Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.259
Filtrar
1.
J Environ Sci (China) ; 147: 310-321, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003049

RESUMO

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.


Assuntos
Betaína , Salinidade , Esgotos , Eliminação de Resíduos Líquidos , Águas Residuárias , Betaína/metabolismo , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Anaerobiose , Microbiota/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/efeitos dos fármacos
2.
Medicine (Baltimore) ; 103(22): e37825, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-39259062

RESUMO

BACKGROUND: Gut microbial metabolites such as trimethylamine N-oxide (TMAO) and its precursors, namely betaine, L-carnitine, and choline, have been implicated as risk factors for cardiovascular events and mortality development. Therefore, we aim to perform a systematic review and meta-analysis to assess the validity of these associations. METHODS: MEDLINE and Scopus were queried from their inception to August 2023 to identify studies that quantified estimates of the associations of TMAO with the development of major adverse cardiovascular events (MACE) or death. A random-effects meta-analysis was conducted to pool unadjusted or multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals. The primary endpoint was the risk of MACE and all-cause death. RESULTS: 30 prospective observational studies (n = 48 968) were included in the analysis. Elevated TMAO levels were associated with a significantly greater risk of MACE and all-cause death compared to low TMAO levels (HR: 1.41, 95% CI 1.2-1.54, P < .00001, I2 = 43%) and (HR: 1.55, 95% CI 1.37-1.75, P < .00001, I2 = 46%), respectively. Furthermore, high levels of either L-carnitine or choline were found to significantly increase the risk of MACE. However, no significant difference was seen in MACE in either high or low levels of betaine. CONCLUSION: Elevated concentrations of TMAO were associated with increased risks of MACE and all-cause mortality. High levels of L-carnitine/choline were also significantly associated with an increased risk of MACE. However, no significant difference was found between high or low levels of betaine for the outcome of MACE.


Assuntos
Doenças Cardiovasculares , Carnitina , Colina , Microbioma Gastrointestinal , Metilaminas , Humanos , Microbioma Gastrointestinal/fisiologia , Metilaminas/metabolismo , Doenças Cardiovasculares/mortalidade , Colina/metabolismo , Betaína/metabolismo , Fatores de Risco
3.
Physiol Plant ; 176(5): e14514, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39256195

RESUMO

Salinity stress represents a major threat to crop production by inhibiting seed germination, growth of seedlings, and final yield and, therefore, to the social and economic prosperity of developing countries. Recently, plant growth-promoting substances have been widely used as a chemical strategy for improving plant resilience towards abiotic stresses. This study aimed to determine whether melatonin (MT) and glycine betaine (GB) alone or in combination could alleviate the salinity-induced impacts on seed germination and growth of maize seedlings. Increasing NaCl concentration from 100 to 200 mM declined seed germination rate (4.6-37.7%), germination potential (24.5-46.7%), radical length (7.7-40.0%), plumule length (2.2-35.6%), seedling fresh (1.7-41.3%) and dry weight (23.0-56.1%) compared to control (CN) plants. However, MT and GB treatments lessened the adverse effects of 100 and 150 mM NaCl and enhanced germination comparable to control plants. In addition, results from the pot experiments show that 200 mM NaCl stress disrupted the osmotic balance and persuaded oxidative stress, presented by higher electrolyte leakage, hydrogen peroxide, superoxide radicals, and malondialdehyde compared to control plants. However, compared to the NaCl treatment, NaCl+MT+GB treatment decreased the accumulation of malondialdehyde (24.2-42.1%), hydrogen peroxide (36.2-44.0%), and superoxide radicals (20.1-50.9%) by up-regulating the activity of superoxide dismutase (28.4-51.2%), catalase (82.2-111.5%), ascorbate peroxidase (40.3-59.2%), and peroxidase (62.2-117.9%), and by enhancing osmolytes accumulation, thereby reducing NaCl-induced oxidative damages. Based on these findings, the application of MT+GB is an efficient chemical strategy for improving seed germination and growth of seedlings by improving the physiological and biochemical attributes of maize under 200 mM NaCl stress.


Assuntos
Betaína , Germinação , Melatonina , Estresse Salino , Plântula , Sementes , Zea mays , Melatonina/farmacologia , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento , Zea mays/fisiologia , Zea mays/metabolismo , Betaína/farmacologia , Betaína/metabolismo , Germinação/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Estresse Salino/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/fisiologia , Cloreto de Sódio/farmacologia , Malondialdeído/metabolismo , Salinidade , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Sinergismo Farmacológico , Estresse Oxidativo/efeitos dos fármacos
4.
Breast Dis ; 43(1): 243-249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39213043

RESUMO

BACKGROUND: The management of mastodynia plays a central role in improving women quality of life. Despite its high occurrence, specific therapeutic guidelines for mastalgia are still lacking. Available therapies include unspecific anti-inflammatories, even though they may often expose to undesirable effects and low compliance. OBJECTIVE: The aim of this study was to highlight the efficacy of the topical application of combined natural molecules including Boswellia serrata, Betaine and myo-Inositol in improving cyclic mastalgia. METHODS: In this retrospective pilot clinical study, patients with cyclic mastalgia applied a specific breast gel for three months. The severity of the pain was measured through the Visual Analogue Score (VAS) in the treated group compared to untreated one. Treated patients also filled in a questionnaire evaluating acceptance and safety of the breast gel. RESULTS: This pilot clinical study demonstrated for the first time the efficacy of the topical application of a breast gel based on Betaine, Boswellia serrata, and myo-Inositol in improving cyclic mastodynia. The completed questionnaires also revealed high levels of acceptance, as both safety and compliance. CONCLUSIONS: Besides confirming the positive effects of these natural molecules in the management of conditions affecting breast physiology - so far evaluated as oral supplementation - the obtained results pave the way for further studies supporting the use of such molecules as a tailored medical device in the management of breast pain, thus also opening toward a combined oral and topical approach.


Assuntos
Betaína , Boswellia , Géis , Inositol , Mastodinia , Humanos , Feminino , Betaína/administração & dosagem , Betaína/uso terapêutico , Estudos Retrospectivos , Adulto , Inositol/uso terapêutico , Inositol/administração & dosagem , Mastodinia/tratamento farmacológico , Boswellia/química , Projetos Piloto , Medição da Dor , Inquéritos e Questionários , Extratos Vegetais/uso terapêutico , Pessoa de Meia-Idade
5.
ACS Appl Mater Interfaces ; 16(35): 46690-46702, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39165173

RESUMO

The development of nontoxic antifouling coatings in static marine environments is urgent. Herein, the successful synthesis of sulfobetaine borneol fluorinated polymers (PEASBF) by a free radical polymerization method is reported. The PEASBF coatings exhibit outstanding antifouling activity, which effectively resists the adhesion of Bovine serum albumin (FITC-BSA adhesion rate: 0.5%), Pseudomonas sp. (Biofilm: 1.3 absorbance) and Navicula sp. (Diatom attachment rate: 33%). More importantly, the PEASBF coatings display outstanding fouling release properties, achieving a release rate of 98% for Navicula sp., and the absorbance of the Pseudomonas sp. biofilm is only 0.2 under 10 Pa shear stress. XPS and MD studies showed that the fluorinated/isobornyl groups induce more sulfobetaine groups to migrate toward polymer surfaces for intensify antifouling. Additionally, the chiral stereochemical structure of borneol enhances antifouling and fouling release ability of amphiphilic polymers. Therefore, the PEASBF has the potential for static marine antifouling applications.


Assuntos
Incrustação Biológica , Canfanos , Polímeros , Incrustação Biológica/prevenção & controle , Canfanos/química , Canfanos/farmacologia , Polímeros/química , Polímeros/farmacologia , Biofilmes/efeitos dos fármacos , Animais , Pseudomonas/efeitos dos fármacos , Betaína/química , Betaína/análogos & derivados , Betaína/farmacologia , Soroalbumina Bovina/química , Diatomáceas/efeitos dos fármacos , Diatomáceas/química , Tensoativos/química , Tensoativos/farmacologia , Tensoativos/síntese química , Halogenação , Propriedades de Superfície
6.
J Chromatogr A ; 1733: 465232, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39178660

RESUMO

The role of the average pore diameter (APD) of 1.7µm AtlantisTM Premier BEHTM Particles derivatized with a zwitterionic group (propylsulfobetaine) on the efficiency of their 2.1 × 50 mm hydrophilic interaction liquid chromatography (HILIC) packed columns is investigated experimentally. Van Deemter plots for toluene (neutral, hydrophobic), cytosine (neutral, polar), tosylate (negatively charged), bretylium and atenolol (positively charged) were measured on three HILIC columns packed with BEH Z-HILIC Particles having APDs of 95 Å, 130 Å, and 300 Å. The intraparticle diffusivities of the analytes across these three BEH Z-HILIC Particles were measured by the peak parking method. The experimental data reveal that the slope of the C-branch of the van Deemter plots can be reduced by factors of about 15 for toluene, 2.5 for cytosine, 6 for atenolol, 5 for tosylate, and 14 for bretylium with increasing the APD from 95 Å to 300 Å. This observation is explained by: (1) the reduced amount of the highly viscous water diffuse layer and subsequent increase of the amount of acetonitrile-rich eluent in the mesopores, (2) the localized electrostatic adsorption of the retained analytes onto the zwitterion-bonded BEH Particles, and (3) depletion/excess of the analytes into the water diffuse layer. A general model of intraparticle diffusivity was then proposed to account for the impact of the APD of Z-HILIC Particles on the solid-to-liquid mass transfer resistance of small molecules. The model highlights the relevance of the thickness of the water diffuse layer, the access of the bulk eluent into the mesopore, the localized electrostatic adsorption, and the partitioning constant of the retained analyte between the bulk eluent and the water diffuse layer.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Cromatografia Líquida/métodos , Porosidade , Betaína/química , Betaína/análogos & derivados , Difusão , Tolueno/química , Atenolol/química , Atenolol/análise
7.
Int J Biol Macromol ; 278(Pt 1): 134598, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127279

RESUMO

This work reports for the first time the production of condensed tannin nanoparticles stable in water via modification with glycine betaine. Pine bark, as a byproduct from the paper industry, was used as a source of condensed tannins of high molecular weight. Different glycine betaine concentrations were tested to produce condensed tannin nanoparticles, and the obtained nanoparticles were subjected to several characterization techniques (Dynamic Light Scattering, Field emission scanning electron microscopy, Zeta potential, Fourier transform infrared spectroscopy-Attenuated total reflectance, thermogravimetric analysis). The results showed that the highest stability possessed nanoparticles with 40 wt% glycine betaine. The average particle size distribution evaluated by scanning microscopy was 124 nm. Besides, the glycine betaine-modified condensed tannin nanoparticles demonstrated higher thermal stability with the starting degradation temperature at 238 °C. Finally, obtained nanoparticles showed an antioxidant capacity of 34,209 ± 2194 µmol ET/100 g and low cytotoxicity towards healthy human cells, representing the high potential to be used as a carrier of active compounds in agriculture, food, drug and medical sector.


Assuntos
Química Verde , Nanopartículas , Pinus , Casca de Planta , Água , Pinus/química , Nanopartículas/química , Casca de Planta/química , Química Verde/métodos , Água/química , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Tamanho da Partícula , Proantocianidinas/química , Taninos/química , Betaína/química , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Microb Pathog ; 195: 106894, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39214424

RESUMO

Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study was to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition and dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compound's efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein-3 (NS3) might prove as a funamental target for Betanin and Glycine Betaine against Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 µM-10 µM) of selected phytochemicals. The dose-response assay illustrated downregulated expression of DENV-2 NS3 gene after administration of Betanin (IC50 = 4.35 µM) and Glycine Betaine (IC50 = 4.49 µM). Dose response analysis of Betanin (80 µM-10 µM) depicted the significant inhibition of NS3 protein expression as well. These results suggested downregulated expression of DENV-2 NS3 at mRNA and protein level portraying the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.


Assuntos
Antivirais , Betaína , Vírus da Dengue , Simulação de Acoplamento Molecular , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/genética , Humanos , Antivirais/farmacologia , Células HeLa , Animais , Chlorocebus aethiops , Células Vero , Betaína/farmacologia , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Betacianinas/farmacologia , Células CHO , Cricetulus , Compostos Fitoquímicos/farmacologia , Simulação de Dinâmica Molecular , Replicação Viral/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Dengue/tratamento farmacológico , Dengue/virologia , Proteases Virais
9.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-39155798

RESUMO

Betaine supplementation in dairy cattle has gained attention due to its potential benefits to production and health as a methyl donor, which can play a crucial role in the metabolism of dairy cows. The objective of the current meta-analysis was to quantify the effects of betaine supplementation on milk production, composition, ß-hydroxybutyric acid (BHBA), and non-esterified fatty acids (NEFA). A systematic literature search was carried out, all relevant studies were retrieved, and the meta-analysis was carried out. The mean difference (MD) for dry matter intake (DMI) using the random-effects model was 0.499 kg/d (P < 0.0001). The subgroup analysis indicated that supplementing betaine in heat-stressed cows increased DMI by 0.584 kg/d (P < 0.001), while in cows not exposed to heat stress, DMI was increased by 0.381 kg/d (P = 0.007). The energy-corrected milk (ECM) increased by 1.36 kg/d (P < 0.0001). The milk fat yield was significantly increased in betaine-supplemented cows (MD = 0.040 kg/d, 95% CI = 0.015 to 0.065). The milk protein yield (kg/d) (MD = 0.014, P = 0.138) was increased (MD = 0.035, P = 0.0005) by betaine supplementation. The lactose yield (kg/d) was also significantly higher (MD = 0.055, P = 0.020) in betaine-supplemented cows. The standardized mean difference (SMD) for NEFA (SMD = - 0.447, 95% CI = - 1.029 to 0.135, P = 0.114) and BHBA (SMD = - 0.130, 95% CI = - 0.491 to 0.234). In conclusion, the findings from this meta-analysis suggest that betaine supplementation positively influences DMI, ECM, milk fat yield, milk lactose yield, and milk protein yield. Subgroup analysis further indicated that the positive effects on DMI are greater in heat-stressed cows compared to those not exposed to heat stress. The analysis did not find significant effects on the levels of NEFA or BHBA, suggesting that betaine supplementation may not directly influence these metabolic parameters.


The aim of this meta-analysis was to examine the effects of dietary betaine supplementation on dairy cows' dry matter intake, milk production, milk composition, non-esterified fatty acids, and ß-hydroxybutyric acid. The results indicated that the supplementation of betaine increased dry matter intake (+0.584 kg/d/cow), energy-corrected milk (+1.36 kg/d), milk fat yield (+ 0.040 kg/d), milk protein yield (+ 0.014 kg/d), and lactose yield (+ 0.055 kg/d). ß-Hydroxybutyric acid and plasma non-esterified fatty acids were not influenced by betaine supplementation in dairy cattle.


Assuntos
Ácido 3-Hidroxibutírico , Betaína , Suplementos Nutricionais , Ácidos Graxos não Esterificados , Leite , Animais , Bovinos/fisiologia , Leite/química , Betaína/farmacologia , Betaína/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Suplementos Nutricionais/análise , Feminino , Ácido 3-Hidroxibutírico/sangue , Ácido 3-Hidroxibutírico/farmacologia , Dieta/veterinária , Lactação/efeitos dos fármacos , Ração Animal/análise
10.
J Chromatogr A ; 1734: 465316, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39216281

RESUMO

The structure of zwitterion has great impact on the separation properties of zwitterionic hydrophilic stationary phases. To better understand the role of anionic groups of zwitterions, a novel carboxybetaine-based zwitterionic monolithic column was first prepared through thermo-initiated copolymerization of functional monomer (3-acrylamidopropyl)-dimethyl-(2-carboxymethyl) ammonium (CBAA) and crosslinker ethylene dimethacrylate (EDMA) within 100 µm ID capillary. The optimal poly(CBAA-co-EDMA) monolithic column exhibited satisfactory mechanical and chemical stability, good repeatability, high column efficiency (96,000 plates/m), and excellent separation performance for different classes of polar compounds (i.e., phenols, monophosphate nucleotides, urea and allantoin). A comparative study was then performed among three zwitterionic hydrophilic stationary phases containing different anionic groups, i.e. poly(CBAA-co-EDMA) (carboxybetaine), poly(2-{2-(methacryloyloxy) ethyldimethylammonium}ethyl n-butyl phosphate-co-EDMA) (phosphocholine), and poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl) ammonium betaine-co-EDMA) (sulfobetaine) using benzoic acid derivatives, amine compounds, nucleobases and nucleosides as model analytes. The carboxybetaine-based monolithic column exhibited much higher positive zeta-potential and hydrophilicity, which endows it with a stronger retention capacity for acidic and neutral compounds, but sulfobetaine-based monolithic column exhibited much higher selectivity and retention capacity for the amines. Moreover, their enrichment efficiencies for N-glycopeptides were also evaluated based on their different hydrophilicity, and it was observed that the poly(CBAA-co-EDMA) monolithic material captured 4-8 times more N-glycopeptides compared to the other two materials.


Assuntos
Ânions , Interações Hidrofóbicas e Hidrofílicas , Ânions/química , Betaína/química , Betaína/análogos & derivados , Metacrilatos/química , Cromatografia Líquida de Alta Pressão/métodos , Fenóis/química , Fenóis/isolamento & purificação , Reprodutibilidade dos Testes , Polímeros/química
11.
Circ Heart Fail ; 17(8): e011569, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39119698

RESUMO

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. REGISTRATION: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.


Assuntos
Betaína , Carnitina , Colina , Microbioma Gastrointestinal , Insuficiência Cardíaca , Metilaminas , Humanos , Metilaminas/sangue , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/sangue , Microbioma Gastrointestinal/fisiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Incidência , Colina/sangue , Carnitina/análogos & derivados , Carnitina/sangue , Betaína/sangue , Betaína/análogos & derivados , Estados Unidos/epidemiologia , Fatores de Risco , Biomarcadores/sangue , Idoso de 80 Anos ou mais
12.
Int J Pharm ; 663: 124553, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39103063

RESUMO

In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU's de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU's efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.


Assuntos
Betaína , Biofilmes , Desbridamento , Solventes , Cicatrização , Biofilmes/efeitos dos fármacos , Animais , Betaína/farmacologia , Betaína/química , Humanos , Solventes/química , Cicatrização/efeitos dos fármacos , Desbridamento/métodos , Camundongos , Masculino , Feminino , Ureia , Mel , Pele/microbiologia , Pele/efeitos dos fármacos , Doença Crônica , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Pessoa de Meia-Idade , Diabetes Mellitus Experimental/tratamento farmacológico , Idoso
13.
Sci Adv ; 10(33): eado6229, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39141726

RESUMO

The choline-glycine betaine pathway plays an important role in bacterial survival in hyperosmotic environments. Osmotic activation of the choline transporter BetT promotes the uptake of external choline for synthesizing the osmoprotective glycine betaine. Here, we report the cryo-electron microscopy structures of Pseudomonas syringae BetT in the apo and choline-bound states. Our structure shows that BetT forms a domain-swapped trimer with the C-terminal domain (CTD) of one protomer interacting with the transmembrane domain (TMD) of a neighboring protomer. The substrate choline is bound within a tryptophan prism at the central part of TMD. Together with functional characterization, our results suggest that in Pseudomonas species, including the plant pathogen P. syringae and the human pathogen Pseudomonas aeruginosa, BetT is locked at a low-activity state through CTD-mediated autoinhibition in the absence of osmotic stress, and its hyperosmotic activation involves the release of this autoinhibition.


Assuntos
Proteínas de Bactérias , Colina , Microscopia Crioeletrônica , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Colina/metabolismo , Colina/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Pseudomonas syringae/metabolismo , Modelos Moleculares , Osmorregulação , Pressão Osmótica , Betaína/metabolismo , Conformação Proteica , Ligação Proteica , Relação Estrutura-Atividade , Domínios Proteicos
15.
EMBO J ; 43(17): 3787-3806, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39009676

RESUMO

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.


Assuntos
Aminoacetonitrila , Anti-Helmínticos , Betaína , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Microscopia Crioeletrônica , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/efeitos dos fármacos , Anti-Helmínticos/farmacologia , Anti-Helmínticos/metabolismo , Anti-Helmínticos/química , Betaína/análogos & derivados , Betaína/metabolismo , Betaína/farmacologia , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Aminoacetonitrila/análogos & derivados , Aminoacetonitrila/farmacologia , Receptores Colinérgicos/metabolismo , Receptores Colinérgicos/química , Receptores Colinérgicos/genética , Conformação Proteica , Modelos Moleculares
16.
Nat Genet ; 56(8): 1614-1623, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38977856

RESUMO

Organisms maintain metabolic homeostasis through the combined functions of small-molecule transporters and enzymes. While many metabolic components have been well established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Association Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions and even pinpoint genes that are distant from the variants implicated by GWAS. In particular, our analysis identified solute carrier family 25 member 48 (SLC25A48) as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite betaine. Integrative rare variant and polygenic score analyses in UK Biobank provide strong evidence that the SLC25A48 causal effects on human disease may in part be mediated by the effects of choline. Altogether, our study provides a discovery platform for metabolic gene function and proposes SLC25A48 as a mitochondrial choline transporter.


Assuntos
Colina , Estudo de Associação Genômica Ampla , Mitocôndrias , Colina/metabolismo , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/genética , Transporte Biológico/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Metaboloma , Betaína/metabolismo
17.
Int J Biol Macromol ; 276(Pt 2): 133949, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025172

RESUMO

Different methods of starch modification have been proposed to broaden its application. In this study, the effects of ternary mixtures of natural crosslinking agents: chitosan-betaine-vanillin and gelatin-betaine-vanillin on the properties of pea starch were explored. These combinations of substances were selected because they have complementary crosslinking mechanisms. The effects of the ternary crosslinker mixtures on the gelatinization, mechanical properties, thermal stability, and microstructure of pea starch were compared. Both combinations of crosslinkers enhanced the gelatinization viscosity, viscoelasticity, gel hardness, and thermal stability of the pea starch, by an amount that depended on the ratio of the different components in the ternary mixtures. In all cases, the crystal structure of the starch granules disappeared after gelatinization. The modified starch had a more compact and uniform microstructure than the non-modified version, especially when it was crosslinked by vanillin, gelatin, and betaine. The improvement in the gelation properties of the starch were primarily attributed to hydrogen bonding, electrostatic attraction, and Schiff base crosslinking of the various components present. Gelatin enhanced the gel strength more than chitosan, which was probably because of greater hydrogen bonding. Our findings suggest that the properties of starch can be enhanced by adding ternary mixtures of natural crosslinkers.


Assuntos
Benzaldeídos , Betaína , Quitosana , Reagentes de Ligações Cruzadas , Gelatina , Pisum sativum , Amido , Gelatina/química , Amido/química , Quitosana/química , Betaína/química , Benzaldeídos/química , Pisum sativum/química , Reagentes de Ligações Cruzadas/química , Viscosidade , Géis/química
18.
Artigo em Inglês | MEDLINE | ID: mdl-39029648

RESUMO

Methamphetamine abuse has been associated with central nervous system damage, contributing to the development of neuropsychiatric disorders such as depressive-like behavior and cognitive impairment. With the escalating prevalence of METH abuse, there is a pressing need to explore effective therapeutic interventions. Thus, the objective of this research was to investigate whether betaine can protect against depressive-like behavior and cognitive impairment induced by METH. Following intraperitoneal injections of METH in mice, varying doses of betaine were administered. Subsequently, the behavioral responses of mice and the impact of betaine intervention on METH-induced neural damage, synaptic plasticity, microglial activation, and NLRP3 inflammatory pathway activation were assessed. Administration 30 mg/kg and 100 mg/kg of betaine ameliorated METH-induced depressive-like behaviors in the open field test, tail suspension test, forced swimming test, and sucrose preference test and cognitive impairment in the novel object recognition test and Barnes maze test. Moreover, betaine exerted protective effects against METH-induced neural damage and reversed the reduced synaptic plasticity, including the decline in dendritic spine density, as well as alterations in the expression of hippocampal PSD95 and Synapsin-1. Additionally, betaine treatment suppressed hippocampal microglial activation induced by METH. Likewise, it also inhibited the activation of the hippocampal NLRP3 inflammasome pathway and reduced IL-1ß and TNF-α release. These results collectively suggest that betaine's significant role in mitigating depressive-like behavior and cognitive impairment resulting from METH abuse, presenting potential applications in the prevention and treatment of substance addiction.


Assuntos
Betaína , Disfunção Cognitiva , Depressão , Inflamassomos , Metanfetamina , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Metanfetamina/toxicidade , Camundongos , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/metabolismo , Betaína/farmacologia , Depressão/tratamento farmacológico , Depressão/induzido quimicamente , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia
19.
Dent Mater ; 40(10): 1575-1583, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39068090

RESUMO

OBJECTIVES: This study aimed to use a carboxybetaine methacrylate (CBMA) copolymer solution to surface treat 3D printed clear aligners at different fabrication stages, to impart antifouling properties, and assess the surface treatment at various fabrication stages' impact on physico-mechanical characteristics. METHODS: Surface treatments using a blend of 2-hydroxyethyl methacrylate (HEMA) and CBMA, termed CCS, were performed at various stages of 3D printed clear aligner fabrication. Experimental groups, CB1, CB2, and CB3, were determined by the stage of surface treatment during post-processing. CB1, CB2, and CB3 received treatment before post-curing, after post-curing, and after post-processing, respectively. Untreated samples served as controls. Physical and mechanical properties were assessed through tensile testing, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and UV-Vis spectroscopy. The surface was further characterized through scanning electron microscopy and contact angle measurements. The cytotoxicity was assessed with 7-day elution and agar diffusion assays. Lastly, bacterial biofilm resistance was evaluated using confocal laser scanning microscopy. Crystal violet assay was performed using Streptococcus mutans. RESULTS: Surface treatment during CB1 stage exerted the most significantly unfavorable influence on properties of the 3D printed aligner resin. CB2 samples showed the maximum preservation of translucency even after 7-day aging. CB2 and CB3 phases showed enhanced hydrophilicity of sample surfaces with reduced adhesion of multispecies biofilm and S. mutans. SIGNIFICANCE: Application of CCS surface treatment immediately after post-curing (CB2) can enhance the biofilm resistance of 3D printed clear aligners while maintaining high fidelity to optical translucency and constituent mechanical properties.


Assuntos
Biofilmes , Teste de Materiais , Metacrilatos , Impressão Tridimensional , Propriedades de Superfície , Biofilmes/efeitos dos fármacos , Metacrilatos/química , Betaína/química , Betaína/farmacologia , Betaína/análogos & derivados , Microscopia Eletrônica de Varredura , Streptococcus mutans/efeitos dos fármacos , Polímeros/química , Resistência à Tração , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Biomater Adv ; 163: 213965, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39053386

RESUMO

The unique amino acid composition of elastin peptide (EP) makes it an excellent resource to obtain antioxidant peptides. It exhibits high elastase inhibitory activity with the potential to resist skin aging and is currently used in a many cosmetic products. However, the inherent low permeability of the skin limits its ability to penetrate the skin. To address this issue, a deep eutectic solvent (SAB) with excellent bioactivity was synthesized from betaine and succinic acid and used as a permeation enhancer to improve the absorption and utilization of EP in this paper. The results showed that low SAB concentrations significantly increased the transdermal delivery of EP. The 3D epidermal skin model (EpiKutis®) demonstrated that SAB/EP induced the synthesis of hyaluronic acid (HA) and filaggrin (FLG), accelerated skin barrier repair, and reduced water loss. Additionally, the zebrafish embryonic model showed that SAB/EP could reduce melanin secretion, decrease melanin deposition, and have an ameliorative effect on skin photoaging. Cellular experiments proved that SAB/EP can stimulate human skin fibroblasts to secrete procollagen I and elastin, improving skin elasticity and anti-wrinkle. The combination of EP and DES is a new attempt that is expected to be used as a safe and effective anti-wrinkle cosmetic material.


Assuntos
Administração Cutânea , Betaína , Elastina , Proteínas Filagrinas , Envelhecimento da Pele , Pele , Elastina/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Humanos , Animais , Betaína/farmacologia , Betaína/administração & dosagem , Betaína/química , Betaína/análogos & derivados , Pele/metabolismo , Pele/efeitos dos fármacos , Peixe-Zebra , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Peptídeos/farmacologia , Peptídeos/administração & dosagem , Peptídeos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA