBHs) and breast cancer risk is a topic of research that is rapidly gaining the public’s attention due to the conflicting reports surrounding glyphosate’s potential carcinogenicity. In this review, we synthesize the current published biomedical literature works that have explored associations of glyphosate, its metabolite, aminomethylphosphonic acid (AMPA), and GBHs with breast cancer risk in humans and human cell-based models. Using PubMed as our search engine, we identified a total of 14 articles that were included in this review. In the four human studies, urinary glyphosate and/or AMPA were associated with breast cancer risk, endocrine disruption, oxidative stress biomarkers, and changes in DNA methylation patterns. Among most of the 10 human cell-based studies, glyphosate exhibited endocrine disruption, induced altered gene expression, increased DNA damage, and altered cell viability, while GBHs were more cytotoxic than glyphosate alone. In summary, numerous studies have shown glyphosate, AMPA, and GBHs to have potential carcinogenic, cytotoxic, or endocrine-disruptive properties. However, more human studies need to be conducted in order for more definitive and supported conclusions to be made on their potential effects on breast cancer risk. Full article

Arsenic (As) has been classified as a carcinogen for humans. There is abundant evidence indicating that arsenic increases the risk of bladder cancer among human populations. However, the underlying mechanisms have yet to be fully understood and elucidated. NADPH oxidases (NOXs) are the main enzymes for ROS production in the body. NADPH Oxidase 2 (NOX2), which is the most distinctive and ubiquitously expressed subunit of NOXs, can promote the formation and development of tumors. The utilization of NOX2 as a therapeutic target has been proposed to modulate diseases resulting from the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Matrine has been reported to exhibit various pharmacological effects, including anti-inflammatory, antifibrotic, antitumor, and analgesic properties. However, it has not been reported whether matrine can inhibit malignant transformation induced by arsenic in uroepithelial cells through NOX2. We have conducted a series of experiments using both a sub-chronic NaAsO₂ exposure rat model and a long-term NaAsO₂ exposure cell model. Our findings indicate that arsenic significantly increases cell proliferation, migration, and angiogenesis in vivo and in vitro. Arsenic exposure resulted in an upregulation of reactive oxygen species (ROS), NOX2, and NLRP3 inflammasome expression. Remarkably, both in vivo and in vitro, the administration of matrine demonstrated a significant improvement in the detrimental impact of arsenic on bladder epithelial cells. This was evidenced by the downregulation of proliferation, migration, and angiogenesis, as well as the expression of the NOX2 and NLRP3 inflammasomes. Collectively, these findings indicate that matrine possesses the ability to reduce NOX2 levels and inhibit the transformation of bladder epithelial cells. Full article