Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).
Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.
- MeSH
- Acrylamides chemistry MeSH
- Complement Activation drug effects MeSH
- Cholesterol chemistry blood MeSH
- Hydrophobic and Hydrophilic Interactions * MeSH
- Rabbits MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Liposomes * MeSH
- Mice MeSH
- Polyethylene Glycols * chemistry MeSH
- Polymers chemistry MeSH
- Surface Properties * MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.
- Publication type
- Journal Article MeSH
The COVID-19 outbreak led to the discovery of SARS-CoV-2 in sewage; thus, wastewater treatment plants (WWTPs) could have the virus in their effluent. However, whether SARS-CoV-2 is eradicated by sewage treatment is virtually unknown. Specifically, the objectives of this study include (i) determining whether a mixed matrixed membrane (MMM) is able to remove SARS-CoV-2 (polycarbonate (PC)-hydrous manganese oxide (HMO) and PC-silver nanoparticles (Ag-NP)), (ii) comparing filtration performance among different secondary treatment processes, and (iii) evaluating whether artificial neural networks (ANNs) can be employed as performance indicators to reduce SARS-CoV-2 in the treatment of sewage. At Shariati Hospital in Mashhad, Iran, secondary treatment effluent during the outbreak of COVID-19 was collected from a WWTP. There were two PC-Ag-NP and PC-HMO processes at the WWTP targeted. RT-qPCR was employed to detect the presence of SARS-CoV-2 in sewage fractions. For the purposes of determining SARS-CoV-2 prevalence rates in the treated effluent, 10 L of effluent specimens were collected in middle-risk and low-risk treatment MMMs. For PC-HMO, the log reduction value (LRV) for SARS-CoV-2 was 1.3-1 log10 for moderate risk and 0.96-1 log10 for low risk, whereas for PC-Ag-NP, the LRV was 0.99-1.3 log10 for moderate risk and 0.94-0.98 log10 for low risk. MMMs demonstrated the most robust absorption performance during the sampling period, with the least significant LRV recorded in PC-Ag-NP and PC-HMO at 0.94 log10 and 0.96 log10, respectively.
- MeSH
- COVID-19 * epidemiology MeSH
- Metal Nanoparticles * MeSH
- Humans MeSH
- Neural Networks, Computer MeSH
- Wastewater MeSH
- Sewage MeSH
- SARS-CoV-2 MeSH
- Silver MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Bisphenol S (BPS) is an industrial chemical used in the process of polymerization of polycarbonate plastics and epoxy resins and thus can be found in various plastic products and thermal papers. The microbiota disrupting effect of BPS on the community structure of the microbiome has already been reported, but little is known on how BPS affects bacterial activity and function. To analyze these effects, we cultivated the simplified human intestinal microbiota (SIHUMIx) in bioreactors at a concentration of 45 µM BPS. By determining biomass, growth of SIHUMIx was followed but no differences during BPS exposure were observed. To validate if the membrane composition was affected, fatty acid methyl esters (FAMEs) profiles were compared. Changes in the individual membrane fatty acid composition could not been described; however, the saturation level of the membranes slightly increased during BPS exposure. By applying targeted metabolomics to quantify short-chain fatty acids (SCFA), it was shown that the activity of SIHUMIx was unaffected. Metaproteomics revealed temporal effect on the community structure and function, showing that BPS has minor effects on the structure or functionality of SIHUMIx.
- Publication type
- Journal Article MeSH
BACKGROUND: There is an urgent need to develop better materials to provide anatomical support to the pelvic floor without compromising its function. OBJECTIVE: Our aim was to assess outcomes after simulated vaginal prolapse repair in a sheep model using three different materials: (1) ultra-lightweight polypropylene (PP) non-degradable textile (Restorelle) mesh, (2) electrospun biodegradable ureidopyrimidinone-polycarbonate (UPy-PC), and (3) electrospun non-degradable polyurethane (PU) mesh in comparison with simulated native tissue repair (NTR). These implants may reduce implant-related complications and avoid vaginal function loss. DESIGN, SETTING, AND PARTICIPANTS: A controlled trial was performed involving 48 ewes that underwent NTR or mesh repair with PP, UPy-PC, or PU meshes (n=12/group). Explants were examined 60 and 180 d (six per group) post-implantation. INTERVENTION: Posterior rectovaginal dissection, NTR, or mesh repair. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Implant-related complications, vaginal contractility, compliance, and host response were assessed. Power calculation and analysis of variance testing were used to enable comparison between the four groups. RESULTS: There were no visible implant-related complications. None of the implants compromised vaginal wall contractility, and passive biomechanical properties were similar to those after NTR. Shrinkage over the surgery area was around 35% for NTR and all mesh-augmented repairs. All materials were integrated well with similar connective tissue composition, vascularization, and innervation. The inflammatory response was mild with electrospun implants, inducing both more macrophages yet with relatively more type 2 macrophages present at an early stage than the PP mesh. CONCLUSIONS: Three very different materials were all well tolerated in the sheep vagina. Biomechanical findings were similar for all mesh-augmented repair and NTR. Constructs induced slightly different mid-term inflammatory profiles. PATIENT SUMMARY: Product innovation is needed to reduce implant-related complications. We tested two novel implants, electrospun and an ultra-lightweight polypropylene textile mesh, in a physiologically relevant model for vaginal surgery. All gave encouraging outcomes.
- MeSH
- Biocompatible Materials MeSH
- Surgical Mesh * MeSH
- Gynecologic Surgical Procedures MeSH
- Disease Models, Animal MeSH
- Models, Animal MeSH
- Sheep MeSH
- Polypropylenes * MeSH
- Uterine Prolapse surgery MeSH
- Prosthesis Design MeSH
- Pyrimidinones MeSH
- Materials Testing MeSH
- Textiles MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
A wide range of substances currently present in the environment may interact with biologically important macromolecules and may thus negatively affect their function. One of them, bisphenol A (BPA), is a basic material used in the production of polycarbonate plastics and epoxy resins, which adds flexibility and durability to the products. Because of its ability to migrate from these products, it represents a potential risk to the environment and to the quality of life of the organisms living there. One of the known mechanisms of BPA's action on organisms acts via estrogen receptors, leading to the blocking or mimicking of natural ligands, i.e., sex hormones. Another way BPA can affect cells is to induce oxidative damage to macromolecules including DNA. Therefore, BPA is referred to as a genotoxic agent. Moreover, BPA can also act epigenetically, through altered methylation of some genes, which may affect their expression. This process may represent a risk of inducing or promoting the transformation of healthy cells into tumorous ones. Such disruption of the body's natural environment is therefore undesirable and in contradiction with a healthy and prosperous individual's life.
- Keywords
- bisfenol,
- MeSH
- Cell Division drug effects MeSH
- Endocrine Disruptors chemistry adverse effects MeSH
- Gene Expression drug effects MeSH
- Phenols * chemistry adverse effects MeSH
- Humans MeSH
- Neoplasms etiology genetics MeSH
- DNA Damage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice. METHODS: To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 μg/kg body weight (bw)/day, BPS1-3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS). RESULTS: The results indicate that compared to vehicle, 100 μg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 μg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 μg/kg/day; BPS1), although the dose is several times lower than what has been published so far. CONCLUSIONS: In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.
- MeSH
- Acetylation drug effects MeSH
- Endocrine Disruptors pharmacology MeSH
- Epigenesis, Genetic MeSH
- Phenols pharmacology MeSH
- Phosphorylation drug effects MeSH
- Mice MeSH
- DNA Damage drug effects MeSH
- Protein Processing, Post-Translational drug effects MeSH
- Spermatozoa drug effects MeSH
- Sulfones pharmacology MeSH
- Testis drug effects pathology MeSH
- Dose-Response Relationship, Drug MeSH
- Sperm Maturation drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Therefore, we aimed to develop a functionalized electrospun mesh that promotes tissue ingrowth and provides adequate mechanical strength and compliance during degradation. We describe the in vivo function of a new supramolecular bioactivated polycarbonate (PC) material based on fourfold hydrogen bonding ureidopyrimidinone (UPy) units (UPy-PC). The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Morphometric analysis of the musculofascial content during wound healing showed that cRGD functionalization promotes myogenesis with inhibition of collagen deposition at 14 days. It also prevents muscle atrophy at 90 days and exerts an immunomodulatory effect on infiltrating macrophages at 14 days and foreign body giant cell formation at 14 and 90 days. Additionally, the bioactivated material promotes neovascularization and connective tissue ingrowth. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in the rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. Our results provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. STATEMENT OF SIGNIFICANCE: Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Ureidopyrimidinone-polycarbonate is a elastomeric and biodegradable electrospun mesh, which could mimic physiological compliance. The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. These data provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP.
- MeSH
- Biocompatible Materials chemistry pharmacology MeSH
- Abdominal Wall surgery MeSH
- Surgical Mesh * MeSH
- Cartilage metabolism MeSH
- Peptides, Cyclic chemistry pharmacology MeSH
- Granuloma prevention & control MeSH
- Polycarboxylate Cement chemistry pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Pyrimidinones chemistry pharmacology MeSH
- Muscular Atrophy prevention & control MeSH
- Muscle Development drug effects MeSH
- Inflammation prevention & control MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Quantum dots (QDs) absorb ultraviolet and long-wavelength visible light energy much more efficiently than natural bacterial light-harvesting proteins and can transfer the excitation energy to photosynthetic reaction centers (RCs). Inclusion of RCs combined with QDs as antennae into liposomes opens new opportunities for using such hybrid systems as a basis for artificial energy-transforming devices that potentially can operate with greater efficiency and stability than devices based only on biological components or inorganic components alone. RCs from Rhodobacter sphaeroides and QDs (CdSe/ZnS with hydrophilic covering) were embedded in lecithin liposomes by extrusion of a solution of multilayer lipid vesicles through a polycarbonate membrane or by dialysis of lipids and proteins dispersed with excess detergent. The efficiency of RC and QD interaction within the liposomes was estimated using fluorescence excitation spectra of the photoactive bacteriochlorophyll of the RCs and by measuring the fluorescence decay kinetics of the QDs. The functional activity of the RCs in hybrid complexes was fully maintained, and their stability was even increased. The efficiency of energy transfer between QDs and RCs and conditions of long-term stability of function of such hybrid complexes in film preparations were investigated as well. It was found that dry films containing RCs and QDs, maintained at atmospheric humidity, are capable of maintaining their functional activity for at least some months as judged by measurements of their spectral characteristics, efficiency of energy transfer from QDs to RCs and RC electron transport activity. Addition of trehalose to the films increases the stability further, especially for films maintained at low humidity. These stable hybrid film structures are promising for further studies towards developing new phototransformation devices for biotechnological applications.
