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1.
Cells ; 13(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38994998

RESUMO

Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.


Assuntos
Proliferação de Células , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Transportador de Glucose Tipo 3 , Ferro , Fígado , Proliferação de Células/efeitos dos fármacos , Animais , Humanos , Transportador de Glucose Tipo 3/metabolismo , Transportador de Glucose Tipo 3/genética , Células Hep G2 , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ferro/metabolismo , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Compostos de Amônio Quaternário/farmacologia , Compostos Férricos/farmacologia , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética
2.
Anal Chem ; 96(28): 11172-11180, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38946102

RESUMO

Improving separation efficiency in capillary electrophoresis (CE) requires systematic study of the influence of the electric field (or solute linear velocity) on plate height for a better understanding of the critical parameters controlling peak broadening. Even for poly(diallyldimethylammonium chloride) (PDADMAC)/poly(sodium styrenesulfonate) (PSS) successive multiple ionic-polymer layer (SMIL) coatings, which lead to efficient and reproducible separations of proteins, plate height increases with migration velocity, limiting the use of high electric fields in CE. Solute adsorption onto the capillary wall was generally considered as the main source of peak dispersion, explaining this plate height increase. However, experiments done with Taylor dispersion analysis and CE in the same conditions indicate that other phenomena may come into play. Protein adsorption with slow kinetics and few adsorption sites was established as a source of peak broadening for specific proteins. Surface charge inhomogeneity was also identified as a contribution to plate height due to local electroosmotic fluctuations. A model was proposed and applied to partial PDADMAC/poly(ethylene oxide) capillary coatings as well as PDADMAC/PSS SMIL coatings. Atomic force microscopy with topography and recognition imaging enabled the determination of roughness and charge distribution of the PDADMAC/PSS SMIL surface.


Assuntos
Eletro-Osmose , Eletroforese Capilar , Polietilenos , Eletroforese Capilar/métodos , Adsorção , Polietilenos/química , Proteínas/isolamento & purificação , Proteínas/química , Proteínas/análise , Compostos de Amônio Quaternário/química , Animais , Propriedades de Superfície
3.
Soft Matter ; 20(28): 5553-5563, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38957095

RESUMO

The addition of a surfactant and/or an increase in temperature disrupt the native structure of proteins, where high temperature further results in protein gelation. However, in a mixed protein-surfactant system, surfactant concentration and temperature have been observed to exhibit both mutually associative and counter-balancing effects towards heat-induced gelation of protein-surfactant dispersion. This study is conducted on globular bovine serum albumin (BSA) protein and cationic surfactant dodecyl trimethyl ammonium bromide (DTAB), which interact strongly owing to their oppositely charged nature. The findings reveal that the BSA-DTAB suspension undergoes gelation with increasing temperature but only at lower concentrations of DTAB, where the presence of the surfactant facilitates gelation (associative effect). Conversely, as the surfactant concentration increases beyond a critical value, temperature-driven gelation of the BSA-DTAB system is completely inhibited, despite surfactant-induced protein denaturation (counter-balancing effect). To conceptualize these results, we compared them with observations made in a system comprising protein and a similarly charged surfactant, sodium dodecyl sulfate (SDS). It has been further demonstrated that the anionic surfactant (SDS) can restrict protein gelation at much lower concentration compared to the cationic surfactant (DTAB). The evolution of the structure and interaction during gel formation/inhibition has been examined to understand the underlying mechanism guiding these sol-gel transitions. We present a comprehensive phase diagram, encompassing the solution/gel states of the protein-surfactant dispersion, with respect to the dispersion temperature, surfactant concentration, and ionic behavior (anionic or cationic) of the surfactants.


Assuntos
Géis , Temperatura Alta , Compostos de Amônio Quaternário , Soroalbumina Bovina , Tensoativos , Tensoativos/química , Soroalbumina Bovina/química , Géis/química , Bovinos , Compostos de Amônio Quaternário/química , Animais , Dodecilsulfato de Sódio/química
4.
Water Sci Technol ; 90(1): 287-302, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007320

RESUMO

Extracellular polymeric substances (EPS) are a critical influencing factor in sludge dewatering. Disrupting such EPS contributes to the release of bound water in sludge, enhancing the sludge dewatering performance. In This study, quaternized straw fibers that are destructive to the EPS structure and components in active sludge were prepared useing heterogeneous free radical graft polymerization. Straw fibers, dimethyl diallyl ammonium chloride (DMDAAC), ammonium persulfate (APS), and acrylamide (AM) were taken as the substrate, grafting monomer, catalyst, and cross-linking agent, respectively.The optimal processing conditions determined for the DMDAAC-based quaternization and graft modification of straw fibers were as follows: reaction temperature of 60 °C, reaction time of 5 h, 0.100 g of catalyst APS dosage per gram of straw, and 3.000 ml of DMDAAC dosage per gram of straw. The optimal processing conditions yielded 1.335 g of modified straw fibers per gram of straw, 33.67% grafting rate, and 31.70% substitution of the quaternary ammonium groups. The capillary suction time (CST) was conditioned from 243.3 ± 22.6 s in the original sludge to 134.5 ± 34.45 s. The specific resistance to filtration (SRF) was reduced from 8.82 ± 0.51 × 1012 m/kg in the original sludge to 4.59 ± 0.23 × 1012 m/kg.


Assuntos
Esgotos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Compostos de Amônio Quaternário/química , Compostos Alílicos/química
5.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000264

RESUMO

Selecting the appropriate disinfectant to control and prevent healthcare-associated infections (HAIs) is a challenging task for environmental health experts due to the large number of available disinfectant products. This study aimed to develop a label-free flow cytometry (FCM) method for the rapid evaluation of bactericidal activity and to compare its efficacy with that of standard qualitative/quantitative suspension tests. The bactericidal efficiency of eight commercial disinfectants containing quaternary ammonium compounds (QACs) was evaluated against four strains recommended by EN 13727 (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae) and four multidrug-resistant pathogens. The proposed FCM protocol measures changes in scattered light and counts following disinfectant exposure, neutralization, and culture steps. Unlike other available FCM-based methods, this approach does not rely on autofluorescence measurements, impedance cytometry, or fluorescent dyes. The FCM scattered light signals revealed both decreased count rates and morphological changes after treatment with minimum inhibitory concentrations (MICs) and higher concentrations for all tested bacteria. The results from the FCM measurements showed excellent correlation with those from standard assays, providing a rapid tool for monitoring the susceptibility profile of clinical, multidrug-resistant pathogens to chemical disinfectants, which could support infection prevention and control procedures for healthcare environments. This label-free FCM protocol offers a novel and rapid tool for environmental health experts, aiding in the optimization of disinfectant selection for the prevention and control of HAIs.


Assuntos
Desinfetantes , Citometria de Fluxo , Testes de Sensibilidade Microbiana , Desinfetantes/farmacologia , Citometria de Fluxo/métodos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos
6.
Int J Biol Macromol ; 272(Pt 2): 132933, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38862322

RESUMO

Quaternary-ammonium chitosan (CT-CTA) is a popular water treatment agent, and its electropositivity and cation strength are improved compared with chitosan. The use of CT-CTA is widely advocated to remove suspended particles and organic matter from wastewater. However, the solubility of CT-CTA is an important factor affecting the performance of CT-CTA, which is a neglected problem in previous studies. In the study, CT-CTA with different solubilities were prepared by adjusting pH from 2 to 7 in preparation, and their applications were explored in wastewater. When the pH was 2, 2.5, or 3, the obtained CT-CTA was a dissolved state. The turbidity and color removal were 95 % - 98 % and 60 % - 74 %, respectively. When the pH was 4, 5, 6, or 7, the obtained CT-CTA was a solid state. The turbidity and color removal were 30 % - 63 % and 90 % - 97 %, respectively. For domestic-wastewater treatment, CT-CTA in a dissolved state removed 92 % of turbidity and 50 % of chemical oxygen demand (COD). CT-CTA in a solid state removed 86 % of turbidity and 64 % of COD with poly aluminum chloride (PAC). The results illustrated the performance of CT-CTA with different solubilities, which can broaden its application in wastewater treatment.


Assuntos
Quitosana , Solubilidade , Águas Residuárias , Purificação da Água , Quitosana/química , Águas Residuárias/química , Purificação da Água/métodos , Concentração de Íons de Hidrogênio , Compostos de Amônio Quaternário/química , Análise da Demanda Biológica de Oxigênio , Poluentes Químicos da Água/química
7.
Environ Int ; 189: 108812, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878503

RESUMO

The linkage between biocides and antibiotic resistance has been widely suggested in laboratories and various environments. However, the action mechanism of biocides on antibiotic resistance genes (ARGs) spread is still unclear. Thus, 6 quaternary ammonium biocides (QACs) with different bonded substituents or alkyl chain lengths were selected to assess their effects on the conjugation transfer of ARGs in this study. Two conjugation models with the same donor (E. coli DH5α (RP4)) into two receptors, E. coli MG1655 and pathogenic S. sonnei SE6-1, were constructed. All QACs were found to significantly promote intra- and inter-genus conjugative transfer of ARGs, and the frequency was highly impacted by their structure and receptors. At the same environmental exposure level (4 × 10-1 mg/L), didecyl dimethyl ammonium chloride (DDAC (C10)) promoted the most frequency of conjugative transfer, while benzathine chloride (BEC) promoted the least. With the same donor, the enhanced frequency of QACs of intra-transfer is higher than inter-transfer. Then, the acquisition mechanisms of two receptors were further determined using biochemical combined with transcriptome analysis. For the recipient E. coli, the promotion of the intragenus conjugative transfer may be associated with increased cell membrane permeability, reactive oxygen species (ROS) production and proton motive force (PMF)-induced enhancement of flagellar motility. Whereas, the increase of cell membrane permeability and decreased flagellar motility due to PMF disruption but encouraged biofilm formation, maybe the main reasons for promoting intergenus conjugative transfer in the recipient S. sonnei. As one pathogenic bacterium, S. sonnei was first found to acquire ARGs by biocide exposure.


Assuntos
Conjugação Genética , Desinfetantes , Escherichia coli , Compostos de Amônio Quaternário , Desinfetantes/farmacologia , Compostos de Amônio Quaternário/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Transferência Genética Horizontal
8.
BMC Oral Health ; 24(1): 699, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880907

RESUMO

BACKGROUND: The black staining effect of silver-containing solutions for use to arrest caries can have a negative aesthetic impact on children and parents. This study aims to assess the staining effects of Silver Diamine Fluoride/Potassium Iodide (SDF/KI), SDF and Nanosilver Fluoride (NSF). MATERIALS AND METHODS: Forty-four extracted carious primary molars were collected and randomly divided into four groups (n = 11). The carious tissue in all teeth was removed using a chemo-mechanical caries removal agent with an excavator. After caries removal in all groups, SDF, SDF/KI, and NSF were applied to the different groups, while no solution was applied to the control group. Subsequently, the teeth in all groups were restored with compomer. Color values L*, a* and b* were measured using a spectrophotometer at three time points: immediately after compomer restoration (T0), one week later (T1), and four week later (T2). Changes in brightness (ΔL) and color (ΔE) over time were calculated and comparisons among groups were made. RESULTS: The SDF solution induced statistically significant black staining (p = 0.013) and a decrease in L* value (p < 0.001) on the compomer material compared to the other groups over time. CONCLUSIONS: It was observed that SDF/KI has the potential to reduce the black staining effect of SDF, though not entirely. Novel experimental solutions like NSF may offer an alternative to counteract the staining effect of SDF.


Assuntos
Fluoretos Tópicos , Iodeto de Potássio , Compostos de Amônio Quaternário , Compostos de Prata , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Iodeto de Potássio/uso terapêutico , Humanos , Fluoretos Tópicos/uso terapêutico , Técnicas In Vitro , Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Descoloração de Dente/induzido quimicamente , Dente Decíduo , Espectrofotometria , Dente Molar
9.
BMC Oral Health ; 24(1): 686, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872123

RESUMO

BACKGROUND: Using Silver Diamine Fluoride (SDF) may be an effective public health approach for managing dental caries in children. Parental acceptance of SDF has rarely been investigated in low-income and middle-income countries (LMICs). The aim of this study was to evaluate parental acceptance of SDF to manage dental caries in children aged 2-12 in Iran and Tajikistan. METHODS: This cross-sectional study was conducted in the Kurdistan province of Iran and Khatlon region of Tajikistan, 2022-2023. Parents watched a video about SDF and its weaknesses and strengths as compared to conventional approaches before completing the questionnaire. We also reported Prevalence Ratios with 95% confidence intervals for the relationship between parental acceptance and associated demographic factors as well as dental attitude and experience. RESULTS: Participants were 245 and 160 parents in Iran and Tajikistan, respectively. In both countries, a majority (Iran: 61.6%, Tajikistan: 77.9%) accepted SDF over conventional treatments for all primary teeth. The majority also accepted SDF only for posterior permanent teeth (Iran: 73.5%, Tajikistan: 78.7%). Black discoloration was the main reason for rejecting SDF. Overall, demographic factors and dental experience and attitude were not significantly associated with SDF acceptance. CONCLUSIONS: SDF was widely accepted by Iranian and Tajik parents. Establishing parental acceptance of SDF is an important step toward its application in LMICs where inexpensive solutions are needed.


Assuntos
Cariostáticos , Fluoretos Tópicos , Pais , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Estudos Transversais , Fluoretos Tópicos/uso terapêutico , Criança , Pais/psicologia , Feminino , Masculino , Irã (Geográfico) , Tadjiquistão , Pré-Escolar , Compostos de Amônio Quaternário/uso terapêutico , Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Adulto , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
10.
BMC Oral Health ; 24(1): 737, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937760

RESUMO

BACKGROUND: The desirable properties of silver diamine fluoride (SDF) make it an effective agent for managing dental caries and tooth hypersensitivity. There are several clinical instances that SDF application might precede the placement of direct tooth-colored restorations. On the other hand, SDF stains demineralized/carious dental tissues black, which might affect the esthetic outcomes of such restorations. Color is a key parameter of esthetics in dentistry. Therefore, this study aims to systematically review dental literature on color/color change of tooth-colored restorations placed following the application of SDF on dentine. METHODS: Comprehensive search of PubMed, Embase, Scopus and ISI Web of Science databases (until August 2023) as well as reference lists of retrieved studies was performed. In vitro studies reported color or color change of tooth-colored restorative materials applied on SDF-treated dentine were included. Methodological quality assessment was performed using RoBDEMAT tool. Pooled weighted mean difference (WMD) and 95% confidence interval (95% CI) was calculated. RESULTS: Eleven studies/reports with a total of 394 tooth-colored restorations placed following a) no SDF (control) or b) SDF with/without potassium iodide (KI)/glutathione dentine pre-treatments were included. Color change was quantified using ∆E formulas in most reports. The pooled findings for the comparison of resin-based composite (RBC) restorations with and without prior 38% SDF + KI application revealed no statistically significant differences in ∆E values at short- and long-term evaluations (~ 14 days: WMD: -0.56, 95% CI: -2.09 to 0.96; I2: 89.6%, and ~ 60 days: WMD: 0.11; 95% CI: -1.51 to 1.72; I2: 76.9%). No studies provided sufficient information for all the items in the risk of bias tool (moderate to low quality). CONCLUSIONS: The limited evidence suggested comparable color changes of RBC restorations with and without 38% SDF + KI pre-treatment up to 60 days. The included studies lacked uniformity in methodology and reported outcomes. Further studies are imperative to draw more definite conclusions. PROTOCOL REGISTRATION: The protocol of this systematic review was registered in PROSPERO database under number CRD42023485083.


Assuntos
Cor , Restauração Dentária Permanente , Dentina , Fluoretos Tópicos , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Dentina/efeitos dos fármacos , Restauração Dentária Permanente/métodos
11.
Ecotoxicol Environ Saf ; 280: 116581, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875820

RESUMO

Screening and prioritizing research on frequently detected mixture systems in the environment is of great significance, as conducting toxicity testing on all mixtures is impractical. Therefore, the frequent itemset mining (FIM) was introduced and applied in this paper to identify variables that commonly co-occur in a dataset. Based on the dataset of the quaternary ammonium compounds (QACs) in the water environment, the four frequent QAC mixture systems with detection rate ≥ 35 % were found, including [BDMM]+Cl--[BTMM]+Cl- (M1), [BDMM]+Cl--[BHMM]+Cl- (M2), [BTMM]+Cl- -[BHMM]+Cl- (M3), and [BDMM]+Cl--[BTMM]+Cl--[BHMM]+Cl- (M4). [BDMM]+Cl-, [BTMM]+Cl-, and [BHMM]+Cl- are benzyl dodecyl dimethyl ammonium chloride, benzyl tetradecyl dimethyl ammonium chloride, and benzyl hexadecyl dimethyl ammonium chloride, respectively. Then, the toxicity of the representative mixture rays and components for the four frequently detected mixture systems was tested using Vibrio qinghaiensis sp.-Q67 (Q67) as a luminescent indicator organism at 0.25 and 12 h. The toxicity of the mixtures was predicted using concentration addition (CA) and independent action (IA) models. It was shown that both the components and the representative mixture rays for the four frequently detected mixture systems exhibited obvious acute and chronic toxicity to Q67, and their median effective concentrations (EC50) were below 7 mg/L. Both CA and IA models predicted the toxicity of the four mixture systems well. However, the CA model had a better predictive ability for the toxicity of the M3 and M4 mixtures than IA at 12 h.


Assuntos
Compostos de Amônio Quaternário , Poluentes Químicos da Água , Compostos de Amônio Quaternário/toxicidade , Poluentes Químicos da Água/toxicidade , Monitoramento Ambiental/métodos , Testes de Toxicidade/métodos , Mineração de Dados
12.
BMC Oral Health ; 24(1): 701, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890627

RESUMO

BACKGROUND: One of the most prevalent health problems affecting children worldwide is untreated caries in primary teeth. Agents to arrest caries are used to manage untreated decay in children in disadvantaged communities. Nano Silver Fluoride (NSF) overcomes the staining problems of Silver Diamine Fluoride (SDF). This study compared the clinical cariostatic effect of NSF to 38% SDF for arresting caries lesions. METHODS: The study included 360 children younger than 4 years, with at least one active lesion, ICDAS score ≥ 3, recruited from nurseries in a rural area in Alexandria, Egypt, in 2022. They were randomly assigned to receive a single application of NSF at baseline, or two applications of SDF at baseline and after 6 months. The arrest of active carious lesions was assessed after 6 and 12 months using ICDAS criteria, and parents' satisfaction with child appearance was also assessed. Chi-Square test was used to compare the groups and multi-level multiple logistic regression was used to assess the effect of the intervention on caries arrest at lesion level and binary logistic regression was used to assess the effect at patient level. RESULTS: 1853 active lesions were included in children whose mean (SD) age was 42.3 (8.2) months. The arrest rate was significantly higher in the NSF than the SDF group at lesion level (78.4% and 65.0% at 6 months and 71.3% and 56.3% at 12 months, p < 0.001). In regression analysis, NSF had significantly higher odds of caries arrest than SDF at lesion level (at 6 months, AOR = 2.57, 95% CI: 1.55, 4.26 and at 12 month, AOR = 3.27, 95% CI: 1.89, 5.67). Parents of children receiving NSF had significantly greater satisfaction with their children's dental appearance than those receiving SDF: (97.2% and 76.1%, respectively, p < 0.001). CONCLUSION: NSF demonstrated greater effectiveness in arresting caries in preschool children without inducing black staining of teeth and with greater parental satisfaction than SDF. NSF can be an alternative to SDF in arresting caries especially in underprivileged communities. TRIAL REGISTRATION: The trial was registered in the clinicaltrials.gov registry (#NCT05255913)-16/02/2022.


Assuntos
Cariostáticos , Cárie Dentária , Fluoretos Tópicos , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Cárie Dentária/prevenção & controle , Compostos de Prata/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Pré-Escolar , Feminino , Masculino , Cariostáticos/uso terapêutico , Fluoretos/uso terapêutico , Lactente , Resultado do Tratamento
13.
Sci Rep ; 14(1): 14110, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898117

RESUMO

Newly synthesized gemini quaternary ammonium salts (QAS) with different counterions (bromide, hydrogen chloride, methylcarbonate, acetate, lactate), chain lengths (C12, C14, C16) and methylene linker (3xCH2) were tested. Dihydrochlorides and dibromides with 12 carbon atoms in hydrophobic chains were characterized by the highest biological activity against planktonic forms of yeast and yeast-like fungi. The tested gemini surfactants also inhibited the production of filaments by C. albicans. Moreover, they reduced the adhesion of C. albicans cells to the surfaces of stainless steel, silicone and glass, and slightly to polystyrene. In particular, the gemini compounds with 16-carbon alkyl chains were most effective against biofilms. It was also found that the tested surfactants were not cytotoxic to yeast cells. Moreover, dimethylcarbonate (2xC12MeCO3G3) did not cause hemolysis of sheep erythrocytes. Dihydrochlorides, dilactate and diacetate showed no mutagenic potential.


Assuntos
Antifúngicos , Biofilmes , Candida albicans , Compostos de Amônio Quaternário , Biofilmes/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Animais , Ovinos , Tensoativos/farmacologia , Tensoativos/síntese química , Tensoativos/química , Hemólise/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Adesão Celular/efeitos dos fármacos , Aço Inoxidável/química
14.
Biomolecules ; 14(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38927133

RESUMO

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.


Assuntos
Ferroptose , Ferro , Peroxidação de Lipídeos , Lipofuscina , Miócitos Cardíacos , Espécies Reativas de Oxigênio , Peroxidação de Lipídeos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Lipofuscina/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Animais , Ratos , Espécies Reativas de Oxigênio/metabolismo , Ferro/metabolismo , Linhagem Celular , Compostos de Amônio Quaternário/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Azul de Metileno/farmacologia , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Compostos Férricos , Plastoquinona/análogos & derivados
15.
Environ Sci Technol ; 58(26): 11707-11717, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38871667

RESUMO

Antimicrobial resistance (AMR) undermines the United Nations Sustainable Development Goals of good health and well-being. Antibiotics are known to exacerbate AMR, but nonantibiotic antimicrobials, such as quaternary ammonium compounds (QACs), are now emerging as another significant driver of AMR. However, assessing the AMR risks of QACs in complex environmental matrices remains challenging due to the ambiguity in their chemical structures and antibacterial activity. By machine learning prediction and high-resolution mass spectrometric analysis, a list of antibacterial QACs (n = 856) from industrial chemical inventories is compiled, and it leads to the identification of 50 structurally diverse antibacterial QACs in sediments, including traditional hydrocarbon-based compounds and new subclasses that bear additional functional groups, such as choline, ester, betaine, aryl ether, and pyridine. Urban wastewater, aquaculture, and hospital discharges are the main factors influencing QAC distribution patterns in estuarine sediments. Toxic unit calculations and metagenomic analysis revealed that these QACs can influence antibiotic resistance genes (particularly sulfonamide resistance genes) through cross- and coresistances. The potential to influence the AMR is related to their environmental persistence. These results suggest that controlling the source, preventing the co-use of QACs and sulfonamides, and prioritizing control of highly persistent molecules will lead to global stewardship and sustainable use of QACs.


Assuntos
Antibacterianos , Estuários , Aprendizado de Máquina , Compostos de Amônio Quaternário , Antibacterianos/farmacologia , Compostos de Amônio Quaternário/química , Espectrometria de Massas , China , População do Leste Asiático
16.
Proc Natl Acad Sci U S A ; 121(25): e2403273121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38865266

RESUMO

In secondary active transporters, a relatively limited set of protein folds have evolved diverse solute transport functions. Because of the conformational changes inherent to transport, altering substrate specificity typically involves remodeling the entire structural landscape, limiting our understanding of how novel substrate specificities evolve. In the current work, we examine a structurally minimalist family of model transport proteins, the small multidrug resistance (SMR) transporters, to understand the molecular basis for the emergence of a novel substrate specificity. We engineer a selective SMR protein to promiscuously export quaternary ammonium antiseptics, similar to the activity of a clade of multidrug exporters in this family. Using combinatorial mutagenesis and deep sequencing, we identify the necessary and sufficient molecular determinants of this engineered activity. Using X-ray crystallography, solid-supported membrane electrophysiology, binding assays, and a proteoliposome-based quaternary ammonium antiseptic transport assay that we developed, we dissect the mechanistic contributions of these residues to substrate polyspecificity. We find that substrate preference changes not through modification of the residues that directly interact with the substrate but through mutations peripheral to the binding pocket. Our work provides molecular insight into substrate promiscuity among the SMRs and can be applied to understand multidrug export and the evolution of novel transport functions more generally.


Assuntos
Compostos de Amônio Quaternário , Especificidade por Substrato , Compostos de Amônio Quaternário/metabolismo , Compostos de Amônio Quaternário/química , Cristalografia por Raios X , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Transporte Biológico , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Farmacorresistência Bacteriana Múltipla/genética , Anti-Infecciosos Locais/metabolismo , Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/química , Modelos Moleculares
17.
J Hazard Mater ; 475: 134924, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38880045

RESUMO

Nanofiltration (NF) is a promising technology in the treatment of microelectronic wastewater. However, the treatment of concentrate derived from NF system remains a substantial technical challenge, impeding the achievement of the zero liquid discharge (ZLD) goal in microelectronic wastewater industries. Herein, a ZLD system, coupling a two-stage NF technology with anaerobic biotechnology was proposed for the treatment of tetramethylammonium hydroxide (TMAH)-contained microelectronic wastewater. The two-stage NF system exhibited favorable efficacy in the removal of conductivity (96 %), total organic carbon (TOC, 90 %), and TMAH (96 %) from microelectronic wastewater. The membrane fouling of this system was dominated by organic fouling, with the second stage NF membrane experiencing a more serious fouling compared to the first stage membrane. The anaerobic biotechnology achieved a near-complete removal of TMAH and an 80 % reduction in TOC for the first stage NF concentrate. Methyloversatilis was the key genus involved in the anaerobic treatment of the microelectronic wastewater concentrate. Specific genes, including dmd-tmd, mtbA, mttB and mttC were identified as significant players in mediating the dehydrogenase and methyl transfer pathways during the process of TMAH biodegradation. This study highlights the potential of anaerobic biodegradation to achieve ZLD in the treatment of TMAH-contained microelectronic wastewater by NF system.


Assuntos
Biodegradação Ambiental , Filtração , Compostos de Amônio Quaternário , Águas Residuárias , Águas Residuárias/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , Anaerobiose , Eliminação de Resíduos Líquidos/métodos , Membranas Artificiais , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo , Reatores Biológicos , Resíduo Eletrônico , Nanotecnologia
18.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891947

RESUMO

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a "state-of-the-art" snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity, or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including the functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.


Assuntos
Betaína , Cátions , Colina , Betaína/química , Betaína/análogos & derivados , Colina/química , Colina/análogos & derivados , Cátions/química , Ésteres/química , Compostos de Amônio Quaternário/química , Humanos
19.
ACS Appl Mater Interfaces ; 16(23): 29867-29875, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38825754

RESUMO

Antimicrobial surfaces limit the spread of infectious diseases. To date, there is no antimicrobial coating that has widespread use because of short-lived and limited spectrum efficacy, poor resistance to organic material, and/or cost. Here, we present a paint based on waterborne latex particles that is supramolecularly associated with quaternary ammonium compounds (QACs). The optimal supramolecular pairing was first determined by immobilizing selected ions on self-assembled monolayers exposing different groups. The QAC surface loading density was then increased by using polymer brushes. These concepts were adopted to develop inexpensive paints to be applied on many different surfaces. The paint could be employed for healthcare and food production applications. Its slow release of QAC allows for long-lasting antimicrobial action, even in the presence of organic material. Its efficacy lasts for more than 90 washes, and importantly, once lost, it can readily be restored by spraying an aqueous solution of the QAC. We mainly tested cetyltrimethylammonium as QAC as it is already used in consumer care products. Our antimicrobial paint is broad spectrum as it showed excellent antimicrobial efficiency against four bacteria and four viruses.


Assuntos
Compostos de Amônio Quaternário , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Pintura , Propriedades de Superfície , Látex/química , Látex/farmacologia , Testes de Sensibilidade Microbiana , Bactérias/efeitos dos fármacos
20.
J Oleo Sci ; 73(7): 953-961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38945924

RESUMO

Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after handwashing with fatty acid salt-based hand soap. To this end, we developed a new in vitro test method to measure persistence, utilizing coacervation formed by anionic surfactants and cationic polymers to retain highly effective soap components against each bacterium and virus on the skin. Coacervation with fatty acid salts and poly diallyldimethylammonium chloride (PDADMAC) as a cationic polymer allowed the persistence of antibacterial and antiviral effects against E. coli, S. aureus, and influenza virus even 4 h after handwashing. Furthermore, we confirmed an increase in the number of residual components effective against each bacterium and virus on the skin. In summary, the current findings describe an effective approach for enhancing the protective effects of handwashing.


Assuntos
Antibacterianos , Antivirais , Escherichia coli , Desinfecção das Mãos , Polietilenos , Compostos de Amônio Quaternário , Pele , Sabões , Staphylococcus aureus , Tensoativos , Sabões/farmacologia , Escherichia coli/efeitos dos fármacos , Desinfecção das Mãos/métodos , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antivirais/farmacologia , Pele/efeitos dos fármacos , Pele/microbiologia , Tensoativos/farmacologia , Humanos , Ácidos Graxos/farmacologia , Ácidos Graxos/análise , Fatores de Tempo , Orthomyxoviridae/efeitos dos fármacos
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