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Introduction: According to the Institute of Environmental Sciences, endocrine-disrupting chemicals (EDCs) are "natural or human-made chemicals that may mimic, block, or interfere with the body's hormones, associated with a wide array of health issues", mainly in the endocrine system. Recent studies have discussed the potential contribution of EDCs as risk factors leading to diabetes mellitus type 1 (T1DM), through various cellular and molecular pathways. Purpose: The purpose of this study was to investigate the correlation between the EDCs and the development of T1DM. Methodology: Thus, a 5-year systematic review was conducted to bring light to this research question. Using the meta-analysis and systematic review guideline protocol, a PRISMA flow diagram was constructed and, using the keywords (diabetes mellitus type 1) AND (endocrine-disrupting chemicals) in the databases PubMed, Scopus and ScienceDirect, the relevant data was collected and extracted into tables. Quality assessment tools were employed to evaluate the quality of the content of each article retrieved. Results: Based on the data collected and extracted from both human and animal studies, an association was found between T1DM and certain EDCs, such as bisphenol A (BPA), bisphenol S (BPS), persistent organic pollutants (POPs), phthalates and dioxins. Moreover, based on the quality assessments performed, using the Newcastle–Ottawa Scale and ARRIVE quality assessment tool, the articles were considered of high quality and thus eligible to justify the correlation of the EDCs and the development of T1DM. Conclusion: Based on the above study, the correlation can be justified; however, additional studies can be made focusing mainly on humans to understand further the pathophysiologic mechanism involved in this association. [ABSTRACT FROM AUTHOR]

The antibiotic resistance crisis has seriously jeopardized public health and human safety. As one of the ways of horizontal transfer, transformation enables bacteria to acquire exogenous genes naturally. Bisphenol compounds are now widely used in plastics, food, and beverage packaging, and have become a new environmental pollutant. However, their potential relationship with the spread of antibiotic resistance genes (ARGs) in the environment remains largely unexplored. In this study, we aimed to assess whether the ubiquitous bisphenol S (BPS) could promote the transformation of plasmid-borne ARGs. Using plasmid pUC19 carrying the ampicillin resistance gene as an extracellular ARG and model microorganism E. coli DH5α as the recipient, we established a transformation system. Transformation assays revealed that environmentally relevant concentrations of BPS (0.1–10 μg/mL) markedly enhanced the transformation frequency of plasmid-borne ARGs into E. coli DH5α up to 2.02-fold. Fluorescent probes and transcript-level analyses suggest that BPS stimulated increased reactive oxygen species (ROS) production, activated the SOS response, induced membrane damage, and increased membrane fluidity, which weakened the barrier for plasmid transfer, allowing foreign DNA to be more easily absorbed. Moreover, BPS stimulates ATP supply by activating the tricarboxylic acid (TCA) cycle, which promotes flagellar motility and expands the search for foreign DNA. Overall, these findings provide important insight into the role of bisphenol compounds in facilitating the horizontal spread of ARGs and emphasize the need to monitor the residues of these environmental contaminants. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis. [ABSTRACT FROM AUTHOR]

The evolving history of BRCA1 research demonstrates the profound interconnectedness of a single protein within the web of crucial functions in human cells. Mutations in BRCA1, a tumor suppressor gene, have been linked to heightened breast and ovarian cancer risks. However, despite decades of extensive research, the mechanisms underlying BRCA1's contribution to tissue-specific tumor development remain elusive. Nevertheless, much of the BRCA1 protein's structure, function, and interactions has been elucidated. Individual regions of BRCA1 interact with numerous proteins to play roles in ubiquitination, transcription, cell checkpoints, and DNA damage repair. At a cellular scale, these BRCA1 functions coordinate tumor suppression, R-loop prevention, and cellular differentiation, all of which may contribute to BRCA1's role in cancer tissue specificity. As research on BRCA1 and breast cancer continues to evolve, it will become increasingly evident that modern materials such as Bisphenol A should be examined for their relationship with DNA stability, cancer incidence, and chemotherapy. Overall, this review offers a comprehensive understanding of BRCA1's many roles at a molecular, cellular, organismal, and environmental scale. We hope that the knowledge gathered here highlights both the necessity of BRCA1 research and the potential for novel strategies to prevent and treat cancer in individuals carrying BRCA1 mutations.

The article discusses the impact of endocrine-disrupting chemicals (EDCs) on human health. EDCs are exogenous compounds that disrupt the synthesis, secretion, and elimination of natural hormones, leading to various health issues such as asthma, cardiovascular diseases, obesity, infertility, and cancers. The article highlights the diverse mechanisms of action of EDCs, including disruption of ligand-receptor interaction, interference of signal transduction, and alteration of epigenetic landscapes. It also presents several studies that explore the effects of specific EDCs on male fertility, testicular function, reproductive health, liver injuries, brain development, behavioral disorders, and cancer development. The research emphasizes the need for updated toxicological approaches to assess the low-dose effects of EDCs and calls for further investigation into the potential risks posed by these chemicals. [Extracted from the article]

Mammalian embryos are very vulnerable to environmental toxicants (ETs) exposure. Bisphenol A (BPA), one of the most diffused ETs, exerts endocrine-disrupting effects through estro-gen-mimicking and hormone-like properties, with detrimental health effects, including on reproduction. However, its impact during the peri-implantation stages is still unclear. This study, using gastruloids as a 3D stem cell-based in vitro model of embryonic development, showed that BPA exposure arrests their axial elongation when present during the Wnt/β-catenin pathway activation period by β-catenin protein reduction. Gastruloid reshaping might have been impeded by the downregulation of Snail, Slug and Twist, known to suppress E-cadherin expression and to activate the N-cadherin gene, and by the low expression of the N-cadherin protein. Also, the lack of gastruloids elongation might be related to altered exit of BPA-exposed cells from the pluripotency condition and their following differentiation. In conclusion, here we show that the inhibition of gastruloids' axial elongation by BPA might be the result of the concomitant Wnt/β-catenin perturbation, reduced N-cadherin expression and Oct4, T/Bra and Cdx2 altered patter expression, which all together concur in the impaired development of mouse gastruloids. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA), a synthetic compound ubiquitously present in the environment, can act as an endocrine disruptor by binding to both canonical and non-canonical estrogen receptors (ERs). Exposure to BPA has been linked to various cancers, in particular, those arising in hormone-targeted tissues such as the breast. In this study, we evaluated the effect of BPA intake through drinking water on ErbB2/neu-driven cancerogenesis in BALB–neuT mice, transgenic for a mutated ErbB2/neu receptor gene, which reproducibly develop carcinomas in all mammary glands. In this model, BPA accelerated mammary cancerogenesis with an increase in the number of tumors per mouse and a concurrent decrease in tumor-free and overall survival. As assessed by immunohistochemistry, BALB–neuT tumors were ER-negative but expressed high levels of the alternative estrogen receptor GPR30, regardless of BPA exposure. On the other hand, BPA exposure resulted in a marked upregulation of progesterone receptors in preinvasive tumors and of Ki67, CD31, and phosphorylated Akt in invasive tumors. Moreover, based on several infiltration markers of immune cells, BPA favored an immunosuppressive tumor microenvironment. Finally, in vitro cell survival studies performed on a cell line established from a BALB–neuT breast carcinoma confirmed that BPA's impact on cancer progression can be particularly relevant after chronic, low-dose exposure. [ABSTRACT FROM AUTHOR]

BPA has demonstrated enormous multisystem and multi-organ toxicity shown mainly in animal models. Meanwhile, the effects of its exposure in humans still require years of observation, research, and answers to many questions. Even minimal and short-term exposure contributes to disorders or various types of dysfunction. It is released directly or indirectly into the environment at every stage of the product life cycle, demonstrating its ease of penetration into the body. The ubiquity and general prevalence of BPA influenced the main objective of the study, which was to assess the toxicity and health effects of BPA and its derivatives based on the available literature. In addition, the guidelines of various international institutions or regions of the world in terms of its reduction in individual products were checked. Bisphenol A is the most widely known chemical and perhaps even the most studied by virtually all international or national organizations, but nonetheless, it is still controversial. In general, the level of BPA biomonitoring is still too high and poses a potential threat to public health. It is beginning to be widely argued that future toxicity studies should focus on molecular biology and the assessment of human exposure to BPA, as well as its substitutes. The effects of its exposure still require years of observation, extensive research, and answers to many questions. It is necessary to continue to deepen the knowledge and interest of many organizations, companies, and consumers around the world in order to make rational purchases as well as future choices, not only consumer ones. [ABSTRACT FROM AUTHOR]

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial–mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms. [ABSTRACT FROM AUTHOR]

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS—used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ. [ABSTRACT FROM AUTHOR]

Mammalian embryos are very vulnerable to environmental toxicants (ETs) exposure. Bisphenol A (BPA), one of the most diffused ETs, exerts endocrine-disrupting effects through estro-gen-mimicking and hormone-like properties, with detrimental health effects, including on reproduction. However, its impact during the peri-implantation stages is still unclear. This study, using gastruloids as a 3D stem cell-based in vitro model of embryonic development, showed that BPA exposure arrests their axial elongation when present during the Wnt/β-catenin pathway activation period by β-catenin protein reduction. Gastruloid reshaping might have been impeded by the downregulation of Snail, Slug and Twist, known to suppress E-cadherin expression and to activate the N-cadherin gene, and by the low expression of the N-cadherin protein. Also, the lack of gastruloids elongation might be related to altered exit of BPA-exposed cells from the pluripotency condition and their following differentiation. In conclusion, here we show that the inhibition of gastruloids’ axial elongation by BPA might be the result of the concomitant Wnt/β-catenin perturbation, reduced N-cadherin expression and Oct4, T/Bra and Cdx2 altered patter expression, which all together concur in the impaired development of mouse gastruloids.

Bisphenols are dangerous endocrine disruptors that pollute the environment. Due to their chemical properties, they are globally used to produce plastics. Structural similarities to oestrogen allow bisphenols to bind to oestrogen receptors and affect internal body systems. Most commonly used in the plastic industry is bisphenol A (BPA), which also has negative effects on the nervous, immune, endocrine, and cardiovascular systems. A popular analogue of BPA-bisphenol S (BPS) also seems to have harmful effects similar to BPA on living organisms. Therefore, with the use of double immunofluorescence labelling, this study aimed to compare the effect of BPA and BPS on the enteric nervous system (ENS) in mouse jejunum. The study showed that both studied toxins impact the number of nerve cells immunoreactive to substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), the neuronal isoform of nitric oxide synthase (nNOS), and vesicular acetylcholine transporter (VAChT). The observed changes were similar in the case of both tested bisphenols. However, the influence of BPA showed stronger changes in neurochemical coding. The results also showed that long-term exposure to BPS significantly affects the ENS.

BPA has demonstrated enormous multisystem and multi-organ toxicity shown mainly in animal models. Meanwhile, the effects of its exposure in humans still require years of observation, research, and answers to many questions. Even minimal and short-term exposure contributes to disorders or various types of dysfunction. It is released directly or indirectly into the environment at every stage of the product life cycle, demonstrating its ease of penetration into the body. The ubiquity and general prevalence of BPA influenced the main objective of the study, which was to assess the toxicity and health effects of BPA and its derivatives based on the available literature. In addition, the guidelines of various international institutions or regions of the world in terms of its reduction in individual products were checked. Bisphenol A is the most widely known chemical and perhaps even the most studied by virtually all international or national organizations, but nonetheless, it is still controversial. In general, the level of BPA biomonitoring is still too high and poses a potential threat to public health. It is beginning to be widely argued that future toxicity studies should focus on molecular biology and the assessment of human exposure to BPA, as well as its substitutes. The effects of its exposure still require years of observation, extensive research, and answers to many questions. It is necessary to continue to deepen the knowledge and interest of many organizations, companies, and consumers around the world in order to make rational purchases as well as future choices, not only consumer ones.

The interaction mechanism of hemoglobin (Hb) with bisphenol A (BPA) in diabetic patients and the difference with healthy people have been studied using spectroscopic and molecular docking techniques at several glucose (Glc) concentration, with bovine hemoglobin (BHb) instead of Hb. It is found that Glc can interact with BHb–BPA and affect its molecular structure, resulting in an altered microenvironment for tyrosine (Tyr) and tryptophan (Trp) in BHb–BPA. It is also found that Glc can bind to BHb alone, and its effect on the molecular structure of BHb is weaker than that on the structure of BHb in BHb–BPA complex. The results of circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) indicate that Glc causes an increase in the content of the α-helix and a decrease in that of the β-sheet of BHb–BPA by 1.5–1.9% and 3.1%, respectively. The results of molecular docking show that Glc binds to BHb–BPA through hydrogen and hydrophobic bonds, and the position of binding differs from that of Glc binding to BHb alone, which may be attributed to the fact that BPA affects the protein molecular structure of BHb and has an effect on the binding of BHb to Glc. This study provides some theoretical basis for the mechanism of BPA toxicity in vivo for people with different blood glucose levels. [ABSTRACT FROM AUTHOR]

The liver is the organ responsible for the metabolism and detoxification of BPF, the BPA analogue that is replacing it in plastic-based products. It is not known whether BPF can trigger inflammatory responses via the NLRP3 inflammasome, which plays a major role in the development of liver disease. The aim of this study was to evaluate nitrosative stress species (RNS) and NLRP3 inflammasome activation in the liver of lactating dams after BPF exposure. Moreover, it was studied whether this effect could also be observed in the liver of female and male offspring at postnatal day 6 (PND6). 36 Long Evans rats were randomly distributed according to oral treatment into three groups: Control, BPF-low dose (LBPF; 0.0365 mg/kg b.w./day) group and BPF-high dose (HBPF; 3.65 mg/kg b.w./day) group. The levels of nitrosative stress-inducing proteins (eNOS, iNOS, HO-1d), NLRP3 inflammasome components (NLRP3, PyCARD, CASP1) and proinflammatory cytokines (IL-1β, IL-18, IFN-γ and TNF-α) were measured by gene and protein expression in the liver of lactating dams and in female and male PND6 offspring. Lactating dams treated with LBPF showed a significant increase in iNOS and HO-1d, activation of NLRP3 components (NLRP3, PyCARD, CASP1) and promoted the release of proinflammatory cytokines such as IL-1β, IL-18, IFN-γ and TNF-α. Similar effects were found in female and male PND6 offspring after perinatal exposure. LBPF oral administration and perinatal exposure caused an increase of nitrosative stress markers and proinflammatory cytokines. Also, NLRP3 inflammasome activation was significantly increased in in the liver of lactating dams and PND6 offspring. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine-disrupting compound, and the binding mechanism of BPA with carrier proteins has drawn widespread attention. Halogen substitutions can significantly impact the properties of BPA, resulting in various effects for human health. Here, we selected tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) to investigate the interaction between different halogen-substituted BPAs and human serum albumin (HSA). TBBPA/TCBPA spontaneously occupied site I and formed stable binary complexes with HSA. Compared to TCBPA, TBBPA has higher binding affinity to HSA. The effect of different halogen substituents on the negatively charged surface area of BPA was an important reason for the higher binding affinity of TBBPA to HSA compared to TCBPA. Hydrogen bonds and van der Waals forces were crucial in the TCBPA–HSA complex, while the main driving factor for the formation of the TBBPA–HSA complex was hydrophobic interactions. Moreover, the presence of TBBPA/TCBPA changed the secondary structure of HSA. Amino acid residues such as Lys199, Lys195, Phe211, Arg218, His242, Leu481, and Trp214 were found to play crucial roles in the binding process between BPA compounds and HSA. Furthermore, the presence of halogen substituents facilitated the binding of BPA compounds with HSA. [ABSTRACT FROM AUTHOR]

Endocrine disruptor chemicals (EDCs) can have a harmful effect on the human body's endocrine system and thus adversely affect the development, reproduction, neurological, cardiovascular, and immune systems and metabolism in humans and wildlife. According to the World Health Organization, EDCs are mostly man-made and found ubiquitously in our daily lives, notably in pesticides, metals, and additives or contaminants in food and personal care products. Human exposure occurs through ingestion, inhalation, and dermal contact. Bisphenol A (BPA) is a proven EDC capable of mimicking or blocking receptors and altering hormone concentrations and metabolism. Although consumed in low doses, it can stimulate cellular responses and affect the body's functions. In humans, exposure to BPA has been correlated with the onset or development of several diseases. This literature review aimed to verify the effects of BPA on human male infertility using the most recently published literature. Thus, this review allowed us to conclude that this compound seems to have harmful effects on human male fertility, causing changes in hormonal and semen characteristics. However, these conclusions lack more robust and reproducible scientific studies. Even so, and since male infertility prevalence is increasing, preventive measures must be taken to ensure male fertility. [ABSTRACT FROM AUTHOR]

Plastic production, disposal, and recycling systems represent one of the higher challenges for the planet's health. Its direct consequence is the release of endocrine disruptors, such as bisphenol A (BPA), and its emerging substitute molecules, bisphenol F and S (BPF and BPS), into the environment. Consequently, bisphenols are usually present in human biological fluids. Since BPA, BPS, and BPF have structural analogies and similar hormonal activity, their combined study is urgently needed. The present manuscript studied the effect of the mixture of bisphenols (BPmix) in one of the world's largest human cohorts (NHANES cohort). Descriptive and comparative statistics, binomial and multinomial logistic regression, weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression analysis determined a positive association between BPmix and heart disease, including confounders age, gender, BMI, ethnicity, Poverty/Income Ratio, and serum cotinine. Endothelial dysfunction is a hallmark of cardiovascular disease; thus, the average ratio of bisphenols found in humans was used to conduct murine aortic endothelial cell studies. The first results showed that BPmix had a higher effect on cell viability than BPA, enhancing its deleterious biological action. However, the flow cytometry, Western blot, and immunofluorescence assays demonstrated that BPmix induces a differential effect on cell death. While BPA exposure induces necroptosis, its combination with the proportion determined in the NHANES cohort induces apoptosis. In conclusion, the evidence suggests the need to reassess research methodologies to study endocrine disruptors more realistically. [ABSTRACT FROM AUTHOR]

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26–13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50–45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA: 2,3-bis (4-hydroxyphenyl) propane) is an environmental chemical widely used in the manufacturing of epoxy polymers and many thermoplastic consumer products. Serious concerns about its safety led to the development of analogs, such as BPS (4-hydroxyphenyl sulfone). Very limited studies about BPS's impact on reproduction, specifically in spermatozoa, exist in comparison with BPA. Therefore, this work aims to study the in vitro impact of BPS in pig spermatozoa in comparison with BPA, focusing on sperm motility, intracellular signaling pathways and functional sperm parameters. We have used porcine spermatozoa as an optimal and validated in vitro cell model to investigate sperm toxicity. Pig spermatozoa were exposed to 1 and 100 μM BPS or BPA for 3 and 20 h. Both bisphenol S and A (100 μM) significantly reduce pig sperm motility in a time-dependent manner, although BPS exerts a lower and slower effect than BPA. Moreover, BPS (100 μM, 20 h) causes a significant increase in the mitochondrial reactive species, whereas it does not affect sperm viability, mitochondrial membrane potential, cell reactive oxygen species, GSK3α/β phosphorylation or phosphorylation of PKA substrates. However, BPA (100 μM, 20 h) leads to a decrease in sperm viability, mitochondrial membrane potential, GSK3β phosphorylation and PKA phosphorylation, also causing an increase in cell reactive oxygen species and mitochondrial reactive species. These intracellular effects and signaling pathways inhibited might contribute to explaining the BPA-triggered reduction in pig sperm motility. However, the intracellular pathways and mechanisms triggered by BPS are different, and the BPS-caused reduction in motility can be only partially attributed to an increase in mitochondrial oxidant species. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1β, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a high-production-volume chemical with numerous industrial and consumer applications. BPA is extensively used in the manufacture of polycarbonate plastics and epoxy resins. The widespread utilities of BPA include its use as internal coating for food and beverage cans, bottles, and food-packaging materials, and as a building block for countless goods of common use. BPA can be released into the environment and enter the human body at any stage during its production, or in the process of manufacture, use, or disposal of materials made from this chemical. While the general population is predominantly exposed to BPA through contaminated food and drinking water, non-dietary exposures through the respiratory system, integumentary system, and vertical transmission, as well as other routes of exposure, also exist. BPA is often classified as an endocrine-disrupting chemical as it can act as a xenoestrogen. Exposure to BPA has been associated with developmental, reproductive, cardiovascular, neurological, metabolic, or immune effects, as well as oncogenic effects. BPA can disrupt the synthesis or clearance of hormones by binding and interfering with biological receptors. BPA can also interact with key transcription factors to modulate regulation of gene expression. Over the past 17 years, an epigenetic mechanism of action for BPA has emerged. This article summarizes the current state of research on the epigenetic effects of BPA by analyzing the findings from various studies in model systems and human populations. It evaluates the weight of evidence on the ability of BPA to alter the epigenome, while also discussing the direction of future research. [ABSTRACT FROM AUTHOR]

The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus–pituitary–gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life. [ABSTRACT FROM AUTHOR]

Bisphenols, parabens (PBs), and benzophenones (BPs) are widely used environmental chemicals that have been linked to several adverse health effects due to their endocrine disrupting properties. However, the cellular pathways through which these chemicals lead to adverse outcomes in humans are still unclear, suggesting some evidence that inflammation might play a key role. Thus, the aim of this study was to summarize the current evidence on the relationship between human exposure to these chemicals and levels of inflammatory biomarkers. A systematic review of peer-reviewed original research studies published up to February 2023 was conducted using the MEDLINE, Web of Science, and Scopus databases. A total of 20 articles met the inclusion/exclusion criteria. Most of the reviewed studies reported significant associations between any of the selected chemicals (mainly bisphenol A) and some pro-inflammatory biomarkers (including C-reactive protein and interleukin 6, among others). Taken together, this systematic review has identified consistent positive associations between human exposure to some chemicals and levels of pro-inflammatory biomarkers, with very few studies exploring the associations between PBs and/or BPs and inflammation. Therefore, a larger number of studies are required to get a better understanding on the mechanisms of action underlying bisphenols, PBs, and BPs and the critical role that inflammation could play. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) promotes colon cancer by altering the physiological functions of hormones. Quercetin (Q) can regulate signaling pathways through hormone receptors, inhibiting cancer cells. The antiproliferative effects of Q and its fermented extract (FEQ, obtained by Q gastrointestinal digestion and in vitro colonic fermentation) were analyzed in HT-29 cells exposed to BPA. Polyphenols were quantified in FEQ by HPLC and their antioxidant capacity by DPPH and ORAC. Q and 3,4-dihydroxyphenylacetic acid (DOPAC) were quantified in FEQ. Q and FEQ exhibited antioxidant capacity. Cell viability with Q+BPA and FEQ+BPA was 60% and 50%, respectively; less than 20% of dead cells were associated with the necrosis process (LDH). Treatments with Q and Q+BPA induced cell cycle arrest in the G0/G1 phase, and FEQ and FEQ+BPA in the S phase. Compared with other treatments, Q positively modulated ESR2 and GPR30 genes. Using a gene microarray of the p53 pathway, Q, Q+BPA, FEQ and FEQ+BPA positively modulated genes involved in apoptosis and cell cycle arrest; bisphenol inhibited the expression of pro-apoptotic and cell cycle repressor genes. In silico analyses demonstrated the binding affinity of Q > BPA > DOPAC molecules for ERα and ERβ. Further studies are needed to understand the role of disruptors in colon cancer. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems, and have been shown to interfere with physiological systems, especially by disrupting the hormone balance. During the last few decades, EDCs have been shown to affect reproductive, neurological, and metabolic development and function and even stimulate tumor growth. EDC exposure during development can disrupt normal development patterns and alter susceptibility to disease. Many chemicals have endocrine-disrupting properties, including bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols, and phthalates. These compounds have gradually been elucidated as risk factors for many diseases, such as reproductive, neural, and metabolic diseases and cancers. Endocrine disruption has been spread to wildlife and species that are connected to the food chains. Dietary uptake represents an important source of EDC exposure. Although EDCs represent a significant public health concern, the relationship and specific mechanism between EDCs and diseases remain unclear. This review focuses on the disease-EDC relationship and the disease endpoints associated with endocrine disruption for a better understanding of the relationship between EDCs-disease and elucidates the development of new prevention/treatment opportunities and screening methods. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a phenolic compound used in plastics elaboration for food protection or packaging. BPA-monomers can be released into the food chain, resulting in continuous and ubiquitous low-dose human exposure. This exposure during prenatal development is especially critical and could lead to alterations in ontogeny of tissues increasing the risk of developing diseases in adulthood. The aim was to evaluate whether BPA administration (0.036 mg/kg b.w./day and 3.42 mg/kg b.w./day) to pregnant rats could induce liver injury by generating oxidative stress, inflammation and apoptosis, and whether these effects may be observed in female postnatal day-6 (PND6) offspring. Antioxidant enzymes (CAT, SOD, GR, GPx and GST), glutathione system (GSH/GSSG) and lipid-DNA damage markers (MDA, LPO, NO, 8-OHdG) were measured using colorimetric methods. Inducers of oxidative stress (HO-1d, iNOS, eNOS), inflammation (IL-1β) and apoptosis (AIF, BAX, Bcl-2 and BCL-XL) were measured by qRT-PCR and Western blotting in liver of lactating dams and offspring. Hepatic serum markers and histology were performed. Low dose of BPA caused liver injury in lactating dams and had a perinatal effect in female PND6 offspring by increasing oxidative stress levels, triggering an inflammatory response and apoptosis pathways in the organ responsible for detoxification of this endocrine disruptor. [ABSTRACT FROM AUTHOR]

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

In the present study, mulberry branch-derived biochar CuO (MBC/CuO) composite was successfully synthesized and used as a catalyst to activate persulfate (PS) for the degradation of bisphenol A (BPA). The MBC/CuO/PS system exhibited a high degradation efficiency (93%) of BPA, under the conditions of 0.1 g/L MBC/CuO, 1.0 mM PS, 10 mg/L BPA. Free radical quenching and electron spin-resonance spectroscopy (ESR) experiments confirmed that both free radicals •OH, SO4•− and O2•− and non-radicals 1O2 were involved in the MBC/CuO reaction system. Cl− and NOM displayed negligible influence on the degradation of BPA, while HCO3− promoted the removal of BPA. In addition, the toxicity tests of BPA, MBC/CuO and the degraded BPA solution were conducted by the 5th instar silkworm larvae. The toxicity of BPA was reduced after the treatment in the MBC/CuO/PS system, and no obvious toxicity of the synthesized MBC/CuO composite was found in the toxicity evaluation experiments. This work provides a new value-added utilization of mulberry branches as a cost-effective and environmentally friendly PS activator. [ABSTRACT FROM AUTHOR]

Bisphenol A (4,4-isopropylidenediphenol, BPA) is an organic compound widely used, e.g., in the production of epoxy resins, plastics, and thermal receipt papers. Unfortunately, bisphenol A has negative effects on human health, which has prompted the search for an effective method of its removal. One of the most promising methods of its elimination is photocatalytic removal. The aim of this study was to design an effective method for the photocatalytic removal of bisphenol A using, for the first time, hierarchical zeolites and ruthenium ion-modified diatom biosilica, and silver as photocatalysts and optimization of the reaction conditions: temperature, pH, and composition of the reaction mixture as well as the electromagnetic wavelength. Additionally, for the first time, the electromagnetic wavelength that would be most suitable for the study was selected. All materials used were initially characterized by XRD and low-temperature nitrogen adsorption/desorption isotherms. Ruthenium ion-modified biosilica proved to be the most effective catalyst for bisphenol A removal, which occurred at a rate higher than 99%. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disease that currently affects nearly half a billion people worldwide. β-cells dysfunction is one of the main causes of diabetes. Exposure to endocrine-disrupting chemicals is correlated with increased diabetes incidence. We hypothesized that treatment with bisphenol A (BPA) induces endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR), leading to impaired function of the β-cells, which over time, can cause diabetes. In this study, we aimed to evaluate UPR pathways activation under BPA treatment in β-cells and possible recovery of ER homeostasis. MIN6 cells (mouse insulinoma cell line) and isolated pancreatic islets from NOR (non-obese diabetes resistant) mice were treated with BPA. We analyzed the impact of BPA on β-cell viability, the architecture of the early secretory pathway, the synthesis and processing of insulin and the activation of UPR sensors and effectors. We found that the addition of the chemical chaperone TUDCA rescues the deleterious effects of BPA, resulting in improved viability, morphology and function of the β-cells. In conclusion, we propose that modulators of UPR can be used as therapeutic interventions targeted towards regaining β-cells homeostasis. [ABSTRACT FROM AUTHOR]

Several studies in recent years have shown that endocrine disrupting chemicals (EDCs) can exert deleterious effects within several systems of the human body, such as the immune, neurological, and reproductive systems, among others. This review aims to summarize the investigations into the effect of EDC exposure on reproductive systems, namely preterm birth (PTB), and the efforts that international organizations have made to curb the harmful results of EDC exposure. To gather information, PubMed was initially searched for relevant articles containing the following terms: endocrine disrupting chemicals; preterm birth. PubMed was subsequently used to identify articles discussing the association between preterm birth and specific EDC exposures (BPA; phthalates; organochlorine pesticides; organophosphate pesticides; lead; PBDE; preterm birth). Both searches, limited to articles published within the past 20 years, identified several publications that have examined the association between various EDCs and PTB. While the findings of the studies differed, collectively they revealed sufficient evidence of a potential association between EDC exposure and risk of PTB. Thus, international organizations such as the United Nations Environmental Programme (UNEP) and World Health Organization (WHO) should continue to limit EDC exposure across the globe and monitor levels among individuals of reproductive age. [ABSTRACT FROM AUTHOR]

The aim of this work has been to study the possible degradation path of BPA under the Fenton reaction, namely to determine the energetically favorable intermediate products and to compare the cytotoxicity of BPA and its intermediate products of degradation. The DFT calculations of the Gibbs free energy at M06-2X/6-311G(d,p) level of theory showed that the formation of hydroquinone was the most energetically favorable path in a water environment. To explore the cytotoxicity the erythrocytes were incubated with BPA and three intermediate products of its degradation, i.e., phenol, hydroquinone and 4-isopropylphenol, in the concentrations 5–200 μg/mL, for 1, 4 and 24 h. BPA induced the strongest hemolytic changes in erythrocytes, followed by hydroquinone, phenol and 4-isopropylphenol. In the presence of hydroquinone, the highest level of RONS was observed, whereas BPA had the weakest effect on RONS generation. In addition, hydroquinone decreased the level of GSH the most. Generally, our results suggest that a preferable BPA degradation path under a Fenton reaction should be controlled in order to avoid the formation of hydroquinone. This is applicable to the degradation of BPA during waste water treatment and during chemical degradation in sea water. [ABSTRACT FROM AUTHOR]

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in south compared to central and northern Italy and for BPA in northern compared to central and southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary tolerable daily intake of 4 μg/kg per day established by the EFSA in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. Further, the reduction of exposure to DEHP and BPA, through specific legislative measures, is necessary to limit the harmfulness of these substances. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) hierarchical microspheres of Bi12O17Cl2 (BOC) were prepared via a facile solvothermal method using a binary solvent for the photocatalytic degradation of Rhodamine-B (RhB) and Bisphenol-A (BPA). Co3O4 nanoparticles (NPs)-decorated BOC (Co3O4/BOC) heterostructures were synthesized to further enhance their photocatalytic performance. The microstructural, morphological, and compositional characterization showed that the BOC microspheres are composed of thin (~20 nm thick) nanosheets with a 3D hierarchical morphology and a high surface area. Compared to the pure BOC photocatalyst, the 20-Co3O4/BOC heterostructure showed enhanced degradation efficiency of RhB (97.4%) and BPA (88.4%). The radical trapping experiments confirmed that superoxide (•O2−) radicals played a primary role in the photocatalytic degradation of RhB and BPA. The enhanced photocatalytic performances of the hierarchical Co3O4/BOC heterostructure are attributable to the synergetic effects of the highly specific surface area, the extension of light absorption to the more visible light region, and the suppression of photoexcited electron-hole recombination. Our developed nanocomposites are beneficial for the construction of other bismuth-based compounds and their heterostructure for use in high-performance photocatalytic applications. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS—used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ.

The interaction mechanism of hemoglobin (Hb) with bisphenol A (BPA) in diabetic patients and the difference with healthy people have been studied using spectroscopic and molecular docking techniques at several glucose (Glc) concentration, with bovine hemoglobin (BHb) instead of Hb. It is found that Glc can interact with BHb–BPA and affect its molecular structure, resulting in an altered microenvironment for tyrosine (Tyr) and tryptophan (Trp) in BHb–BPA. It is also found that Glc can bind to BHb alone, and its effect on the molecular structure of BHb is weaker than that on the structure of BHb in BHb–BPA complex. The results of circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) indicate that Glc causes an increase in the content of the α-helix and a decrease in that of the β-sheet of BHb–BPA by 1.5–1.9% and 3.1%, respectively. The results of molecular docking show that Glc binds to BHb–BPA through hydrogen and hydrophobic bonds, and the position of binding differs from that of Glc binding to BHb alone, which may be attributed to the fact that BPA affects the protein molecular structure of BHb and has an effect on the binding of BHb to Glc. This study provides some theoretical basis for the mechanism of BPA toxicity in vivo for people with different blood glucose levels.

Bisphenol A (BPA) and bisphenol S (BPS) are synthetic chemicals used to produce plastics which can be released in food and water. Once ingested, BPA and BPS are metabolized by the liver, mainly as glucuronidated metabolites, and are excreted through urine. Since urine can be stored for many hours, the bladder is chronically exposed to BP metabolites, and studies have shown that these metabolites can remain active in the organism. Therefore, the effect of physiological concentrations of glucuronidated BPs was evaluated on the bioenergetics (glycolysis and mitochondrial respiration), migration and proliferation of normal urothelial cells, and non-invasive and invasive bladder cancer cells. The results demonstrated that an exposure of 72 h to glucuronidated BPA or BPS decreased the bioenergetics and activity of normal urothelial cells, while increasing these parameters for bladder cancer cells. These findings suggest that BP metabolites are not as inactive as initially believed, and their ubiquitous presence in the urine could promote bladder cancer progression. [ABSTRACT FROM AUTHOR]

The ubiquitous environmental endocrine disruptor bisphenol A (BPA) can induce prostatic dysfunction. However, to date, studies have focused little on the perturbations of prostate health initiated by the BPA derivative bisphenol AF (BPAF) and co-exposure to bisphenol compounds. An in vivo study orally administrated male rats with BPA (10, 90 μg/kg), BPAF (10, 90 μg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg). Based on the anatomical analysis, pathological observations and PCNA over-expression, we considered that low-dose BPA and BPAF facilitated ventral prostatic hyperplasia in rats. The results of IHC and ELISA mirrored the regulation of NF-κB p65, COX-2, TNF-α and EGFR in BPA- and BPAF-induced prostatic toxicity. An in vitro study found that the additive effect of combined exposure to BPA (10 nM) and BPAF (10 nM) could cause an elevation in the proliferation of and a reduction in the apoptosis level of human prostate stromal cells (WPMY−1) and fibroblasts (HPrF). Meanwhile, the underlying biomarkers of the NF-κB signaling pathway also involved the abnormal proliferative progression of prostate cells. The findings recapitulated the induction of BPAF exposure and co-treatment with BPA and BPAF on prostatic hyperplasia and emphasized the modulation of the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a common cancer with a poor prognosis in both males and females. The influence of bisphenol A (BPA), a widely used environmental contaminant, in colon cancer development and progression is not well identified, in spite of the fact that the most common mode of exposure to BPA is ingestion. The aim of this work is to elucidate the carcinogenic effects of BPA in the colon in vitro. We analyzed BPA's effects on human colon epithelial (HCoEpiC) and colon cancer (HCT116) cells. BPA exerted cytotoxic effects and augmented the 5FU cytotoxicity on both cell lines at high doses, while it did not show this effect at low doses. Therefore, we focused on studying the effects of low-dose (0.0043 nM) exposure on normal colonic epithelial cells for a long period of time (two months), which is more consistent with environmental exposure levels and patterns. BPA increased cellular invasiveness through collagen and the ability to anchorage-independent cell growth, as measured by colony formation in soft agar, which could support oncogenicity. To gain insights into the mechanism of these actions, we performed transcriptomic analysis using next-generation sequencing, which revealed 340 differentially expressed transcripts by BPA in HCT116 and 75 in HCoEpiC. These transcripts belong in many cancer-related pathways such as apoptosis, cell proliferation, signal transduction, and angiogenesis. Some of the significant genes (FAM83H, CXCL12, PITPNA, HMOX1, DGKZ, NR5A2, VMP1, and ID1) were confirmed by quantitative RT-PCR. Furthermore, BPA induced the phosphorylation of protein kinases such as JNK1/2/3, GSK-3α/β, AMPKα1, AKT1/2/3, AMPKα2, HSP27, β-catenin, STAT2, Hck, Chk2, FAK, and PRAS40 in HCoEpiC, as well as GSK-3α/β, p53, AKT1/2/3, p70 S6 kinase, and WNK1 in HCT116. The majority of these proteins are involved in potential carcinogenic pathways. Taken together, these data suggest that BPA plays a role in colon carcinogenesis, and they provide insights into the molecular mechanisms of colon epithelial cell transformation by BPA. Increasing exposure to environmental toxins such as BPA can explain the increasing incidence of colorectal cancer. [ABSTRACT FROM AUTHOR]

Bisphenol S (BPS) is increasingly being used as an alternative for bisphenol A; however, its health effects remain unclear. We investigated the effects of oral exposure to low-dose BPS on allergic asthma. C3H/HeJ male mice were intratracheally administered with allergen (ovalbumin (OVA), 1 μg/animal) every 2 weeks from 6 to 11 weeks old. BPS was ingested by drinking water at doses equivalent to 0.04, 0.4, and 4 μg/kg/day. We then examined pulmonary inflammation, airway hyperresponsiveness, serum OVA-specific immunoglobulin (Ig) levels, Th2 cytokine/chemokine production, and mediastinal lymph node (MLN) cell activities. Compared with OVA alone, moderate-dose BPS (BPS-M) with OVA significantly enhanced pulmonary inflammation, airway hyperresponsiveness, and OVA-specific IgE and IgG1. Furthermore, interleukin (IL)-5, IL-13, IL-33, and CCL11/Eotaxin protein levels in the lungs increased. Conversely, these allergic responses were reduced in the high-dose BPS+OVA group. In MLN cells, BPS-M with OVA increased the total cell count and activated antigen-presenting cells including conventional dendritic cell subset (cDC2). After OVA restimulation, cell proliferation and Th2 cytokine production (IL-4, IL-5, and IL-13) in the culture supernatant also increased. Therefore, oral exposure to low-dose BPS may exacerbate allergic asthmatic responses by enhancing Th2-polarized responses and activating the MLN cells. [ABSTRACT FROM AUTHOR]

Endocrine disruptor chemicals (EDCs) can have a harmful effect on the human body’s endocrine system and thus adversely affect the development, reproduction, neurological, cardiovascular, and immune systems and metabolism in humans and wildlife. According to the World Health Organization, EDCs are mostly man-made and found ubiquitously in our daily lives, notably in pesticides, metals, and additives or contaminants in food and personal care products. Human exposure occurs through ingestion, inhalation, and dermal contact. Bisphenol A (BPA) is a proven EDC capable of mimicking or blocking receptors and altering hormone concentrations and metabolism. Although consumed in low doses, it can stimulate cellular responses and affect the body’s functions. In humans, exposure to BPA has been correlated with the onset or development of several diseases. This literature review aimed to verify the effects of BPA on human male infertility using the most recently published literature. Thus, this review allowed us to conclude that this compound seems to have harmful effects on human male fertility, causing changes in hormonal and semen characteristics. However, these conclusions lack more robust and reproducible scientific studies. Even so, and since male infertility prevalence is increasing, preventive measures must be taken to ensure male fertility.

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26–13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50–45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend.

Bisphenol A (BPA) is a globally utilized industrial chemical and is commonly used as a monomer of polycarbonate plastics and epoxy resins. Recent research reveals that BPA could cause potential adverse biological effects and liver dysfunction. However, the underlying mechanisms of BPA-induced hepatoxicity and gut dysbiosis remain unclear and deserve further study. In this study, male Sprague Dawley rats were exposed to different doses (0, 30, 90, and 270 mg/kg bw) of BPA by gavage for 30 days. The results showed that the high dose of BPA decreased superoxide dismutase (SOD), glutathione (GSH), and increased malondialdehyde (MDA) levels. Moreover, a high dose of BPA caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while high-density lipoprotein cholesterol (HDL-C) was significantly decreased in BPA-treated rats. The gene expression of PGC-1α and Nrf1 were decreased in the liver of high doses of BPA-administrated rats, as well as the protein levels of SIRT1, PGC-1α, Nrf2, and TFAM. However, the protein expression of IL-1β was significantly increased in BPA-treated rats. In addition, BPA weakened the mitochondrial function of hepatocytes and promoted cell apoptosis in the liver by up-regulating the protein levels of Bax, cleaved-Caspase3, and cleaved-PARP1 while down-regulating the Bcl-2 in the liver. More importantly, a high dose of BPA caused a dramatic change in microbiota structure, as characterized at the genus level by increasing the ratio of Firmicutes to Bacteroidetes (F/B), and the relative abundance of Proteobacteria in feces, while decreasing the relative abundance of Prevotella_9 and Ruminococcaceae_UCG-014, which is positively correlated with the content of short-chain fatty acids (SCFAs). In summary, our data indicated that BPA exposure caused hepatoxicity through apoptosis and the SIRT1/PGC-1α pathway. BPA-induced intestinal flora and SCFA changes may be associated with hepatic damage. The results of this study provide a new sight for the understanding of BPA-induced hepatoxicity. [ABSTRACT FROM AUTHOR]

Hazardous chemical compounds such as endocrine-disrupting chemicals (EDCs) are widespread and part of the materials we use daily. Among these compounds, bisphenol A (BPA) is the most common endocrine-disrupting chemical and is prevalent due to the chemical raw materials used to manufacture thermoplastic polymers, rigid foams, and industrial coatings. General exposure to endocrine-disrupting chemicals constitutes a serious health hazard, especially to reproductive systems, and can lead to transgenerational diseases in adults due to exposure to these chemicals over several years. Thus, it is necessary to develop sensors for early detection of endocrine-disrupting chemicals. In recent years, the use of metal–organic frameworks (MOFs) as sensors for EDCs has been explored due to their distinctive characteristics, such as wide surface area, outstanding chemical fastness, structural tuneability, gas storage, molecular separation, proton conductivity, and catalyst activity, among others which can be modified to sense hazardous environmental pollutants such as EDCs. In order to improve the versatility of MOFs as sensors, semiconductor quantum dots have been introduced into the MOF pores to form metal–organic frameworks/quantum dots composites. These composites possess a large optical absorption coefficient, low toxicity, direct bandgap, formidable sensing capacity, high resistance to change under light and tunable visual qualities by varying the size and compositions, which make them useful for applications as sensors for probing of dangerous and risky environmental contaminants such as EDCs and more. In this review, we explore various synthetic strategies of (MOFs), quantum dots (QDs), and metal–organic framework quantum dots composites (MOFs@QDs) as efficient compounds for the sensing of ecological pollutants, contaminants, and toxicants such as EDCs. We also summarize various compounds or materials used in the detection of BPA as well as the sensing ability and capability of MOFs, QDs, and MOFs@QDs composites that can be used as sensors for EDCs and BPA. [ABSTRACT FROM AUTHOR]