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Acta Biomaterialia Aug 2019Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides...
Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14 ± 3 and 24 ± 3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. STATEMENT OF SIGNIFICANCE: A new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinyl sulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.
Topics: Age Factors; Animals; Cross-Linking Reagents; Disease Models, Animal; Elasticity; Electroretinography; Glaucoma; Hyaluronic Acid; Hydrogels; Injections; Injections, Intraocular; Intraocular Pressure; Kinetics; Magnetic Resonance Imaging; Mice, Inbred C57BL; Neurodegenerative Diseases; Optic Nerve; Retinal Ganglion Cells; Sulfhydryl Compounds; Sulfones; Viscosity
PubMed: 31176841
DOI: 10.1016/j.actbio.2019.06.005 -
Environmental Toxicology and... Nov 2023Freshwater animals are exposed to anthropogenic contaminants and are biomonitors of water quality and models of the deleterious impacts of exposure. Sponges, such as...
Freshwater animals are exposed to anthropogenic contaminants and are biomonitors of water quality and models of the deleterious impacts of exposure. Sponges, such as Ephydatia muelleri, constantly pump water and are effective indicators of water-soluble contaminants. Zebrafish (Danio rerio), native to Southeast Asia, live in the water column and feed at the water-sediment interface and are exposed to both water-soluble and insoluble contaminants. While sponges and zebrafish diverged ∼700 million years ago, they share common genetic elements, and their response to contaminants can be predictive to a wide-range of animals. An emerging contaminant, bisphenol S, was tested to evaluate its toxicity during development. The toxicity and mechanism(s) of action of BPS is not well known. Water-borne exposures to BPS caused differing hatching rates, morphological changes, and shared gene expression changes of toxicologically-relevant genes. This study shows that BPS causes similarly adverse developmental impacts pointing to some overlapping mechanisms of action.
Topics: Animals; Zebrafish; Water Pollutants, Chemical; Phenols; Sulfones
PubMed: 37939749
DOI: 10.1016/j.etap.2023.104311 -
International Journal of Molecular... Nov 2020Despite numerous advantages of using porous hydroxyapatite (HAp) scaffolds in bone regeneration, the material is limited in terms of osteoinduction. In this study, the...
Despite numerous advantages of using porous hydroxyapatite (HAp) scaffolds in bone regeneration, the material is limited in terms of osteoinduction. In this study, the porous scaffold made from nanosized HAp was coated with different concentrations of osteoinductive aqueous methylsulfonylmethane (MSM) solution (2.5, 5, 10, and 20%) and the corresponding MH scaffolds were referred to as MH2.5, MH5, MH10, and MH20, respectively. The results showed that all MH scaffolds resulted in burst release of MSM for up to 7 d. Cellular experiments were conducted using MC3T3-E1 preosteoblast cells, which showed no significant difference between the MH2.5 scaffold and the control with respect to the rate of cell proliferation ( > 0.05). There was no significant difference between each group at day 4 for alkaline phosphatase (ALP) activity, though the MH2.5 group showed higher level of activity than other groups at day 10. Calcium deposition, using alizarin red staining, showed that cell mineralization was significantly higher in the MH2.5 scaffold than that in the HAp scaffold ( < 0.0001). This study indicated that the MH2.5 scaffold has potential for both osteoinduction and osteoconduction in bone regeneration.
Topics: 3T3 Cells; Animals; Bone Regeneration; Cell Differentiation; Cell Line; Cell Proliferation; Dimethyl Sulfoxide; Durapatite; Mice; Osteogenesis; Porosity; Sulfones; Tissue Engineering; Tissue Scaffolds
PubMed: 33198074
DOI: 10.3390/ijms21228501 -
Applied and Environmental Microbiology Jul 2020Bacterial alkane metabolism is associated with a number of cellular stresses, including membrane stress and oxidative stress, and the limited uptake of charged ions such...
Bacterial alkane metabolism is associated with a number of cellular stresses, including membrane stress and oxidative stress, and the limited uptake of charged ions such as sulfate. In the present study, the genes and in DR1 cells, which encode an alkanesulfonate monooxygenase and a taurine dioxygenase, respectively, were found to be responsible for hexadecanesulfonate (CSOH) and taurine metabolism, and Cbl was experimentally identified as a potential regulator of and expression. The expression of and occurred under sulfate-limited conditions generated during -hexadecane degradation. Interestingly, expression analysis and knockout experiments suggested that both genes are required to protect cells against oxidative stress, including that generated by -hexadecane degradation and HO exposure. Measurable levels of intracellular hexadecanesulfonate were also produced during -hexadecane degradation. Phylogenetic analysis suggested that and are mainly present in soil-dwelling aerobes within the and classes, which suggests that they function as controllers of the sulfur cycle and play a protective role against oxidative stress in sulfur-limited conditions. and , which play a role in the degradation of organosulfonate, were expressed during -hexadecane metabolism and oxidative stress conditions in DR1. Our study confirmed that hexadecanesulfonate was accidentally generated during bacterial -hexadecane degradation in sulfate-limited conditions. Removal of this by-product by SsuD and TauD must be necessary for bacterial survival under oxidative stress generated during -hexadecane degradation.
Topics: Acinetobacter; Alkanes; Alkanesulfonates; Bacterial Proteins; Hydrogen Peroxide; Mixed Function Oxygenases; Oxidative Stress
PubMed: 32503904
DOI: 10.1128/AEM.00692-20 -
Environmental Science & Technology Apr 2023Aqueous film-forming foams historically were used during fire training activities on Joint Base Cape Cod, Massachusetts, and created an extensive per- and...
Uptake of Per- and Polyfluoroalkyl Substances by Fish, Mussel, and Passive Samplers in Mobile-Laboratory Exposures Using Groundwater from a Contamination Plume at a Historical Fire Training Area, Cape Cod, Massachusetts.
Aqueous film-forming foams historically were used during fire training activities on Joint Base Cape Cod, Massachusetts, and created an extensive per- and polyfluoroalkyl substances (PFAS) groundwater contamination plume. The potential for PFAS bioconcentration from exposure to the contaminated groundwater, which discharges to surface water bodies, was assessed with mobile-laboratory experiments using groundwater from the contamination plume and a nearby reference location. The on-site continuous-flow 21-day exposures used male and female fathead minnows, freshwater mussels, polar organic chemical integrative samplers (POCIS), and polyethylene tube samplers (PETS) to evaluate biotic and abiotic uptake. The composition of the PFAS-contaminated groundwater was complex and 9 PFAS were detected in the reference groundwater and 17 PFAS were detected in the contaminated groundwater. The summed PFAS concentrations ranged from 120 to 140 ng L in reference groundwater and 6100 to 15,000 ng L in contaminated groundwater. Biotic concentration factors (CF) for individual PFAS were species, sex, source, and compound-specific and ranged from 2.9 to 1000 L kg in whole-body male fish exposed to contaminated groundwater for 21 days. The fish and mussel CF generally increased with increasing fluorocarbon chain length and were greater for sulfonates than for carboxylates. The exception was perfluorohexane sulfonate, which deviated from the linear trend and had a 10-fold difference in CF between sites, possibly because of biotransformation of precursors such as perfluorohexane sulfonamide. Uptake for most PFAS in male fish was linear over time, whereas female fish had bilinear uptake indicated by an initial increase in tissue concentrations followed by a decrease. Uptake of PFAS was less for mussels (maximum CF = 200) than for fish, and mussel uptake of most PFAS also was bilinear. Although abiotic concentration factors were greater than CF, and values for POCIS were greater than for PETS, passive samplers were useful for assessing PFAS that potentially bioconcentrate in fish but are present at concentrations below method quantitation limits in water. Passive samplers also accumulate short-chain PFAS that are not bioconcentrated.
Topics: Animals; Male; Female; Water Pollutants, Chemical; Fishes; Water; Fluorocarbons; Groundwater; Alkanesulfonates; Massachusetts; Polyethylene
PubMed: 36972291
DOI: 10.1021/acs.est.2c06500 -
Environment International Mar 2020Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being...
The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels.
BACKGROUND
Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being exposed from a vast number of sources and via several routes. Estrogenic and anti-androgenic effects are exerted by the chemical BPA, and also by its analogs. Therefore, realistic exposure assessments are needed for assessing risks related to cumulative exposure.
OBJECTIVES
Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concentrations were compared to source-to-dose calculations for source allocation and plausibility test of the model.
METHODS
For two 24-hour study periods separated by 2-3 weeks, 144 adult volunteers in Norway kept detailed diaries on food consumption, personal care product (PCP) use, and thermal paper (TP) handling. Concurrently, 24 h urine was collected and urinary levels of BPA, BPS, and BPF were analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). In line with the information obtained from the first study day, bisphenol exposure from food, PCPs, TP, and dust was modeled primarily individual-based with probabilistic models. Estimates for BP excretion over 24 h were obtained with the models and compared to measured amounts.
RESULTS
Modeled aggregate internal exposures covered the full range of measured urinary amounts for all BP analogs. In general, individual-based medians of modeled BPA exposures were in good agreement with the measurements, but individual-specific correlation was lacking. Modeled exposures mostly underestimated BPS and BPF levels in participants with positive measurements (53% and 8%), except for the P95 values of modeled BPS exposure that were higher than measured amounts if TP was handled. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amounts of canned food consumed, the number of PCPs used, or the number of TP handling events and levels of BPA, BPS, or BPF.
CONCLUSIONS
The good agreement between the ranges of modeled BPA exposure and measured BPA amounts indicates that available concentrations, especially from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amounts and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concentrations in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the respective exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concentration and occurrence data.
Topics: Adult; Benzhydryl Compounds; Biological Monitoring; Chromatography, Liquid; Cosmetics; Diet; Environmental Exposure; Humans; Norway; Phenols; Sulfones; Tandem Mass Spectrometry
PubMed: 31884417
DOI: 10.1016/j.envint.2019.105397 -
Molecules (Basel, Switzerland) Jan 2023Eighteen per-and polyfluoroalkyl substances (PFASs) were investigated in surface waters of four river basins in Portugal (Ave, Leça, Antuã, and Cértima) during the...
Eighteen per-and polyfluoroalkyl substances (PFASs) were investigated in surface waters of four river basins in Portugal (Ave, Leça, Antuã, and Cértima) during the dry and wet seasons. All sampling sites showed contamination in at least one of the seasons. In the dry season, perfluorooctanoate acid (PFOA) and perfluoro-octane sulfonate (PFOS), were the most frequent PFASs, while during the wet season these were PFOA and perfluobutane-sulfonic acid (PFBS). Compounds detected at higher concentrations were PFOS (22.6 ng L) and perfluoro-butanoic acid (PFBA) (22.6 ng L) in the dry and wet seasons, respectively. Moreover, the prospective environmental risks of PFASs, detected at higher concentrations, were evaluated based on the Risk Quotient (RQ) classification, which comprises acute and chronic toxicity. The results show that the RQ values of eight out of the nine PFASs were below 0.01, indicating low risk to organisms at different trophic levels in the four rivers in both seasons, wet and dry. Nevertheless, in the specific case of perfluoro-tetradecanoic acid (PFTeA), the RQ values calculated exceeded 1 for fish (96 h) and daphnids (48 h), indicating a high risk for these organisms. Furthermore, the RQ values were higher than 0.1, indicating a medium risk for fish, daphnids and green algae (96 h).
Topics: Animals; Rivers; Alkanesulfonic Acids; Portugal; Prospective Studies; Water Pollutants, Chemical; Environmental Monitoring; Fluorocarbons; Alkanesulfonates; Fishes
PubMed: 36770878
DOI: 10.3390/molecules28031209 -
Environmental Science & Technology May 2021The UV-sulfite reductive treatment using hydrated electrons () is a promising technology for destroying perfluorocarboxylates (PFCAs, CFCOO) in any chain length....
The UV-sulfite reductive treatment using hydrated electrons () is a promising technology for destroying perfluorocarboxylates (PFCAs, CFCOO) in any chain length. However, the C-H bonds formed in the transformation products strengthen the residual C-F bonds and thus prevent complete defluorination. Reductive treatments of fluorotelomer carboxylates (FTCAs, CF-CHCH-COO) and sulfonates (FTSAs, CF-CHCH-SO) are also sluggish because the ethylene linker separates the fluoroalkyl chain from the end functional group. In this work, we used oxidation () with hydroxyl radicals (HO•) to convert FTCAs and FTSAs to a mixture of PFCAs. This process also cleaved 35-95% of C-F bonds depending on the fluoroalkyl chain length. We probed the stoichiometry and mechanism for the oxidative defluorination of fluorotelomers. The subsequent reduction () with UV-sulfite achieved deep defluorination of the PFCA mixture for up to 90%. The following use of HO• to oxidize the H-rich residues led to the cleavage of the remaining C-F bonds. We examined the efficacy of integrated oxidative and reductive treatment of n = 1-8 PFCAs, n = 4,6,8 perfluorosulfonates (PFSAs, CF-SO), n = 1-8 FTCAs, and n = 4,6,8 FTSAs. A majority of structures yielded near-quantitative overall defluorination (97-103%), except for n = 7,8 fluorotelomers (85-89%), n = 4 PFSA (94%), and n = 4 FTSA (93%). The results show the feasibility of complete defluorination of legacy PFAS pollutants and will advance both remediation technology design and water sample analysis.
Topics: Alkanesulfonates; Carboxylic Acids; Environmental Pollutants; Fluorocarbons; Oxidation-Reduction; Water Pollutants, Chemical
PubMed: 33950686
DOI: 10.1021/acs.est.1c00353 -
Nature Chemistry Jan 2020The field of synthetic biology has used the engineered assembly of synthetic gene networks to create a wide range of functions in biological systems. To date,...
The field of synthetic biology has used the engineered assembly of synthetic gene networks to create a wide range of functions in biological systems. To date, gene-circuit-based sensors have primarily used optical proteins (for example, fluorescent, colorimetric) as reporter outputs, which has limited the potential to measure multiple distinct signals. Here we present an electrochemical interface that permits expanded multiplexed reporting for cell-free gene-circuit-based sensors. We have engineered a scalable system of reporter enzymes that cleave specific DNA sequences in solution, which results in an electrochemical signal when these newly liberated strands are captured at the surface of a nanostructured microelectrode. We describe the development of this interface and show its utility using a ligand-inducible gene circuit and toehold switch-based sensors by demonstrating the detection of multiple antibiotic resistance genes in parallel. This technology has the potential to expand the field of synthetic biology by providing an interface for materials, hardware and software.
Topics: Alkanesulfonates; Azo Compounds; DNA Restriction Enzymes; DNA, Single-Stranded; DNA-Directed RNA Polymerases; Drug Resistance, Multiple; Electrochemical Techniques; Fluoresceins; Gene Regulatory Networks; Genes, MDR; Methylene Blue; Microelectrodes; Nucleic Acid Hybridization; Proof of Concept Study; RNA, Messenger; Viral Proteins
PubMed: 31767994
DOI: 10.1038/s41557-019-0366-y -
International Journal of Molecular... Oct 2022Metallic nanoparticles exhibit broad-spectrum activity against bacteria, fungi, and viruses. The antiviral activity of nanoparticles results from the multivalent...
Metallic nanoparticles exhibit broad-spectrum activity against bacteria, fungi, and viruses. The antiviral activity of nanoparticles results from the multivalent interactions of nanoparticles with viral surface components, which result from the nanometer size of the material and the presence of functional compounds adsorbed on the nanomaterial surface. A critical step in the virus infection process is docking and entry of the virus into the host cell. This stage of the infection can be influenced by functional nanomaterials that exhibit high affinity to the virus surface and hence can disrupt the infection process. The affinity of the virus to the nanomaterial surface can be tuned by the specific surface functionalization of the nanomaterial. The main purpose of this work was to determine the influence of the ligand type present on nanomaterial on the antiviral properties against herpes simplex virus type 1 and 2. We investigated the metallic nanoparticles (gold and silver) with different sizes (5 nm and 30 nm), coated either with polyphenol (tannic acid) or sulfonates (ligands with terminated sulfonate groups). We found that the antiviral activity of nano-conjugates depends significantly on the ligand type present on the nanoparticle surface.
Topics: Polyphenols; Ligands; Metal Nanoparticles; Herpesvirus 1, Human; Antiviral Agents; Nanoparticles; Alkanesulfonates
PubMed: 36361890
DOI: 10.3390/ijms232113104