Search Results (131)

The global increase in early-onset cancers among adolescents and young adults has happened at the same time as the rise in the consumption of ultra-processed foods (UPFs). Far beyond their poor nutritional quality, UPFs are increasingly seen as Trojan horses, complex biological agents that interfere with many functions of the human organism. In this review, we utilise the Trojan horse model to explain the quiet and building health risks from UPFs as foods that seem harmless, convenient, and affordable while secretly delivering endocrine-disrupting chemicals (EDCs), causing chronic low-grade inflammation, altering the microbiome, and producing epigenetic alterations. We bring together new proof showing that UPFs mess up hormonal signals, harm the body’s ability to fight off harmful germs, lead to an imbalance of microbes, and cause detrimental changes linked to cancer. Important components, such as bisphenols and phthalates, can migrate from containers into food, while additional ingredients and effects from cooking disrupt the normal balance of cells. These exposures are especially harmful during vulnerable developmental periods and may lay the groundwork for disease many years later. The Trojan horse model illustrates the hidden nature of UPF-related damage, not through a sudden toxin but via chronic dysregulation of metabolic, hormonal, and genetic control. This model changes focus from usual diet worries to a bigger-picture view of UPFs as causes of life-disrupting damage. Ultimately, this review aims to identify gaps in current knowledge and epidemiological approaches and highlight the need for multi-omics, long-term studies and personalised nutrition plans to assess and reduce the cancer risk associated with UPFs. Recognising UPFs as a silent disruptor is crucial in shaping public health policies and cancer prevention programs targeting younger people. Full article

Background/Objectives: In 4-octylphenol (4-OP), a toxic environmental pollutant with endocrine disruptive effect, the use of 4-OP causes pollution in the freshwater environment and poses risks to aquatic organisms. Common carps (Cyprinus carpio L.) live in freshwater and are experimental animals for studying the toxic effects of environmental pollutants on fish. Its heart is susceptible to toxicants. However, whether 4-OP has a toxic effect on common carp heart remains unknown. Methods: Here, we conducted a common carp 4-OP exposure experiment (carp treated with 17 μg/L 4-OP for 45 days), aiming to investigate whether 4-OP has a toxic effect on common carp hearts. We observed the microstructure and ultrastructure of carp heart and detected autophagy genes, mitochondrial fission genes, mitochondrial fusion genes, glycolytic enzymes, AMPK, ATPase, and oxidative stress factors, to investigate the molecular mechanism of 4-OP induced damage in common carp hearts. Results: Our results showed that 4-OP exposure caused mitochondrial damage, autophagy, and damage in common carp hearts. 4-OP exposure increased the levels of miR-144, and eight autophagy factors (Beclin1, RB1CC1, ULK1, LC3-I, LC3-II, ATG5, ATG12, and ATG13), and decreased the levels of four autophagy factors (PI3K, AKT, mTOR, and SQSTM1). Furthermore, 4-OP exposure induced the imbalance between mitochondrial fission and fusion and mitochondrial dynamics imbalance, as demonstrated by the increase in three mitochondrial fission factors (Mff, Drp1, and Fis1) and the decrease in three mitochondrial fusion factors (Mfn1, Mfn2, and Opa1). Moreover, excess 4-OP treatment caused energy metabolism disorder, as demonstrated by the reduction in four ATPase (Na⁺K⁺-ATPase, Ca²⁺Mg²⁺-ATPase, Ca²⁺-ATPase, and Mg²⁺-ATPase), elevation in four glycolysis genes (HK1, HK2, LDHA, and PGK1), reduction in glycolysis gen (PGAM2), and the elevation in energy-sensing AMPK. Finally, 4-OP treatment induced the imbalance between antioxidant and oxidant and oxidative stress, as demonstrated by the increase in oxidant H₂O₂, and the decreases in five antioxidant factors (CAT, SOD, T-AOC, Nrf2, and HO-1). Conclusions: miR-144 mediated autophagy by targeting PI3K, mTOR, and SQSTM1, and the miR-144/PI3K-AKT-mTOR/ULK1 pathway was involved in 4-OP-induced autophagy. Mff-Drp1 axis took part in 4-OP-caused mitochondrial dynamics imbalance, and mitochondrial dynamics imbalance mediated autophagy via Mfn2-SQSTM1, Mfn2/Beclin1, and Mff-LC3-II axes. Energy metabolism disorder mediated mitochondrial dynamics imbalance through the AMPK-Mff-Drp1 pathway. Oxidative stress mediated energy metabolism disorder via the H₂O₂-AMPK axis. Taken together, oxidative stress triggered energy metabolism disorder, induced mitochondrial dynamics imbalance, and caused autophagy via the H₂O₂-AMPK-Mff-LC3-II pathway. Our study provided references for the toxic effects of endocrine disruptor on common carp hearts, and provided a basis for assessing environmental pollutant-induced damage in common carp heart. We only studied the toxic effects of 4-OP on common carp, and the toxic effects of 4-OP on other fish species need to be further studied. Full article

Tributyltin (TBT), a recognized endocrine disruptor, is associated with metabolic diseases, including obesity, type 2 diabetes, non-alcoholic steatohepatitis, and osteoporosis. Bile acids (BAs) play pivotal roles in lipid digestion and absorption. However, there are no studies to illustrate the effects of TBT on BA pool composition in circulation. Here, rats were treated with TBT (50 μg/kg) or a vehicle control once every three days for sixty days to analyze serum BA levels using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). The liver tissue sections and lipid levels of rats were examined using conventional methods. TBT induced sporadic cholestasis in the livers of rats and significantly reduced the levels of five BAs, including four conjugated BAs [acidtaurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), and tauro-β-muricholic acid (Tβ-MCA)] and one unconjugated bile acid [dehydrolithocholic acid (DLCA)], while the serum levels of triglyceride, cholesterol, and bilirubin were unaltered by TBT treatment. These results indicate that TBT exposure affected the BA pool composition in circulation, especially the taurine-conjugated BAs. Full article

Ageing is influenced by a complex interplay of genetic, environmental, and lifestyle factors, with increasing evidence highlighting the exposome as a key determinant of healthspan. This review explores the impact of environmental exposures, focusing in particular on pollution, endocrine disruptors, and climate change on the development of age-related diseases such as cardiovascular diseases (CVDs), cancer, and metabolic disorders. Additionally, it examines protective factors that contribute to healthy ageing. A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar, focusing on studies published between 2000 and 2025. Findings indicate that chronic exposure to pollutants accelerates cellular ageing through mechanisms such as oxidative stress, inflammation, and epigenetic dysregulation. In contrast, longevity hotspots—Blue Zones, Cilento and the mountain villages of Sicily (Sicani and Madonie Mountains)—illustrate how traditional dietary patterns, strong social structures, and reduced environmental toxicity contribute to exceptional health and longevity. Mechanistically, exposome-driven alterations in immune-inflammatory pathways and epigenetic regulation play a central role in modulating ageing trajectories. Understanding these interactions is essential for developing targeted strategies to mitigate harmful exposures and enhance protective factors. This review underscores the urgent need for integrative public health policies that address the environmental determinants of ageing, ultimately promoting a longer and healthier lifespan. Full article

Bisphenol A (BPA) is one of the most produced compounds worldwide. It acts as an endocrine disruptor and can cause adverse effects in the body, even at low-dose exposures. By interacting with estrogen receptors, it can play an important role in the pathogenesis of several endocrine diseases, such as infertility, hormone-dependent tumours and various metabolic disorders. Exposure in humans, especially early in life, is of particular concern, since it can have a big impact on an individual’s development and growth. The objective of this study was to evaluate, in vivo, the genotoxicity of BPA and its effects on longevity, prolificacy and behaviour in Drosophila melanogaster. To evaluate the biological and behavioural effects, flies were crossed and subjected to different concentrations of BPA (0.5 mM, 1 mM, 2 mM, 5 mM and 10 mM) in Drosophila instant “Carolina” medium hydrated with the BPA solution for 3 days, and then transferred to a non-treated medium, where they continued to lay eggs. This procedure was repeated to obtain the F₂ generation. To evaluate genotoxicity, the somatic mutation and recombination test (SMART) and Comet assays were performed. In these cases, higher concentrations of BPA were chosen (1 mM, 10 mM, 20 mM and 50 mM). The results showed that this compound caused changes in longevity and prolificacy, and that these changes also affected subsequent generations. They also showed that BPA affected Drosophila’s behaviour and social interaction, but at the exposure levels investigated here, it did not cause significant genotoxic effects. Full article

The human microbiota plays a crucial role in maintaining host health through its considerable influence on immune function, nutrient metabolism, and overall homeostasis. While trace metals such as cobalt, lithium, and nickel are essential micronutrients at low concentrations, their increasing environmental accumulation presents emerging risks for microbial dysbiosis and related systemic health effects. This review examines the dual role of these trace metals as both beneficial nutrients and potential disruptors of microbial balance. Specifically, cobalt supports microbial diversity through its role in vitamin B12 synthesis, but excessive exposure can lead to dysbiosis. Lithium, beneficial at therapeutic concentrations by enhancing beneficial microbial populations, adversely affects gut barrier integrity by promoting inflammation and epithelial damage at higher concentrations. Similarly, nickel participates in essential enzymatic activities but promotes dysbiosis and inflammatory responses at elevated exposures. Furthermore, the growing environmental contamination by these metals poses risks to food systems and various microbial communities in the environment. Highlighting these environmental concerns, this review calls for sustainable management and multidisciplinary research to mitigate health risks to mitigate health risks associated with trace metal exposure. Full article

Nanoplastics (NPs) represent a major challenge in environmental contamination resulting from the physical, chemical, and biological degradation of plastics. Their characterization requires advanced and expensive methods, which limit routine analyses. The biological effects of NPs depend on their chemical and physical properties, which influence toxicity and interactions with biological systems. Studies in animal models, such as Daphnia magna and Danio rerio, show that NPs induce oxidative stress, inflammation, DNA damage, and metabolic alterations, often related to charge and particle size. NPs affect endocrine functions by acting as endocrine disruptors, interfering with thyroid and sex hormones and showing potential transgenerational effects through epigenetic modifications, including DNA hyper- and hypomethylation. Behavioral and neurofunctional alterations have been observed in Danio rerio and mouse models, suggesting a link between NP exposure and neurotransmitters such as dopamine and serotonin. Despite limited human studies, the presence of NPs in breast milk and placenta underscores the need for further investigation of health effects. Research focusing on genetic and epigenetic markers is encouraged to elucidate the molecular mechanisms and potential risks associated with chronic exposure. Full article

MYC plays a pivotal role in the biology of various sarcoma subtypes, acting as a key regulator of tumor growth, proliferation, and metabolic reprogramming. This oncogene is frequently dysregulated across different sarcomas, where its expression is closely intertwined with the molecular features unique to each subtype. MYC interacts with critical pathways such as cell cycle regulation, apoptosis, and angiogenesis, amplifying tumor aggressiveness and resistance to standard therapies. Furthermore, MYC influences the tumor microenvironment by modulating cell–extracellular matrix interactions and immune evasion mechanisms, further complicating therapeutic management. Despite its well-established centrality in sarcoma pathogenesis, targeting MYC directly remains challenging due to its “undruggable” protein structure. However, emerging therapeutic strategies, including indirect MYC inhibition via epigenetic modulators, transcriptional machinery disruptors, and metabolic pathway inhibitors, offer new hope for sarcoma treatment. This review underscores the importance of understanding the intricate roles of MYC across sarcoma subtypes to guide the development of effective targeted therapies. Given MYC’s central role in tumorigenesis and progression, innovative approaches aiming at MYC inhibition could transform the therapeutic landscape for sarcoma patients, providing a much-needed avenue to overcome therapeutic resistance and improve clinical outcomes. Full article

The purpose of this article is to present selected food additives as disruptors of normal intestinal homeostasis with a potential impact on the development of metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive literature search was conducted in three major electronic databases: PubMed, ScienceDirect, and Google Scholar. MASLD is a prevalent liver condition that is closely related to the global rise in obesity. Its pathogenesis is multifactorial, with genetic, environmental, and metabolic factors playing a key role. The “multiple-hit” hypothesis suggests that a Western-style diet, rich in ultra-processed foods, saturated fats, and food additives, combined with low physical activity, contributes to obesity, which promotes lipid accumulation in the liver. Recent studies underscore the role of impaired intestinal homeostasis in the development of MASLD. Food additives, including preservatives, emulsifiers, and sweeteners, affect gut health and liver function. Selected preservatives inhibit pathogenic microorganisms but disrupt the intestinal microbiota, leading to changes in intestinal permeability and liver dysfunction. Some emulsifiers and thickeners can cause inflammation and alter the gut microbiome, contributing to liver steatosis. Furthermore, the use of sweeteners such as sucralose and aspartame has been linked to changes in liver metabolism and intestinal microbial composition, which in turn promotes metabolic disorders. Full article

Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum Bacteroidota, while taxa from the phylum Actinomycetota were promoted. Consistently, Bacteroides species were classified as sensitive to BPA, whereas bacteria belonging to the class Clostridia were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children. Full article

Bisphenol S (BPS) is a typical endocrine disruptor associated with obesity. To observe BPS effects on lipid metabolism in HepG2 and SK-Hep-1 human HCC cells, a CCK-8 assay was used to assess cell proliferation in response to BPS, and the optimal concentration of BPS was selected. Biochemical indices such as triglyceride (TG) and total cholesterol (T-CHO), and oxidative stress indices such as malondialdehyde (MDA) and catalase (CAT) were measured. ROS and MDA levels were significantly increased after BPS treatment for 24 h and 48 h (p < 0.05), indicating an oxidative stress response. Alanine aminotransferase (ALT), T-CHO, and low-density lipoprotein cholesterol (LDL-C) levels also increased significantly after 24 or 48 h BPS treatments (p < 0.05). RT-PCR and Western blot analyses detected mRNA or protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP1C). The results indicated that BPS could inhibit the mRNA expression of PPARα and carnitine palmitoyl transferase 1B (CPT1B), reduce lipid metabolism, promote mRNA or protein expression of SREBP1C and fatty acid synthase (FASN), and increase lipid synthesis. Increased lipid droplets were observed using morphological Oil Red O staining. Our study demonstrates that BPS may cause lipid accumulation by increasing oxidative stress and perturbing cellular lipid metabolism. Full article

This review delves into the impact of benzo(a)pyrene (B(a)P), which is a toxic and pervasive polycyclic aromatic hydrocarbon (PAH) and known carcinogen, on the human health risk from a gut microbiome perspective. We retrieved the relevant articles on each PAH and summarized the reporting to date, with a particular focus on benzo(a)pyrene, which has been reported to have a high risk of gut microbiome-related harm. B(a)P exposure can compromise the homeostasis of the gut microbiota, leading to dysbiosis, a state of microbial imbalance. The consequences of B(a)P-induced gut dysbiosis can be far-reaching, potentially contributing to inflammation, metabolic disorders, and an increased risk of various diseases. Additionally, due to the strong coupling between B(a)P and microparticles, the toxicity of B(a)P may be further compounded by its reaction with strong gut disruptors such as micro-/nanoplastics, which have recently become a serious environmental concern. This review summarizes current research on the impact of B(a)P on the gut microbiome, highlighting the intricate relationship between environmental exposure, gut health, and human disease. Further research is necessary to elucidate the underlying mechanisms and develop effective strategies to mitigate the adverse health effects of B(a)P exposure. Full article

Dibutyl phthalate (DBP) is a low-molecular-weight phthalate commonly found in personal care products, such as perfumes, aftershaves, and nail care items, as well as in children’s toys, pharmaceuticals, and food products. It is used to improve flexibility, make polymer products soft and malleable, and as solvents and stabilizers in personal care products. Pregnancy represents a critical period during which both the mother and the developing embryo can be significantly impacted by exposure to endocrine disruptors. This article aims to elucidate the effects of prenatal exposure to DBP on the health and development of offspring, particularly on the reproductive, neurological, metabolic, renal, and digestive systems. Extensive research has examined the effects of DBP on the male reproductive system, where exposure is linked to decreased testosterone levels, reduced anogenital distance, and male infertility. In terms of the female reproductive system, DBP has been shown to elevate serum estradiol and progesterone levels, potentially compromising egg quality. Furthermore, exposure to this phthalate adversely affects neurodevelopment and is associated with obesity, metabolic disorders, and conditions such as hypospadias. These findings highlight how urgently stronger laws prohibiting the use of phthalates during pregnancy are needed to lower the risks to the fetus’s health and the child’s development. Full article

Background: Autism spectrum disorders (ASDs), attention-deficit disorder (ADHD), Parkinson’s disease (PD), polycystic ovary disease (PCOS), and Alzheimer’s disease (AD) have all been linked to exposure to bisphenol A (BPA). Methods: This paper is a review and discussion of the published literature. Results: Animal studies have shown BPA to be a broad-spectrum endocrine disruptor. BPA is metabolized via the glucuronidation pathway, which involves the addition of glucose to the target molecule, and is catalyzed by uridine 5′-diphospho-glucuronosyltransferases (UGTs). Evidence of compromised glucuronidation has been found for ASD, DHD, PD, and PCOS. Genetic polymorphisms that alter the catalytic activity of the UGTs and efflux transporters involved are common. There are two ways to interpret the findings of associations between BPA glucuronidation efficiency and disease, a ‘direct’ pathway and an ‘indirect’ pathway. With the ‘direct’ pathway, free BPA is the actual causative agent. Compromised BPA detoxification leads to higher concentrations of free BPA in vulnerable tissues. Decreased BPA detoxification leads to increased exposure of vulnerable tissues to free BPA, where it can function as an endocrine disruptor. With the ‘indirect’ pathway, BPA is not the causative agent. BPA serves as a marker for the decreased glucuronidation efficiency of another unknown compound of endogenous origin detoxified by a similar combination of UGTs and efflux transporters as BPA. It is this compound(s), acting as an endocrine disruptor, that leads to a metabolic environment that favors disease development over an extended time period. Conclusion: A review of the existing literature supports the indirect ‘marker’ hypothesis over the ‘direct’ hypothesis. Full article

Background/Objectives: Endocrine disruptors are substances capable of altering the functions of the endocrine system. There is evidence that some pesticides can be endocrine disruptors and, among some of their effects, we find alterations in pubertal development and in the function of the thyroid gland, which could be related to a greater tendency of obesity. The aim was to evaluate the evidence from clinical and preclinical studies on the association between pesticides used in agriculture and found in plant-based foods with overweight/obesity. Methods: This is a systematic review of articles on the impact of the use of endocrine disrupting pesticides on obesity, conducted according to the PRISMA-2020 guidelines. Results: There was evidence that some pesticides, such as chlorpyrifos, pyrethroids, and neonicotinoids, may promote obesity and other anthropometric changes by altering lipid and glucose metabolism, modifying genes, or altering hormone levels such as leptin. Other studies suggest that perinatal exposure to chlorpyrifos or pesticides such as vinclozolin may alter lipid metabolism and promote weight gain in adulthood, whereas other pesticides such as boscalib, captan, thiacloprid, and ziram were not associated with changes in weight. Exposure to pesticides such as vinclozolin may be associated with a higher prevalence of overweight/obesity in later generations. Conclusions: The few studies that do not show these associations have methodological limitations in data collection with confounding variables. Further studies are needed to provide more and higher quality evidence to determine the true effect of these substances on obesity. Full article