RESUMO
Herbicide exposure can pose a considerable threat to non-target aquatic animals. We aimed to study changes in the liver proteome of a model cyprinid fish species, zebrafish Danio rerio, to provide a molecular basis for the adverse effects of environmentally relevant concentrations of glyphosate (100 µg/L), its breakdown product aminomethylphosphonic acid (AMPA; 100 µg/L), and a mixture of both (50 + 50 µg/L) in the presence of humic acid (20 mg/L), which simulated a component of natural organic matter in the aquatic environment. Proteomic analysis was performed by means of high-performance liquid chromatography-tandem mass spectrometry employing a label-free quantification approach. The results present molecular evidence of the stress responses and disturbance of primary metabolic processes such as immune response, dysregulation in DNA repair, necroptosis and apoptosis signaling pathways, oxidative phosphorylation, cholesterol, lipoprotein, and carbohydrate metabolism. We registered the synergistic effect of the glyphosate and AMPA co-exposure, which was expressed in a substantial increase in the number of dysregulated proteins compared to the solo treatments. Humic acid alleviated the effects of glyphosate and its mixture with AMPA and aggravated the impact of AMPA exposure. RuvB-like 2, a protein taking part in DNA repair, and EIF2S1, involved in the regulation of stress-induced gene expression, were downregulated in the liver of zebrafish from all treatments.
Assuntos
Glicina , Glifosato , Herbicidas , Substâncias Húmicas , Fígado , Proteoma , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Glicina/análogos & derivados , Glicina/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteoma/metabolismo , Proteoma/efeitos dos fármacos , Herbicidas/toxicidade , Organofosfonatos/toxicidade , Poluentes Químicos da Água/toxicidadeAssuntos
Cidofovir , Citosina , Organofosfonatos , Cidofovir/administração & dosagem , Cidofovir/uso terapêutico , Humanos , Citosina/análogos & derivados , Citosina/administração & dosagem , Citosina/uso terapêutico , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Injeções Intralesionais , Papiloma/tratamento farmacológico , Administração Tópica , Neoplasias dos Seios Paranasais/tratamento farmacológico , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêuticoRESUMO
This research describes the synthesis of a silane derivative containing phosphorus and nitrogen atoms, leveraging their synergistic flame retardant effect through the incorporation of a PH bond to the isocyanate moiety. The synthesized silane featured alkoxysilyl groups, facilitating permanent bonds with the cotton fabric surface via hydrolysis. Cotton fabrics were modified using silane solutions of varying concentrations (2.5 %, 5 %, and 10 %) through a dip-coating process to determine the effect of the modifier amount on fabric properties. The modified fabrics were subjected to FT-IR, TGA, SEM, and EDS analyses, as well as microcalorimetric and LOI tests, to assess changes in flammability. FT-IR, SEM/EDS, and add-on analyses confirmed effective coverage of the cotton fabric with the flame retardant. Thermogravimetric tests indicated a significant reduction in the mass loss rate during thermal degradation. LOI analyses demonstrated a decrease in flammability (increase in LOI value), while microcalorimetric tests showed a substantial decrease in the heat release rate, correlating with increased modifier concentration on the fabric surface. Post-washing analyses revealed that, although some of the modifier was washed out, the samples still retained reduced flammability.
Assuntos
Fibra de Algodão , Retardadores de Chama , Retardadores de Chama/síntese química , Silanos/química , Têxteis , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Organofosfonatos/químicaRESUMO
The potential connection between exposure to glyphosate and glyphosate-based herbicides (GBHs) and breast cancer risk is a topic of research that is rapidly gaining the public's attention due to the conflicting reports surrounding glyphosate's potential carcinogenicity. In this review, we synthesize the current published biomedical literature works that have explored associations of glyphosate, its metabolite, aminomethylphosphonic acid (AMPA), and GBHs with breast cancer risk in humans and human cell-based models. Using PubMed as our search engine, we identified a total of 14 articles that were included in this review. In the four human studies, urinary glyphosate and/or AMPA were associated with breast cancer risk, endocrine disruption, oxidative stress biomarkers, and changes in DNA methylation patterns. Among most of the 10 human cell-based studies, glyphosate exhibited endocrine disruption, induced altered gene expression, increased DNA damage, and altered cell viability, while GBHs were more cytotoxic than glyphosate alone. In summary, numerous studies have shown glyphosate, AMPA, and GBHs to have potential carcinogenic, cytotoxic, or endocrine-disruptive properties. However, more human studies need to be conducted in order for more definitive and supported conclusions to be made on their potential effects on breast cancer risk.
Assuntos
Neoplasias da Mama , Glicina , Glifosato , Herbicidas , Humanos , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/toxicidade , Neoplasias da Mama/induzido quimicamente , Feminino , Organofosfonatos/toxicidadeRESUMO
Malaria, caused by Plasmodium falciparum, remains a significant health burden. One major barrier for developing antimalarial drugs is the ability of the parasite to rapidly generate resistance. We previously demonstrated that salinipostin A (SalA), a natural product, potently kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism that results in a low propensity for resistance. Given the difficulty of employing natural products as therapeutic agents, we synthesized a small library of lipidic mixed alkyl/aryl phosphonates as bioisosteres of SalA. Two constitutional isomers exhibited divergent antiparasitic potencies that enabled the identification of therapeutically relevant targets. The active compound kills parasites through a mechanism that is distinct from both SalA and the pan-lipase inhibitor orlistat and shows synergistic killing with orlistat. Our compound induces only weak resistance, attributable to mutations in a single protein involved in multidrug resistance. These data suggest that mixed alkyl/aryl phosphonates are promising, synthetically tractable antimalarials.
Assuntos
Antimaláricos , Organofosfonatos , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/síntese química , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Organofosfonatos/química , Organofosfonatos/farmacologia , Organofosfonatos/síntese química , Humanos , Testes de Sensibilidade Parasitária , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Glyphosate is a globally dominant herbicide. Here, we studied the degradation and microbial response to glyphosate application in a wetland soil in central Delaware for controlling invasive species (Phragmites australis). We applied a two-step solid-phase extraction method using molecularly imprinted polymers designed for the separation and enrichment of glyphosate and aminomethylphosphonic acid (AMPA) from soils before their analysis by ultra-high-performance liquid chromatography (UHPLC) and Q Exactive Orbitrap mass spectrometry methods. Our results showed that approximately 90 % of glyphosate degraded over 100 d after application, with AMPA being a minor (<10 %) product. Analysis of glyphosate-specific microbial genes to identify microbial response and function revealed that the expression of the phnJ gene, which codes C-P lyase enzyme, was consistently dominant over the gox gene, which codes glyphosate oxidoreductase enzyme, after glyphosate application. Both gene and concentration data independently suggested that C-P bond cleavage-which forms sarcosine or glycine-was the dominant degradation pathway. This is significant because AMPA, a more toxic product, is reported to be the preferred pathway of glyphosate degradation in other soil and natural environments. The degradation through a safer pathway is encouraging for minimizing the detrimental impacts of glyphosate on the environment.
Assuntos
Glicina , Glifosato , Herbicidas , Microbiologia do Solo , Poluentes do Solo , Áreas Alagadas , Glicina/análogos & derivados , Glicina/metabolismo , Herbicidas/metabolismo , Herbicidas/química , Poluentes do Solo/metabolismo , Delaware , Biodegradação Ambiental , Isoxazóis/metabolismo , Liases/metabolismo , Liases/genética , Organofosfonatos/metabolismo , TetrazóisRESUMO
The most widely used herbicide glyphosate contaminates surface waters around the globe. Both agriculture and urban applications are discussed as sources for glyphosate. To better delineate these sources, we investigated long-term time series of concentrations of glyphosate and its main transformation product aminomethylphosphonic acid (AMPA) in a large meta-analysis of about 100 sites in the USA and Europe. The U.S. data reveal pulses of glyphosate and AMPA when the discharge of the river is high, likely indicating mobilization by rain after herbicide application. In contrast, European concentration patterns of glyphosate and AMPA show a typical cyclic-seasonal component in their concentration patterns, correlating with patterns of wastewater markers such as pharmaceuticals, which is consistent with the frequent detection of these compounds in wastewater treatment plants. Our large meta-analysis clearly shows that for more than a decade, municipal wastewater was a very important source of glyphosate. In addition, European river water data show rather high and constant base mass fluxes of glyphosate all over the year, not expected from herbicide application. From our meta-analysis, we define criteria for a source of glyphosate, which was hidden so far. AMPA is known to be a transformation product not only of glyphosate but also of aminopolyphosphonates used as antiscalants in many applications. As they are used in laundry detergents in Europe but not in the USA, we hypothesize that glyphosate may also be a transformation product of aminopolyphosphonates.
Assuntos
Monitoramento Ambiental , Glicina , Glifosato , Herbicidas , Rios , Poluentes Químicos da Água , Europa (Continente) , Glicina/análogos & derivados , Glicina/análise , Glifosato/análise , Herbicidas/análise , Organofosfonatos/análise , Rios/química , Estados Unidos , Águas Residuárias/química , Poluentes Químicos da Água/análiseRESUMO
Human adenovirus infection (HAdV) may be fatal in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cidofovir is effective in only a part of the post-HCT HAdV infection. Therefore, posttransplant immune reconstitution is important for HAdV clearance. We describe the detailed immune reconstitution and response of adenovirus-specific T cells in a patient with inborn errors of immunity who had disseminated HAdV infection with hepatitis post-HCT and was treated with cidofovir. Though the patient received cidofovir for only 19 days starting from Day 72 after HCT because of renal dysfunction, we observed T-cell reconstitution, a decrease in HAdV copy number, and amelioration of the symptoms of HAdV infection after Day 90. We initially observed expanded NK and CD8+CD45RO+ memory subsets and later gradual increase of naïve T cells eveloped after cessation of cidofovir treatment. An increase in adenovirus-specific IFN-γ secretion from 2 to 4 months after HCT was confirmed by ELISpot assay. The progression of immune reconstitution and cidofovir treatment are considered to have contributed to survival in this patient. Optimization of transplantation methods, prompt appropriate antiviral medication, and virus-specific T-cell therapy would be necessary as the better strategy for systemic HAdV infection.
Assuntos
Infecções por Adenovirus Humanos , Antivirais , Cidofovir , Citosina , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Organofosfonatos , Humanos , Cidofovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Organofosfonatos/uso terapêutico , Citosina/análogos & derivados , Citosina/uso terapêutico , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/imunologia , Infecções por Adenovirus Humanos/terapia , Antivirais/uso terapêutico , Transplante Homólogo , Adenovírus Humanos/imunologia , Masculino , Hepatite Viral Humana/tratamento farmacológico , Hepatite Viral Humana/imunologiaRESUMO
Many acyclic nucleoside phosphonates such as cidofovir, adefovir dipivoxil, tenofovir disoproxil fumarate, and tenofovir alafenamide have been marketed for the treatment or prophylaxis of infectious diseases. Here, this review highlights potent acyclic nucleoside phosphonates for their potential in the treatment of retrovirus (e.g., human immunodeficiency virus) and DNA virus (e.g., adeno-, papilloma-, herpes- and poxvirus) infections. If properly assessed and/or optimized, some potent acyclic nucleoside phosphonates can be possibly applied in the control of current and emerging infectious diseases.
Assuntos
Antivirais , Organofosfonatos , Humanos , Organofosfonatos/química , Organofosfonatos/farmacologia , Antivirais/farmacologia , Antivirais/química , Animais , Nucleosídeos/química , Nucleosídeos/farmacologia , Viroses/tratamento farmacológico , Adenina/análogos & derivados , Adenina/química , Adenina/farmacologia , Tenofovir/análogos & derivadosRESUMO
Fish reared under seminatural conditions can be challenged by exposure to herbicides. Farming facilities relying on the surrounding area's water quality can be affected by glyphosate and aminomethylphosphonic acid (AMPA) contamination. This review summarizes findings on how glyphosate and AMPA in the amounts registered in surface waterbodies affect redox status and biotransformation in fish and covers the aspect of diet supplementation for oxidative stress relief. Environmentally relevant concentrations of glyphosate and AMPA can alter the transcription and catalytic activities of antioxidant enzymes, decrease the content of reduced glutathione, and increase the accumulation of lipid peroxidation products, all of which are signs of a redox imbalance. Glyphosate has been shown to affect complex I in the mitochondrial respiratory chain and dysregulate iron transport-related genes, causing redox disturbance. Relatively high but environmentally realistic glyphosate concentrations can initiate the induction of cytochrome P450 biotransformation enzymes, alter the regulation of ABC exporters, and cause the inhibition of the redox-sensitive Nrf2 signaling pathway. Studies on reducing herbicide toxicity through dietary supplementation are a promising area of research. Natural functional supplements have been proven to have great potential for mitigating glyphosate-induced oxidative stress and thereby improving fish health, which in turn means maintaining productivity in fish farms that use natural water. However, data on the effects of AMPA on fish are scarce, and studies on the alleviation of its toxicity in fish are lacking. Considering the variety of AMPA contamination routes, one cannot underestimate the need for further research.
Assuntos
Biotransformação , Suplementos Nutricionais , Peixes , Glicina , Glifosato , Herbicidas , Oxirredução , Glicina/análogos & derivados , Glicina/farmacologia , Glicina/metabolismo , Animais , Oxirredução/efeitos dos fármacos , Herbicidas/farmacologia , Suplementos Nutricionais/análise , Peixes/metabolismo , Organofosfonatos/farmacologia , Dieta/veterinária , Estresse Oxidativo/efeitos dos fármacos , Ração Animal/análise , Poluentes Químicos da ÁguaRESUMO
Glyphosate is the most widely used systemic herbicide. There is ample scientific literature on the effects of this compound and its metabolite aminomethylphosphonic acid (AMPA), whereas their possible combined genotoxic action has not yet been studied. With the present study, we aimed to determine the level of genomic damage caused by glyphosate and AMPA in cultured human lymphocytes and to investigate the possible genotoxic action when both compounds were present at the same concentrations in the cultures. We used a micronuclei assay to test the genotoxicity of glyphosate and AMPA at six concentrations (0.0125, 0.025, 0.050, 0.100, 0.250, 0.500 µg/mL), which are more realistic than the highest concentrations used in previous published studies. Our data showed an increase in micronuclei frequency after treatment with both glyphosate and AMPA starting from 0.050 µg/mL up to 0.500 µg/mL. Similarly, a genomic damage was observed also in the cultures treated with the same concentrations of both compounds, except for exposure to 0.0065 and 0.0125 µg/mL. No synergistic action was observed. Finally, a significant increase in apoptotic cells was observed in cultures treated with the highest concentration of tested xenobiotics, while a significant increase in necrotic cells was observed also at the concentration of 0.250 µg/mL of both glyphosate and AMPA alone and in combination (0.125 + 0.125 µg/mL). Results of our study indicate that both glyphosate and its metabolite AMPA are able to cause genomic damage in human lymphocyte cultures, both alone and when present in equal concentrations.
Assuntos
Dano ao DNA , Glicina , Glifosato , Herbicidas , Linfócitos , Testes para Micronúcleos , Organofosfonatos , Glicina/análogos & derivados , Glicina/toxicidade , Humanos , Herbicidas/toxicidade , Linfócitos/efeitos dos fármacos , Organofosfonatos/toxicidade , Mutagênicos/toxicidade , Adulto , MasculinoRESUMO
INTRODUCTION: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. METHODS: We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. RESULTS: Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69-0.97) and 0.76 (95% CI 0.59-0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). DISCUSSION: The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. CONCLUSIONS: Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients.
Assuntos
Injúria Renal Aguda , Glicina , Glifosato , Herbicidas , Tensoativos , Humanos , Glicina/análogos & derivados , Glicina/intoxicação , Glicina/sangue , Masculino , Feminino , Herbicidas/intoxicação , Herbicidas/sangue , Pessoa de Meia-Idade , Tensoativos/intoxicação , Adulto , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/sangue , Idoso , Aminas/sangue , Aminas/intoxicação , Organofosfonatos/sangue , Espectrometria de Massas em Tandem , Isoxazóis , TetrazóisRESUMO
Phosphonates are widely used scale inhibitors, but the residual phosphonates in drainage are challenging to remove because of their chelating capacity and resistance to biodegradation. Here, we reported a highly efficient and robust Fe-electrocoagulation (Fe-EC) system for phosphonate removal. Surprisingly, we found for the first time that phosphonates like NTMP were more efficiently removed under anoxic conditions (80% of total soluble phosphorus (TSP) in 4 min) than oxic conditions (0% of TSP within 6 min) in NaCl solution. A similar phenomenon was observed when other phosphonates, such as EDTMP and DTPMP, were removed, highlighting the importance of iron complexation and floc formation toward phosphonate removal with Fe-EC. We also showed that the removal efficiency of NTMP by electrochemically in-situ formed flocs (97%) was much higher than post-adsorption systems (ex-situ, 40%), revealing that the growth of flocs consumed the active site for NTMP adsorption. Beyond the removal of TSP, 10 % of NTMP-P was also degraded after the electrolysis phase, evidenced by the evolution of phosphate-P. However, this did not happen in anoxic or chemical coagulation processes, which confirms the formation of reactive oxygen species via Fe(II) oxidation in the oxic Fe-EC system. The primary removal mechanism of phosphonates is due to their complexation with iron (hydr)oxide generated in the Fe-EC system by forming a Fe-O-P bond. Encouragingly, the Fe-EC system exhibits comparable or even better performance in treating phosphonate-laden wastewater (i.e., cooling water). Our preliminary cost calculation suggests the proposed system ( 0.009/m3) has a much lower OPEX under oxic conditions than existing approaches. This study sheds light on the removal mechanism of phosphonate and the treatment of phosphonate-laden wastewater by playing with the iron complexion and flocs formation in classical Fe-EC systems.
Assuntos
Ferro , Organofosfonatos , Ferro/química , Organofosfonatos/química , Adsorção , Poluentes Químicos da Água/química , Eletrocoagulação , Fósforo/química , Purificação da Água/métodosRESUMO
Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases, there are no currently approved antivirals for treating polyomavirus infection. Brincidofovir (BCV) is an antiviral approved for the treatment of poxvirus infections and has shown activity against other double-stranded DNA viruses. In this study, we tested the efficacy of BCV against polyomavirus infection in vitro and in vivo using mouse polyomavirus (MuPyV). BCV inhibited virus production in primary mouse kidney cells and brain cortical cells. BCV treatment of cells transfected with MuPyV genomic DNA resulted in a reduction in virus levels, indicating that viral inhibition occurs post-entry. Although in vitro BCV treatment had a limited effect on viral DNA and RNA levels, drug treatment was associated with a reduction in viral protein, raising the possibility that BCV acts post-transcriptionally to inhibit MuPyV infection. In mice, BCV treatment was well tolerated, and prophylactic treatment resulted in a reduction in viral DNA levels and a potent suppression of infectious virus production in the kidney and brain. In mice with chronic polyomavirus infection, therapeutic administration of BCV decreased viremia and reduced infection in the kidney. These data demonstrate that BCV exerts antiviral activity against polyomavirus infection in vivo, supporting further investigation into the use of BCV to treat clinical polyomavirus infections. IMPORTANCE: Widespread in the human population and able to persist asymptomatically for the life of an individual, polyomavirus infections cause a significant disease burden in the immunocompromised. Individuals undergoing immune suppression, such as kidney transplant patients or those treated for autoimmune diseases, are particularly at high risk for polyomavirus-associated diseases. Because no antiviral agent exists for treating polyomavirus infections, management of polyomavirus-associated diseases typically involves reducing or discontinuing immunomodulatory therapy. This can be perilous due to the risk of transplant rejection and the potential development of adverse immune reactions. Thus, there is a pressing need for the development of antivirals targeting polyomaviruses. Here, we investigate the effects of brincidofovir, an FDA-approved antiviral, on polyomavirus infection in vivo using mouse polyomavirus. We show that the drug is well-tolerated in mice, reduces infectious viral titers, and limits viral pathology, indicating the potential of brincidofovir as an anti-polyomavirus therapeutic.
Assuntos
Antivirais , Citosina , Organofosfonatos , Infecções por Polyomavirus , Polyomavirus , Animais , Citosina/análogos & derivados , Citosina/farmacologia , Citosina/uso terapêutico , Infecções por Polyomavirus/tratamento farmacológico , Infecções por Polyomavirus/virologia , Polyomavirus/efeitos dos fármacos , Camundongos , Antivirais/farmacologia , Antivirais/uso terapêutico , Organofosfonatos/farmacologia , Organofosfonatos/uso terapêutico , Replicação Viral/efeitos dos fármacos , Rim/virologia , Rim/efeitos dos fármacos , Feminino , DNA Viral/genética , Células Cultivadas , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Encéfalo/virologiaRESUMO
Glyphosate, a commonly used organophosphorus herbicide in rice-crayfish cropping regions, may alter regional phosphorus cycle processes while affecting the structure of microbial communities. However, the effects of glyphosate residues on rice-crayfish systems remain unclear. In this study, we assessed the spatial and temporal distribution characteristics of glyphosate and its primary degradation products, as well as the impact mechanisms of glyphosate on microbial communities and the phosphorus cycle in rice-crayfish systems such as paddy fields, breeding ditches and recharge rivers. The detection rates of glyphosate and aminomethylphosphonic acid (AMPA) were 100% in rice-crayfish systems. Concentrations of glyphosate in the water phase and soil/sediment were as high as 0.012 µg/L and 7.480 µg/kg, respectively, and concentrations of AMPA were as high as 17.435 µg/L and 13.200 µg/kg, respectively. Glyphosate concentrations were not affected by rainfall or sampling site, but concentrations of AMPA in the water phase of recharge rivers were affected by rainfall. The glyphosate concentration was significantly and positively correlated with RBG-16-58-14 abundance, and the AMPA concentration was significantly and positively correlated with Actinobacteria and Lysobacter abundance, and negatively correlated with Cyanobacteria abundance (P < 0.05). The highest abundances of phoD, phnK, and ppx genes were found in all soils/sediments. Glyphosate concentration in soil/sediment was significantly and positively correlated with the abundance of phoD gene encoding an organophosphorus-degrading enzyme and ppx gene encoding poly inorganic phosphate (Pi) hydrolase (P < 0.05). In addition, the glyphosate concentration was significantly and positively correlated with the Ca-bonded Pi content (P < 0.05). This implies that glyphosate may promote the production of stable Pi in rice-crayfish systems by increasing the abundance of phoD and ppx genes. The results of this study reveal the impact mechanism of glyphosate on the phosphorus cycle in rice-crayfish systems and provide a basis for the risk assessment of glyphosate.
Assuntos
Glicina , Glifosato , Herbicidas , Organofosfonatos , Fósforo , Glicina/análogos & derivados , Glicina/toxicidade , Glicina/análise , Animais , Fósforo/análise , Herbicidas/análise , Organofosfonatos/análise , Oryza/microbiologia , Microbiota/efeitos dos fármacos , Poluentes Químicos da Água/análise , Microbiologia do SoloRESUMO
A simple, cost-effective, one-pot method was proposed to introduce bis-phosphonic groups onto alginic acid and carboxymethyl cellulose (CMC). New derivatives were characterized by means of nuclear magnetic resonance, X-ray photoelectron, and attenuated total reflectance Fourier transform infrared spectroscopy. These analyses confirmed the successful transformation of carboxylic groups present in alginic acid and CMC into bis-phosphonic groups. Additionally, thermogravimetric analysis coupled with differential scanning calorimetry was employed to investigate the thermal properties of the bis-phosphonic derivatives of alginate and CMC. The results clearly demonstrate the char-forming ability of both studied bis-phosphonated polycarbohydrates, suggesting their potential as intumescent materials.
Assuntos
Alginatos , Alginatos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Varredura Diferencial de Calorimetria , Carboximetilcelulose Sódica/química , Espectroscopia de Ressonância Magnética , Termogravimetria , Espectroscopia Fotoeletrônica , Organofosfonatos/química , Organofosfonatos/síntese químicaRESUMO
Glyphosate is widely used in agriculture for weed control; however, it may pollute water systems with its by-product, aminomethylphosphonic acid (AMPA). Therefore, a better understanding of the flows of glyphosate and AMPA from soils into rivers is required. We developed the spatially explicit MARINA-Pesticides model to estimate the annual inputs of glyphosate and AMPA into rivers, considering 10 crops in 10,226 sub-basins globally for 2020. Our model results show that, globally, 880 tonnes of glyphosate and 4,090 tonnes of AMPA entered rivers. This implies that 82 % of the river inputs were from AMPA, with glyphosate accounting for the remainder. Over half of AMPA and glyphosate in rivers globally originated from corn and soybean production; however, there were differences among sub-basins. Asian sub-basins accounted for over half of glyphosate in rivers globally, with the contribution from corn production being dominant. South American sub-basins accounted for approximately two-thirds of AMPA in rivers globally, originating largely from soybean production. Our findings constitute a reference for implementing and supporting effective control strategies to achieve Sustainable Development Goals 2 and 6 (food production and clean water, respectively) simultaneously in the future.
Assuntos
Glycine max , Glicina , Glifosato , Rios , Poluentes Químicos da Água , Zea mays , Glicina/análogos & derivados , Glicina/análise , Rios/química , Poluentes Químicos da Água/análise , Herbicidas/análise , Organofosfonatos/análise , Monitoramento Ambiental , AgriculturaRESUMO
Purpose: The World Health Organization's International Agency on Research for Cancer has determined that glyphosate is "probably carcinogenic to humans." There is a great public interest to investigate whether glyphosate are detected in breast milk. Thus, the goal of this study was to assess the concentration of glyphosate and its main metabolite in breast milk. Materials and Methods: Liquid chromatography was performed at 25°C using a Luna NH2, 50 × 2 mm, 3â m (Phenomenex) analytical column. Electrospray ionization mass spectrometry was collected using negative ionization mode. The calibration curve for glyphosate ranged from 10 to 250 ng/mL. The detection limit was 1 ng/mL. Results: Breast milk samples were collected from 74 women, which included vegans (n = 26), vegetarians (n = 22), and nonvegetarians (n = 26). One of the 74 milk samples contained a detectable concentration of glyphosate and an additional 7 were found to contain aminomethylphosphonic acid. Conclusions: In breast milk samples collected mainly from women residing in urban regions of the United States, glyphosate detection was rare. Consistently, breastfed infants have a low or minimal risk of being exposed to glyphosate through ingestion of mother's milk. It is possible that the presence/absence and/or level of concentration of milk glyphosate depend on a place of residency and time of breastfeeding vis-à-vis time of its agricultural application.
Assuntos
Glicina , Glifosato , Leite Humano , Humanos , Feminino , Leite Humano/química , Glicina/análogos & derivados , Glicina/análise , Adulto , Cromatografia Líquida , Herbicidas/análise , Organofosfonatos/análise , Aleitamento Materno , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massa com Cromatografia Líquida , Isoxazóis , TetrazóisRESUMO
Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.
Assuntos
Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Peróxido de Hidrogênio , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Humanos , Peróxido de Hidrogênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Ácidos Borônicos/síntese química , Adenina , OrganofosfonatosRESUMO
Integrating lipid conjugation strategies into the design of nucleoside monophosphate and monophosphonate prodrugs is a well-established approach for discovering potential therapeutics. The unique prodrug design endows nucleoside analogues with strong lipophilicity and structures resembling lysoglycerophospholipids, which improve cellular uptake, oral bioavailability and pharmacological activity. In addition, the metabolic stability, pharmacological activity, pharmacokinetic profiles and biodistribution of lipid prodrugs can be finely optimized by adding biostable caps, incorporating transporter-targeted groups, inserting stimulus-responsive bonds, adjusting chain lengths, and applying proper isosteric replacements. This review summarizes recent advances in the structural features and application fields of lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs. This collection provides deep insights into the increasing repertoire of lipid prodrug development strategies and offers design inspirations for medicinal chemists for the development of novel chemotherapeutic agents.