RESUMEN
The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from â¼88 to 100%. Reducing substances consumed ABTSâ¢+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Phâ¢), promoting the transformation of Fe(VI) â Fe(V) â Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTSâ¢+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.
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Electrones , Oxidación-Reducción , Hierro/química , Compuestos Orgánicos/química , Benzotiazoles/química , Ácidos SulfónicosRESUMEN
Dye-decolorizing peroxidases (DyPs) belong to a novel superfamily of heme peroxidases that can oxidize recalcitrant compounds. In the current study, the GlDyP2 gene from Ganoderma lucidum was heterologously expressed in Escherichia coli, and the enzymatic properties of the recombinant GlDyP2 protein were investigated. The GlDyP2 protein could oxidize not only the typical peroxidase substrate ABTS but also two lignin substrates, namely guaiacol and 2,6-dimethoxy phenol (DMP). For the ABTS substrate, the optimum pH and temperature of GlDyP2 were 4.0 and 35 °C, respectively. The pH stability and thermal stability of GlDyP2 were also measured; the results showed that GlDyP2 could function normally in the acidic environment, with a T50 value of 51 °C. Moreover, compared to untreated controls, the activity of GlDyP2 was inhibited by 1.60 mM of Mg2+, Ni2+, Mn2+, and ethanol; 0.16 mM of Cu2+, Zn2+, methanol, isopropyl alcohol, and Na2EDTA·2H2O; and 0.016 mM of Fe2+ and SDS. The kinetic constants of recombinant GlDyP2 for oxidizing ABTS, Reactive Blue 19, guaiacol, and DMP were determined; the results showed that the recombination GlDyP2 exhibited the strongest affinity and the most remarkable catalytic efficiency towards guaiacol in the selected substrates. GlDyP2 also exhibited decolorization and detoxification capabilities towards several dyes, including Reactive Blue 19, Reactive Brilliant Blue X-BR, Reactive Black 5, Methyl Orange, Trypan Blue, and Malachite Green. In conclusion, GlDyP2 has good application potential for treating dye wastewater.
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Colorantes , Estabilidad de Enzimas , Escherichia coli , Guayacol , Proteínas Recombinantes , Reishi , Temperatura , Colorantes/metabolismo , Colorantes/química , Reishi/genética , Reishi/enzimología , Reishi/metabolismo , Concentración de Iones de Hidrógeno , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Guayacol/metabolismo , Guayacol/análogos & derivados , Biodegradación Ambiental , Cinética , Benzotiazoles/metabolismo , Especificidad por Sustrato , Lignina/metabolismo , Oxidación-Reducción , Peroxidasa/genética , Peroxidasa/metabolismo , Peroxidasa/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Peroxidasas/genética , Peroxidasas/metabolismo , Peroxidasas/química , Contaminantes Químicos del Agua/metabolismo , Compuestos Azo/metabolismo , Aguas Residuales/microbiología , Aguas Residuales/química , Ácidos Sulfónicos/metabolismo , Antraquinonas , Colorantes de RosanilinaRESUMEN
Perfluorohexane sulfonate (PFHxS) is a member of the per- and polyfluoroalkyls (PFAS) superfamily of molecules, characterized by their fluorinated carbon chains and use in a wide range of industrial applications. PFHxS and perfluorooctane sulfonate are able to accumulate in the environment and in humans with the approximated serum elimination half-life in the range of several years. More recently, some PFAS compounds have also been suggested as potential immunosuppressants. In this study, we analyze immune cell numbers in mice following 28-d repeated oral exposure to potassium PFHxS at 12, 120, 1,200, and 12,000 ng/kg/d, with resulting serum levels ranging up to â¼1,600 ng/ml, approximating ranges found in the general population and at higher levels in PFAS workers. The immunosuppressant cyclophosphamide was analyzed as a positive control. B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We found that at these exposures, there was no effect of PFHxS on major T or B cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, or circulating Ab isotypes. By contrast, mice exposed to cyclophosphamide exhibited depletion of several granulocyte and T and B cell populations in the thymus, bone marrow, and spleen, as well as reductions in IgG1, IgG2b, IgG2c, IgG3, IgE, and IgM. These data indicate that exposures of up to 12,000 ng/kg of PFHxS for 28 d do not affect immune cell numbers in naive mice, which provides valuable information for assessing the risks and health influences of exposures to this compound.
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Fluorocarburos , Animales , Ratones , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Ácidos Sulfónicos , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Femenino , Bazo/inmunología , Bazo/efectos de los fármacos , Bazo/citología , Timo/efectos de los fármacos , Timo/inmunología , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , MasculinoRESUMEN
Sorghum, a cereal grain rich in nutrients, is a major source of phenolic compounds that can be altered by different processes, thereby modulating their phenolic content and antioxidant properties. Previous studies have characterised phenolic compounds from pigmented and non-pigmented varieties. However, the impact of processing via the cooking and fermentation of these varieties remains unknown. Wholegrain flour samples of Liberty (WhiteLi1 and WhiteLi2), Bazley (RedBa1 and RedBa2), Buster (RedBu1 and RedBu2), Shawaya black (BlackSb), and Shawaya short black 1 (BlackSs) were cooked, fermented, or both then extracted using acidified acetone. The polyphenol profiles were analysed using a UHPLC-Online ABTS and QTOF LC-MS system. The results demonstrated that combining the fermentation and cooking of the BlackSs and BlackSb varieties led to a significant increase (p < 0.05) in total phenolic content (TPC) and antioxidant activities, as determined through DPPH, FRAP, and ABTS assays. The 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity of WhiteLi1, BlackSb, RedBu2, and BlackSs increased by 46%, 32%, 25%, and 10%, respectively, post fermentation and cooking. Conversely, fermentation only or cooking generally resulted in lower phenolic content and antioxidant levels than when samples were fully processed compared to raw. Notably, most of the detected antioxidant peaks (53 phenolic compounds) were only detected in fermented and cooked black and red pericarp varieties. The phenolic compounds with the highest antioxidant activities in pigmented sorghum included 3-aminobenzoic acid, 4-acetylburtyic acid, malic acid, caffeic acid, and luteolin derivative. Furthermore, the growing location of Bellata, NSW, showed more detectable phenolic compounds following processing compared to Croppa Creek, NSW. This study demonstrates that sorghum processing releases previously inaccessible polyphenols, making them available for human consumption and potentially providing added health-promoting properties.
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Antioxidantes , Fenoles , Sorghum , Sorghum/química , Antioxidantes/química , Antioxidantes/análisis , Fenoles/análisis , Fenoles/química , Polifenoles/análisis , Polifenoles/química , Fermentación , Cromatografía Líquida de Alta Presión , Culinaria , Extractos Vegetales/química , Harina/análisis , Ácidos Sulfónicos/química , BenzotiazolesRESUMEN
The Veneto Region (Northern Italy) conducted a monitoring campaign in the years 2016-2017 in order to evaluate the concentration of per- and polyfluoroalkyl substances (PFASs) in foods in the area affected by the water contamination discovered in 2013. The risk assessment for the resident population was conducted by the Italian National Institute of Health (ISS) in 2018 and updated in 2021. The European Food Safety Agency (EFSA) updated the limits used by ISS, in particular adding a limit for the sum of four PFAS molecules in 2020. In this work, the risk assessment conducted by ISS is reviewed in light of the new limit of 4.4 ng/kg body weight for the sum of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonate (PFHxS). In the adult population (18-65 years), total weekly intakes, calculated for the years preceding 2013, resulted more than ten times the EFSA 2020 limit, more than five times in the intermediate period 2013-2017 - preceding the implementation of mitigation actions through double filtration of the water of the aqueduct -, by more than three times in the period after 2018, and yet by almost seven times for those who supply contaminated groundwater through private wells. The food contribution for those who use filtered water from the aqueduct is equal to 20% of the total weekly income.
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Ácidos Alcanesulfónicos , Caprilatos , Fluorocarburos , Contaminación de Alimentos , Contaminantes Químicos del Agua , Italia , Fluorocarburos/análisis , Humanos , Medición de Riesgo , Adulto , Ácidos Alcanesulfónicos/análisis , Adolescente , Caprilatos/análisis , Persona de Mediana Edad , Contaminantes Químicos del Agua/análisis , Anciano , Exposición Dietética/análisis , Adulto Joven , Monitoreo del Ambiente , Femenino , Ácidos SulfónicosRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125-2.5% or 7.82-62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b+ monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression.
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Ácidos Alcanesulfónicos , Fluorocarburos , Animales , Fluorocarburos/toxicidad , Fluorocarburos/administración & dosificación , Ratones , Ácidos Alcanesulfónicos/toxicidad , Ácidos Alcanesulfónicos/administración & dosificación , Femenino , Humanos , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Ácidos Sulfónicos/toxicidad , Ácidos Sulfónicos/administración & dosificación , Administración Tópica , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Masculino , Piel/efectos de los fármacos , Piel/inmunología , Piel/patologíaRESUMEN
A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 µM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.
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Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica , Ácidos Sulfónicos , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Ácidos Sulfónicos/química , Animales , Bovinos , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/farmacología , Estructura MolecularRESUMEN
Erythrogram, despite its prevalent use in assessing red blood cell (RBC) disorders and can be utilized to evaluate various diseases, still lacks evidence supporting the effects of per- and polyfluoroalkyl substances (PFASs) and organophosphate esters (OPEs) on it. A cross-sectional study involving 467 adults from Shijiazhuang, China was conducted to assess the associations between 12 PFASs and 11 OPEs and the erythrogram (8 indicators related to RBC). Three models, including multiple linear regression (MLR), sparse partial least squares regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate both the individual and joint effects of PFASs and OPEs on the erythrogram. Perfluorohexane sulfonic acid (PFHxS) showed the strongest association with HGB (3.68%, 95% CI: 2.29%, 5.10%) when doubling among PFASs in MLR models. BKMR indicated that PFASs were more strongly associated with the erythrogram than OPEs, as evidenced by higher group posterior inclusion probabilities (PIPs) for PFASs. Within hemoglobin and hematocrit, PFHxS emerged as the most significant component (conditional PIP = 1.0 for both). Collectively, our study emphasizes the joint effect of PFASs and OPEs on the erythrogram and identified PFASs, particularly PFHxS, as the pivotal contributors to the erythrogram. Nonetheless, further investigations are warranted to elucidate the underlying mechanisms.
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Ésteres , Organofosfatos , Humanos , Adulto , China , Femenino , Estudios Transversales , Masculino , Fluorocarburos , Persona de Mediana Edad , Eritrocitos/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/análisis , Teorema de Bayes , Adulto Joven , Pueblos del Este de Asia , Ácidos SulfónicosRESUMEN
Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats.
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Fluorocarburos , Hígado , Ratas Sprague-Dawley , Transcriptoma , Animales , Fluorocarburos/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Transcriptoma/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Ratas , Ácidos Sulfónicos/toxicidad , Alanina Transaminasa/sangre , Peso Corporal/efectos de los fármacos , Dieta , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Perfluoroalkyl substances (PFAS) are common environmental pollutants, but their toxicity framework remains elusive. This research focused on ten PFAS, evaluating their impacts on two ecotoxicologically relevant model organisms from distinct trophic levels: the crustacean Daphnia magna and the unicellular green alga Raphidocelis subcapitata. The results showed a greater sensitivity of R. subcapitata compared to D. magna. However, a 10-day follow-up to the 48 h immobilisation test in D. magna showed delayed mortality, underlining the limitations of relying on EC50 s from standard acute toxicity tests. Among the compounds scrutinized, Perfluorodecanoic acid (PFDA) was the most toxic to R. subcapitata, succeeded by Perfluorooctane sulfonate (PFOS), Perfluorobutanoic acid (PFBA), and Perfluorononanoic acid (PFNA), with the latter being the only one to show an algicidal effect. In the same species, assessment of binary mixtures of the compounds that demonstrated high toxicity in the single evaluation revealed either additive or antagonistic interactions. Remarkably, with an EC50 of 31 mg L-1, the short-chain compound PFBA, tested individually, exhibited toxicity levels akin to the notorious long-chain PFOS, and its harm to freshwater ecosystems cannot be ruled out. Despite mounting toxicological evidence and escalating environmental concentrations, PFBA has received little scientific attention and regulatory stewardship. It is strongly advisable that regulators re-evaluate its use to mitigate potential risks to the environmental and human health.
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Ácidos Alcanesulfónicos , Daphnia , Fluorocarburos , Agua Dulce , Contaminantes Químicos del Agua , Fluorocarburos/toxicidad , Daphnia/efectos de los fármacos , Animales , Contaminantes Químicos del Agua/toxicidad , Ácidos Alcanesulfónicos/toxicidad , Ecosistema , Ácidos Decanoicos/toxicidad , Ácidos Grasos , Pruebas de Toxicidad , Ácidos SulfónicosRESUMEN
Bone morphogenetic proteins (BMPs) are important targets to incorporate in biomaterial scaffolds to orchestrate tissue repair. Glycosaminoglycans (GAGs) such as heparin allow the capture of BMPs and their retention at the surface of biomaterials at safe concentrations. Although heparin has strong affinities for BMP2 and BMP4, two important types of growth factors regulating bone and tissue repair, it remains difficult to embed stably at the surface of a broad range of biomaterials and degrades rapidly in vitro and in vivo. In this report, biomimetic poly(sulfopropyl methacrylate) (PSPMA) brushes are proposed as sulfated GAG mimetic interfaces for the stable capture of BMPs. The growth of PSPMA brushes via a surface-initiated activator regenerated by electron transfer polymerization is investigated via ellipsometry, prior to characterization of swelling and surface chemistry via X-ray photoelectron spectroscopy and Fourier transform infrared. The capacity of PSPMA brushes to bind BMP2 and BMP4 is then characterized via surface plasmon resonance. BMP2 is found to anchor particularly stably and at high density at the surface of PSPMA brushes, and a strong impact of the brush architecture on binding capacity is observed. These results are further confirmed using a quartz crystal microbalance with dissipation monitoring, providing some insights into the mode of adsorption of BMPs at the surface of PSPMA brushes. Primary adsorption of BMP2, with relatively little infiltration, is observed on thick dense brushes, implying that this growth factor should be accessible for further binding of corresponding cell membrane receptors. Finally, to demonstrate the impact of PSPMA brushes for BMP2 capture, dermal fibroblasts were then cultured at the surface of functionalized PSPMA brushes. The presence of BMP2 and the architecture of the brush are found to have a significant impact on matrix deposition at the corresponding interfaces. Therefore, PSPMA brushes emerge as attractive coatings for scaffold engineering and stable capture of BMP2 for regenerative medicine applications.
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Proteína Morfogenética Ósea 2 , Proteína Morfogenética Ósea 4 , Proteína Morfogenética Ósea 2/química , Proteína Morfogenética Ósea 2/metabolismo , Proteína Morfogenética Ósea 4/química , Proteína Morfogenética Ósea 4/metabolismo , Humanos , Ácidos Sulfónicos/química , Metacrilatos/química , Propiedades de Superficie , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Glicosaminoglicanos/química , Glicosaminoglicanos/metabolismoRESUMEN
BACKGROUND: Per- and polyfluoroalkyl Substances (PFAS) are synthetic chemicals widely detected in humans and the environment. Exposure to perfluorooctanesulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) was previously shown to cause dark-phase hyperactivity in larval zebrafish. OBJECTIVES: The objective of this study was to elucidate the mechanism by which PFOS or PFHxS exposure caused hyperactivity in larval zebrafish. METHODS: Swimming behavior was assessed in 5-d postfertilization (dpf) larvae following developmental (1-4 dpf) or acute (5 dpf) exposure to 0.43-7.86µM PFOS, 7.87-120µM PFHxS, or 0.4% dimethyl sulfoxide (DMSO). After developmental exposure and chemical washout at 4 dpf, behavior was also assessed at 5-8 dpf. RNA sequencing was used to identify differences in global gene expression to perform transcriptomic benchmark concentration-response (BMCT) modeling, and predict upstream regulators in PFOS- or PFHxS-exposed larvae. CRISPR/Cas9-based gene editing was used to knockdown peroxisome proliferator-activated receptors (ppars) pparaa/ab, pparda/db, or pparg at day 0. Knockdown crispants were exposed to 7.86µM PFOS or 0.4% DMSO from 1-4 dpf and behavior was assessed at 5 dpf. Coexposure with the ppard antagonist GSK3787 and PFOS was also performed. RESULTS: Transient dark-phase hyperactivity occurred following developmental or acute exposure to PFOS or PFHxS, relative to the DMSO control. In contrast, visual startle response (VSR) hyperactivity only occurred following developmental exposure and was irreversible up to 8 dpf. Similar global transcriptomic profiles, BMCT estimates, and enriched functions were observed in PFOS- and PFHxS-exposed larvae, and ppars were identified as putative upstream regulators. Knockdown of pparda/db, but not pparaa/ab or pparg, blunted PFOS-dependent VSR hyperactivity to control levels. This finding was confirmed via antagonism of ppard in PFOS-exposed larvae. DISCUSSION: This work identifies a novel adverse outcome pathway for VSR hyperactivity in larval zebrafish. We demonstrate that developmental, but not acute, exposure to PFOS triggered persistent VSR hyperactivity that required ppard function. https://doi.org/10.1289/EHP13667.
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Fluorocarburos , Larva , Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/fisiología , Fluorocarburos/toxicidad , Larva/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Receptores Activados del Proliferador del Peroxisoma/genética , Ácidos Alcanesulfónicos/toxicidad , Reflejo de Sobresalto/efectos de los fármacos , Ácidos Sulfónicos/toxicidad , NataciónRESUMEN
Liver cancer is a complex disease that involves various oncoproteins and the inactivation of tumor suppressor proteins (TSPs). Gankyrin is one such oncoprotein, first identified in human hepatocellular carcinoma, that is known to inactivate multiple TSPs, leading to proliferation and metastasis of tumor cells. Despite this, there has been limited development of small molecule gankyrin binders for the treatment of liver cancer. In this study, we are reporting the structure-based design of gankyrin-binding small molecules which inhibit the proliferation of HuH6 and HepG2 cells while also increasing the levels of certain TSPs, such as Rb and p53. Interestingly the first molecule to exhibit inhibition by 3D structure stabilization is seen. These results suggest a possible mechanism for small-molecule inhibition of gankyrin and demonstrate that gankyrin is a viable therapeutic target for the treatment of liver cancer.
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Antineoplásicos , Proliferación Celular , Proteínas Proto-Oncogénicas , Triazoles , Humanos , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Relación Estructura-Actividad , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacología , Ácidos Sulfónicos/antagonistas & inhibidores , Línea Celular Tumoral , Ésteres/química , Ésteres/farmacología , Ésteres/síntesis química , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/química , Relación Dosis-Respuesta a Droga , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , BencenosulfonatosRESUMEN
The physiological parameters such as growth, Chl a content, and photosynthetic performance of the experimental cyanobacterium Anabaenopsis circularis HKAR-22 were estimated to evaluate the cumulative effects of photosynthetically active radiation (PAR) and ultraviolet (UV) radiation. Maximum induction of UV-screening molecules, MAAs, was observed under the treatment condition of PAR + UV-A + UV-B (PAB) radiations. UV/VIS absorption spectroscopy and HPLC-PDA detection primarily confirmed the presence of MAA-shinorine (SN) having absorption maxima (λmax) at 332.3 nm and retention time (RT) of 1.47 min. For further validation of the presence of SN, HRMS, FTIR and NMR were utilized. UV-stress elevated the in vivo ROS scavenging and in vitro enzymatic antioxidant capabilities. SN exhibited substantial and concentration-dependent antioxidant capabilities which was determined utilizing 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS), ferric reducing power (FRAP) and superoxide radical scavenging assay (SRSA). The density functional theory (DFT) method using B3LYP energy model and 6-311G++(d,p) basis set was implied to perform the quantum chemical calculation to systematically investigate the antioxidant nature of SN. The principal pathways involved in the antioxidant reactions along with the basic molecular descriptors affecting the antioxidant potentials of a compound were also studied. The results favor the potential of SN as an active ingredient to be used in cosmeceutical formulations.
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Antioxidantes , Cianobacterias , Teoría Funcional de la Densidad , Rayos Ultravioleta , Antioxidantes/química , Cianobacterias/química , Cianobacterias/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Ciclohexanonas/química , Fotosíntesis , Especies Reactivas de Oxígeno/metabolismo , Clorofila A/química , Clorofila A/metabolismo , Compuestos de Bifenilo/química , Picratos/antagonistas & inhibidores , Picratos/química , Depuradores de Radicales Libres/química , Ciclohexilaminas , Glicina/análogos & derivados , Ácidos Sulfónicos , BenzotiazolesRESUMEN
As the most abundant renewable resource, cellulose fibers are potential candidates for use in health-protective clothing. Herein, we demonstrate a novel strategy for preparing cellulose fiber with prominent antibacterial and antiviral performance by the synergistic effect of amino groups and sulfonic acid groups. Specifically, guanylated chitosan oligosaccharide (GCOS) and N-sulfopropyl chitosan oligosaccharide (SCOS) were synthesized and chemically grafted onto cellulose fibers (CFs) to endow the fibers with antibacterial and antiviral properties. Moreover, a compounding strategy was applied to make the fibers with simultaneously high antibacterial and antiviral activity, especially in short contact time. The bacteriostatic rate (against S. aureus: 95.81 %, against E. coli: 92.07 %, 1 h) of the compounded fibers improved substantially when a few GCOS-CFs were mixed with SCOS-CFs; especially, it was much higher than both the individual GCOS-CFs and SCOS-CFs. By contrast, the improvement of the antiviral properties was less dramatic; however, even a few SCOS-CFs was mixed, the antiviral properties increased pronouncedly. Although the electrostatic interaction between SCOS and GCOS can make the SCOS-GCOS mixture lose some extent of antibacterial activity, the long chains of cellulose restrain the electrostatic interaction between sulfonic and amino groups, leading to their synergistic action and eventually superior antibacterial and antiviral effects.
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Antibacterianos , Antivirales , Celulosa , Quitosano , Escherichia coli , Staphylococcus aureus , Ácidos Sulfónicos , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Quitosano/farmacología , Antivirales/farmacología , Antivirales/química , Celulosa/química , Celulosa/farmacología , Celulosa/análogos & derivados , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Ácidos Sulfónicos/química , Oligosacáridos/química , Oligosacáridos/farmacología , Pruebas de Sensibilidad Microbiana , Sinergismo Farmacológico , HumanosRESUMEN
Hexadimethrine bromide (HB), a synthetic polycationic species, was introduced to clinical practice as a heparin antidote and recently used in gene therapy. However, HB causes various complications such as severe red blood cells (RBCs) aggregation and tissue damage. Herein, we have synthesized a water-soluble quaterphen[3]arene containing multiple sulfonate moieties (SQP3) as a novel macrocyclic neutralizer to reverse HB via direct host-guest complexation. SQP3 exhibited a robust binding affinity toward HB with a considerably high association constant of (4.73 ± 0.61) × 107 M-1. Co-dosed with 1 equiv of SQP3, HB-induced RBCs aggregation and blood coagulation could be effectively reversed. In vitro cellular assay verified that complexation of HB with SQP3 significantly decreased reactive oxygen species production, thereby suppressing cell apoptosis. In vivo neutralization efficacy studies demonstrated that HB/SQP3 was capable of alleviating related organic damage caused by HB and improving the survival rate of HB-treated mice from 20 to 100%.
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Compuestos Macrocíclicos , Animales , Ratones , Humanos , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/farmacología , Compuestos Macrocíclicos/síntesis química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Agregación Eritrocitaria/efectos de los fármacos , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacologíaRESUMEN
BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10â 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.
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Ácidos Alcanesulfónicos , Fluorocarburos , Hipertensión , Humanos , Fluorocarburos/sangre , Femenino , Hipertensión/epidemiología , Hipertensión/sangre , Masculino , Estudios Transversales , China/epidemiología , Persona de Mediana Edad , Adulto , Ácidos Alcanesulfónicos/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Ácidos Decanoicos/sangre , Disruptores Endocrinos/sangre , Disruptores Endocrinos/efectos adversos , Ácidos Grasos/sangre , Prevalencia , Hormonas Esteroides Gonadales/sangre , Ácidos Sulfónicos/sangre , Contaminantes Ambientales/sangre , Contaminantes Ambientales/efectos adversos , Ácidos Láuricos/sangre , Ácidos Láuricos/farmacologíaRESUMEN
N-(sodium 2-hydroxypropylsulfonate) chitosan (HSCS), N-sulfonate chitosan (SCS) and N-isonicotinic sulfonate chitosan (ISCS) were prepared. The structures of the prepared chitosan derivatives were characterized by nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and elemental analysis (EA). Antibacterial and antibiofilm activities of these chitosan derivatives were evaluated in vitro. The minimum inhibitory concentration (MIC) of HSCS and SCS against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were 0.625 mg/mL and 0.156 mg/mL, respectively. ISCS exhibited MIC values of 0.313 mg/mL and 0.078 mg/mL against E. coli and S. aureus, respectively. ISCS demonstrated superior antibacterial and antibiofilm properties compared to SCS and HSCS. These findings suggest that the incorporation of a pyridine structure into sulfonate chitosan enhances its antibacterial and antibiofilm activities, and the prepared ISCS has a promising application prospect for controlling the reproduction of microorganisms in the field of food packaging.
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Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Quitosano/síntesis química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacología , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
This study prepared sulfonated Camellia oleifera shell biochar using Camellia oleifera shell agricultural waste as a carbon source, and evaluated its performance as a catalyst for preparing biodiesel. The biochar obtained from carbonizing Camellia oleifera shells at 500 °C for 2 h serves as the carbon skeleton, and then the biochar is sulfonated with chlorosulfonic acid. The sulfonic acid groups are mainly grafted onto the surface of Camellia oleifera shell biochar through covalent bonding to obtain sulfonic acid type biochar catalysts. The catalysts were characterized by Scanning Electron Microscope (SEM), X-ray diffraction (XRD), Nitrogen adsorption-desorption Brunel-Emmett-Taylor Theory (BET), and Fourier-transform infrared spectroscopy (FT-IR). The acid density of the sulfonated Camellia oleifera fruit shell biochar catalyst is 2.86 mmol/g, and the specific surface area is 2.67 m2/g, indicating high catalytic activity. The optimal reaction conditions are 4 wt% catalyst with a 6:1 alcohol to oil ratio. After esterification at 70 °C for 2 h, the yield of biodiesel was 91.4%. Under the optimal reaction conditions, after four repeated uses of the catalyst, the yield of biodiesel still reached 90%. Therefore, sulfonated Camellia oleifera shell biochar is a low-cost, green, non-homogeneous catalyst with great potential for biodiesel production by esterification reaction in future development.
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Biocombustibles , Camellia , Carbón Orgánico , Camellia/química , Carbón Orgánico/química , Catálisis , Ácidos Sulfónicos/química , Espectroscopía Infrarroja por Transformada de Fourier , Esterificación , Difracción de Rayos XRESUMEN
Meat from farm animals (pigs, cattle and poultry) and game (wild boar and deer) was analysed in terms of thirteen perfluoroalkyl substances (PFASs). Wild boar muscle tissue was statistically significantly more contaminated than muscle tissue from other animals, and the species order of the lower-bound (LB) sum of four (∑4) PFAS (perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorononanoic acid and perfluorohexanesulfonic acid) concentrations was wild boar > cattle > deer > pigs > poultry. None of the samples exceeded the maximum levels set by Commission Regulation (EU) 2023/915. Linear PFOS was the most frequently detected compound (in 21 % of all samples analysed and 100 % of wild boar samples), reaching its highest concentration of 1.87 µg/kg wet weight in wild boar. Dietary intake was estimated on the basis of the average per-serving consumption of pork, beef and poultry, and in the absence of such data for game, a 100 g portion was used for the calculation. Mean LB∑4 PFAS concentrations led to intakes between 0.000 and 1.75 ng/kg body weight (BW) for children and 0.000 and 0.91 ng/kg BW for adults. The potential risk to consumers was assessed in relation to the tolerable weekly intake (TWI) of 4.4 ng/kg BW established by the European Food Safety Authority in 2020. Exposure associated with the consumption of poultry, pork, beef and venison was negligible, being only <1 % of the TWI for children and adults; higher exposure was found to associate with the consumption of wild boar, being 63 % and 21 % of the TWI for children and adults, respectively. The findings of this research suggest that the intake of PFASs through the consumption of meat from Polish livestock and deer is unlikely to be a health concern. However, frequent consumption of wild boar meat could be a significant source of PFASs.